Glucose Metabolism In Subjects Research Articles

The impact of high-intensity interval training and alternate-day fasting on glucose metabolism in rats on a high-fat diet

Abstract The effect of lifestyle modifications in the form of exercise training and fasting intervention on glucose metabolism in subjects on a high-fat diet is not completely understood. The present study aimed to examine the effects of alternate-day fasting (ADF) and high-intensity interval training (HIIT) on serum levels of C-peptide, fructosamine, and glucose in rats under a high-fat diet. Twenty-eight male Wistar rats were initially fed a high-fat diet for 12 weeks, then randomised into the following four groups: HIIT, ADF, HIIT + ADF, and control (CON). The HIIT and ADF interventions were conducted 3 days per week for 6 weeks. The HIIT induced a significant reduction in serum fructosamine levels compared to other groups (), as well as there was a significant reduction in serum glucose levels compared to the ADF and HIIT + ADF groups (). ADF and HIIT + ADF did not cause any significant changes in fructosamine, glucose, and C-peptide serum levels compared to the CON group (). In subjects under a high-fat diet, HIIT but not ADF or HIIT + ADF may be associated with favourable improvements in glucose metabolism markers.

Thigh muscle fat fraction is independently associated with impaired glucose metabolism in individuals with obesity.

The aim of this study was to address the intramuscular adipose tissue (IMAT) accumulation in the lower extremities and further detect the relationship between adipose tissue (AT) distribution in the muscle and glucose metabolism in subjects with obesity. We conducted a cross-sectional study in 120 Chinese obese adults (80 male and 40 female) with BMI ≥ 28 kg/m2. MRI was applied to access the IMAT content in lower extremities. The oral glucose tolerance test was used to evaluate the glucose metabolism and insulin secretion in all individuals. The correlations between glucose metabolism and the fat content of the lower extremities were further assessed. Among 120 included subjects, 54 were classified as subjects with normal glucose tolerance (NGT) and 66 with impaired glucose regulation (IGR). We presented that those with IGR had higher fat accumulation in semitendinosus, adductor magnus, gracilis and sartorius than those with NGT (all P < 0.05). In sex-specific analyses, females have higher IMAT in adductor magnus than males (P < 0.001). Males with IGR had higher fat fraction of semitendinosus and sartorius than those with NGT (P = 0.020, P = 0.014, respectively). Logistic regression analyses revealed that IMAT content in semitendinosus was the independent factor of IGR in individuals with obesity after adjustment for age, gender, triglycerides, creatinine and albumin (odds ratio: 1.13, 95% CI: 1.02-1.26, P = 0.024). Increased adipose tissue accumulation in thigh muscles was associated with glucose dysregulation in patients with obesity. IMAT content in semitendinosus may serve as a possible risk factor for impaired glucose metabolism.

Effects of acute changes in fasting glucose and free fatty acid concentrations on indices of β-cell function and glucose metabolism in subjects without diabetes.

Elevated fasting free fatty acids (FFAs) and fasting glucose are additively associated with impaired glucose tolerance (IGT) and decreased β-cell function [quantified as disposition index (DI)]. We sought to examine how changes in fasting FFA and glucose alter islet function. We studied 10 subjects with normal fasting glucose (NFG) and normal glucose tolerance (NGT) on two occasions. On one occasion, Intralipid and glucose were infused overnight to mimic conditions present in IFG/IGT. In addition, we studied seven subjects with IFG/IGT on two occasions. On one occasion, insulin was infused to lower overnight FFA and glucose concentrations to those observed in people with NFG/NGT. The following morning, a labeled mixed meal was used to measure postprandial glucose metabolism and β-cell function. Elevation of overnight fasting FFA and glucose in NFG/NGT did not alter peak or integrated glucose concentrations (2.0 ± 0.1 vs. 2.0 ± 0.1 Mol per 5 h, Saline vs. Intralipid/glucose, P = 0.55). Although overall β-cell function quantified by the Disposition Index was unchanged, the dynamic component of β-cell responsivity (ϕd) was decreased by Intralipid and glucose infusion (9 ± 1 vs. 16 ± 3 10-9, P = 0.02). In people with IFG/IGT, insulin did not alter postprandial glucose concentrations or indices of β-cell function. Endogenous glucose production and glucose disappearance were also unchanged in both groups. We conclude that acute, overnight changes in FFA, and glucose concentrations do not alter islet function or glucose metabolism in prediabetes.NEW & NOTEWORTHY This experiment studied the effect of changes in overnight concentrations of free fatty acids (FFAs) and glucose on β-cell function and glucose metabolism. In response to elevation of these metabolites, the dynamic component of the β-cell response to glucose was impaired. This suggests that in health overnight hyperglycemia and FFA elevation can deplete preformed insulin granules in the β-cell.

