Glucose Area Research Articles

(-)-Epicatechin Reverses Glucose Intolerance in Rats Housed at Thermoneutrality.

Diabetes is a life-threatening and debilitating disease with pathological hallmarks, including glucose intolerance and insulin resistance. Plant compounds are a source of novel and effective therapeutics, and the flavonoid (−)-epicatechin, common to popular foods worldwide, has been shown to improve carbohydrate metabolism in both clinical studies and preclinical models. We hypothesized that (−)-epicatechin would alleviate thermoneutral housing-induced glucose intolerance. Male rats were housed at either thermoneutral (30 °C) or room temperature (24 °C) for 16 weeks and gavaged with either 1 mg/kg body weight or vehicle for the last 15 days before sacrifice. Rats housed at thermoneutrality had a significantly elevated serum glucose area under the curve (p < 0.05) and reduced glucose-mediated insulin secretion. In contrast, rats at thermoneutrality treated with (−)-epicatechin had improved glucose tolerance and increased insulin secretion (p < 0.05). Insulin tolerance tests revealed no differences in insulin sensitivity in any of the four groups. Pancreatic immunohistochemistry staining showed significantly greater islet insulin positive cells in animals housed at thermoneutrality. In conclusion, (−)-epicatechin improved carbohydrate tolerance via increased insulin secretion in response to glucose challenge without a change in insulin sensitivity.

OZ101, an oligofructose prebiotic, may prolong sulphonylurea efficcy in patients with type 2 diabetes: a pilot study: OZ101 and sulphonylurea-mediated glycaemic control

Aims: The sulphonylurea class of anti-diabetes drugs lose efficacy over time due to progressive beta-cell failure. Their long-term use may exacerbate gut microbial dysbiosis as they are derivatives of sulphonamide antibiotics. We conducted a pilot study to test the hypothesis that OZ101, administered as adjunctive prebiotic therapy, improves beta-cell function and glycaemic control in sulphonylurea-treated patients. Materials and Methods: Subjects with type 2 diabetes on sulphonylurea monotherapy (n=30) were randomized in a 24-week parallel dose range-finding study to either continue receiving their usual sulphonylurea-only treatment or add a thrice-daily regimen of 13.5 or 27 g/d doses of OZ101. HOMA-B, glycaemic parameters after 12 hours fasting, and glucose area under the curve (AUC; over 240 minutes) after intake of a pre-defined calorie milkshake were collected at baseline and 24 weeks. Results: Over 24-weeks, control subjects on sulphonylurea-only showed a decline in beta-cell function (35.54% decrease in HOMA-B from baseline, p = 0.01), whereas subjects taking sulphonylurea+13.5 g/d OZ101 improved (22.9% increase in HOMA-B from baseline, p = 0.031). There was a 0.95% (10mmol/mol) difference in HbA1c (p = 0.047) and 607 mmol/l*240min AUC (p = 0.039) in favour of the sulphonylurea +13.5g/d OZ101 compared with control group. HbA1c and AUC were not altered in subjects treated with sulphonylurea+27 g/d OZ101 compared with the control group. Microbiome profiling suggested reciprocal relationships in beneficial versus detrimental bacteria between control and treatment groups. Conclusions: Adjunctive intake of 13.5g/d OZ101 in patients on sulphonylurea therapy was safe, well-tolerated and associated with improved beta-cell function and stabilization of glycaemic control over 24 weeks. Absence of similar response for the 27 g/d OZ101 group may relate to changes in gut microbiome profiles. Future studies will determine the mechanistic link between OZ101 therapy, changes in gut microbiome, and metabolic responses.

Fat Distribution Patterns and Future Type 2 Diabetes.

