Metabolism - Clinical and Experimental via MedWorm.com

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Metabolism - Clinical and Experimental — Tue, 24 Jan 2012 19:16:00 +0100

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Metabolism - Clinical and Experimental — Tue, 24 Jan 2012 19:16:00 +0100

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Dietary calcium and body weight: what's the “skinny”?

Metabolism - Clinical and Experimental — Tue, 24 Jan 2012 19:15:58 +0100

There has been growing interest in mechanisms underlying the observation that high dietary calcium intake may attenuate weight gain. Both animal and human studies have explored this association . However, the metabolic alterations that explain this phenomenon remain unclear, as are the molecular mechanisms that may be at play. This month's article by Zhang et al provides new insights into this question. (Source: Metabolism - Clinical and Experimental)

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Metabolism - Clinical and Experimental — Tue, 24 Jan 2012 19:15:58 +0100

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Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

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Editorial Board

Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

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Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

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Elsevier/Oxford Centre for Diabetes, Endocrinology and Metabolism Junior Research Prize in Endocrinology: ENDO 2011 conference report

Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

In June 2011, I was privileged to travel to Boston, MA, to attend ENDO 2011, the Annual Meeting of the American Endocrine Society. Eight months earlier, I had participated in the Elsevier/Oxford Centre for Diabetes, Endocrinology and Metabolism Junior Research Prize in Endocrinology, a competition open to DPhil students and first-year postdoctoral researchers at the University of Oxford, with a prize of free registration, accommodation, and travel to the ENDO conference. The competition involved the submission of a 300-word abstract describing your contribution to endocrinology research. Four abstracts were selected for oral presentations to a panel of judges and an audience of researchers; and my presentation, entitled “Functional Studies of GATA3 Mutants in Oestrogen Receptor Positive ...

The Metabolism Award for Junior Investigators

Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

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Metabolism - Clinical and Experimental — Thu, 08 Dec 2011 07:52:27 +0100

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Metabolism - Clinical and Experimental — Thu, 17 Nov 2011 21:54:33 +0100

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Metabolism - Clinical and Experimental — Thu, 17 Nov 2011 21:54:33 +0100

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Metabolism - Clinical and Experimental — Thu, 17 Nov 2011 21:54:33 +0100

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Metabolism - Clinical and Experimental — Wed, 19 Oct 2011 17:57:09 +0100

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Metabolism - Clinical and Experimental — Wed, 19 Oct 2011 17:57:09 +0100

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Mutational analysis of human bone morphogenetic protein 15 in Chinese women with polycystic ovary syndrome

Metabolism - Clinical and Experimental — Wed, 19 Oct 2011 17:57:09 +0100

Abstract: Polycystic ovary syndrome (PCOS) is one of the common defects that cause ovary dysfunction and link to the aberrant process of folliculogenesis. Bone morphogenetic protein 15 (BMP15) is expressed in human oocytes and functions importantly to regulate early follicle growth and fertility. Previous studies have discovered several mutations in the screening of BMP15 in premature ovarian failure but none in PCOS. In this current study, we focused on the mutational analysis of the coding region of BMP15 among 216 Chinese PCOS patients. Five novel missense mutations in BMP15 were discovered, namely, c.34C>G, c.109G>C, c.169C>G, c.288G>C, and c.598C>T. These results are the first to indicate that BMP15 gene mutations may be potentially associated with PCOS patients. (Source: Metabolism -...

Masthead

Metabolism - Clinical and Experimental — Wed, 19 Oct 2011 17:57:09 +0100

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Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box

Metabolism - Clinical and Experimental — Mon, 26 Sep 2011 04:00:00 +0100

Abstract: Familial hypercholesterolemia (FH) is a dominantly inherited disorder principally due to mutations in the low-density lipoprotein (LDL) receptor that classically cause markedly elevated plasma LDL cholesterol concentrations and premature coronary heart disease (CHD). However, elevated plasma LDL cholesterol alone does not fully account for the increase or variation in risk of CHD. We propose a hypothetical model for the role of postprandial dyslipoproteinemia based on the overproduction and decreased catabolism of triglyceride-rich lipoproteins, which may be a consequence of LDL receptor deficiency. Expression of postprandial dyslipoproteinemia in FH may also depend on the type of pathogenic gene variants and on coexistent conditions, particularly obesity and insulin resistance. ...

One year of changes for Metabolism, Clinical and Experimental: evolution and intelligent design at work

Metabolism - Clinical and Experimental — Mon, 26 Sep 2011 04:00:00 +0100

July 2011 marked the completion of 1 year of my being Editor-in-Chief, at the helm of Metabolism, Clinical and Experimental. Over the past year, many of our readers have observed a number of enhancements in the journal that have generated positive comments. We encourage those who have not yet noticed these new features to check them out. Several innovations have materialized during this past year, some in the context of a much-needed evolution in response to the electronic and information technology that is changing so many aspects of our personal and professional lives, whereas others may hopefully reflect what one could call intelligent design. I would like to take this time to provide an update for our authors, reviewers, and readers. (Source: Metabolism - Clinical and Experimental)

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Metabolism - Clinical and Experimental — Fri, 23 Sep 2011 07:59:59 +0100

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Metabolism - Clinical and Experimental — Fri, 23 Sep 2011 07:59:59 +0100

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Metabolism - Clinical and Experimental — Fri, 23 Sep 2011 07:59:59 +0100

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Adiponectin levels in nonalcoholic fatty liver disease

Metabolism - Clinical and Experimental — Wed, 14 Sep 2011 04:00:00 +0100

We read with great interest the recent review produced by Sofer et al on the effect of metformin treatment (at a dose of 850 to 1700 mg/d) on arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease (NAFLD). Adiponectin is exclusively secreted by adipocytes and is considered as an anti-inflammatory adipokine. It reduces body fat; improves hepatic and peripheral insulin sensitivity; and is inversely associated with body mass index, insulin resistance, and hepatic fat. Low serum adiponectin level predisposes to the development of NAFLD and insulin resistance. On the contrary, a high level of this adipokine suggests lack or low grade of liver steatosis . In the “Results” paragraph, the authors reported that serum adiponectin level ten...

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients

Metabolism - Clinical and Experimental — Fri, 26 Aug 2011 04:00:00 +0100

This study was designed to elucidate the associations of salivary cortisol levels with weight reduction and CVD risk factors in obese patients. As a marker of HPA axis activity, we measured the morning salivary cortisol levels of 83 obese Japanese outpatients. We also examined metabolic parameters, inflammatory markers, and indicators of arterial stiffness, that is, the pulse wave velocity and cardio-ankle vascular index. All 83 obese patients underwent 3-month weight reduction therapy with lifestyle modification. At the baseline, multivariate regression analysis revealed that only logarithmic transformation of C-reactive protein (β = 0.258, P < .05) and cardio-ankle vascular index (β = 0.233, P < .05) were independent determinants of the salivary cortisol levels. However, other metaboli...

S100A16 mediation of weight gain attenuation induced by dietary calcium

Metabolism - Clinical and Experimental — Fri, 26 Aug 2011 04:00:00 +0100

This study aimed to investigate the effect of S100A16 on weight gain attenuation with a calcium-rich diet. An obese rat model was produced after feeding with a high-fat diet. Animals were randomly divided into 4 groups according to the diet provided over 8 weeks: normal diet group; high-fat, normal-calcium diet group; high-fat, high-calcium diet (HH) group; and high-fat, low-calcium diet group. Serum biochemistry was analyzed, and body weight and visceral fat pads were measured. Expression of S100A16 was assayed by Western blotting. Adipogenesis was detected by oil red O staining. Increases in body weight and visceral fat weight were attenuated in the HH group. High-calcium diets decreased the concentrations of serum total cholesterol and triglyceride. Expression of S100A16 decreased in th...

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

The objective of this study was to evaluate whether hyperuricemia, acidic urine, or their combination predicts metabolic syndrome (MetS). In study 1, 69 094 subjects who received a general health checkup between 1985 and 2005 were included in a cross-sectional study of serum uric acid (SUA) and urine pH in relation to MetS. In study 2, the association of SUA and urine pH with MetS development over a 5-year period was evaluated in 5617 subjects with body mass index less than 25 kg/m2 at the first examination. In study 1, higher SUA and lower urine pH were both positively correlated to MetS status (P < .001). The combination of high SUA and low urine pH was significantly associated with higher MetS prevalence compared with the combination of low SUA and high urine pH (odds ratio, 3.383; 95%...

Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

The objective was to verify if 6 months of mixed training combined with phytoestrogens could have an additional effect on adipokine levels and systemic inflammation in obese postmenopausal women. Fifty-two obese women aged between 50 and 70 years were randomly assigned to (1) exercise with placebo (EX + PL; n = 25) or (2) exercise with phytoestrogens (EX + PHY; n = 27). Body weight, waist circumference, fat mass, and lean body mass (dual-energy x-ray absorptiometry) were assessed. Fasting plasma glucose and insulin, adiponectin, leptin, and C-reactive protein (CRP) levels were obtained after a 12-hour overnight fast. Total energy intake was measured with a 3-day dietary record. All measurements were performed before and after the 6-month intervention. Although energy intake remained unchan...

Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

The objectives of the study were to quantify the effect of a 1-year healthy eating–physical activity/exercise lifestyle modification program on insulin sensitivity in viscerally obese men classified according to their glucose tolerance status and to evaluate the respective contributions of changes in body fat distribution vs changes in cardiorespiratory fitness (CRF) to the improvements in indices of plasma glucose/insulin homeostasis. Abdominally obese, dyslipidemic men (waist circumference ≥90 cm, triglycerides ≥1.69 mmol/L, and/or high-density lipoprotein cholesterol (Source: Metabolism - Clinical and Experimental)

Combined hypertriglyceridemic and insulin-glucose clamps for the characterization of substrate oxidation and plasma elimination of a long-chain triglyceride emulsion in healthy men

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

This study examines the effect of glucose and insulin on the plasma elimination rate and oxidation of a fat emulsion by using indirect calorimetry in conjunction with lipid and insulin-glucose clamp techniques. Ten healthy subjects were studied on 2 occasions in a randomized, open, crossover study. On one occasion, a hypertriglyceridemic (HTG) clamp was administrated alone; and, on the other, HTG and insulin-glucose (IG) clamps were administrated simultaneously. During HTG clamps, serum triglyceride (TG) concentration was maintained at 4 mmol × L−1. During the IG clamp, insulin was administered at a rate of 20 mU × m−2 × min−1; and the glucose level was maintained at 7 mmol × L−1. Continuous indirect calorimetry was carried out throughout the study period. The infusion rate req...

Acute resistance exercise augments integrative myofibrillar protein synthesis

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

Abstract: The purpose of this study was to determine whether an acute bout of high-intensity resistance exercise (RE) would augment integrative mixed muscle and myofibrillar protein fractional synthesis rates (FSRs) when total energy and macronutrient intake was controlled. Twelve healthy young men were studied over 24 hours and performed an acute bout of exhaustive (5 sets until volitional failure of their 85% 1-repetition maximum) unilateral leg press and knee extension exercise, such that one leg was exercised (EX) and the other served as a control (CON). 2H2O (70%) was provided to measure mixed muscle and myofibrillar FSR, and muscle biopsies (vastus lateralis) were collected from the EX and CON legs 16 hours following the RE session. 2H-labeling of body water over the course of the ex...

The effects of glucocorticoids on adipose tissue lipid metabolism

Metabolism - Clinical and Experimental — Wed, 24 Aug 2011 04:00:00 +0100

Abstract: Glucocorticoids (GCs) have long been accepted as being catabolic in nature, liberating energy substrates during times of stress to supply the increased metabolic demand of the body. The effects of GCs on adipose tissue metabolism are conflicting, however, because patients with elevated GCs present with central adiposity. We performed an extensive literature review of the effects of GCs on adipose tissue metabolism. The contradictory effects of GCs on lipid metabolism occur through a number of different mechanisms, some of which are well defined and others remain to be elucidated. Firstly, through increases in caloric and dietary fat intake, along with increased hydrolysis of circulating triglycerides (chylomicrons, very low-density lipoproteins) by lipoprotein lipase activity, GC...

Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

Metabolism - Clinical and Experimental — Mon, 22 Aug 2011 04:00:00 +0100

Abstract: During feeding, dietary galactose is a potential source of hepatic glycogen synthesis; but its contribution has not been measured to date. In the presence of deuterated water (2H2O), uridine diphosphate (UDP)–glucose derived from galactose is not enriched, whereas the remainder derived from glucose-6-phosphate (G6P) is enriched in position 2 to the same level as body water, assuming complete G6P–fructose-6-phosphate (F6P) exchange. Hence, the difference between UDP-glucose position 2 and body water enrichments reflects the contribution of galactose to glycogen synthesis relative to all other sources. In study 1, G6P-F6P exchange in 6 healthy subjects was quantified by supplementing a milk-containing breakfast meal with 10 g of [U-2H7]glucose and quantifying the depletion of p...

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Metabolism - Clinical and Experimental — Wed, 17 Aug 2011 16:24:35 +0100

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Metabolism - Clinical and Experimental — Wed, 17 Aug 2011 16:24:35 +0100

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Metabolism - Clinical and Experimental — Wed, 17 Aug 2011 16:24:26 +0100

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Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Metabolism - Clinical and Experimental — Mon, 08 Aug 2011 04:00:00 +0100

This study determined whether reductions in postprandial plasma nonesterified fatty acid (FFA) flux would lead to reductions in plasma acylcarnitine (AC) concentrations. Plasma AC was measured by liquid chromatography with tandem mass spectrometry in the fasting state and over 6 hours after a high-fat (50% energy) meal was fed to 16 overweight and obese subjects with a wide range of insulin sensitivities. Body composition was measured by dual-energy x-ray absorptiometry; insulin sensitivity by insulin-modified, frequently sampled intravenous glucose tolerance test; substrate oxidation by indirect calorimetry; blood metabolite and hormone concentrations biochemically; and fatty acid flux by using stable isotope tracers. Lean body mass and fasting fat oxidation correlated positively (r > 0.5...

Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats

Metabolism - Clinical and Experimental — Mon, 08 Aug 2011 04:00:00 +0100

The objectives were to assess the potential of long-term prophylactic administration of telmisartan, an angiotensin II receptor antagonist and a partial peroxisome proliferator activator receptor (PPAR)γ agonist, in preventing the development of hypertension and hyperglycemia and to demonstrate the alteration in gene expression associated with the development of hyperglycemia and insulin resistance in Cohen-Rosenthal diabetic hypertensive rat, a unique model of hypertension and type 2 diabetes mellitus comorbidity. Cohen-Rosenthal diabetic hypertensive rats were continuously treated with telmisartan (3 mg/[kg d]) starting at age 6 to 8 weeks before developing hypertension or diabetes. Weight changes, blood pressure, blood insulin, adiponectin, glucose tolerance, and insulin sensitivity we...

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

This study aimed to investigate whether the strong association of cancer and diabetes is independent from the influence of hypertension, dyslipidemia, and gout in the Taiwanese population. A total of 985 815 study subjects were identified from the National Health Insurance in 1997 and followed up from 1998 to 2009. The demographic characteristics between patients with diabetes and cancer, including age, sex, hypertension, dyslipidemia, and gout, were analyzed using the χ2 test. Cox proportional hazard regression models were used to determine the independent effects of diabetes on the risks of cancer. A total of 104 343 diabetic patients were followed up from 1998 to 2009. After adjusting for sex, age, hypertension, dyslipidemia, and gout, the incidences of cancer at any site and in the ...

Influence of resting energy expenditure on blood pressure is independent of body mass and a marker of sympathetic tone

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

This study affirms previous findings that REE may be a potential mediator in resting BP, independent of many well-cited factors and, additionally, a marker of sympathetic tone. (Source: Metabolism - Clinical and Experimental)

Acute hypoglycemia causes depressive-like behaviors in mice

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

Abstract: Reports in humans advocate a link between hypoglycemia and altered mood. Such observations, however, have not been mechanistically explored. Here we examined depressive-like behaviors in mice resulting from acute hypoglycemia. Mice were fasted for 12 hours and then administered intraperitoneal insulin to induce a blood glucose nadir of 50 mg/dL at 0.75 hour after injection that by 2 hours postinjection had returned to normal. The behaviors of locomotion, forced swim, saccharin preference, and novel object recognition were subsequently examined. Mice made hypoglycemic showed depressive-like behaviors 24 hours after resolution of hypoglycemia as evidenced by increased immobility in the forced swim test (FST) and reduced saccharin preference. Movement and memory were not impacted by...

Fatness, fitness, and cardiometabolic risk factors in middle-aged white men

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

The objective was to test the hypothesis that traditional and novel cardiometabolic risk factors would be significantly different in groups of men of different fatness and fitness. Total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, insulin, high-sensitivity C-reactive protein, alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, leptin, adiponectin, tumor necrosis factor–α, interleukin-6, interleukin-10, fibrinogen, and insulin resistance were assessed in 183 nonsmoking white men aged 35 to 53 years, including 62 who were slim and fit (waist girth ≤90 cm and maximal oxygen consumption [VO2max] above average), 24 who were slim and unfit (waist girth ≤90 cm and VO2max average or below), 39 who ...

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

This study aims to examine the association between endogenous sex hormones and indices of vascular function and structure. Serum follicle-stimulating hormone, luteinizing hormone, estradiol, testosterone, sex hormone–binding globulin, dehydroepiandrosterone sulfate (DHEAS), and Δ4-androstenedione were measured in 120 healthy postmenopausal women aged 41 to 60 years. Possible associations with surrogate markers of subclinical atherosclerosis, arterial stiffness, and endothelial function were investigated. Indices of arterial structure included carotid and femoral intima-media thickness and atheromatous plaques presence. Indices of arterial function included flow-mediated dilation of the brachial artery, carotid-femoral pulse wave velocity (PWV), and augmentation index. Total testosterone...

Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

Abstract: The positive association between the ratio of serum low-density lipoprotein cholesterol (LDL-C) to serum high-density lipoprotein cholesterol (HDL-C) and cardiovascular events has recently been receiving much attention. However, the association between the severity of obstructive sleep apnea (OSA) and this ratio has not yet been investigated. Accordingly, we sought to clarify this association and the effect of continuous positive airway pressure (CPAP) therapy on the ratio. We performed polysomnography and LDL-C/HDL-C measurements in 215 patients who were suspected of having OSA. Furthermore, LDL-C/HDL-C was again evaluated 6 months after polysomnography in 30 OSA patients for whom CPAP therapy was initiated and continued, and in 11 age- and sex-matched OSA patients for whom the ...

Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

Abstract: Exercise training may decrease insulin resistance (IR) and increase glucose tolerance. However, the adaptive responses in skeletal muscle at the molecular and genetic level have not been clearly understood. Here we used oligonucleotide microarray analysis to dissect the effects of high-fat diet (HFD) and regular aerobic exercise on global gene expression in the skeletal muscle of C57BL/6 mice. C57BL/6 male mice (n = 40) were fed with normal chow (n = 20) and HFD (n = 20) for 8 weeks. The animals were then divided into 1 of 4 intervention groups: groups of mice fed with normal chow and HFD accompanied with 6-week treadmill running (60 min/d) at 75% maximum oxygen consumption (NE and HE) and their sedentary control groups (NC and HC). Oligonucleotide microarray was applied to analy...

Severity and outcome of acute stroke in women: relation to adrenal sex steroid levels

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

The objective of our study was to investigate the role of adrenal sex steroids in a female population suffering an acute stroke. We addressed the question of whether their levels are associated with disease severity and prognosis. A 2-year cohort study was performed in 2 tertiary hospitals, where we prospectively studied 302 consecutive postmenopausal female patients hospitalized for an acute stroke. Neurological severity on admission was assessed by the National Institutes of Health Stroke Scale; and handicap 1 month after stroke, with the modified Rankin Scale. Δ4-androstenedione levels were positively and dehydroepiandrosterone sulfate was inversely associated with stroke severity (r = 0.142, P = .014 and r = −0.153, P = .008, respectively), and both parameters remained as significan...

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

This study examined the association among serum adiponectin levels, a single nucleotide polymorphism (SNP) of the adiponectin gene, and the size of serum high-density lipoprotein (HDL) particles in a general population. A total of 275 subjects were examined as part of the community-based Mima study. Serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Serum small-sized HDL was measured with the electrophoretic separation of lipoproteins using the Lipoprint system. Single nucleotide polymorphism G276T (rs1501299, SNP276) of the adiponectin gene was determined with a fluorescent allele-specific DNA primer assay system. Age- and sex-adjusted correlation test revealed a significant inverse relationship between small-sized HDL and adiponectin levels (r = −0.236, P...

Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

Abstract: Differences in insulin regulation of free fatty acids (FFAs) are not readily apparent at the same insulin concentrations used to differentiate relative insulin-mediated glucose disposal. Resistance to insulin-mediated glucose disposal and higher daylong FFA concentrations occur more commonly in obese individuals. However, the relationship between the ability of insulin to suppress FFA release from adipose tissue and stimulate glucose disposal in muscle has not been clearly defined in this population. The current study was initiated to test the hypothesis that these 2 facets of insulin action are related, with greater defects in insulin-mediated glucose disposal associated with less effective insulin inhibition of FFA release from adipose tissue. Subjects included 56 healthy nondi...

The quest for the perfect biomarker of long-term glycemia: new studies, new trials and tribulations

Metabolism - Clinical and Experimental — Fri, 05 Aug 2011 04:00:00 +0100

Frequent evaluation as well as precise measurement of glycemic control form a critical part of diabetes management because the success of treating diabetic patients depends, to a large extent, on the attainment of target glycemic levels. Currently, glycated hemoglobin (HbA1c) remains the most widely used test for the assessment of glycemic control. HbA1c is formed from the nonenzymatic glycation of hemoglobin in erythrocytes and provides a reliable reflection of average glycemic status in the preceding 2 to 3 months, allowing clinicians to evaluate success of their treatment and also make treatment adjustments based on its measurement. HbA1c has been well correlated with diabetes-related micro- and macrovascular complications in large epidemiological trials and can be conveniently measured...

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: The delicate homeostatic balance between glucose and fatty acid metabolism in relation to whole-body energy regulation is influenced by mitochondrial function. We determined expression and regulation of mitochondrial enzymes including pyruvate dehydrogenase kinase (PDK) 4, PDK2, carnitine palmitoyltransferase 1b, and malonyl–coenzyme A decarboxylase in skeletal muscle from people with normal glucose tolerance (NGT) or type 2 diabetes mellitus (T2DM). Vastus lateralis biopsies were obtained from NGT (n = 79) or T2DM (n = 33) men and women matched for age and body mass index. A subset of participants participated in a 4-month lifestyle intervention program consisting of an unsupervised walking exercise. Muscle biopsies were analyzed for expression and DNA methylation status. Prim...

Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation–derived criteria and associations with adiponectin and leptin

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: The aims of the study were to determine the prevalence of metabolic syndrome (MS) components and examine associations with adipokine concentrations in a healthy pediatric cohort. A cross-sectional study of 1138 children (53% girls; mean age of all participants, 11.2 ± 0.7 years) was performed. Anthropometric and medical information was obtained; and a fasting blood sample was used to measure glucose, insulin, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, leptin, and adiponectin serum concentrations. Insulin resistance was assessed by the insulin resistance homeostasis model assessment. Body weight status (normal, overweight, and obese) was determined according to the International Obesity Task Force. Estimation of the MS was based on t...

Inducible nitric oxide synthase deficiency ameliorates skeletal muscle insulin resistance but does not alter unexpected lower blood glucose levels after burn injury in C57BL/6 mice

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: Burn injury is associated with inflammatory responses and metabolic alterations including insulin resistance. Impaired insulin receptor substrate-1 (IRS-1)–mediated insulin signal transduction is a major component of insulin resistance in skeletal muscle following burn injury. To further investigate molecular mechanisms that underlie burn injury–induced insulin resistance, we study a role of inducible nitric oxide synthase (iNOS), a major mediator of inflammation, on burn-induced muscle insulin resistance in iNOS-deficient mice. Full-thickness third-degree burn injury comprising 12% of total body surface area was produced in wild-type and iNOS-deficient C57BL/6 mice. Insulin-stimulated activation (phosphorylation) of IR, IRS-1, and Akt was assessed by immunoblotting and immun...

Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: Exercise is considered to elicit a physiological response of the heart. Previous studies investigated the influence of repetitive exercise only at the end of the training period. We assessed the impact of 2 exercise protocols, differing in their treadmill inclination, on cardiac and mitochondrial function at different times during the training period. Within 10 weeks, animals trained with 16% incline developed hypertrophy (left ventricular posterior wall thickness: 1.6 ± 0.1 vs 2.4 ± 0.1 mm; P < .05) with normal function (ejection fraction: 75.2% ± 2.5% vs 75.6% ± 2.1%). However, at 6 weeks, there was temporary impairment of contractile function (ejection fraction: 74.5% ± 1.67% vs 65.8% ± 2.3%; P < .05) associated with decreased mitochondrial respiratory capacity (state 3 ...