Intestinimonas butyriciproducens improves glucose metabolism in subjects with obesity and prediabetes: preliminary data from a randomized controlled trial

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Once-Weekly Semaglutide 2.4 mg Improved Glucose Metabolism and Prediabetes in Adults With Overweight/Obesity in the STEP 1 Trial

Semaglutide 2.4 mg demonstrated 14.9% body weight (BW) loss in adults with overweight/obesity in STEP 1. We evaluated effects on glucose metabolism in subjects with prediabetes at baseline (BL). Subjects (N=1,961) were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, plus lifestyle intervention, for 68 weeks. Post-hoc analyses included change from BL to week 68 in glycemic status (normoglycemia, prediabetes or type 2 diabetes; all investigator assessed), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG) and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR).

Latency-associated DNA methylation patterns among HIV-1 infected individuals with distinct disease progression courses or antiretroviral virologic response

DNA methylation is one of the epigenetic modifications that configures gene transcription programs. This study describes the DNA methylation profile of HIV-infected individuals with distinct characteristics related to natural and artificial viremia control. Sheared DNA from circulating mononuclear cells was subjected to target enrichment bisulfite sequencing designed to cover CpG-rich genomic regions. Gene expression was assessed through RNA-seq. Hypermethylation in virologic responders was highly distributed closer to Transcription Start Sites (p-value = 0.03). Hyper and hypomethylation levels within TSS adjacencies varied according to disease progression status (Kruskal–Wallis, p < 0.001), and specific differentially methylated regions associated genes were identified for each group. The lower the promoter methylation, the higher the gene expression in subjects undergoing virologic failure (R = − 0.82, p = 0.00068). Among the inversely correlated genes, those supporting glycolysis and its related pathways were hypomethylated and up-regulated in virologic failures. Disease progression heterogeneity was associated with distinct DNA methylation patterns in terms of rates and distribution. Methylation was associated with the expression of genes sustaining intracellular glucose metabolism in subjects undergoing antiretroviral virologic failure. Our findings highlight that DNA methylation is associated with latency, disease progression, and fundamental cellular processes.

A Glucose-Only Model to Extract Physiological Information from Postprandial Glucose Profiles in Subjects with Normal Glucose Tolerance.

Current mathematical models of postprandial glucose metabolism in people with normal and impaired glucose tolerance rely on insulin measurements and are therefore not applicable in clinical practice. This research aims to develop a model that only requires glucose data for parameter estimation while also providing useful information on insulin sensitivity, insulin dynamics and the meal-related glucose appearance (GA). The proposed glucose-only model (GOM) is based on the oral minimal model (OMM) of glucose dynamics and substitutes the insulin dynamics with a novel function dependant on glucose levels and GA. A Bayesian method and glucose data from 22 subjects with normal glucose tolerance are utilised for parameter estimation. To validate the results of the GOM, a comparison to the results of the OMM, obtained by using glucose and insulin data from the same subjects is carried out. The proposed GOM describes the glucose dynamics with comparable precision to the OMM with an RMSE of 5.1 ± 2.3 mg/dL and 5.3 ± 2.4 mg/dL, respectively and contains a parameter that is significantly correlated to the insulin sensitivity estimated by the OMM (r = 0.7) Furthermore, the dynamic properties of the time profiles of GA and insulin dynamics inferred by the GOM show high similarity to the corresponding results of the OMM. The proposed GOM can be used to extract useful physiological information on glucose metabolism in subjects with normal glucose tolerance. The model can be further developed for clinical applications to patients with impaired glucose tolerance under the use of continuous glucose monitoring data.