Fat accumulation in the liver, pancreas, skeletal muscle, and visceral bed relates to type 2 diabetes (T2D). However, the distribution of fat among these compartments is heterogenous and whether specific distribution patterns indicate high T2D risk is unclear. We therefore investigated fat distribution patterns and their link to future T2D. From 2,168 individuals without diabetes who underwent computed tomography in Japan, this case-cohort study included 658 randomly selected individuals and 146 incident cases of T2D over 6 years of follow-up. Using data-driven analysis (k-means) based on fat content in the liver, pancreas, muscle, and visceral bed, we identified four fat distribution clusters: hepatic steatosis, pancreatic steatosis, trunk myosteatosis, and steatopenia. In comparisons with the steatopenia cluster, the adjusted hazard ratios for incident T2D were 4.02 (95% CI 2.27-7.12) for the hepatic steatosis cluster, 3.38 (1.65-6.91) for the pancreatic steatosis cluster, and 1.95 (1.07-3.54) for the trunk myosteatosis cluster. The clusters were replicated in 319 German individuals without diabetes who underwent MRI and metabolic phenotyping. The distribution of the glucose area under the curve across the four clusters found in Germany was similar to the distribution of T2D risk across the four clusters in Japan. Insulin sensitivity and insulin secretion differed across the four clusters. Thus, we identified patterns of fat distribution with different T2D risks presumably due to differences in insulin sensitivity and insulin secretion.

Incretin Response to Mixed Meal Challenge in Active Cushing's Disease and after Pasireotide Therapy.

Cushing’s disease (CD) causes diabetes mellitus (DM) through different mechanisms in a significant proportion of patients. Glucose metabolism has rarely been assessed with appropriate testing in CD; we aimed to evaluate hormonal response to a mixed meal tolerance test (MMTT) in CD patients and analyzed the effect of pasireotide (PAS) on glucose homeostasis. To assess gastro-entero-pancreatic hormones response in diabetic (DM+) and non-diabetic (DM–) patients, 26 patients with CD underwent an MMTT. Ten patients were submitted to a second MMTT after two months of PAS 600 µg twice daily. The DM+ group had significantly higher BMI, waist circumference, glycemia, HbA1c, ACTH levels and insulin resistance indexes than DM− (p < 0.05). Moreover, DM+ patients exhibited increased C-peptide (p = 0.004) and glucose area under the curve (AUC) (p = 0.021) during MMTT, with a blunted insulinotropic peptide (GIP) response (p = 0.035). Glucagon levels were similar in both groups, showing a quick rise after meals. No difference in estimated insulin secretion and insulin:glucagon ratio was found. After two months, PAS induced an increase in both fasting glycemia and HbA1c compared to baseline (p < 0.05). However, this glucose trend after meal did not worsen despite the blunted insulin and C-peptide response to MMTT. After PAS treatment, patients exhibited reduced insulin secretion (p = 0.005) and resistance (p = 0.007) indexes. Conversely, glucagon did not change with a consequent impairment of insulin:glucagon ratio (p = 0.009). No significant differences were observed in incretins basal and meal-induced levels. Insulin resistance confirmed its pivotal role in glucocorticoid-induced DM. A blunted GIP response to MMTT in the DM+ group might suggest a potential inhibitory role of hypercortisolism on enteropancreatic axis. As expected, PAS reduced insulin secretion but also induced an improvement in insulin sensitivity as a result of cortisol reduction. No differences in incretin response to MMTT were recorded during PAS therapy. The discrepancy between insulin and glucagon trends while on PAS may be an important pathophysiological mechanism in this iatrogenic DM; hence restoring insulin:glucagon ratio by either enhancing insulin secretion or reducing glucagon tone can be a potential therapeutic target.