Treatment of genetically obese mice with the iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin reduces body weight by decreasing food intake and increasing fat oxidation

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: Obesity and its associated conditions such as type 2 diabetes mellitus are major causes of morbidity and mortality. The iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin (AMP-DNM) improves insulin sensitivity in rodent models of insulin resistance and type 2 diabetes mellitus. In the current study, we characterized the impact of AMP-DNM on substrate oxidation patterns, food intake, and body weight gain in obese mice. Eight ob/ob mice treated with 100 mg/(kg d) AMP-DNM mixed in the food and 8 control ob/ob mice were placed in metabolic cages during the first, third, and fifth week of the experiment for measurement of substrate oxidation rates, energy expenditure, activity, and food intake. Mice were killed after 6 weeks of treatment. Initiation of treatment with AMP...

Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

Abstract: High-fat, low-carbohydrate diets have been shown to raise plasma cholesterol levels, an effect associated with the formation of large low-density lipoprotein (LDL) particles. However, the impact of dietary intervention on time-course changes in LDL particle size has not been investigated. To test whether a short-term dietary intervention affects LDL particle size, we conducted a randomized, double-blind, crossover study using an intensive dietary modification in 12 nonobese healthy men with normal plasma lipid profile. Participants were subjected to 2 isocaloric 3-day diets: high-fat diet (37% energy from fat and 50% from carbohydrates) and low-fat diet (25% energy from fat and 62% from carbohydrates). Plasma lipid levels and LDL particle size were assessed on fasting blood sampl...

Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women

Metabolism - Clinical and Experimental — Thu, 04 Aug 2011 04:00:00 +0100

The objective of the present study is to examine the association between the endogenous melatonin level and various established blood biomarkers of risk of CVD, including white blood cell (WBC) count and plasma concentrations of lipids, homocysteine, uric acid (UA), and high-sensitivity C-reactive protein (hs-CRP). This cross-sectional study included 181 Japanese women who attended a health checkup program provided by a general hospital between March 2005 and March 2006. All study subjects responded to a self-administered questionnaire and were measured for weight, height, and blood pressure. Venous fasting blood and first-void morning urine were obtained from all subjects. Statistically significant inverse correlations were observed between urinary 6-sulfatoxymelatonin (aMT6s), the major ...

Dietary glycemic index and risk of type 2 diabetes mellitus in middle-aged Japanese men

Metabolism - Clinical and Experimental — Mon, 01 Aug 2011 04:00:00 +0100

Abstract: This cohort study investigated the association between dietary glycemic index (GI), glycemic load (GL), and the incidence of type 2 diabetes mellitus in middle-aged Japanese men, and the effect of insulin resistance and pancreatic B-cell function on the association. Participants were 1995 male employees of a metal products factory in Japan. Dietary GI and GL were assessed using a self-administered diet history questionnaire. The incidence of diabetes was detected in annual medical examinations over a 6-year period. The association between GI, GL, and the incidence of diabetes was evaluated using Cox proportional hazards models. During the study, 133 participants developed diabetes. Age- and body mass index–adjusted hazard ratios across the GI quintiles were 1.00 (reference), 1....

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Metabolism - Clinical and Experimental — Thu, 21 Jul 2011 23:17:03 +0100

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Metabolism - Clinical and Experimental — Thu, 21 Jul 2011 23:17:03 +0100

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Metabolism - Clinical and Experimental — Thu, 21 Jul 2011 23:16:56 +0100

(Source: Metabolism - Clinical and Experimental)

Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats, Metabolism 2005;54(4):482-487

Metabolism - Clinical and Experimental — Thu, 21 Jul 2011 23:00:00 +0100

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). The editor would like to confirm the retraction of this article at the request of the corresponding author. This article contains material that has appeared in Diabetologia 2005;48:1066-1074. (Source: Metabolism - Clinical and Experimental)

Drug-drug interactions in HIV medicine: a not so simple and straightforward road to the future

Metabolism - Clinical and Experimental — Mon, 11 Jul 2011 04:00:00 +0100

Ritonavir is a well-known antiretroviral that has been extensively used in HIV therapeutics over the last 15 years. It is one of the first protease inhibitors to be developed and used in HIV-1 medicine. It is now rarely—if ever—used for its antiretroviral activity because it is associated with significant metabolic adverse effects such as hyperlipidemia . On the other hand, ritonavir continues to be frequently used for its boosting effects in the plasma levels of other HIV drugs by means of potent inhibition of both liver cytochromes and efflux transport proteins . The downside is that numerous adverse interactions are possible when ritonavir is concomitantly used with other medications, and may even lead to potentially serious and/or life-threatening adverse events . (Source: Metaboli...

Leptin and the skeleton—where is the fat?

Metabolism - Clinical and Experimental — Sun, 10 Jul 2011 23:00:00 +0100

Despite years of active research, there is still debate over the skeletal effects of leptin. Leptin is a hormone well known for its importance in the regulation of food intake and energy expenditure, as well as neuroendocrine function and both glucose and fat metabolism. However, its effects on bone turnover and bone density are still under investigation. Two articles in this month's edition of Metabolism afford insight into the effects of leptin replacement therapy in two unique clinical models: hypothalamic amenorrhea (a state of leptin deficiency) and obesity (a state of leptin tolerance or resistance) . In these studies, the efficacy of leptin replacement appeared to vary depending on the body composition and accompanying hormonal profile of the individuals studied. The differing effec...

Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo

Metabolism - Clinical and Experimental — Fri, 08 Jul 2011 04:00:00 +0100

Abstract: The ratio of unsaturated to saturated long-chain fatty acids (LC-FAs) in skeletal muscle has been associated with insulin resistance. Some animal data suggest a modulatory effect of peroxisome proliferator receptor γ (PPARγ) stimulation on stearoyl-CoA desaturase 1 (SCD1) and LC-FA composition in skeletal muscle, but human data are rare. We here investigate whether treatment with a PPARγ agonist affects myocellular SCD1 expression and modulates the intramyocellular fatty acid profile in individuals with impaired glucose tolerance. Muscle biopsies and hyperinsulinemic-euglycemic clamps were performed in 7 men before and after 8 weeks of rosiglitazone treatment. Intramyocellular saturated, monounsaturated, and polyunsaturated intramuscular fatty acid profiles were measured by ga...

Retinol-binding protein 4 is not associated with insulin resistance in pregnancy

Metabolism - Clinical and Experimental — Fri, 08 Jul 2011 04:00:00 +0100

We examined whether serum levels of RBP4 were associated with IR in pregnancy. One hundred seventy-two women with gestational diabetes mellitus (GDM) and 361 pregnant Thai women who did not have GDM but had a positive 50-g glucose challenge test result (plasma glucose level was ≥7.2 mmol/L after 1 hour) were enrolled. We measured fasting serum levels of RBP4 and assessed IR at a 100-g oral glucose tolerance test. We found a higher degree of IR in the GDM group compared with the non-GDM group, but serum RBP4 levels between the 2 groups were not different. Retinol-binding protein 4 levels were associated with serum triglyceride levels but were not associated with the degree of IR assessed by homeostasis model assessment or quantitative insulin sensitivity check index. Our results suggest t...

Circulating levels of insulin-like growth factor binding protein–1 in relation to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai Urban Rural Epidemiology Study 118)

Metabolism - Clinical and Experimental — Fri, 08 Jul 2011 04:00:00 +0100

The objective was to assess the association of insulin-like growth factor binding protein–1 (IGFBP-1) with insulin resistance (IR), type 2 diabetes mellitus (T2DM), and metabolic syndrome (MS) in Asian Indians. Fifty subjects with normal glucose tolerance (NGT) and 50 with T2DM were randomly selected from the Chennai Urban Rural Epidemiology Study. Insulin-like growth factor binding protein–1 was measured by sandwich enzyme-linked immunosorbent assay. Serum insulin was estimated using Dako (Glostrup, Denmark) kits. Insulin resistance was calculated using the homeostasis model assessment. Subjects with T2DM had significantly decreased levels of IGFBP-1 (21.7 ± 3.5 ng/mL) compared with NGT subjects (34.4 ± 7.6 ng/mL, P < .001). The IGFBP-1 was significantly lower in NGT subjects with I...

Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women

Metabolism - Clinical and Experimental — Thu, 07 Jul 2011 23:00:00 +0100

Abstract: Strenuously exercising young women with hypothalamic amenorrhea are hypoleptinemic and have low bone mineral density (BMD) and content (BMC), which predispose them to increased fracture risk. Short-term leptin replacement in these women corrects many neuroendocrine abnormalities and increases circulating levels of bone formation markers. Whether treatment with recombinant methionyl human leptin (metreleptin) for a long period improves BMD and BMC remains unknown. We studied 20 strenuously exercising young women with hypoleptinemia (leptin concentration (Source: Metabolism - Clinical and Experimental)

Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary artery disease in women

Metabolism - Clinical and Experimental — Wed, 06 Jul 2011 04:00:00 +0100

Abstract: The aim of the present study was to compare the ability of the hypertriglyceridemic waist phenotype and the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP III) clinical criteria to predict coronary artery disease (CAD) risk in a sample of women. We studied 254 women among whom the presence/absence of CAD was assessed by angiography. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (≥85 cm) and increased fasting triglyceride levels (≥1.5 mmol/L), whereas the presence of at least 3 of the 5 NCEP-ATP III criteria was used as the “reference” screening approach to identify women with the features of the metabolic syndrome. Women with hypertriglyceridemic waist were characterized by higher adiposity ind...

Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

Metabolism - Clinical and Experimental — Mon, 27 Jun 2011 04:00:00 +0100

Abstract: 11-β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) converts cortisone to cortisol, mainly in the liver and visceral adipose tissue (VAT), and has been implicated in several metabolic disorders. The absence of systemic hypercortisolism in central obesity could be due to increased inactivation of cortisol to its tetrahydrometabolites by the hepatic enzymes 5α- and 5β-reductases. Our aim was to assess the expression of the reductases in the liver and of 11β-HSD1 in the liver and VAT in morbidly obese patients and to analyze their association with clinical, anthropometric, and biochemical parameters. Hepatic and VAT samples were obtained during bariatric surgery. 5α- and 5β-reductases, 11β-HSD1, and 18S expression was measured using real-time polymerase chain reaction. Anthr...

The dynamic insulin sensitivity and secretion test—a novel measure of insulin sensitivity

Metabolism - Clinical and Experimental — Mon, 27 Jun 2011 04:00:00 +0100

The objective was to validate the methodology for the dynamic insulin sensitivity and secretion test (DISST) and to demonstrate its potential in clinical and research settings. One hundred twenty-three men and women had routine clinical and biochemical measurements, an oral glucose tolerance test, and a DISST. For the DISST, participants were cannulated for blood sampling and bolus administration. Blood samples were drawn at t = 0, 10, 15, 25, and 35 minutes for measurement of glucose, insulin, and C-peptide. A 10-g bolus of intravenous glucose at t = 5 minutes and 1 U of intravenous insulin immediately after the t = 15 minute sample were given. Fifty participants also had a hyperinsulinemic-euglycemic clamp. Relationships between DISST insulin sensitivity (SI) and the clamp, and both DISS...

Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals

Metabolism - Clinical and Experimental — Thu, 23 Jun 2011 04:00:00 +0100

Abstract: Long-term cardiorespiratory fitness (CRF) and the development of type 2 diabetes mellitus are inversely correlated. Here, we examined the relationships between peak oxygen uptake (VO2peak), on the one hand, and glucose infusion rate at rest (GIRrest) and during exercise (GIRexercise), as well as insulin secretion (both the early and late phases of response [area under the curve {AUC}insulin]), on the other. Eight male and 4 female healthy, lean, nonsmoking volunteers were recruited. The VO2peak was measured during graded exercise on a cycle ergometer until exhaustion was reached. The GIRrest and GIRexercise were determined using a euglycemic-hyperinsulinemic clamp, and insulin secretion at rest was evaluated with an intravenous glucose tolerance test. The VO2peak correlated posit...

