Impacts of COVID-19 on Glycemia and Risk of Diabetic Ketoacidosis
Reports indicate that coronavirus disease 2019 (COVID-19) may impact pancreatic function and increase type 2 diabetes (T2D) risk, although real-world COVID-19 impacts on HbA1c and T2D are unknown. We tested whether COVID-19 increased HbA1c, risk of T2D, or diabetic ketoacidosis (DKA). We compared pre – and post–COVID-19 HbA1c and T2D risk in a large real-world clinical cohort of 8,755 COVID-19(+) patients and 11,998 COVID-19( −) matched control subjects. We investigated whether DKA risk was modified in COVID-19(+) patients with type 1 diabetes (T1D) (N = 701) or T2D (N = 21,830), or by race and sex. We observed a sta...
Source: Diabetes - May 18, 2023 Category: Endocrinology Source Type: research
Distinct Roles for Brain and Pancreas in Basal and Postprandial Glucose Homeostasis
The glucose homeostasis system ensures that the circulating glucose level is maintained within narrow physiological limits both in the fasting (or basal) state and following a nutrient challenge. Although glucose homeostasis is traditionally conceptualized as a single overarching system, evidence reviewed here suggests that basal glycemia and glucose tolerance are governed by distinct control systems. Specifically, whereas glucose tolerance appears to be determined largely by interactions between insulin secretion and insulin sensitivity, basal-state glucose homeostasis is predominated by insulin-independent mechanisms gov...
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Issues and Events
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Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
In This Issue of Diabetes
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Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Response to Comment on Carrasco et al. Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells. Diabetes 2022;71:862–869
We thank Memon and Abdelalim (1) for their comments on our article (2). In short, they point out that the induced pluripotent stem cell (iPSC) lines that we used in our experiments contained mosaic trisomy 1 (47,XY,+1) in the mutated lines with the potential consequence that this trisomy would invalidate the study results. Memon and Abdelalim also point out that the genome-edited lines used as control lines did not contain this trisomy 1 (47,XY,+1), i.e., these gene-edited lines were 46,XY (with additional mosaicism, including deletions of chromosome 18) and hence did not represent appropriate controls. Furthermore, Memon ...
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Comment on Tabatabaei Dakhili et al. The Antipsychotic Dopamine 2 Receptor Antagonist Diphenylbutylpiperidines Improve Glycemia in Experimental Obesity by Inhibiting Succinyl-CoA:3-Ketoacid CoA Transferase. Diabetes 2023;72:126 –134
The recent article from Tabatabaei Dakhili et al. (1) describes some elegant studies that indicate that the antipsychotic diphenybutylpyridine (DPBP) drugs, particularly pimozide, can alleviate obesity-induced type 2 diabetes. They use in vitro, in vivo, and in silico techniques to demonstrate a noncanonical action of these dopamine 2 (D2) receptor antagonists in reducing hyperglycemia via a reduction of succinyl CoA:3-ketoacid CoA transferase (SCOT) activity. They conclude that this indicates the potential for drug repurposing of the DPBPs, as they “appear relatively safe in humans,” a conclusion reiterated by Ma...
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Increased Risk of Diabetes and Diabetic Ketoacidosis Associated With COVID-19
It is known that pancreatic β-cells are permissive to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection through the expression of ACE receptor 2 (1) and that the infection may also induce indirect β-cell damage through a cytokine storm and a proinflammatory milieu (2). It has also been shown that inflammatory and immunological alterations (3) following a coronavirus disease 2019 (COVID-19) infection may lead to acute and long-term disruption of glucose metabolism (4–6). A recent study showed that the combination of augmented circulating inflammatory factors that exert toxic effects on human pancrea...
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Comment on Carrasco et al. Spatial Environment Affects HNF4A Mutation-Specific Proteome Signatures and Cellular Morphology in hiPSC-Derived β-Like Cells. Diabetes 2022;71:862–869
Human pluripotent stem cells (hPSCs) are a valuable tool for the study of the cellular and molecular mechanisms that underlie different types of diabetes. However, one pitfall of hPSCs is that genomic aberrations can develop during the reprogramming process as a result of gene editing or simply during extended cell culture (1). Some of these aberrations, such as trisomy 1, hamper embryonic development and lead to elimination of the fetus (2). Such detrimental aberrations acquired in hPSCs can cause genetic imbalance, thus affecting cellular identity and function. Therefore, given the fatal phenotypes observed in their in ...