Investigating the influence of the gut microbiome on diabetic renal disease

BackgroundGut microbiota have been implicated in a large array of pathophysiological processes including obesity and diabetes. In this study, we utilized a diabetic renal disease model with or without oral antibiotic treatment to investigate how gut microbiota alter diabetic renal disease.MethodsGut microbiota biomass was depleted using a modified antibiotic treatment protocol with a mixture of 1g/L ampicillin, 1g/L neomycin, and 0.5 g/L vancomycin (modified from Rakoff‐Nahoum et al. 2004). C57BL/6J male and female mice (6‐week‐old) were randomly assigned to four different groups (n=8 per sex per group): control diet (CD), high‐fat diet (HFD), CD + antibiotics, HFD + antibiotics. The mice were treated with different diets and/or with antibiotics in drinking water for nine weeks. We measured body weight (BW), non‐fasting glucose, insulin, and glomerular filtration rate (GFR). In addition, we performed a glucose tolerance test (GTT), insulin tolerance test (ITT), and blood analysis. Finally, we did H&amp;E staining of the kidney, and analyzed urine Na+.Results1) BW was significantly increased by HFD (vs CD) in both males and females regardless of antibiotic treatment. 2) Non‐fasting glucose showed no difference among these four groups in males and females. 3) Fasting glucose was dramatically elevated by HFD in males but not females (vs CD). For the GTT, both the peak glucose level and area under curve (AUC) were significantly increased in HFD vs CD, regardless of antibiotic treatment or sex. 4) For the ITT, HFD promoted insulin resistance as measured by changes in the AUC in both males and females. For males on a CD, antibiotics improved insulin responsiveness. 5) GFR was increased by HFD vs CD in both males and females, consistent with a HFD‐induced hyperfiltration, as we published previously with this same model (Halperin Kuhns, AJP Renal 2018). Intriguingly, GFR in females was also enhanced by antibiotic treatment on both the CD and HFD (week 9: CD, F: 182±12.7; HFD, F: 290±19.9, p&lt;0.0001; CD + antibiotics, F: 282±12.6; HFD + antibiotics, F: 373±20.1; p=0.0005 CD vs. CD+antibiotics; p=0.01 HF vs. HF+antibiotics). Similarly, GFR in males also increased with antibiotic treatment in CD, but, not HFD (week 9: CD, M: 191±10.0; HFD, M: 385±19.3, p&lt;0.0001; CD + antibiotics, M: 263±10.5; HFD + antibiotics, M: 390±32.7; p=0.04 CD vs. CD+antibiotics; p&gt;0.99 HF vs. HF+antibiotics). Preliminary data using germ‐free (GF) mice, which do not have microbiota, show that GFR was also increased in GF males and females (vs. conventional mice with gut microbes).ConclusionIn this study, depletion of the gut microbiota via antibiotics increased GFR in both males and females on CD. Interestingly, on a HFD, GFR increased with antibiotics in females but not males. These data suggest that gut microbial signals may directly influence renal function; we are now working to confirm these findings and to explore the underlying mechanisms.

Impact of Cotadutide drug on patients with type 2 diabetes mellitus: a systematic review and meta-analysis

BackgroundThe food and drug administration approved many drugs to treat diabetes mellitus, but those drugs do not have a noticeable effect on weight management. Recently, glucagon-like peptide 1 agonist known as Cotadutide serve as a potent drug in treating type 2 diabetes by reducing blood glucose levels and body weight indices. This study aimed to explore the safety and efficacy of Cotadutide as a treatment for type 2 diabetes individuals.MethodsA comprehensive literature search was done on different databases, including PubMed, Scopus, Web of Science, and Cochrane Library to capture all relevant articles using an established search strategy. The inclusion criteria were randomized controlled trials that assessed the safety and efficacy of Cotadutide versus placebo or any anti-diabetes drugs in patients with type 2 diabetes mellitus and a BMI between 22 kg/m2 and 40 kg/m2. We conducted the analysis using Revman software version 5.4.ResultsWe found 663 relevant articles. From which nine studies were included and subjected to qualitative analysis and eight for quantitative analysis. The pooled effect showed that Cotadutide was better than placebo in reducing body weight (kg) (Mean difference (MD) = 3.31, p < 0.00001), glycated hemoglobin (HbA1c) (MD = 0.68, p > 0.00001), glucose area under the plasma concentration curve (AUC [0-4 h]) (MD = 30.15, p < 0.00001), and fasting plasma glucose over time (mg/dl) (MD = 31.31, p < 0.00001).ConclusionCotadutide is safe and effective in reducing plasma glucose levels, HbA1c and body weight in individuals with type 2 diabetes.Trial registrationThe study protocol was registered on PROSPERO (CRD: CRD42021257670).

Sleep Quality is an Independent Predictor of Blood Glucose and Gestational Diabetes Mellitus: A Longitudinal Study of 4550 Chinese Women.