Effect of Dietary Supplementation with a Natural Extract of Sclerocarya birrea on Glycemic Metabolism in Subjects with Prediabetes: A Randomized Double-Blind Placebo-Controlled Study.

A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.

81-OR: Once-Weekly Semaglutide 2.4 mg Improved Glucose Metabolism and Prediabetes in Adults with Overweight/Obesity in the STEP 1 Trial

Semaglutide 2.4 mg demonstrated 14.9% body weight (BW) loss in adults with overweight/obesity in STEP 1. We evaluated effects on glucose metabolism in subjects with prediabetes at baseline (BL). Subjects (N=1961) were randomized 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo (PBO), plus lifestyle intervention, for 68 wks. Post-hoc analyses included change from BL to wk 68 in glycemic status (normoglycemia, prediabetes, or type 2 diabetes; all investigator assessed), HbA1c, fasting plasma glucose (FPG), and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Statistical analyses were not adjusted for multiplicity. At BL, 856 (43.7%) subjects had prediabetes (593 semaglutide/263 PBO; mean HbA1c: 5.9/5.9%, FPG: 98.7/97.6 mg/dL, HOMA-IR: 4.2/4.1, BW: 106.9/106.9 kg). By wk 68, 84.1% of those with prediabetes at BL were normoglycemic with semaglutide vs. 47.8% with PBO (p<0.0001) (Figure); of those who reverted from prediabetes to normoglycemia in the semaglutide group, the majority achieved weight loss ≥10%. Treatment with semaglutide vs. PBO lowered HbA1c (difference: -0.35 percentage‑points; p<0.0001), FPG (-8.49 mg/dL; p<0.0001) and HOMA-IR (relative % change: -28%; p<0.0001).In conclusion, once weekly semaglutide 2.4 mg allowed most adults with overweight/obesity and prediabetes to revert to normoglycemia at wk 68.View largeDownload slideView largeDownload slide DisclosureL. Perreault: Advisory Panel; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Novo Nordisk, Consultant; Self; Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck & Co., Inc., Novo Nordisk. C. Le roux: Advisory Panel; Self; Boehringer Ingelheim International GmbH, GI Dynamics, Herbalife International of America, Inc., Johnson & Johnson, Medtronic, Novo Nordisk A/S. M. J. Davies: Advisory Panel; Self; Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Eli Lilly and Company, Lexicon Pharmaceuticals, Inc., Novo Nordisk A/S, Sanofi, Other Relationship; Self; AstraZeneca, NIHR Leicester Biomedical Research Centre, Novo Nordisk, Speaker’s Bureau; Self; Astra Zeneca Pharma India Ltd, Boehringer Ingelheim (China), Boehringer Ingelheim (Philippines), Inc., Boehringer Ingelheim International GmbH, Boehringer Ingelheim Limited (UK), Boehringer Ingelheim Saudi Arabia Trading, Boehringer Ingelheim Singapore Pte. Ltd, Boehringer Ingelheim Sp. Z o. o., Eli Lilly and Company, Napp Pharmaceuticals, Novo Nordisk, Novo Nordisk A/S, S. C. Sanofi Romania SRL, Sanofi K. K. J. P. Frias: Consultant; Self; 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Gilead Sciences, Inc., Intercept Pharmaceuticals, Inc., Merck & Co., Inc., Novo Nordisk, Pfizer Inc., Sanofi, Research Support; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, CymaBay Therapeutics, Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Novo Nordisk, Pfizer Inc., Sanofi, Speaker’s Bureau; Self; Merck & Co., Inc., Sanofi. P. N. Laursen: Employee; Self; Novo Nordisk A/S. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. S. Machineni: Consultant; Self; Novo Nordisk, Rhythm Pharmaceuticals, Inc., Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. A. Varbo: Employee; Self; Novo Nordisk A/S. J. Wilding: Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Mundipharma International, Napp Pharmaceuticals, Novo Nordisk, Rhythm Pharmaceuticals, Inc., Saniona, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Napp Pharmaceuticals. S. O. R. Wallenstein: Employee; Self; Novo Nordisk.FundingNovo Nordisk A/S

Effect of Eating Glutinous Brown Rice Twice a Day for 6 Weeks on Serum 1,5-Anhydroglucitol in Japanese Subjects without Diabetes.