Intensive practical lifestyle intervention improves endothelial function in metabolic syndrome independent of weight loss: a randomized controlled trial

Metabolism - Clinical and Experimental — Thu, 23 Jun 2011 04:00:00 +0100

The objective was to evaluate the metabolic and vascular effects of lifestyle interventions involving a healthy diet and either a moderate- or a high-intensity exercise regimen in nondiabetic subjects with metabolic syndrome. The effects of these interventions on flow-mediated vasodilation (FMD) and risk profiles were compared with a standard low-fat diet and engaging in daily walking (standard of care). Seventy-five healthy adults with metabolic syndrome (30-55 years old) were randomized to a 10 000-steps-a-day exercise program, a 3-times-a-week fitness (>75% peak VO2) program, or a 1-hour-walking-a-day program for 12 weeks. The first 2 interventions were combined with an accessible healthy, no-sugar diet; and the third was combined with a tailored low-fat diet. The outcomes, including F...

Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding

Metabolism - Clinical and Experimental — Wed, 22 Jun 2011 04:00:00 +0100

Abstract: It is currently believed that metabolic syndrome, in general, and type 2 diabetes mellitus, in particular, depend more on visceral than on subcutaneous adipose tissue. However, the relationship between insulin resistance and fatty acid composition in visceral and subcutaneous adipose tissues remains to be clarified. In the present study, we extracted the triacylglycerol from visceral (epididymis and mesentery) and subcutaneous adipose tissues in normal and insulin-resistant, high-fat–fed (HFF) rats and determined the composition of each fatty acid. The concentrations of palmitoleic, docosapentaenoic, docosahexaenoic, dihomo-γ-linolenic, arachidonic, and docosatetraenoic acids were higher in epididymal adipose tissue than in mesenteric and subcutaneous adipose tissues; but no s...

Serum adipokine zinc α2-glycoprotein and lipolysis in cachectic and noncachectic heart failure patients: relationship with neurohormonal and inflammatory biomarkers

Metabolism - Clinical and Experimental — Wed, 22 Jun 2011 04:00:00 +0100

Abstract: Chronic heart failure is often complicated by the development of cachexia with the loss of fat mass. Zinc α2-glycoprotein (ZAG) is a serum adipokine with lipolytic effects in cancer cachexia. We evaluated in patients with advanced heart failure with (CxHF) or without cachexia (nCxHF) the relationship of ZAG with circulating free fatty acid (FFA), as an index of lipolysis, and with other neurohormonal and inflammatory biomarkers. Two groups, nCxHF (n = 46) and CxHF (n = 18), the latter having a documented, involuntary, edema-free loss of body weight of at least 7.5% in the previous 6 months, underwent plasma determination of FFA, ZAG, norepinephrine (NE), tumor necrosis factor–α, and natriuretic peptide levels (atrial natriuretic, B-type natriuretic peptide). The patients were...

Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study

Metabolism - Clinical and Experimental — Wed, 22 Jun 2011 04:00:00 +0100

The objective was to investigate the association between specific glucose-lowering agents and cancer incidence in diabetic members of an Israeli health maintenance organization. We studied a cohort of 36 342 diabetic patients aged at least 18 years with no history of cancer or treatment with insulin as of January 1, 2003. For the period from January 2003 to December 2007, we searched pharmacy records for purchases of glucose-lowering agents, including metformin, sulfonylureas, human insulin, and analogue insulins. Incident cancer diagnoses were identified from the health maintenance organization cancer registry. We studied the association of cancer incidence with the use of specific glucose-lowering agents, controlling for age, sex, and baseline glycohemoglobin measurement. Cancer was dia...

Editorial Board

Metabolism - Clinical and Experimental — Tue, 21 Jun 2011 16:52:41 +0100

(Source: Metabolism - Clinical and Experimental)

Metabolism - Clinical and Experimental — Tue, 21 Jun 2011 16:52:41 +0100

(Source: Metabolism - Clinical and Experimental)

trans-Fatty acids, insulin resistance/diabetes, and cardiovascular disease risk: should policy decisions be based on observational cohort studies, or should we be waiting for results from randomized placebo-controlled trials?

Metabolism - Clinical and Experimental — Tue, 21 Jun 2011 16:52:32 +0100

Cardiovascular disease remains the leading cause of morbidity and mortality in the United States . Although the number of deaths from cardiovascular disease appears to be decreasing, primarily because of more aggressive interventional approaches, the prevalence of many of the risk factors associated with and leading to cardiovascular morbidity has been increasing constantly . Of special interest is the dramatic increase in the prevalence of obesity and diabetes mellitus (DM) . (Source: Metabolism - Clinical and Experimental)

Masthead

Metabolism - Clinical and Experimental — Tue, 21 Jun 2011 16:52:32 +0100

(Source: Metabolism - Clinical and Experimental)

Triglyceride–high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Wed, 15 Jun 2011 04:00:00 +0100

Abstract: The purpose of this study was to evaluate whether a high triglyceride/high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with an increased incidence of retinopathy and chronic kidney disease (CKD) in type 2 diabetes mellitus. Individuals with type 2 diabetes mellitus (n = 979) with an estimated glomerular filtration rate greater than 60 mL/min and without retinopathy and cardiovascular disease at baseline were followed up for the incidence of diabetic retinopathy (diagnosed by retinography) and CKD (diagnosed by estimated glomerular filtration rate ≤60 mL/min/1.73 m2). On follow-up (mean, 4.9 years), 217 (22.2% of total) subjects experienced CKD and/or diabetic-specific retinal lesions (microvascular complication). Of these, 111 subjects developed isolated reti...

Mitochondrial DNA copy number in peripheral blood in polycystic ovary syndrome

Metabolism - Clinical and Experimental — Wed, 15 Jun 2011 04:00:00 +0100

We report decreased mtDNA copy numbers in PCOS patients in relation to controls independently of insulin resistance or other metabolic factors. The pathophysiological and clinical significance of this finding requires further investigation. (Source: Metabolism - Clinical and Experimental)

Higher ratio of triglyceride to high-density lipoprotein cholesterol may predispose to diabetes mellitus: 15-year prospective study in a general population

Metabolism - Clinical and Experimental — Mon, 13 Jun 2011 04:00:00 +0100

Abstract: The aims of the study were to examine whether the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) could predict future diabetes mellitus (DM) in a general population during a 15-year follow-up. The data were collected in 1992 and then again in 2007 from the same group of 711 individuals. Because 24 of them were found to be diabetic in 1992, our analysis was eventually based on the usable data collected from the remaining 687 individuals (male, 58.1%). During the period 1992-2007, 74 individuals were found to have developed DM (10.8%). After adjusting the associated variables, it was found that TG and TG/HDL-C were independent DM risk factors, with the odds ratios being 1.292 (P = .047) and 1.341 (P = .010), respectively, although they were poor in their DM d...

Nicotinic acid induces apolipoprotein A-I gene expression in HepG2 and Caco-2 cell lines

Metabolism - Clinical and Experimental — Mon, 13 Jun 2011 04:00:00 +0100

The objective was to test the effect of nicotinic acid on apolipoprotein A-I (apo A-I) gene expression in hepatic (HepG2) and intestinal (Caco-2) cell lines. HepG2 and Caco-2 cells were treated with 0.1, 0.3, 1.0, 3.0, and 10 mmol/L of nicotinic acid; and apo A-I concentrations in conditioned media were measured with Western blots. Relative apo A-I messenger RNA (mRNA) levels, normalized to glyceraldehyde-3-phosphate dehydrogenase mRNA, were measured with quantitative real-time polymerase chain reaction method. The nicotinic acid response element in the apo A-I promoter was identified using a series of apo A-I reporter plasmids containing deletion constructs of the promoter. In other experiments, HepG2 cells were also transfected with the apo A-I reporter plasmid and the hepatocyte nuclear...

Involvement of visfatin in palmitate-induced upregulation of inflammatory cytokines in hepatocytes

Metabolism - Clinical and Experimental — Mon, 13 Jun 2011 04:00:00 +0100

Abstract: Free fatty acids (FFAs) lead to the activation of inflammatory pathways related to the induction of insulin resistance. Visfatin is known to play a role in obesity-related metabolic diseases and inflammatory conditions. Here, the role of visfatin in FFA-induced inflammation was investigated in hepatocytes. The following factors were examined: (1) the protein and messenger RNA (mRNA) expression of visfatin in the liver tissue of insulin-resistant rats and in (2) in HepG2 cells treated with palmitate, (3) the palmitate-induced mRNA expression and protein synthesis of interleukin-6 and tumor necrosis factor–α in HepG2 cells transfected with visfatin-specific small interfering RNA, and (4) the expression of visfatin in HepG2 cells treated with a nuclear factor–κB (NF-κB) inhib...

Hormonal appetite control is altered by shift work: a preliminary study

Metabolism - Clinical and Experimental — Mon, 13 Jun 2011 04:00:00 +0100

The objective of the study was to evaluate the daily concentrations of leptin, nonacylated ghrelin, and acylated ghrelin and the appetite ratings in men working different shift schedules. Daily concentrations of nonacylated ghrelin, acylated ghrelin, and leptin and appetite were measured in 3 groups of subjects: workers on fixed night shifts (n = 9), fixed early morning shifts (n = 6), and fixed day shifts (n = 7). Appetite was evaluated by a validated questionnaire. Blood samples were collected every 4 hours over the course of 24 hours for a total of 6 samples. When comparing the 3 groups, leptin concentrations at 8:00 am and 4:00 pm for those workers on the day shift were significantly lower than for those on the early morning shift; and concentrations at noon for those workers on the da...

Adipose tissue depot-specific differences in adipocyte apolipoprotein E expression

Metabolism - Clinical and Experimental — Mon, 13 Jun 2011 04:00:00 +0100

Abstract: Important differences in gene expression have been documented in adipocytes derived from specific adipose tissue depots. We have previously documented an important role for adipocyte apolipoprotein E (apoE) in modulating adipocyte and adipose tissue triglyceride and lipoprotein metabolism. We now evaluate the endogenous expression of apoE in adipocytes isolated from unique adipose tissue depots in 4 different species. Adipocyte apoE expression is higher in subcutaneous fat compared with visceral fat in humans, mice, rats, and baboons. In baboons, evaluation of apoE expression in 5 adipose tissue depots (subcutaneous abdominal, subcutaneous gluteal, visceral, pericardial, epicardial) showed that, compared with subcutaneous abdominal adipocytes, the level of apoE expression is simi...

Prophylactic vitamin D in healthy infants: assessing the need

Metabolism - Clinical and Experimental — Fri, 10 Jun 2011 04:00:00 +0100

The objective was to evaluate the need for vitamin D prophylaxis in healthy infants. This was a prospective and randomized study performed at primary care clinics. Eighty-eight full-term 1-month-old healthy infants were randomly assigned to receive (n = 41) or not (n = 47) 402 IU/d of vitamin D for 1 year. Primary outcome measures were serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) concentrations at 3, 6, and 12 months of age; secondary measures included data on feeding, habitat, season of birth, sun exposure, and physical examination. At 3 and 6 months of age, serum 25OHD levels (±SD) were significantly higher (P < .001) in the prophylaxis group. In the group without prophylaxis, serum 25OHD increased with age; and breast-fed infants aged 3 months had the lowest value (2...

Mitochondrial bioenergetics is not impaired in nonobese subjects with type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Fri, 10 Jun 2011 04:00:00 +0100

Abstract: Although mitochondrial dysfunction has been well documented in obese people with type 2 diabetes mellitus, its presence or absence in nonobese subjects with type 2 diabetes mellitus has not been well studied so far. The aim of the present study was to assess the status of mitochondrial oxidative phosphorylation in subcutaneous adipose tissue of nonobese type 2 diabetes mellitus subjects in comparison to control, obese nondiabetic, and obese type 2 diabetes mellitus subjects. Mitochondria were isolated from subcutaneous white adipose tissue obtained from the abdominal region of control, obese nondiabetic, nonobese type 2 diabetes mellitus, and obese type 2 diabetes mellitus subjects. The activities of complex I, I to III, II to III, and IV; transmembrane potential; and inorganic p...

Nebivolol improves insulin sensitivity in the TGR(Ren2)27 rat

Metabolism - Clinical and Experimental — Fri, 03 Jun 2011 04:00:00 +0100

Abstract: Hypertension is often associated with increased oxidative stress and systemic insulin resistance. Use of β-adrenergic receptor blockers in hypertension is limited because of potential negative influence on insulin sensitivity and glucose homeostasis. We sought to determine the impact of nebivolol, a selective vasodilatory β1-adrenergic blocker, on whole-body insulin sensitivity, skeletal muscle oxidative stress, insulin signaling, and glucose transport in the transgenic TG(mRen2)27 rat (Ren2). This rodent model manifests increased tissue renin angiotensin expression, excess oxidative stress, and whole-body insulin resistance. Young (age, 6-9 weeks) Ren2 and age-matched Sprague-Dawley control rats were treated with nebivolol 10 mg/(kg d) or placebo for 21 days. Basal measurement...