PurposeTo investigate whether pregnant women’s subjective sleep quality during the first trimester independently predicted blood glucose and gestational diabetes mellitus (GDM).MethodsA total of 4550 pregnant women in the first trimester were enrolled in Chongqing Health Center for Women and Children, China, from January to October 2020.The Pittsburgh Sleep Quality Index (PSQI) was used to measure subjective sleep quality. Depression symptoms and anxiety were measured with the Patient Health Questionnaire-9 (PHQ-9) and General Anxiety Disorder-7 (GAD-7). Oral glucose tolerance tests (OGTT) and blood glucose area under the curve (AUC) were used for estimation of blood glucose and diagnosis of GDM during the second trimester. Linear, mixed model, and logistic regression were used to analyze the association between PSQI and blood glucose as well as GDM.Results946/4550 were diagnosed with GDM (20.8%). In the mixed model analysis, the blood glucose level of the highest-scoring group (PSQI score = 18) was 1.94 (95% CI: 0.45~3.43, P = 0.011) mmol/L higher than that of the lowest-scoring group (PSQI score = 0). After adjusting for potential confounders, a one-point PSQI score increase was associated with a 0.014 (95% CI: 0.001~0.027, P = 0.039) mmol/L increase in blood glucose level. Blood glucose AUC was also positively associated with PSQI scores (β = 0.034, 95% CI: 0.003~0.064, P = 0.030). The results for the logistic regression model showed that PSQI was marginal positively correlated with GDM (OR = 1.146, 95% CI: 0.995~1.321, P = 0.059) when age and BMI were not controlled for. When investigating the association between PSQI and the GDM-diagnosed time window, the 1-h diagnosed GDM had a borderline positive correlation with PSQI (OR = 1.182, 95% CI: 0.993~1.405, P = 0.060).ConclusionSleep quality during the first trimester may be a risk factor for elevated blood glucose and GDM later in gestation.

Fixed-ratio combination of insulin glargine plus lixisenatide (iGlarLixi) improves ß-cell function in people with type 2 diabetes.

AimMultiple studies support the efficacy of combining a glucagon‐like peptide 1 receptor agonist (GLP‐1RA) with basal insulin in people with type 2 diabetes inadequately controlled on dual/triple oral therapy. Fixed‐ratio combinations of basal insulin + GLP‐1RA represent a further advance to facilitate management. We assessed the impact of fixed‐ratio combination basal insulin + GLP‐1RA treatment on β‐cell function.Materials and MethodsWe analysed data from 351 participants in the LixiLan‐G trial (NCT02787551) randomized to receive iGlarLixi (insulin glargine 100 U/ml + lixisenatide) or to continue daily/weekly GLP‐1RA, both on top of metformin. Participants received a 2‐h meal tolerance test before randomization and at study end (26 weeks), with timed plasma glucose and C‐peptide determinations. β‐cell function parameters were resolved using mathematical modelling.ResultsIn the GLP‐1RA group (n = 162), both body weight and glycated haemoglobin decreased at week 26, yet none of the insulin secretion/β‐cell function parameters changed significantly. In contrast, in the iGlarLixi group (n = 189), glycated haemoglobin decreased significantly more than in the GLP‐1RA group (p < .0001) despite an increase in body weight (+1.7 ± 3.9 kg, p < .0001). Fasting and stimulated insulin secretion decreased at Week 26 (both p < .0001 vs. GLP‐1RA), while β‐cell glucose sensitivity increased by a median 35% (p = .0032 vs. GLP‐1RA). The incremental meal tolerance test glucose area showed a larger reduction with iGlarLixi versus GLP‐1RA (p < .0001).ConclusionsIn people with type 2 diabetes on metformin, 26‐week treatment with iGlarLixi resulted in a marked improvement in β‐cell function concomitant with sparing of endogenous insulin release and a reduction in meal absorption.

Effect of artemisinin on improving islet function in rats fed with maternal high-fat diet

Background Maternal high-fat diet (HFD) is a detrimental factor in developing glucose intolerance, obesity, and islet dysfunction. However, the effect of artemisinin on maternal HFD and whether it is related to the alterations of islet function is seldom studied since artemisinin treatments not only attenuate insulin resistance (IR) and restore islet ß cell function in Diabetes mellitus type 2. Methods Female rats were randomly fed a HFD (45% kcal from fat), HFD + artemisinin, or a regular chow diet (RCD) before pregnancy and during gestation. Glucose metabolism and the β cell phenotypes were assessed. Results Maternal HFD increased islet load in female rats, proliferation of pancreatic β cells, increased insulinogen, and decreased insulin secretion response to high glucose stimulation with delayed insulin release, increased fasting glucose, and glucose area under the curve compared with the general diet group. HFD inhibited expression of Foxo1 and PAX6 in female rats. Under the effect of both HFD and pregnancy, islet load was further increased, insulinogen was further increased, and fasting insulin level and fasting glucose were higher than RCD fed general-pregnancy group. ALDH1a3 transdifferentiation and PAX6, Foxo1, and PDX1 expression were increased in islets of high-fat pregnant rats. When adding artemisinin in HFD treated pregnant rats, islet function was significantly improved. Conclusions Intervention with artemisinin in maternal HFD resulted in reduced islet size, decreased number of β-cells and improved islet microcirculation, insulin processing shear process, decreased insulinogen/insulin ratio, and restored islet function through increased expression of PC1/3.