We have previously demonstrated that eating glutinous brown rice (GBR) for 1 day or 8 weeks was well accepted and improved glycemic control in patients with type 2 diabetes. The present study evaluated whether eating GBR could also improve glucose metabolism in subjects without diabetes. A prospective 6-week, single-center, randomized, open-label, parallel-group study was carried out in subjects receiving annual medical checkup at our hospital. A total of 42 subjects were randomly assigned to continue their regular diet (RD group) or to switch GBR twice a day (GBR group). The primary outcome was the change in the serum concentration of 1,5-anhydroglucitol (1,5-AG) from baseline after the 6-week dietary intervention. One subject was excluded from the analysis because of a traffic accident. After 6 weeks, the serum 1,5-AG was significantly increased in the GBR group and the mean treatment difference (GBR group − RD group) was 1.1 µg/mL (95% CI: 0.6 to 1.6, p=0.022). Body mass index decreased significantly in both groups, with no significant difference between them (p=0.210). There were no changes in fasting plasma glucose, fasting insulin, or eating behavior. Intake of GBR for 6 weeks significantly increased serum 1,5-AG in Japanese subjects without diabetes. The increase of 1,5-AG may have been due to the alleviation of postprandial hyperglycemia, which could be effective for the primary prevention of diabetes.

18F-FDG-PET brain imaging may highlight brain metabolic alterations in dysautonomic syndrome after human papilloma virus vaccination.

The aim of this study was to evaluate brain glucose metabolism by means of [18F]-fluoro-deoxygluycose (F-FDG) PET in a group of patients presenting dysautonomic syndrome after human papilloma virus (HPV) immunization. Medical records of patients, referred to the 'Second Opinion Medical Consulting Network' Medical Centre (Modena, Italy) diagnosed with dysautonomic syndrome were searched. Inclusion criteria were presence in the medical history of adverse drug reactions following HPV vaccine; a Montreal Cognitive Assessment score <25 and good quality of a F-FDG-PET brain scan performed within 12 months from the diagnosis of dysautonomic syndrome. F-FDG-PET images of patients (HPV-group) were compared to a control group, matched for age and sex, using statistical parametric mapping (SPM). The F-FDG-PET study was available for five female patients. The SPM-group analysis revealed significant hypometabolism (P < 0.05 false discovery rate corrected) in the right superior and medial temporal gyrus (Brodmann areas 22, 21) and insula (Brodmann area 13). At a threshold of P < 0.001 (uncorrected), further hypometabolic regions were revealed in the right superior temporal gyrus (Brodmann area 42) and caudate head and in the left superior temporal gyrus (Brodmann area 22), frontal subcallosal gyrus (Brodmann area 47) and insula (Brodmann area 13). Relative hypermetabolism (P = 0.001) was revealed in the right premotor cortex (Brodmann area 6). This study revealed the possibility of altered brain glucose metabolism in subjects with dysautonomic syndrome post-immunization with HPV vaccine. These results could reinforce the hypothesis of a causal relationship between HPV vaccine, or some component included in the vaccine and the development of clinical manifestations.

Dietary intake of specific amino acids and liver status in subjects with nonalcoholic fatty liver disease: fatty liver in obesity (FLiO) study.