Metabolic and endocrine effects of long-chain versus essential omega-3 polyunsaturated fatty acids in polycystic ovary syndrome

Metabolism - Clinical and Experimental — Fri, 03 Jun 2011 04:00:00 +0100

The objective of the study was to compare the effects of essential vs long-chain omega (n)-3 polyunsaturated fatty acids (PUFAs) in polycystic ovary syndrome. In this 6-week, prospective, double-blinded, placebo (soybean oil)-controlled study, 51 completers received 3.5 g n-3 PUFA per day (essential PUFA from flaxseed oil or long-chain PUFA from fish oil). Anthropometric variables, cardiovascular risk factors, and androgens were measured; oral glucose tolerance test (OGTT) and frequently sampled intravenous GTT (IVGTT) were conducted at baseline and 6 weeks. Between-group comparisons showed significant differences in serum triglyceride response (P = .0368), whereas the changes in disposition index also tended to differ (P = .0621). When within-group changes (after vs before intervention) w...

Genetic deficiency of apolipoprotein D in the mouse is associated with nonfasting hypertriglyceridemia and hyperinsulinemia

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Apolipoprotein D (ApoD) is an atypical apolipoprotein with an incompletely understood function in the regulation of triglyceride and glucose metabolism. We have demonstrated that elevated ApoD production in mice results in improved postprandial triglyceride clearance. This work studies the role of ApoD deficiency in the regulation of triglyceride and glucose metabolism and its dependence on aging. We used ApoD knockout (ApoD-KO) mice of 3 and 21 months of age. Body weight and food intake were measured. Hepatic histology, triglyceride content, lipoprotein lipase levels, and plasma metabolites were studied. Phenotypic characterization of glucose metabolism was performed using glucose tolerance test. β-Cell mass, islet volume, and islet number were analyzed by histomorphometry. Apo...

Effects of nonenzymatic glycation and fatty acids on functional properties of human albumin

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Human serum albumin nonenzymatically condenses with glucose to form stable Amadori adducts that are increased with the hyperglycemia of diabetes. The present study evaluated the influence of fatty acids, which are major endogenous ligands, on albumin glycation and of glycation on albumin conformation and exogenous ligand binding. Physiologic concentrations of palmitate, oleate, and linoleate reduced the ability of albumin to form glucose adducts, whereas glycation decreased intrinsic fluorescence, lowered the affinity for dansylsarcosine, and diminished the fatty acid–induced increase in limiting fluorescence of protein-bound warfarin that was observed with nonglycated albumin. The findings indicate that fatty acids impede the ability of albumin to undergo Amadori glucose modif...

Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with...

Effects of leptin and adiponectin on pancreatic β-cell function

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Leptin and adiponectin are hormones secreted from adipocytes that have important roles in metabolism and energy homeostasis. This review evaluates the effects of leptin and adiponectin on β-cell function by analyzing and compiling results from human clinical trials and epidemiologic studies as well as in vitro and in vivo experiments. Leptin has been shown to inhibit ectopic fat accumulation and thereby prevent β-cell dysfunction and protect the β-cell from cytokine- and fatty acid–induced apoptosis. However, leptin suppresses insulin gene expression and secretion as well as glucose transport into the β-cell. Adiponectin stimulates insulin secretion by enhancing exocytosis of insulin granules and upregulating the expression of the insulin gene; however, this effect depends ...

Bone remodeling and calcium homeostasis in patients with spinal cord injury: a review

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Patients with spinal cord injury exhibit early and acute bone loss with the major functional consequence being a high incidence of pathological fractures. The bone status of these patients is generally investigated by dual-energy x-ray absorptiometry, but this technique does not reveal the pathophysiological mechanism underlying the bone loss. Bone cell activity can be indirectly evaluated by noninvasive techniques, including measurement of specific biochemical markers of bone formation (such as osteocalcin or bone-alkaline phosphatase) and resorption (such as procollagen type I N- or C-terminal propeptide). The bone loss in spinal cord injury is clearly due to an uncoupling of bone remodeling in favor of bone resorption, which starts just after the injury and peaks at about 1 to...

Portal vein and systemic adiponectin concentrations are closely linked with hepatic glucose and lipoprotein kinetics in extremely obese subjects

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

We examined the relationship between hepatic substrate metabolism (glucose rate of appearance into plasma and hepatic very low-density lipoprotein [VLDL]–triglyceride [TG] and VLDL–apolipoprotein B-100 [apoB-100] secretion rates, determined by using stable isotope-labeled tracer techniques) and portal vein adiponectin concentration, in 8 insulin-resistant, extremely obese subjects (body mass index, 65 ± 7 kg/m2). Portal vein adiponectin concentration was inversely associated with basal glucose rate of appearance (r = −0.820, P = .013) and VLDL-TG (r = −0.823, P = .012) and VLDL–apoB-100 (r = −0.787, P = .020) secretion rates. Very similar correlations were obtained for radial artery adiponectin as a result of a mirroring relationship between portal and arterial adiponectin con...

Relationship between glucose volume of distribution and the extracellular space: a multiple tracer study

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Although the use of radioisotopes in the investigation of glucose metabolism dates back more than 50 years, several relevant quantitative aspects have not been definitively determined. These include the volume of distribution (Vd) of glucose and recycling of glucose radioisotopes from liver glycogen. These problems are further complicated by methodological issues such as the following: (1) glucose tracers have different metabolic fates that may influence volume estimates, and (2) the calculation method needs to be based on physical principles to avoid some limitations of compartmental models. To address these issues, we administered boluses of an extracellular marker ([1-14C]-l-glucose, 30 μCi) and 2 glucose tracers ([2-3H]-d-glucose and [3-3H]-d-glucose, 120 μCi of each), foll...

Deletion of interleukin-6 improves pyruvate tolerance without altering hepatic insulin signaling in the leptin receptor–deficient mouse

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

This study was designed to assess the impact of the systemic absence of IL-6 on the development of insulin resistance and glucose intolerance in an obese mouse model. Systemic insulin, glucose, and pyruvate tolerance tests were performed in IL-6 knockout (IL6KO) mice that had been crossed with a genetically obese (leptin receptor–deficient mouse model [Lepdb]) mouse model. Real-time reverse transcriptase polymerase chain reaction and Western blot analysis assessed cellular and molecular markers of insulin signaling, inflammation, and metabolism. Absence of IL-6 did not improve systemic glucose or insulin tolerance, but Lepdb × IL6KO mice displayed a smaller blood glucose increase following a pyruvate challenge. These results suggest that loss of IL-6 in the context of obesity may locall...

Resveratrol attenuates high-fat diet–induced insulin resistance by influencing skeletal muscle lipid transport and subsarcolemmal mitochondrial β-oxidation

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

This study suggests that RES ameliorates insulin sensitivity consistent with an improved balance between skeletal muscle lipid transportation and SS mitochondrial β-oxidation in HFD rats. (Source: Metabolism - Clinical and Experimental)

Functional effects of DAX-1 mutations identified in patients with X-linked adrenal hypoplasia congenita

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

In this study, we investigated the functional defects of DAX-1 caused by mutations identified in 3 unrelated Korean patients with adrenal hypoplasia congenita. The DAX-1 gene was directly sequenced using genomic DNA isolated from peripheral blood leukocytes. The functional defects of DAX-1 caused by mutations were evaluated using an in vitro promoter assay. After mutagenesis of DAX-1 complementary DNA in the pcDNA3.1 vector, steroidogenic factor 1 and the promoter region of steroidogenic acute regulatory protein (StAR) genes in pGL4.10[luc2] were transiently cotransfected into human embryonic kidney 293 cells, followed by luminometry measurements of the luciferase activity of StAR. Mutation analysis of 3 patients revealed p.L386delfsX2, p.W105X, and p.Q252X mutations of the DAX-1 gene. The...

Serum adiponectin and leptin in relation to risk for preeclampsia: results from a large case-control study

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Conditions resulting in insulin resistance, as well as metabolic, immune, and angiogenic perturbations, have been associated with an increased risk of preeclampsia (PE). Our purpose was to assess whether the adipose tissue–secreted hormones adiponectin, which has immune-modulating, metabolic, and angiogenic properties, and leptin, which reflects overall fat mass, are associated with PE risk. We performed a case-control design study within a hospital-based cohort of 368 pregnant women (106 with PE and 262 controls; mean age, 26.6 ± 6.8 years; mean gestational age at admission, 38.2 ± 2.8 weeks) between March 2005 and August 2007 at the Hospital of Pennsylvania University. Serum adiponectin and leptin were measured by radioimmunoassay. Statistical analysis of data was performed...

Serum adiponectin levels and tissue expression of adiponectin receptors are associated with risk, stage, and grade of colorectal cancer

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

This study aims to investigate the association of both adiponectin and tissue expression of its receptors with CRC risk as well as clinicopathological characteristics, notably stage and grade. Determination of serum adiponectin and immunohistochemical expression of adiponectin receptors in adenocarcinoma/normal colorectal tissue was performed in samples from 104 newly diagnosed CRC patients and 208 age- and sex-matched controls. Multiple logistic regression odds ratios and 95% confidence intervals for CRC risk were derived, controlling for a series of covariates. Serum adiponectin was negatively associated with CRC risk (odds ratio, 0.72; confidence interval, 0.53-0.99) and also with tumor grade (P = .05). Expression of both adiponectin receptors was stronger in adenocarcinoma vs normal ti...

Impaired adrenergic- and corticotropic-axis outflow during exercise in chronic obstructive pulmonary disease

Metabolism - Clinical and Experimental — Wed, 01 Jun 2011 04:00:00 +0100

Abstract: Exercise stimulates coordinated release of the sympathoadrenal hormones adrenocorticotropic hormone (ACTH), cortisol, norepinephrine (NE), and epinephrine (Epi). The study hypothesis was that chronic obstructive pulmonary disease (COPD) is marked by heightened sympathoadrenal outflow at comparable relative workloads. The location of the study was at a clinical research unit. Eight healthy men and 9 men with stable COPD (forced expiratory volume at 1 second (Source: Metabolism - Clinical and Experimental)

The effect of two energy-restricted diets, a low-fructose diet versus a moderate natural fructose diet, on weight loss and metabolic syndrome parameters: a randomized controlled trial

Metabolism - Clinical and Experimental — Mon, 30 May 2011 04:00:00 +0100

Abstract: One of the proposed causes of obesity and metabolic syndrome is the excessive intake of products containing added sugars, in particular, fructose. Although the ability of excessive intake of fructose to induce metabolic syndrome is mounting, to date, no study has addressed whether a diet specifically lowering fructose but not total carbohydrates can reduce features of metabolic syndrome. A total of 131 patients were randomized to compare the short-term effects of 2 energy-restricted diets—a low-fructose diet vs a moderate natural fructose diet—on weight loss and metabolic syndrome parameters. Patients were randomized to receive 1500, 1800, or 2000 cal diets according to sex, age, and height. Because natural fructose might be differently absorbed compared with fructose from ad...

High-dose insulin administration is associated with hypoaminoacidemia during cardiac surgery

Metabolism - Clinical and Experimental — Fri, 27 May 2011 04:00:00 +0100

Abstract: Although the effects of insulin on glucose homeostasis are well recognized in surgical patients, its effect on perioperative protein metabolism has received little attention. The purpose of this study was to examine the effect of high-dose insulin therapy on the plasma concentrations of amino acids (AAs) in patients undergoing coronary artery bypass grafting surgery. We studied 20 nondiabetic patients scheduled for elective coronary artery bypass grafting surgery. Patients were randomly allocated to receive either standard metabolic care (target glycemia 6.0-10.0 mmol/L, control group, n = 10) or high-dose insulin therapy (insulin group, n = 10). Insulin was administered at 5 mU.kg−1.min−1 beginning at skin incision. Simultaneously, 20% dextrose was infused at a variable rate...

