The Role of the Kidney in Hyperglycemia

Hinnen, Deborah

doi:10.1097/jcn.0b013e318245633e

Cited by 9 publications

(7 citation statements)

References 64 publications

(62 reference statements)

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“…Type 2 diabetes mellitus (T2DM) is the most common form of diabetes, and is associated with the development of a number of devastating microvascular complications, including diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and diabetic nephropathy (DN) 1. Diabetes-induced microvascular complications are the major causes of morbidity and mortality in patients with T2DM 2.…”

Section: Introductionmentioning

confidence: 99%

Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus

Wang¹,

Song²,

Bai³

et al. 2013

VHRM

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BackgroundRheological disorders of red blood cells (RBC) and decreased RBC deformability have been involved in the development of diabetic microangiopathy. However, few studies have evaluated the association of RBC count with microvascular complications in patients with type 2 diabetes mellitus (T2DM). The purpose of this study was to investigate the association of RBC count with microvascular complications in patients with T2DM.MethodsThis study involved 369 patients with T2DM: 243 with one or more microvascular complications and 126 without microvascular complications. Anticoagulated blood was collected and analyzed in an automated blood cell counter. The presence of risk factors for microvascular complications was determined.ResultsThe proportion of patients with microvascular complications increased as the RBC count decreased (P < 0.001). After adjustment for known risk factors for microvascular complications by logistic regression analysis, lower quartiles of RBC count were associated with a higher risk of microvascular complications compared with the reference group composed of the highest quartile (first quartile, odds ratio 4.98, 95% confidence interval 1.54–6.19, P = 0.008; second quartile, odds ratio 3.21, 95% confidence interval 1.17–5.28, P = 0.024).ConclusionA decreased RBC count is associated with microvascular complications in Chinese patients with T2DM. The RBC count is a potential marker to improve further the ability to identify diabetic patients at high risk of microvascular complications.

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Section: Introductionmentioning

confidence: 99%

Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus

Wang¹,

Song²,

Bai³

et al. 2013

VHRM

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“…Drugs currently used in the treatment of DM vary in their mechanisms of action, including the stimulation of insulin secretion, the suppression of hepatic gluconeogenesis, the inhibition of intestinal glucose absorption, and the reduction of insulin resistance in liver and muscle. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are a novel class of anti-diabetic drugs with a different mechanism of action, reducing blood glucose concentrations by inhibiting glucose reabsorption in renal tubules [3,4]. SGLT2 inhibitors have been shown to have a low risk of hypoglycemia in diabetic patients and to reduce the incidence of obesity, cardiovascular diseases, and diabetic nephropathy [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

“…SGLT2 inhibitors have been shown to have a low risk of hypoglycemia in diabetic patients and to reduce the incidence of obesity, cardiovascular diseases, and diabetic nephropathy [5][6][7]. Although studies have assessed the role of the kidneys in glucose homeostasis, less is known about the kidneys as a therapeutic target for diabetes [4]. However, the success of SGLT2 inhibitors in the treatment of DM has highlighted the kidneys as a target in DM treatment [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…Although studies have assessed the role of the kidneys in glucose homeostasis, less is known about the kidneys as a therapeutic target for diabetes [4]. However, the success of SGLT2 inhibitors in the treatment of DM has highlighted the kidneys as a target in DM treatment [3,4].…”

Section: Introductionmentioning

confidence: 99%

“…The kidneys, which have high energy demands, take up glucose from the blood, while contributing to higher blood glucose levels via gluconeogenesis, insulin degradation, and tubular reabsorption of glucose [3][4][5]8,9]. In a fasting state, the kidneys release lower amounts of endogenous glucose into the circulation than the liver.…”

Section: Introductionmentioning

confidence: 99%

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Characterization of Enlarged Kidneys and Their Potential for Inducing Diabetes in DEK Rats

Domon

Katayama

Yamada

et al. 2021

Biology

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The kidneys participate in the regulation of systemic glucose metabolism via gluconeogenesis, insulin degradation, and the tubular reabsorption of glucose. The present study characterized rats from a strain of a novel type 2 diabetes model with enlarged kidneys (DEK). Histological and biochemical analyses of DEK rats were performed to assess the relationships between their kidneys and hyperglycemia. The kidney weight of diabetic DEK (DEK-DM) gradually increased over time from the onset of diabetes, with the glomerular number being higher in DEK-DM than in normal DEK (DEK-cont). A positive correlation between blood glucose level and kidney weight was observed in DEK-DM. The similar glomerular size and single glomerular creatinine clearance in DEK-cont and DEK-DM indicated that glomerular hypertrophy and hyperfiltration were not involved in the renal enlargement. Uninephrectomy (1/2Nx) in DEK-DM resulted in a reduction in blood glucose level at 7–28 post-operation days, with this concentration remaining lower than in Sham group until 84 days post-operation. 1/2Nx also improved systemic conditions, including reduced body weight gain, polyuria, polydipsia, and hyperphagia. Plasma concentrations of Na, total cholesterol, albumin, and total protein were higher, and urinary excretion of glucose, urea nitrogen, and proteins were lower, in the 1/2Nx than in the Sham group. Remnant kidney weight was two-fold higher in the 1/2Nx than in the Sham group 84 days later. In addition, 1/2Nx resulted in renal tubular dilatation but not in the progression of fibrosis or glomerular lesions. Taken together, these findings indicate that enlarged kidneys were associated with the onset of diabetes and with the resistance to diabetic nephropathy in DEK-DM.

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Effects of Empagliflozin Treatment on Glycerol‐Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial

Neeland

Rocha

Hughes

et al. 2020

Obesity

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The aim of this study was to determine the effects of empagliflozin on glycerol-derived hepatic gluconeogenesis in adults with obesity without type 2 diabetes mellitus (T2DM) using oral carbon 13 (13 C)-labeled glycerol. Methods: A randomized, double-blind, placebo-controlled trial was performed in participants with magnetic resonance imaging assessment of body fat and measurement of glycerol-derived 13 C enrichment in plasma glucose by nuclear magnetic resonance spectroscopy following ingestion of [U-13 C 3 ]glycerol. Participants were randomized to oral empagliflozin 10 mg once daily or placebo for 3 months. Glycerol-derived 13 C enrichment studies were repeated, and treatment differences in the mean percentage of 13 C glycerol enrichment in glucose were compared using mixed linear models. Results: Thirty-five participants completed the study. Empagliflozin increased glycerol-derived 13 C enrichment between baseline and follow-up by 6.5% (P = 0.005), consistent with less glycerol from visceral adipose tissue (VAT). No difference was found with placebo. Glycerolderived 13 C enrichment was lower in participants with high VAT compared with low VAT by 12.6% (P = 0.04), but there was no heterogeneity of the treatment effect by baseline VAT. Glycerol-derived 13 C enrichment was inversely correlated with VAT but was not correlated with weight loss. Conclusions: VAT is associated with endogenous glycerol-derived hepatic gluconeogenesis, and empagliflozin reduces endogenous glycerol gluconeogenesis in adults with obesity without T2DM. These findings suggest a mechanism by which sodium-glucose cotransporter 2 inhibitors may prevent T2DM in obesity.

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The Role of the Kidney in Hyperglycemia

Cited by 9 publications

References 64 publications

Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus

Red blood cell count as an indicator of microvascular complications in Chinese patients with type 2 diabetes mellitus

Characterization of Enlarged Kidneys and Their Potential for Inducing Diabetes in DEK Rats

Effects of Empagliflozin Treatment on Glycerol‐Derived Hepatic Gluconeogenesis in Adults with Obesity: A Randomized Clinical Trial

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