Tag Archives: Diabetic

SGLT2 Inhibitors and the Diabetic Kidney

Paola Fioretto
Aug 1, 2016; 39:S165-S171
III. SGLT2 Therapy
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GLP-1R as a Target for the Treatment of Diabetic Retinopathy: Friend or Foe?

Glucagon-like peptide 1 receptor (GLP-1R) agonists are increasingly being used as treatment for type 2 diabetes. Since the U.S. Food and Drug Administration published recommendations about the cardiovascular safety of new antidiabetes therapies for treating type 2 diabetes in 2008, the results of two outstanding clinical trials using GLP-1R agonists addressing this issue (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation [LEADER] and Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes [SUSTAIN-6]) have been published. Both studies found beneficial effects in terms of reducing the rates of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke. However, their results regarding the progression of diabetic retinopathy (DR) were neutral with liraglutide (LEADER) or worse when compared with placebo in the case of semaglutide (SUSTAIN-6). These results are surprising because of the beneficial effects of GLP-1R analogs reported in experimental models of DR. In this Perspective, an overview of the mechanisms by which GLP-1R activation exerts its effects in preventing or arresting experimental DR is given. In addition, we consider the possible reasons for the negative results regarding the progression of DR in the SUSTAIN-6 study, as well as the gaps that still need to be covered to further clarify this important issue in the management of type 2 diabetes.

Diabetes Journal current issue





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Correcting Postprandial Hyperglycemia in Zucker Diabetic Fatty Rats With an SGLT2 Inhibitor Restores Glucose Effectiveness in the Liver and Reduces Insulin Resistance in Skeletal Muscle

Ten-week-old Zucker diabetic fatty (ZDF) rats at an early stage of diabetes embody metabolic characteristics of obese human patients with type 2 diabetes, such as severe insulin and glucose intolerance in muscle and the liver, excessive postprandial excursion of plasma glucose and insulin, and a loss of metabolic flexibility with decreased lipid oxidation. Metabolic flexibility and glucose flux were examined in ZDF rats during fasting and near-normal postprandial insulinemia and glycemia after correcting excessive postprandial hyperglycemia using treatment with a sodium–glucose cotransporter 2 inhibitor (SGLT2-I) for 7 days. Preprandial lipid oxidation was normalized, and with fasting, endogenous glucose production (EGP) increased by 30% and endogenous glucose disposal (E-Rd) decreased by 40%. During a postprandial hyperglycemic-hyperinsulinemic clamp after SGLT2-I treatment, E-Rd increased by normalizing glucose effectiveness to suppress EGP and stimulate hepatic glucose uptake; activation of glucokinase was restored and insulin action was improved, stimulating muscle glucose uptake in association with decreased intracellular triglyceride content. In conclusion, SGLT2-I treatment improves impaired glucose effectiveness in the liver and insulin sensitivity in muscle by eliminating glucotoxicity, which reinstates metabolic flexibility with restored preprandial lipid oxidation and postprandial glucose flux in ZDF rats.

Diabetes Journal current issue





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Influence of Mulberry Leaf Extract on the Blood Glucose and Breath Hydrogen Response to Ingestion of 75 g Sucrose by Type 2 Diabetic and Control Subjects

Mitchell Mudra
May 1, 2007; 30:1272-1274
BR Clinical Care/Education/Nutrition
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Proximal Tubulopathy: Prime Mover and Key Therapeutic Target in Diabetic Kidney Disease

The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of renal prognosis in diabetes and may not be the primary event in the development of diabetic kidney disease either. Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current “glomerulocentric” paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state. Such findings raise important issues for therapeutic advances specifically targeting the pathophysiological perturbations that develop in this part of the nephron.

Diabetes Journal current issue





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Müller Cell-Microglia Cross Talk Drives Neuroinflammation in Diabetic Retinopathy

Diabetes Journal current issue





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Back to the Future: Glomerular Hyperfiltration and the Diabetic Kidney

Diabetes Journal current issue





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CIN85: Implications for the Development of Proteinuria in Diabetic Nephropathy

Diabetes Journal current issue





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Diabetic Cardiomyopathy: The Case for a Role of Fructose in Disease Etiology

A link between excess dietary sugar and cardiac disease is clearly evident and has been largely attributed to systemic metabolic dysregulation. Now a new paradigm is emerging, and a compelling case can be made that fructose-associated heart injury may be attributed to the direct actions of fructose on cardiomyocytes. Plasma and cardiac fructose levels are elevated in patients with diabetes, and evidence suggests that some unique properties of fructose (vs. glucose) have specific cardiomyocyte consequences. Investigations to date have demonstrated that cardiomyocytes have the capacity to transport and utilize fructose and express all of the necessary proteins for fructose metabolism. When dietary fructose intake is elevated and myocardial glucose uptake compromised by insulin resistance, increased cardiomyocyte fructose flux represents a hazard involving unregulated glycolysis and oxidative stress. The high reactivity of fructose supports the contention that fructose accelerates subcellular hexose sugar-related protein modifications, such as O-GlcNAcylation and advanced glycation end product formation. Exciting recent discoveries link heart failure to induction of the specific high-affinity fructose-metabolizing enzyme, fructokinase, in an experimental setting. In this Perspective, we review key recent findings to synthesize a novel view of fructose as a cardiopathogenic agent in diabetes and to identify important knowledge gaps for urgent research focus.

Diabetes Journal current issue





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A Case of Euglycemic Diabetic Ketoacidosis Following Long-term Empagliflozin Therapy

Peter D. Farjo, Kacie M. Kidd, Josephine L. Reece
Oct 1, 2016; 39:165-166
e-Letters: Observations
Diabetes Care: Most-Read Full-Text Articles





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