Identification of dietary factors involved in the development and progression of nonalcoholic fatty liver disease (NAFLD) is relevant to the current epidemics of the disease. Dietary amino acids appear to play a key role in the onset and progression of NAFLD. The aim of this study was to analyze potential associations between specific dietary amino acids and variables related to glucose metabolism and hepatic status in adults with overweight/obesity and NAFLD. One hundred and twelve individuals from the Fatty Liver in Obesity (FLiO) study were evaluated. Liver assessment was carried out by ultrasonography, magnetic resonance imaging and analysis of biochemical parameters. Dietary amino acid intake (aromatic amino acids (AAA); branched-chain amino acids (BCAA); sulfur amino acids (SAA)) was estimated by means of a validated 137-item food frequency questionnaire. Higher consumption of these amino acids was associated with worse hepatic health. Multiple adjusted regression models confirmed that dietary AAA, BCAA and SAA were positively associated with liver fat content. AAA and BCAA were positively associated with liver iron concentration. Regarding ferritin levels, a positive association was found with BCAA. Dietary intake of these amino acids was positively correlated with glucose metabolism (glycated hemoglobin, triglyceride and glucose index) although the significance disappeared when potential confounders were included in the model. These findings suggest that the consumption of specific dietary amino acids might negatively impact on liver status and, to a lesser extent on glucose metabolism in subjects with overweight/obesity and NAFLD. A control of specific dietary amino acid composition should be considered in the management of NAFLD and associated insulin resistance. NCT03183193; June 2017.

FRIED FOOD AND POSSIBLE HEALTH HAZARDS

FRIED FOOD AND POSSIBLE HEALTH HAZARDS

Mechanism of Action of Inhaled Insulin on Whole Body Glucose Metabolism in Subjects with Type 2 Diabetes Mellitus

In the current study we investigate the mechanisms of action of short acting inhaled insulin Exubera®, on hepatic glucose production (HGP), plasma glucose and free fatty acid (FFA) concentrations. 11 T2D (Type 2 Diabetes) subjects (age = 53 ± 3 years) were studied at baseline (BAS) and after 16-weeks of Exubera® treatment. At BAS and after 16-weeks subjects received: measurement of HGP (3-3H-glucose); oral glucose tolerance test (OGTT); and a 24-h plasma glucose (24-h PG) profile. At end of study (EOS) we observed a significant decrease in fasting plasma glucose (FPG, 215 ± 15 to 137 ± 11 mg/dl), 2-hour plasma glucose (2-h PG, 309 ± 9 to 264 ± 11 mg/dl), glycated hemoglobin (HbA1c, 10.3 ± 0.5% to 7.5 ± 0.3%,), mean 24-h PG profile (212 ± 17 to 141 ± 8 mg/dl), FFA fasting (665 ± 106 to 479 ± 61 μM), post-OGTT (433 ± 83 to 239 ± 28 μM), and triglyceride (213 ± 39 to 120 ± 14 mg/dl), while high density cholesterol (HDL-C) increased (35 ± 3 to 47 ± 9 mg/dl). The basal HGP decreased significantly and the insulin secretion/insulin resistance (disposition) index increased significantly. There were no episodes of hypoglycemia and no change in pulmonary function at EOS. After 16-weeks of inhaled insulin Exubera® we observed a marked improvement in glycemic control by decreasing HGP and 24-h PG profile, and decreased FFA and triglyceride concentrations.

788-P: Effects of Sucralose Ingestion vs. Sucralose Taste on Metabolic Responses to a Glucose Load in Subjects with Normal Weight and Obesity

