1851-P: Renal Denervation Attenuates Endogenous Glucose Production Increase with SGLT2 Inhibition in Patients with Renal Transplant Recipients and Impaired Fasting Glucose

Context: Prediabetes is a heterogeneous disorder classified on the basis of fasting glucose concentrations and 2-hour glucose tolerance. Objective: We sought to determine the relative contributions of insulin secretion and action to the pathogenesis of isolated impaired glucose tolerance (IGT). Design: The study consisted of an oral glucose tolerance test and a euglycemic clamp performed in two cohorts matched for anthropometric characteristics and fasting glucose but discordant for glucose tolerance. Setting: An inpatient clinical research unit at an academic medical center. Patients or Other Participants: Twenty-five subjects who had normal fasting glucose (NFG) and normal glucose tolerance (NGT) and 19 NFG/IGT subjects participated in this study. Intervention(s): Subjects underwent a seven-sample oral glucose tolerance test and a 4-hour euglycemic, hyperinsulinemic clamp on separate occasions. Glucose turnover during the clamp was measured using tracers, and endogenous hormone secretion was inhibited by somatostatin. Main Outcome Measures: We sought to determine whether hepatic glucose metabolism, specifically the contribution of gluconeogenesis to endogenous glucose production, differed between subjects with NFG/NGT and those with NFG/IGT. Results: Endogenous glucose production did not differ between groups before or during the clamp. Insulin-stimulated glucose disappearance was lower in NFG/IGT (24.6 ± 2.2 vs 35.0 ± 3.6 μmol/kg/min; P = .03). The disposition index was decreased in NFG/IGT (681 ± 102 vs 2231 ± 413 × 10−14 dL/kg/min2 per pmol/L; P < .001). Conclusions: We conclude that innate defects in the regulation of glycogenolysis and gluconeogenesis do not contribute to NFG/IGT. However, insulin-stimulated glucose disposal is impaired, exacerbating defects in β-cell function.

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Metformin increases fasting glucose clearance and endogenous glucose production in non-diabetic individuals

Diabetologia ◽

10.1007/s00125-019-05042-1 ◽

2019 ◽

Vol 63 (2) ◽

pp. 444-447 ◽

Cited By ~ 4

Author(s):

Laura J. McCreight ◽

Andrea Mari ◽

Lucy Coppin ◽

Nicola Jackson ◽

A. Margot Umpleby ◽

...

Keyword(s):

Fasting Glucose ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Glucose Clearance ◽

Endogenous Glucose

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Both fasting glucose production and disappearance are abnormal in people with “mild” and “severe” type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00549.2003 ◽

2004 ◽

Vol 287 (1) ◽

pp. E55-E62 ◽

Cited By ~ 53

Author(s):

Rita Basu ◽

W. Frederick Schwenk ◽

Robert A. Rizza

Keyword(s):

Type 2 Diabetes ◽

Fasting Glucose ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Fasting Insulin ◽

Type 2 Diabetics ◽

Severe Diabetes ◽

Endogenous Glucose ◽

Severe Type

To determine whether regulation of fasting endogenous glucose production (EGP) and glucose disappearance (Rd) are both abnormal in people with type 2 diabetes, EGP and Rd were measured in 7 “severe” (SD), 9 “mild” (MD), and 12 nondiabetic (ND) subjects (12.7 ± 0.6 vs. 8.1 ± 0.4 vs. 5.1 ± 0.4 mmol/l) after an overnight fast and during a hyperglycemic pancreatic clamp. Fasting insulin was higher in both the SD and MD than ND subjects, whereas fasting glucagon only was increased ( P < 0.05) in SD. Fasting EGP, glycogenolysis, gluconeogenesis, and Rd all were increased ( P < 0.05) in SD but did not differ in MD or ND. On the other hand, when glucose (∼11 mmol/l), insulin (∼72 pmol/l), and glucagon (∼140 pg/ml) concentrations were raised to values similar to those observed in the severe diabetic subjects, EGP was higher ( P < 0.001) and Rd lower ( P < 0.01) in both SD and MD than in ND. The higher EGP in the SD and MD than ND during the clamp was the result of increased ( P < 0.05) rates of glycogenolysis (4.2 ± 1.7 vs. 3.5 ± 1.0 vs. 0.0 ± 0.8 μmol·kg−1·min−1), since gluconeogenesis did not differ among groups. We conclude that neither glucose production nor disappearance is appropriate for the prevailing glucose and insulin concentrations in people with mild or severe diabetes. Both increased rates of gluconeogenesis (likely because of higher glucagon concentrations) and lack of suppression of glycogenolysis contribute to excessive glucose production in type 2 diabetics.