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Metabolism - Clinical and Experimental — Thu, 19 May 2011 19:28:05 +0100

(Source: Metabolism - Clinical and Experimental)

Metabolism - Clinical and Experimental — Thu, 19 May 2011 19:28:05 +0100

(Source: Metabolism - Clinical and Experimental)

Masthead

Metabolism - Clinical and Experimental — Thu, 19 May 2011 19:27:59 +0100

(Source: Metabolism - Clinical and Experimental)

Plasma adiponectin—an independent indicator of liver fat accumulation

Metabolism - Clinical and Experimental — Thu, 12 May 2011 04:00:00 +0100

Abstract: Proinflammatory cytokines and adipokines have a significant role in the development and progression of fatty liver. The aim of our current study was to explore the major indicators for hepatic fat determined as liver brightness. In addition to peptide hormones, several known cardiovascular and metabolic risk factors were included in the model. This is a population-based, epidemiological, cross-sectional study where 1200 subjects (600 men and 600 women, aged 40-59 years) were randomly selected, half of them having hypertension and half of them being controls. The severity of liver adiposity was measured by ultrasound and based on the brightness of the liver estimated as a numerical value ranging from 0 to 2. With respect to the studied peptide hormones, the associations between li...

Genotype risk score of common susceptible variants for prediction of type 2 diabetes mellitus in Japanese: the Shimanami Health Promoting Program (J-SHIPP study) Development of type 2 diabetes mellitus and genotype risk score

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: Recent genomewide association studies have successfully identified several genotypes susceptible to type 2 diabetes mellitus (T2DM). However, only a few studies have investigated whether these variations confer a risk of the future development of T2DM. We conducted a longitudinal genetic epidemiological study to clarify the prognostic significance of the T2DM-associated variants. The sample population consisted of 2037 middle-aged to elderly community residents. Personal health records were obtained from a clinical database administered by the local government. Genotype risk score was calculated by the following variants, namely, KCNQ1, TCF7L2, CDKAL1, HHEX, IGF2BP2, CDKN2AB, SLC30A8, KCNJ11, PPARG, and GCKR. Susceptibility of these variants in Japanese has been confirmed by asso...

Micronucleus evaluation in mitogen-stimulated lymphocytes of patients with acromegaly

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

This study aims to evaluate the spontaneous micronucleus (MN) frequency by using the cytokinesis-block MN assay to determine genetic damage in the lymphocytes of patients with acromegaly. The study was carried out in 20 patients who had active acromegaly and in 20 age- and sex-matched healthy controls. The MN values were measured in binucleated cells obtained from mitogen-stimulated lymphocytes of patients and control subjects. The distribution of binucleated cells with 1, 2, 3, or more MNs was also measured. We found significantly higher MN frequency values in the lymphocytes of acromegalic patients than in those of the control subjects (2.23 ± 0.68 vs 1.03 ± 0.54, P = .001). The MN frequency increased with increasing IGF-1 levels of acromegalic patients (P = .036, R = 0.47). We observe...

Cinnamon increases liver glycogen in an animal model of insulin resistance

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

The objective of this study was to determine the effects of cinnamon on glycogen synthesis, related gene expression, and protein levels in the muscle and liver using an animal model of insulin resistance, the high-fat/high-fructose (HF/HFr) diet–fed rat. Four groups of 22 male Wistar rats were fed for 12 weeks with (1) HF/HFr diet to induce insulin resistance, (2) HF/HFr diet containing 20 g cinnamon per kilogram of diet, (3) control diet, and (4) control diet containing 20 g cinnamon per kilogram of diet. In the liver, cinnamon added to the HF/HFr diet led to highly significant increases of liver glycogen. There were no significant changes in animals consuming the control diet plus cinnamon. In the liver, cinnamon also counteracted the decreases of the gene expressions due to the consum...

Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug–drug interaction in HIV patients

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: Prasugrel is an antiplatelet prodrug used in patients with acute coronary syndrome. Prasugrel is mainly bioactivated by cytochromes P450 3A4/5 and CYP2B6. HIV patients are at risk of cardiovascular disease, and the protease inhibitor ritonavir is a potent inhibitor of these 2 CYPs. The aim of this in vitro study was to determine the impact of ritonavir in prasugrel metabolism. Human liver microsomes (HLMs) and recombinant microsomes were used to identify the enzymes responsible for the bioactivation of prasugrel. Prasugrel concentrations of 5 to 200 μM were used for Km determination. Inhibition by ritonavir was characterized using HLMs at concentrations of 0.1 to 30 μM. Prasugrel active metabolite determination was performed with a validated liquid chromatography-mass spectrome...

Metabolic imbalance of the insulin-like growth factor–I axis in Zucker diabetic fatty rats

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: In healthy conditions, insulin-like growth factor–I (IGF-I) acts in a coordinated fashion with insulin to lower glycemia, mainly by increasing insulin sensitivity in peripheral tissues. The aim of this study was to explore the relationship between glucose homeostasis and the endocrine IGF-I axis in Zucker diabetic fatty (ZDF) rats. The plasma levels of glucose, insulin, growth hormone, free IGF-I, total IGF-I (associated to insulin-like growth factor binding proteins plus free), and corticosterone were measured in 13-week-old ZDF rats and in age-matched controls under fasting and postprandial conditions. The plasma IGF-I binding capacity was measured by radioligand binding. In ZDF rats, fasting total and free IGF-I levels were reduced by 22% and 92%, respectively, compared with...

Insulin improves β-cell function in glucose-intolerant rat models induced by feeding a high-fat diet

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

This study investigated the effects of insulin treatment on pancreatic lipid content, and β-cell apoptosis and proliferation in glucose-intolerant rats to explore the protective role of insulin on β-cell function. A rat glucose-intolerant model was induced by streptozotocin and a high-fat diet. Plasma and pancreatic triglycerides, free fatty acids, and insulin were measured; and pancreatic β-cell cell apoptosis and proliferation were detected by a propidium iodide cell death assay and immunofluorescence for proliferating cell nuclear antigen. Relative β-cell area was determined by immunohistochemistry for insulin, whereas insulin production in pancreas was assessed by reverse transcriptase polymerase chain reaction. Islet β-cell secreting function was assessed by the index ΔI30/ΔG30...

Treatment with the α-glucosidase inhibitor miglitol from the preonset stage in Otsuka Long-Evans Tokushima Fatty rats improves glycemic control and reduces the expression of inflammatory cytokine genes in peripheral leukocytes

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

In this study, we examined whether dietary supplementation with the α-glucosidase inhibitor miglitol from the preonset stage improves glycemic control and reduces the gene expression of inflammatory cytokines in peripheral leukocytes. The OLETF rats were fed a control diet or a diet containing 800 ppm miglitol (miglitol diet) for 40 weeks from 5 weeks of age (preonset stage). We determined nonfasting blood glucose, blood 1,5-anhydroglucitol, and messenger RNA levels of inflammatory cytokines in peripheral leukocytes in these rats. Nonfasting blood glucose concentrations gradually increased in OLETF rats fed the control diet, with significant increases at weeks 28 and 40 compared with week 0. In contrast, nonfasting blood glucose levels did not increase in miglitol-treated rats during the ...

Different associations of apolipoprotein E polymorphism with metabolic syndrome by sex in an elderly Chinese population

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

This study evaluated the ApoE genetic polymorphism and its relation to MetS defined by the modified National Cholesterol Education Program and International Diabetes Federation criteria in a population-based cross-sectional survey of an elderly Chinese population in Beijing, China. Genotypes of 937 men and 1385 women were included in the study. All participants were measured for blood pressure, anthropometric measurements, and fasting concentrations of glucose, triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. We applied a logistic regression model to derive adjusted odds ratios (ORs) and their 95% confidence intervals. In this Chinese population, the ɛ2, ɛ3, and ɛ4 allele frequencies were 8.3%, 83.4%, and 8.3% for men and 8.7%, 8...

Apolipoprotein A-II and adiponectin as determinants of very low-density lipoprotein apolipoprotein B-100 metabolism in nonobese men

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

In this study, we examined the associations between the kinetics of high-density lipoprotein (HDL)-apoA-II and VLDL-apoB-100 kinetics, and plasma adiponectin concentrations. The kinetics of HDL-apoA-II and VLDL-apoB-100 were measured in 37 nonobese men using stable isotope techniques. Plasma adiponectin concentration was measured using immunoassays. Total plasma apoA-II concentration was positively associated with HDL-apoA-II production rate (PR) (r = 0.734, P < .01); both were positively associated with plasma triglyceride concentration (r = 0.360 and 0.369, respectively) and VLDL-apoB-100 PR (r = 0.406 and 0.427, respectively), and inversely associated with plasma adiponectin concentration (r = −0.449 and −0.375, respectively). Plasma adiponectin was inversely associated with plasma ...

Vitamin D deficiency is common and associated with metabolic risk factors in patients with polycystic ovary syndrome

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

This study sought to investigate (1) the prevalence of vitamin D deficiency in PCOS women in Scotland and (2) the relationship between vitamin D status and metabolic risk factors. This was an observational study on 52 women (25 in PCOS group and 27 in control group). Serum 25-hydroxyvitamin D concentrations less than 25 nmol/L were classified as severe vitamin D deficiency and were found in 44.0% and 11.2% of subjects in the PCOS and control groups, respectively (P = .047). Among the PCOS subjects, 25-hydroxyvitamin D concentrations were negatively correlated with body mass index (P = .033), C-reactive protein (P = .027), and free androgen index (P = .025) and positively correlated with quantitative insulin sensitivity check index (P = .035), high-density lipoprotein cholesterol (HDL-C) (P...

Resting energy expenditure and protein turnover are increased in patients with severe chronic obstructive pulmonary disease

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

The objective of this study was to determine first whether REE was increased in patients with COPD and, second, whether this was associated with increased protein turnover and/or systemic inflammation. Resting energy expenditure was determined using indirect calorimetry in 14 stable outpatients with severe COPD (7 with low and 7 with preserved body mass indices) and 7 healthy controls. Endogenous leucine flux, leucine oxidation, and nonoxidative disposal, indices of whole-body protein breakdown, catabolism, and synthesis, were measured using intravenous infusions of 13C-bicarbonate and 1-13C-leucine. Total body water, from which fat-free mass and fat mass were calculated, was determined using an intravenous bolus of deuterated water. Plasma markers of systemic inflammation were also measur...

Resistant starch promotes equol production and inhibits tibial bone loss in ovariectomized mice treated with daidzein

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

In this study, we investigated the combined effects of daidzein and RS intake on equol production, bone mineral density, and intestinal microflora in ovariectomized (OVX) mice. Female mice of the ddY strain, aged 8 weeks, were either sham operated (n = 6) or OVX. The OVX mice were randomly divided into 5 groups: OVX control (n = 6), OVX fed 0.1% daidzein–supplemented diet (OVX + Dz, n = 8), OVX fed 0.1% daidzein– and 12% RS–supplemented diet (OVX + Dz + RS, n = 8), OVX fed 12% RS–supplemented diet (OVX + RS, n = 8), and OVX who received daily subcutaneous administration of 17 β-estradiol (n = 6). After 6 weeks, urinary equol concentration was significantly higher in the OVX + Dz + RS group than in the OVX + Dz group. The bone mineral density of the whole tibia was higher in the OV...

Three novel CYP17A1 gene mutations (A82D, R125X, and C442R) found in combined 17α-hydroxylase/17,20-lyase deficiency

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: The aim of this study was to analyze the structure and functional consequences of 3 novel mutations (A82D, R125X, and C442R) of the CYP17A1 gene found in 2 patients with combined 17α-hydroxylase/17,20-lyase deficiency (17OHD). Two Chinese 46, XY female patients were diagnosed with 17OHD based on clinical findings and biochemical results. The CYP17A1 gene was analyzed by polymerase chain reaction direct sequencing. An in vitro expression system was performed in HEK293 cells to analyze the mutant P450c17 activity compared with the wild type. Analysis of the CYP17A1 gene sequences in patient 1 showed compound heterozygous mutations A82D (g.417 C > A) in exon 1 and Y329fs (g.4869 T > A, 4871del) in exon 6; DNA sequencing analysis in patient 2 revealed compound heterozygous mutations...

Metabolic syndrome and pancreatic cancer risk: a case-control study in Italy and meta-analysis

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: We assessed the relation between metabolic syndrome (MetS), its components, and pancreatic cancer risk in an Italian case-control study and performed a meta-analysis of epidemiological studies published up to February 2011. The case-control study included 326 patients with incident pancreatic cancer and 652 controls admitted to the same hospitals for acute, non-neoplastic conditions. MetS was defined as having at least 3 conditions among diabetes, drug-treated hypertension, hyperlipidemia, and body mass index at least 25 kg/m2 at age 30 years. We computed multivariate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) from logistic regression models adjusted for tobacco smoking, education, and other sociodemographic variables. For the meta-analysis, we calcula...