Objective: Consumption of low-calorie sweeteners (LCS) is associated with abnormalities of glucose metabolism. Here we evaluate the effects of sucralose ingestion, versus sucralose taste (i.e., sham feeding), on metabolic responses to a labeled oral glucose tolerance test (OGTT) in subjects with normal weight and obesity. Research Design and Methods: Ten normal-weight (BMI: 23±1 kg/m2) and 11 subjects with obesity (BMI: 38±6 kg/m2), all non-habitual users of LCS, underwent 3 dual-tracer OGTTs preceded by consuming 48 mg of sucralose, water, or sham feeding sucralose in randomized order. Indices of β-cell function and insulin sensitivity (SI) were estimated by using oral minimal models of glucose, insulin and C-peptide kinetics. Results: Compared to water, sucralose ingestion (but not sham feeding) increased the glucose incremental area under the curve by 30±10% in both groups. In contrast, sucralose had different effects on plasma insulin concentrations in these groups (P&amp;lt;0.01). Sucralose ingestion decreased the magnitude of the glucose-induced increase in insulin concentrations 20-40 min post-glucose load in normal-weight subjects, but increased it 90-120 min post-glucose load in subjects with obesity. Sucralose sham-fed similarly decreased the magnitude of the glucose-induced increase in insulin concentrations within 60 min of the OGTT in both groups. In addition, sucralose ingestion (but not sham feeding) increased SI in normal-weight subjects by 52±20% but did not affect SI in subjects with obesity (P&amp;lt;0.02). Sucralose did not affect glucose kinetics or indices of the sensitivity of the β-cell response to glucose in either group. Conclusions: Acute sucralose ingestion differentially affects glucose metabolism in subjects with normal weight versus obesity. In addition, our findings underscore a physiological role for sweetness in glucose homeostasis, which supports the notion that sweetness should be used in moderation. Disclosure M. Pepino: None. A.D. Nichol: None. K. Rother: None. C. Salame: None. Funding National Institutes of Health (P30DK020579, P60DK020579, P30DK056341); National Institute of Diabetes and Digestive and Kidney Diseases

Effect of Chronic Hyperglycemia on Glucose Metabolism in Subjects With Normal Glucose Tolerance.

Chronic hyperglycemia causes insulin resistance, but the inheritability of glucotoxicity and the underlying mechanisms are unclear. We examined the effect of 3 days of hyperglycemia on glucose disposal, enzyme activities, insulin signaling, and protein O-GlcNAcylation in skeletal muscle of individuals without (FH−) or with (FH+) family history of type 2 diabetes. Twenty-five subjects with normal glucose tolerance received a [3-3H]glucose euglycemic insulin clamp, indirect calorimetry, and vastus-lateralis biopsies before and after 3 days of saline (n = 5) or glucose (n = 10 FH− and 10 FH+) infusion to raise plasma glucose by ∼45 mg/dL. At baseline, FH+ had lower insulin-stimulated glucose oxidation and total glucose disposal (TGD) but similar nonoxidative glucose disposal and basal endogenous glucose production (bEGP) compared with FH−. After 3 days of glucose infusion, bEGP and glucose oxidation were markedly increased, whereas nonoxidative glucose disposal and TGD were lower versus baseline, with no differences between FH− and FH+ subjects. Hyperglycemia doubled skeletal muscle glycogen content and impaired activation of glycogen synthase (GS), pyruvate dehydrogenase, and Akt, but protein O-GlcNAcylation was unchanged. Insulin resistance develops to a similar extent in FH− and FH+ subjects after chronic hyperglycemia, without increased protein O-GlcNAcylation. Decreased nonoxidative glucose disposal due to impaired GS activation appears to be the primary deficit in skeletal muscle glucotoxicity.

Glucose metabolism in subjects of Mapuche ethnicity and descendants of Europeans: A systematic review and meta-analysis

Glucose metabolism in subjects of Mapuche ethnicity and descendants of Europeans: A systematic review and meta-analysis

Impaired glucose metabolism in subjects with the Williams-Beuren syndrome: A five-year follow-up cohort study.