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Yogurt Consumption Improves Insulin Sensitivity and Hepatic Insulin Action in a Diet Induced Mouse Model of Obesity and Type 2 Diabetes

Current Developments in Nutrition ◽

10.1093/cdn/nzaa063_062 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 1664-1664

Author(s):

Renato Nachbar ◽

Noëmie Daniel ◽

Laurent Quinquis ◽

Marie-Julie Dubois ◽

Philippe St-Pierre ◽

...

Keyword(s):

Insulin Sensitivity ◽

Fasting Glucose ◽

Body Weight Gain ◽

Glucose Production ◽

Endogenous Glucose Production ◽

Whole Body ◽

Fasting Insulin ◽

Sucrose Diet ◽

Endogenous Glucose

Abstract Objectives We investigated the effect of yogurt consumption at 8% energy intake on insulin sensitivity in mice fed high-fat high-sucrose diet that contains a protein mixture representative of US diet (HFHS-PM). Methods Yogurt (2% fat, 5% protein, 7% carbohydrate, Lactobacillus bulgaricus CNCM I-1519, Streptococcus thermophilus CNCM I-1630) was lyophilized and incorporated into the HFHS-PM diet (HFHS-PM + LYP; 4.8 kcal/g). The control group was kept on the HFHS-PM diet (4.8 kcal/g). A group of mice was fed a low-fat low sucrose diet (LFLS-PM; 3.7 kcal/g). Whole-body glucose homeostasis and tissue insulin action were assessed using tracer-coupled hyperinsulinemic-euglycemic clamp studies performed after 12 weeks of dietary intervention. Results At Week 12, mice fed HFHS-PM (n = 36) had increased body weight gain (+10.9 g P < 0.001), fasting glucose (+4.1 mmol/l, P < 0.001) and fasting insulin (+2.7 ng/mL, P < 0.001) when compared to LFLS-PM mice (n = 35). HFHS-PM + LYP fed mice (n = 36) had lower fasting glucose (–0.9 mmol/, P < 0.05) and fasting insulin (–1.1 ng/mL, P < 0.05) as compared to HFHS-PM controls without any impact on body weight gain. Clamp studies revealed that mice fed HFHS-PM (n = 27) had reduced insulin-mediated glucose infusion rate (–17.1 mg/min/kg, P < 0.001) indicating whole-body insulin resistance when compared to LFLS-PM (n = 23). Insulin resistance in HFHS-PM fed animals was linked to increased endogenous glucose production (+7.2 mg/min/kg, P < 0.001) and decrease in the rate of peripheral glucose uptake (–10.3 mg/min/kg, P < 0.001) during the clamp compared to LFLS-PM fed mice. Importantly, mice fed HFHS-PM + LYP (n = 25) exhibited a significantly elevated glucose infusion rate (+3.6 mg/min/kg, P = 0.02), i.e., improved whole-body insulin sensitivity, and a numerical decrease of the endogenous glucose production (–1.9 mg/min/kg, P = 0.06) with lack of changes in peripheral glucose uptake when compared to HFHS-PM mice. Conclusions Incorporation of lyophilized yogurt into the HFHS-PM diet improves insulin sensitivity in a diet-induced mouse model of obesity and type 2 diabetes. The selective improvement of insulin-suppressed endogenous glucose production strongly suggest that the liver is the main target of yogurt beneficial effect. Funding Sources Danone Nutricia Research, Palaiseau, France.

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