Association Between Abdominal Adipose Tissue Distribution and Obstructive Sleep Apnea in Chinese Obese Patients.

PurposeFactors related to the occurrence of obstructive sleep apnea syndrome (OSAS) in obesity have not been fully clarified. The aim of this study was to identify the association between OSAS and abdominal fat distribution in a cohort of Chinese obese patients.MethodsThis cross-sectional study collected demographic data of 122 obese patients who were admitted into the in-patient unit of the Department of Endocrinology, Shanghai Tenth People’s Hospital from July 2018 to January 2021. OSAS was diagnosed based on the results of overnight polysomnography, and the abdominal fat distribution was measured by bioelectrical impedance analysis (BIA). Univariate and multivariate logistic regression analyses were used to investigate the association between OSAS and the distribution of abdominal fat.Results(1) The mean age (SD) of the obese patients included was 32.44 (11.81) years old, and the overall incidence rate of OSAS was 51.06%. Twenty-four (25.53%) patients had mild OSAS, 10 (10.64%) had moderate OSAS, and 14 (14.89%) had severe OSAS. The apnea hypopnea index (AHI) of men was significantly higher than that of women (5.50, interquartile range (IQR) 3.80–30.6 vs. 4.2, IQR 1.4–12 events/h, p = 0.014). Meanwhile, men had a significantly higher visceral fat area when compared with women (180.29 ± 51.64 vs. 143.88 ± 53.42 cm2, p = 0.002). (2) Patients with OSAS had a significantly higher waist circumference, fasting plasma glucose, 2 h postprandial plasma glucose, glycated hemoglobin, and visceral fat area than patients without OSAS (all p < 0.05). (3) AHI was significantly positively associated with BMI, neck circumference, waist circumference, and visceral fat area (r = 0.306, p = 0.003; r = 0.380, p < 0.001; r = 0.328, p = 0.002; r = 0.420, p < 0.001) but not with subcutaneous fat area (p = 0.094). Multivariate analysis demonstrated that abdominal fat area and fasting plasma glucose were independent risk factors for OSAS (odds ratio, 1.016; 95% confidence interval, 1.005–1,026, p = 0.005; odds ratio, 1.618; 95% confidence interval, 1.149–2.278, p = 0.006).ConclusionsIn obese patients, the abdominal visceral adipose deposit but not the subcutaneous fat area was associated with OSAS and was an independent risk factor for OSAS. Therefore, improving the distribution of abdominal fat may contribute to alleviating the severity of OSAS in obesity.

Carbohydrate-Energy Replacement Following High-Intensity Interval Exercise Blunts Next-Day Glycemic Control in Untrained Women.