ObjectiveThe Williams-Beuren syndrome (WS) is associated with impaired glucose metabolism (IGM) early in adulthood. However, the pathophysiology of IGM remains poorly defined, due to the lack of longitudinal studies investigating the contribution of β-cell dysfunction and impaired insulin sensitivity. This study aimed at assessing incidence of IGM and the underlying mechanisms in WS adults.MethodsThis observational, longitudinal (5-year), cohort study enrolled thirty-one consecutive WS subjects attending a tertiary referral center. An oral glucose tolerance test (OGTT) was performed yearly and used to classify patients as normal or IGM, including impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) and diabetes mellitus (DM), and to calculate surrogate measures of insulin secretion and/or sensitivity.ResultsIGM patients were 18 (58.1%, three DM) at baseline and 19 (61.3%, five DM) at end-of-follow-up. However, 13 individuals changed category of glucose homeostasis in both directions during follow-up (8 progressors, 5 regressors) and 18 did not (8 non-progressors, 10 non-regressors). New cases of IGM and DM were 11.1 and 2.53 per 100 persons-year, respectively, and were treated non-pharmacologically. In the whole cohort and, to a higher extent, in progressors, indices of early-phase insulin secretion and insulin sensitivity decreased significantly from baseline to end-of-follow-up, with concurrent reduction of the oral disposition index and insulin secretion-sensitivity index-2 (ISSI-2), compensating insulin secretion for the level of insulin resistance. No baseline measure independently predicted progression, which correlated with change from baseline in ISSI-2. Compared with patients with normal glucose homeostasis, IGT subjects had impaired insulin sensitivity, whereas insulin secretion was reduced only in those with IFG+IGT or DM.ConclusionsIGM incidence is high in young adults with WS, suggesting the need of early screening and timed intervention. As in classical type 2 diabetes, impaired insulin sensitivity and β-cell dysfunction contribute, in this sequence, to progression to IGM and DM.

Short-term interval training alters brain glucose metabolism in subjects with insulin resistance

Brain insulin-stimulated glucose uptake (GU) is increased in obese and insulin resistant subjects but normalizes after weight loss along with improved whole-body insulin sensitivity. Our aim was to study whether short-term exercise training (moderate intensity continuous training (MICT) or sprint interval training (SIT)) alters substrates for brain energy metabolism in insulin resistance. Sedentary subjects (n = 21, BMI 23.7–34.3 kg/m2, age 43–55 y) with insulin resistance were randomized into MICT (n = 11, intensity≥60% of VO2peak) or SIT (n = 10, all-out) groups for a two-week training intervention. Brain GU during insulin stimulation and fasting brain free fatty acid uptake (FAU) was measured using PET. At baseline, brain GU was positively associated with the fasting insulin level and negatively with the whole-body insulin sensitivity. The whole-body insulin sensitivity improved with both training modes (20%, p = 0.007), while only SIT led to an increase in aerobic capacity (5%, p = 0.03). SIT also reduced insulin-stimulated brain GU both in global cortical grey matter uptake (12%, p = 0.03) and in specific regions (p < 0.05, all areas except the occipital cortex), whereas no changes were observed after MICT. Brain FAU remained unchanged after the training in both groups. These findings show that short-term SIT effectively decreases insulin-stimulated brain GU in sedentary subjects with insulin resistance.

Increasing ICA512 autoantibody titers predict development of abnormal oral glucose tolerance tests.

Determine if autoantibody titer magnitude and variability predict glucose abnormalities in subjects at risk for type 1 diabetes. Demographic information, longitudinal autoantibody titers, and oral glucose tolerance test (OGTT) data were obtained from the TrialNet Pathway to Prevention study. Subjects (first and second degree relatives of individuals with type 1 diabetes) with at least 2 diabetes autoantibodies were selected for analysis. Autoantibody titer means were calculated for each subject for the duration of study participation and the relationship between titer tertiles and glucose value tertiles from OGTTs (normal, impaired, and diabetes) was assessed with a proportional odds ordinal regression model. A matched pairs analysis was used to examine the relationship between changes in individual autoantibody titers and 120-minute glucose values. Titer variability was quantified using cumulative titer standard deviations. We studied 778 subjects recruited in the TrialNet Pathway to Prevention study between 2006 and 2014. Increased cumulative mean titer values for both ICA512 and GAD65 (estimated increase in proportional odds = 1.61, 95% CI = 1.39, 1.87, P < 1 × 10-9 and 1.17, 95% CI = 1.03, 1.32, P = .016, respectively) were associated with peak 120-minute glucose values. While fluctuating titer levels were observed in some subjects, no significant relationship between titer standard deviation and glucose values was observed. ICA512 autoantibody titers associate with progressive abnormalities in glucose metabolism in subjects at risk for type 1 diabetes. Fluctuations in autoantibody titers do not correlate with lower rates of progression to clinical disease.