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
“FunDNAmethyl” Mechanism for Developmental Restriction of a β-Cell Subpopulation
National Institute of Diabetes and Digestive and Kidney Diseases10.13039/1000000621R01DK1171371R01DK1180111R01DK129523-021R01DK132535P30 DK036836 (Source: Diabetes)
Source: Diabetes - April 20, 2023 Category: Endocrinology Source Type: research
Glucagon Acting at the GLP-1 Receptor Contributes to β-Cell Regeneration Induced by Glucagon Receptor Antagonism in Diabetic Mice
Dysfunction of glucagon-secreting α-cells participates in the progression of diabetes, and glucagon receptor (GCGR) antagonism is regarded as a novel strategy for diabetes therapy. GCGR antagonism upregulates glucagon and glucagon-like peptide 1 (GLP-1) secretion and, notably, promotes β-cell regeneration in diabetic mice. Here, w e aimed to clarify the role of GLP-1 receptor (GLP-1R) activated by glucagon and/or GLP-1 in the GCGR antagonism–induced β-cell regeneration. We showed that indb/db mice and type 1 diabetic wild-type or Flox/cre mice, GCGR monoclonal antibody (mAb) improved glucose control, upregulated plasm...
Source: Diabetes - February 24, 2023 Category: Endocrinology Source Type: research
Topically Administered NOX4 Inhibitor, GLX7013114, Is Efficacious in Treating the Early Pathological Events of Diabetic Retinopathy
This study provides new findings regarding the pharmacological profile o f the novel NOX4 inhibitor GLX7013114 as a promising therapeutic candidate for the treatment of the early stage of DR.Article HighlightsNADPH oxidases (NOXs) are implicated in the early pathological events of diabetic retinopathy (DR).The NOX4 inhibitor GLX7013114, topically administered, reduced oxidative damage and apoptosis in the rat streptozotocin model of DR.GLX7013114 protected retinal neurons and retinal ganglion cell function and reduced the expression of pro-inflammatory cytokines in the diabetic retina.GLX7013114 diminished the diabetes-ind...
Source: Diabetes - February 23, 2023 Category: Endocrinology Source Type: research
Metrnl Alleviates Lipid Accumulation by Modulating Mitochondrial Homeostasis in Diabetic Nephropathy
In conclusion, our study demonstrates that Metrnl regulated lipid metabolism in the kidney by modula ting mitochondrial function and is a stress-responsive regulator of kidney pathophysiology, which sheds light on novel strategies for treating DKD and associated kidney diseases.Article HighlightsMetrnl is expressed in renal tubules and is reduced under diabetic conditions.The concentration of Metrnl in the kidney is correlated with lipid accumulation and serum creatinine.Metrnl-specific overexpression in the kidney or recombinant Metrnl administration alleviates renal injuries in diabetic mice.Metrnl regulates renal tubule...
Source: Diabetes - February 22, 2023 Category: Endocrinology Source Type: research
Investigating Gene –Diet Interactions Impacting the Association Between Macronutrient Intake and Glycemic Traits
Few studies have demonstrated reproducible gene –diet interactions (GDIs) impacting metabolic disease risk factors, likely due in part to measurement error in dietary intake estimation and insufficient capture of rare genetic variation. We aimed to identify GDIs across the genetic frequency spectrum impacting the macronutrient–glycemia relati onship in genetically and culturally diverse cohorts. We analyzed 33,187 participants free of diabetes from 10 National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program cohorts with whole-genome sequencing, self-reported diet, and glycemic trait data. We...
Source: Diabetes - February 15, 2023 Category: Endocrinology Source Type: research
Plasma Proteomic Risk Markers of Incident Type 2 Diabetes Reflect Physiologically Distinct Components of Glucose-Insulin Homeostasis
High-throughput proteomics allows researchers to simultaneously explore the roles of thousands of biomarkers in the pathophysiology of diabetes. We conducted proteomic association studies of incident type 2 diabetes and physiologic responses to an intravenous glucose tolerance test (IVGTT) to identify novel protein contributors to glucose homeostasis and diabetes risk. We tested 4,776 SomaScan proteins measured in relation to 18-year incident diabetes risk in participants from the Cardiovascular Health Study (N = 2,631) and IVGTT-derived measures in participants from the HERITAGE Family Study (N = 752). We characterize 51 ...
Source: Diabetes - February 7, 2023 Category: Endocrinology Source Type: research
The Impact of Different Implantation Sites and Sex on the Differentiation of Human Pancreatic Endoderm Cells Into Insulin-Secreting Cells In Vivo
Few studies have examined the differentiation of human embryonic stem cell (hESC) –derived pancreatic endoderm cells (PECs) in different implantation sites. Here, we investigate the influence of implantation site and recipient sex on the differentiation of hESC-derived PECs in vivo. Male and female mice were implanted with 5 × 106 hESC-derived PECs under the kidney capsule, in the gonadal fat pad, or subcutaneously within macroencapsulation (TheraCyte) devices. PECs implanted within TheraCyte devices developed glucose-stimulated human C-peptide secretion faster than cells implanted under the kidney capsule or in the go...
Source: Diabetes - February 6, 2023 Category: Endocrinology Source Type: research