Ghrelin levels in patients with juvenile idiopathic arthritis: relation to anti–tumor necrosis factor treatment and disease activity

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Abstract: Studies in adults with rheumatoid arthritis reported low serum ghrelin that increased following anti–tumor necrosis factor (TNF) infusion. Data on juvenile idiopathic arthritis (JIA) are lacking. The aim of this pilot study was to explore serum ghrelin levels in patients with JIA and the possible association with anti-TNF treatment, disease activity, and nutritional status. Fifty-two patients with JIA (14/52 on anti-TNF treatment) were studied. Juvenile idiopathic arthritis was inactive in 3 of 14 anti-TNF–treated patients and in 11 of 38 non–anti-TNF-treated patients. The nutritional status, energy intake/requirements, appetite, and fasting serum ghrelin levels were assessed. Ghrelin control values were obtained from 50 individuals with minor illness matched for age, sex, ...

Diabetes mellitus, medications for type 2 diabetes mellitus, and cancer risk

Metabolism - Clinical and Experimental — Mon, 09 May 2011 04:00:00 +0100

Diabetes is consistently related to the risk of colorectal, liver, pancreas, and endometrial cancer: the relative risk (RR) is of the order of 1.3 for colorectal cancer and around 2 for liver, pancreas, and endometrial cancer . Diabetes is also moderately related to postmenopausal breast cancer (RR = 1.15-1.2) , but residual confounding by overweight is possible, given the absence of association for premenopausal breast cancer. Diabetes is also possibly directly related to bladder cancer and inversely related to prostate cancer risk , whereas no consistent association is observed for any other major cancer site . (Source: Metabolism - Clinical and Experimental)

Reply to Aydin et al: “To what extent is it right to measure serum vaspin, obestatin, and apelin-36 levels without a protease inhibitor in nonalcoholic fatty liver disease?”

Metabolism - Clinical and Experimental — Sun, 08 May 2011 23:00:00 +0100

Reply: We thank Dr Aydin and colleagues for their interest in our article and their questions about the lack of aprotinin pretreatment before measuring serum peptide levels (and obestatin in particular) in patients with nonalcoholic fatty liver disease (NAFLD). However, we respectfully disagree with their comments. First, pretreatment of biological samples with aprotinin is generally required for the extraction of peptides from plasma or tissue homogenates . However, only serum samples were used in our study. Second, the use of aprotinin was not specifically recommended by the manufacturer of the obestatin immunoassay kit used in our study (Yanaihara Institute, Fujinomiya-SHI Shizuoka, Japan). Third, Dr Aydin and coworkers claim that the increase of caspase levels associated with the deve...

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Metabolism - Clinical and Experimental — Wed, 20 Apr 2011 13:57:14 +0100

(Source: Metabolism - Clinical and Experimental)

Metabolism - Clinical and Experimental — Wed, 20 Apr 2011 13:57:14 +0100

(Source: Metabolism - Clinical and Experimental)

Masthead

Metabolism - Clinical and Experimental — Wed, 20 Apr 2011 13:57:01 +0100

(Source: Metabolism - Clinical and Experimental)

Serum resistance to singlet oxygen in patients with diabetes mellitus in comparison to healthy donors

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 23:00:00 +0100

Abstract: Diabetes mellitus causes endothelial injury through oxidative stress involving reactive oxygen species and peroxides as well as inflammation, both of which consume antioxidant defenses. Singlet oxygen (1O2) is produced by leukocytes during inflammatory and biochemical reactions and deactivated by producing reactive oxygen species and peroxides. To determine whether serum was capable of deactivating 1O2, we triggered a photo reaction in sera from 53 healthy donors and 52 diabetic patients. Immediately after light delivery, dichlorofluorescein was added and then its fluorescence was recorded. The mean capacity of 1O2 or secondary oxidant deactivation was reduced in patients with diabetes mellitus. Hemolysis reduced deactivation of 1O2-induced secondary oxidants in both healthy and ...

Pharmacokinetics and tissue distribution of inositol hexaphosphate in C.B17 SCID mice bearing human breast cancer xenografts

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

Abstract: Inositol hexaphosphate (IP6) is effective in preclinical cancer prevention and chemotherapy. In addition to cancer, IP6 has many other beneficial effects for human health, such as reduction in risk of developing cardiovascular disease and diabetes and inhibition of kidney stone formation. Studies presented here describe the pharmacokinetics, tissue distribution, and metabolism of IP6 following intravenous (IV) or per os (PO) administration to mice. SCID mice bearing MDA-MB-231 xenografts were treated with 20 mg/kg IP6 (3 μCi per mouse [14C]-uniformly ring-labeled IP6) and euthanized at various times after IP6 treatment. Plasma and tissues were analyzed for [14C]-IP6 and metabolites by high-performance liquid chromatography with radioactivity detection. Following IV administratio...

Smoking cessation predicts amelioration of microalbuminuria in newly diagnosed type 2 diabetes mellitus: a 1-year prospective study

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

The objective of the study was to assess the effect of smoking cessation on microalbuminuria in subjects with newly diagnosed type 2 diabetes mellitus (DM). From 500 smokers newly diagnosed with type 2 DM and microalbuminuria, only 193 (96 men/97 women; age, 56.4 ± 7.8 years) agreed to participate and were educated on smoking cessation, diet, and exercise. Pharmacological interventions were not different among the studied groups. All subjects were contacted by phone monthly with emphasis on smoking cessation. Anthropometric, biochemical parameters and urine specimens were obtained at baseline and at 12-month follow-up. Microalbuminuria was defined as an albumin to creatinine ratio of 30 to 299.9 μg/mg creatinine. Ankle brachial pressure index was determined by ultrasound. A total of 120 ...

Changes in calcium fluxes in mitochondria, microsomes, and plasma membrane vesicles of livers from monosodium l-glutamate–obese rats

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

Abstract: The purpose of this work was to evaluate if the fat liver accumulation interferes with intracellular calcium fluxes and the liver glycogenolytic response to a calcium-mobilizing α1-adrenergic agonist, phenylephrine. The animal model of monosodium l-glutamate (MSG)–induced obesity was used. The adult rats develop obesity and steatosis. Calcium fluxes were evaluated through measuring the 45Ca2+ uptake by liver microsomes, inside-out plasma membrane, and mitochondria. In the liver, assessments were performed on the calcium-dependent glycogenolytic response to phenylephrine and the glycogen contents. The Ca2+ uptake by microsomes and plasma membrane vesicles was reduced in livers from obese rats as a result of reduction in the Ca2+-ATPase activities. In addition, the plasma membra...

Association of serum ferritin with metabolic syndrome and diabetes mellitus in the South Korean general population according to the Korean National Health and Nutrition Examination Survey 2008

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

We examined the association of serum ferritin levels with metabolic syndrome (MS) and diabetes mellitus in a representative sample of the adult South Korean population using data from the 2008 Korean National Health and Nutrition Examination Survey. We conducted a cross-sectional study of 6311 adults older than 20 years who participated in the 2008 Korean National Health and Nutrition Examination Survey. Metabolic syndrome was defined as the presence of at least 3 of the following: elevated blood pressure, low high-density lipoprotein cholesterol, elevated serum triglycerides, elevated plasma glucose, and abdominal obesity. Diabetes mellitus was defined as fasting glucose of at least 126 mg/dL. Insulin resistance was determined using the homeostasis model assessment estimate of insulin res...

Effect of carbohydrate-protein supplementation postexercise on rat muscle glycogen synthesis and phosphorylation of proteins controlling glucose storage

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

Abstract: To examine whether addition of protein to a carbohydrate supplement enhances muscle glycogen synthesis, we compared the muscle glycogen concentrations of rats that had been depleted of their muscle glycogen stores with a 3-hour swim and immediately supplemented with a placebo (Con), carbohydrate (CHO), or carbohydrate plus protein supplement (C+P). Rats were given either 0.9 g carbohydrate per kilogram body mass for the CHO group or 0.9 g carbohydrate + 0.3 g protein per kilogram body mass for the C+P groups. Muscle samples of the red and white quadriceps were excised immediately, 30 minutes, or 90 minutes postexercise. Glycogen concentration of the C+P group was greater than that of the CHO group at 90 minutes postexercise in both red (C+P, 28.3 ± 2.6 µmol/g vs CHO, 22.4 ± 2....

Short-term increase of plasma free fatty acids does not interfere with intrinsic mitochondrial function in healthy young men

Metabolism - Clinical and Experimental — Wed, 13 Apr 2011 04:00:00 +0100

Abstract: Free fatty acid (FFA)– and obesity-induced insulin resistance has been associated with disturbed mitochondrial function. Elevated plasma FFA can impair insulin-induced increase of adenosine triphosphate synthesis and downregulate the expression of genes important in the biogenesis of mitochondria in human skeletal muscle. Whether FAs have a direct effect on intrinsic mitochondrial capacity remains to be established. Therefore, we measured ex vivo mitochondrial respiratory capacity in human skeletal muscle after exposure to hyperinsulinemia and high levels of plasma FFA. Nine healthy lean men were studied during a 6-hour hyperinsulinemic (600 pmol/L) euglycemic clamp with concomitant infusion of Intralipid (Fresensius Kabi Nederland, Den Bosch, the Netherlands) (FFA clamped at 0...

Lack of association between apelin, insulin resistance, cardiovascular risk factors, and obesity in children: a longitudinal analysis

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: Apelin has been proposed as a novel beneficial adipokine that is related to insulin resistance, cardiovascular risk factors, and obesity. However, findings in humans are controversial; and longitudinal analyses in childhood are still missing. We compared apelin levels between 80 obese and 40 lean children of the same age, sex, and pubertal stage. In addition, we analyzed the relationships between apelin levels and weight status (as standard deviation of body mass index [SDS-BMI]), body fat, insulin resistance (homeostasis model assessment [HOMA]), leptin, and cardiovascular risk factors associated with obesity (waist circumference, blood pressure, lipids, and adiponectin) in 80 obese children before and after participating in a 1-year lifestyle intervention. Apelin levels did not...

Serum calcium is positively correlated with fasting plasma glucose and insulin resistance, independent of parathyroid hormone, in male patients with type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: Patients with primary hyperparathyroidism have impaired glucose tolerance more often than do controls, and parathyroid resection sometimes improves this derangement. However, it is unclear whether serum calcium (Ca) or parathyroid hormone (PTH) is more strongly related to impaired glucose metabolism in subjects without primary hyperparathyroidism. In this cross-sectional study, we examined patients with type 2 diabetes mellitus (DM) (271 men and 209 women) and analyzed the relationships between serum concentrations of Ca or intact PTH and DM-related variables. Simple regression analyses showed that the level of serum Ca was significantly and positively correlated with the levels of fasting plasma glucose, immunoreactive insulin, and homeostasis model assessment insulin resistance...

Genetic variation within the TRPM5 locus associates with prediabetic phenotypes in subjects at increased risk for type 2 diabetes

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: The functional knockout of the calcium-sensitive, nonselective cation channel TRPM5 alters glucose-induced insulin secretion and glucose tolerance. We hypothesized that genetic variation in the TRPM5 gene may contribute to prediabetic phenotypes, including pancreatic β-cell dysfunction. We genotyped 1798 white subjects at increased type 2 diabetes mellitus risk for 9 TRPM5 single nucleotide polymorphisms (namely, rs2301696, rs800344, rs800345, rs800347, rs800348, rs2074234, rs2301698, rs886277, and rs2301699) and also performed correlational analyses with metabolic traits. An oral glucose tolerance test (OGTT) was conducted on all subjects, and a subset (n = 525) additionally underwent a hyperinsulinemic-euglycemic clamp. The 9 chosen single nucleotide polymorphisms cover 100% o...

Maternal supplementation of omega 3 fatty acids to micronutrient-imbalanced diet improves lactation in rat

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: The present study aims to examine the effect of maternal supplementation of omega 3 fatty acids to a micronutrient (folic acid and vitamin B12)-imbalanced diet on gastric milk volume and long-chain polyunsaturated fatty acid composition. Pregnant female rats were divided into 6 groups at 2 levels of folic acid in both the presence and absence of vitamin B12. Both vitamin B12–deficient groups were supplemented with omega 3 fatty acid. Gastric milk volume and long-chain polyunsaturated fatty acids were analyzed. Our results for the first time indicate that imbalance in maternal micronutrients reduces gastric milk volume and milk docosahexaenoic acid levels (P < .01 for both) as compared with control. Supplementation with omega 3 fatty acids to this diet imbalanced in micronutrien...

Almond ingestion at mealtime reduces postprandial glycemia and chronic ingestion reduces hemoglobin A1c in individuals with well-controlled type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: Cohort studies are equivocal regarding a relationship between regular nut consumption and reduced risk of type 2 diabetes mellitus. Although acute trials show reductions in postprandial glycemia in healthy individuals ingesting 60 to 90 g almonds, trials have not been conducted using a single serving of almonds (28 g) in individuals with type 2 diabetes mellitus. This randomized crossover trial examined the impact of one serving of almonds at mealtime on postprandial glycemia, insulinemia, and plasma glucagon-like peptide–1 in healthy individuals and individuals with type 2 diabetes mellitus. On 2 occasions separated by at least 1 week, 19 adults (including 7 adults with type 2 diabetes mellitus) consumed a standardized evening meal and fasted overnight before ingesting the tes...

Lifestyle modification increases circulating adiponectin concentrations but does not change vaspin concentrations

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

The objective of the study was to evaluate the effects of a 10-month lifestyle intervention on the components of the metabolic syndrome (MetSyn) in Koreans with MetSyn as well as on blood concentrations of adiponectin and vaspin. One hundred thirty-eight patients with MetSyn, recruited from a community health care center, were consecutively enrolled in the study; 12 patients dropped of the intervention, leaving 126 subjects (76 men and 50 women; age, 65.3 ± 9.0 years). All participants followed a 10-month lifestyle modification interventional program, including dietary counseling, advice on increasing physical activity, and recommendations to stop or limit smoking and alcohol drinking. Anthropometric and biochemical parameters related to the components of the MetSyn, including blood conce...

Sucrose induces fatty liver and pancreatic inflammation in male breeder rats independent of excess energy intake

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

Abstract: Fructose induces metabolic syndrome in rats; but studies have been criticized for using high concentrations of fructose that are not physiologic, for using only pure fructose, and for not controlling for energy intake. We tested the hypothesis that a 40% sucrose diet (containing 20% fructose) might induce features of metabolic syndrome in male breeder rats independent of excess energy intake. Male Sprague-Dawley breeder rats were pair fed 40% sucrose or isocaloric starch diet for 4 months and evaluated for metabolic syndrome and diabetes. In vitro studies were performed in rat insulinoma cells (RIN-m5F) exposed to uric acid, and markers of inflammation were assessed. Rats fed a 40% sucrose diet developed accelerated features of metabolic syndrome with up-regulation of fructose-de...

Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss

Metabolism - Clinical and Experimental — Tue, 12 Apr 2011 23:00:00 +0100

The objective was to examine the effects of weight loss and leptin administration following weight loss on calciotropic hormones and bone turnover. This was a prospective, single-blinded study of 12 subjects (8 women, 4 men; 2 nonobese, 10 obese; age range, 19-46 years) who were studied on an inpatient basis while maintaining their usual weight [Wtinitial] and during maintenance of 10% weight loss while receiving twice-daily injections of either a placebo [Wt−10%P] or replacement doses of leptin [Wt−10%L]. The main outcome measures were markers of bone formation (bone alkaline phosphatase and procollagen type 1 amino terminal propeptide) and resorption (N-telopeptide) as well as parathyroid hormone, calcium, and 25-hydroxy vitamin D measured from fasting morning serum. As expected, ser...

A systematic evaluation of the insulin resistance syndrome as an independent risk factor for cardiovascular disease mortality and derivation of a clinical index

Metabolism - Clinical and Experimental — Mon, 04 Apr 2011 04:00:00 +0100

Abstract: Insulin resistance–related risk factor clustering (the insulin resistance syndrome or IRS) may be a cardiovascular disease (CVD) risk factor, but a convincing demonstration of this requires a rigorously derived reference measure and a systematic evaluation of measures and indices that derive from that measure. Using established IRS characteristics, factor analysis in 832 white men, generally healthy at baseline, generated a priori an IRS reference measure. An IRS diagnostic was chosen by evaluating CVD mortality risk in percentiles of the reference measure. An IRS clinical index was derived by (1) identification of readily measured, independent predictors of the IRS reference measure by multiple linear regression; (2) assignment to each predictor of a cut point optimal for disc...

Editorial Board

Metabolism - Clinical and Experimental — Wed, 30 Mar 2011 02:52:28 +0100

(Source: Metabolism - Clinical and Experimental)

Metabolism - Clinical and Experimental — Wed, 30 Mar 2011 02:52:28 +0100

(Source: Metabolism - Clinical and Experimental)

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Metabolism - Clinical and Experimental — Wed, 30 Mar 2011 02:52:22 +0100

(Source: Metabolism - Clinical and Experimental)

Adolescent oligomenorrhea in a biracial schoolgirl cohort: a simple clinical parameter predicting impaired fasting glucose plus type 2 diabetes mellitus, insulin, glucose, insulin resistance, and centripetal obesity from age 19 to 25 years

Metabolism - Clinical and Experimental — Fri, 18 Mar 2011 00:00:00 +0100

Abstract: We hypothesized that adolescent oligomenorrhea (ages 14-19) would independently predict impaired fasting glucose (IFG; ≥110 to (Source: Metabolism - Clinical and Experimental)

Effect of a high-protein diet on ghrelin, growth hormone, and insulin-like growth factor–I and binding proteins 1 and 3 in subjects with type 2 diabetes mellitus

Metabolism - Clinical and Experimental — Wed, 16 Mar 2011 00:00:00 +0100

Abstract: We have developed a diet that over 5 weeks dramatically lowers plasma glucose in people with type 2 diabetes mellitus. This diet consists of 30% carbohydrate, 30% protein, and 40% fat and is referred to as a Low Biologically Available Glucose (LoBAG) diet. The diet also resulted in an approximately 30% increase in fasting insulin-like growth factor–I (IGF-I). Thus, we were interested in determining if the IGF-I elevation was due to an increase in ghrelin and growth hormone (GH) or to a change in IGF-I binding proteins (IGFBPs). Eight men with type 2 diabetes mellitus ingested a control diet (15% protein, 55% carbohydrate, and 30% fat) and a LoBAG30 diet for 5 weeks in a randomized crossover design with a washout period in between. Before and after each 5-week period, subjects h...

Treatment with insulin sensitizer metformin improves arterial properties, metabolic parameters, and liver function in patients with nonalcoholic fatty liver disease: a randomized, placebo-controlled trial

Metabolism - Clinical and Experimental — Wed, 16 Mar 2011 00:00:00 +0100

Abstract: Insulin resistance has an important role in the development of nonalcoholic fatty liver disease (NAFLD) and is involved in both pathological processes: hepatic steatosis and atherosclerosis. Therefore, treatment of NAFLD with insulin sensitizers is likely to have a favorable effect toward hepatic steatosis and cardiovascular outcomes. The present study investigated the effect of metformin on arterial properties, metabolic parameters, and liver function in patients with NAFLD. In a randomized, placebo-controlled study, 63 patients with NAFLD were assigned to 1 of 2 groups: Group 1 received daily metformin; group 2 received placebo. Pulse wave velocity (PWV) and augmentation index (AI) were measured using SphygmoCor (version 7.1; AtCor Medical, Sydney, Australia) at baseline and at...

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Dietary calcium and body weight: what's the “skinny”?

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Elsevier/Oxford Centre for Diabetes, Endocrinology and Metabolism Junior Research Prize in Endocrinology: ENDO 2011 conference report

The Metabolism Award for Junior Investigators

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Mutational analysis of human bone morphogenetic protein 15 in Chinese women with polycystic ovary syndrome

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Postprandial lipoprotein metabolism in familial hypercholesterolemia: thinking outside the box

One year of changes for Metabolism, Clinical and Experimental: evolution and intelligent design at work

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Adiponectin levels in nonalcoholic fatty liver disease

Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients

S100A16 mediation of weight gain attenuation induced by dietary calcium

High serum uric acid level and low urine pH as predictors of metabolic syndrome: a retrospective cohort study in a Japanese urban population

Effect of exercise training combined with phytoestrogens on adipokines and C-reactive protein in postmenopausal women: a randomized trial

Improvement in insulin sensitivity following a 1-year lifestyle intervention program in viscerally obese men: contribution of abdominal adiposity

Combined hypertriglyceridemic and insulin-glucose clamps for the characterization of substrate oxidation and plasma elimination of a long-chain triglyceride emulsion in healthy men

Acute resistance exercise augments integrative myofibrillar protein synthesis

The effects of glucocorticoids on adipose tissue lipid metabolism

Sources of hepatic glycogen synthesis following a milk-containing breakfast meal in healthy subjects

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Postprandial changes in plasma acylcarnitine concentrations as markers of fatty acid flux in overweight and obesity

Prophylactic treatment with telmisartan induces tissue-specific gene modulation favoring normal glucose homeostasis in Cohen-Rosenthal diabetic hypertensive rats

The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients

Influence of resting energy expenditure on blood pressure is independent of body mass and a marker of sympathetic tone

Acute hypoglycemia causes depressive-like behaviors in mice

Fatness, fitness, and cardiometabolic risk factors in middle-aged white men

Circulating androgen levels are associated with subclinical atherosclerosis and arterial stiffness in healthy recently menopausal women

Association between the severity of obstructive sleep apnea and the ratio of low-density lipoprotein cholesterol to high-density lipoprotein cholesterol

Effects of high-fat diet and regular aerobic exercise on global gene expression in skeletal muscle of C57BL/6 mice

Severity and outcome of acute stroke in women: relation to adrenal sex steroid levels

The relationship between adiponectin, an adiponectin gene polymorphism, and high-density lipoprotein particle size: from the Mima study

Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women

The quest for the perfect biomarker of long-term glycemia: new studies, new trials and tribulations

Mitochondrial regulators of fatty acid metabolism reflect metabolic dysfunction in type 2 diabetes mellitus

Metabolic syndrome in a Mediterranean pediatric cohort: prevalence using International Diabetes Federation–derived criteria and associations with adiponectin and leptin

Inducible nitric oxide synthase deficiency ameliorates skeletal muscle insulin resistance but does not alter unexpected lower blood glucose levels after burn injury in C57BL/6 mice

Exercise can induce temporary mitochondrial and contractile dysfunction linked to impaired respiratory chain complex activity

Treatment of genetically obese mice with the iminosugar N-(5-adamantane-1-yl-methoxy-pentyl)-deoxynojirimycin reduces body weight by decreasing food intake and increasing fat oxidation

Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects

Associations of urinary 6-sulfatoxymelatonin with biomarkers related to cardiovascular disease in Japanese women

Dietary glycemic index and risk of type 2 diabetes mellitus in middle-aged Japanese men

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Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats, Metabolism 2005;54(4):482-487

Drug-drug interactions in HIV medicine: a not so simple and straightforward road to the future

Leptin and the skeleton—where is the fat?

Rosiglitazone increases fatty acid Δ9-desaturation and decreases elongase activity index in human skeletal muscle in vivo

Retinol-binding protein 4 is not associated with insulin resistance in pregnancy

Circulating levels of insulin-like growth factor binding protein–1 in relation to insulin resistance, type 2 diabetes mellitus, and metabolic syndrome (Chennai Urban Rural Epidemiology Study 118)

Long-term metreleptin treatment increases bone mineral density and content at the lumbar spine of lean hypoleptinemic women

Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary artery disease in women

Overexpression of hepatic 5α-reductase and 11β-hydroxysteroid dehydrogenase type 1 in visceral adipose tissue is associated with hyperinsulinemia in morbidly obese patients

The dynamic insulin sensitivity and secretion test—a novel measure of insulin sensitivity

Cardiorespiratory fitness predicts insulin action and secretion in healthy individuals

Intensive practical lifestyle intervention improves endothelial function in metabolic syndrome independent of weight loss: a randomized controlled trial

Site dependency of fatty acid composition in adipose triacylglycerol in rats and its absence as a result of high-fat feeding

Serum adipokine zinc α2-glycoprotein and lipolysis in cachectic and noncachectic heart failure patients: relationship with neurohormonal and inflammatory biomarkers

Incidence of malignancies in patients with diabetes mellitus and correlation with treatment modalities in a large Israeli health maintenance organization: a historical cohort study

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trans-Fatty acids, insulin resistance/diabetes, and cardiovascular disease risk: should policy decisions be based on observational cohort studies, or should we be waiting for results from randomized placebo-controlled trials?

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Triglyceride–high-density lipoprotein cholesterol is associated with microvascular complications in type 2 diabetes mellitus