BackgroundImproved glycemic control has been reported for ∼24 h following low-volume high-intensity interval exercise (HIIE), but it is unclear if this is a direct effect of exercise or an indirect effect of the exercise-induced energy deficit. The purpose of this study was to investigate the effect of carbohydrate-energy replacement after low-volume HIIE on 24 h glycemic control in women.MethodsSeven untrained women (age: 22 ± 2 yr; BMI: 22 ± 3 kg/m2; VO2peak: 33 ± 7 ml/kg/min) completed three 2-day trials in the mid-follicular phase of the menstrual cycle. Continuous glucose monitoring was used to measure blood glucose concentrations during, and for 24 h following three conditions: (1) HIIE followed by a high-carbohydrate energy replacement drink (EX-HC); (2) HIIE followed by a non-caloric taste-matched placebo drink (EX-NC); and (3) seated control with no drink (CTL). HIIE involved an evening session (1,700 h) of 10 × 1-min cycling efforts at ∼90% maximal heart rate with 1 min recovery. Diet was standardized and identical across all three 2-day trials, apart from the post-exercise carbohydrate drink in EX-HC, which was designed to replenish the exercise-induced energy expenditure. Postprandial glycemic responses to the following days breakfast, snack, lunch, and dinner, as well as 24 h indices of glycemic control, were analyzed.ResultsThe day after HIIE, postprandial glycemia following breakfast and snack were reduced in EX-NC compared to EX-HC, as reflected by lower 3 h glucose mean (breakfast: 5.5 ± 0.5 vs. 6.7 ± 1, p = 0.01, Cohen’s d = 1.4; snack: 4.9 ± 0.3 vs. 5.7 ± 0.8 mmol/L, p = 0.02, d = 1.4) and/or area under the curve (AUC) (breakfast: 994 ± 86 vs. 1,208 ± 190 mmol/L x 3 h, p = 0.01, d = 1.5). Postprandial glycemic responses following lunch and dinner were not different across conditions (p > 0.05). The 24 h glucose mean (EX-NC: 5.2 ± 0.3 vs. EX-HC: 5.7 ± 0.7 mmol/L; p = 0.02, d = 1.1) and AUC (EX-NC: 7,448 ± 425 vs. EX-HC: 8,246 ± 957 mmol/L × 24 h; p = 0.02, d = 1.1) were reduced in EX-NC compared to EX-HC.ConclusionPost-exercise carbohydrate-energy replacement attenuates glycemic control the day following a single session of low-volume HIIE in women.

Characterization of glucose metabolism in youth with vs. without cystic fibrosis liver disease: A pilot study

BackgroundDiabetes and liver disease are life-threatening complications of cystic fibrosis (CF). CF-liver disease is a risk factor for CF related diabetes (CFRD) development, but the underlying mechanisms linking the two co-morbidities are not known. The objective of this pilot study was to characterize glucose metabolism in youth with CF with and without liver disease. MethodsIn this two-center cross-sectional study, 20 youth with CF with and without liver disease underwent a 3-hour oral glucose tolerance test. Subjects were categorized by liver disease (LD) status [no LD, mild LD, severe LD] and diabetes status. Measures of glucose excursion, islet cell secretory responses, insulin sensitivity and clearance were obtained. ResultsParticipants with severe LD had the highest fasting, peak, and glucose area under the curve over 3 h (AUC3h) among individuals with CFRD (interaction p < 0.05). In parallel with glycemic changes, prandial β-cell secretory response (AUC C-peptide 3h) was lower in those with severe LD compared to mild or no LD (p < 0.01). There was a trend of higher HOMA-IR in those with severe LD (p = 0.1) as well as lower fasting insulin clearance in those with mild and severe LD compared to no LD (p = 0.06) and lower prandial insulin clearance in severe LD among those with CFRD (interaction p = 0.1). ConclusionIn this small cohort, subjects with severe LD tended to have more impaired glycemia, insulin secretion, insulin sensitivity and clearance. Larger studies are imperative to define the pathogenesis to inform clinical care guidelines in terms of CFRD screening, diagnosis, and treatment options.

A Study on Legume-Based Noodles as Staple Food for Office Workers.

This study aims to verify the effects of “legume-based noodles” as a staple food for lunch, specifically: blood glucose, cognitive function tests, Kansei value, work questionnaires, typing, and body weight. The experiment is divided into two groups: the intervention group (legumes-based noodle) and the control group (regular lunch). Both groups have similar menu except the staple food. The intervention group resulted in a statistically significant lower blood glucose area under the curve (AUC) and lower maximum blood glucose levels during the afternoon work hours on weekdays. In addition, the Kansei value “concentration” decreased at the end of the workday in the control group compared to before and after lunch but did not decrease in the intervention group. Furthermore, the number of typing accuracy was higher in the intervention group than in the control group, and the questionnaire responses for “work efficiency” and “motivation” were more positive. These results suggest that eating legume-based noodles may lead to improved performance of office workers.

Continuous Glucose Monitoring in Adolescents With Obesity: Monitoring of Glucose Profiles, Glycemic Excursions, and Adherence to Time Restricted Eating Programs.

BackgroundRandomized controlled trials of time restricted eating (TRE) in adults have demonstrated improvements in glucose variability as captured by continuous glucose monitors (CGM). However, little is known about the feasibility of CGM use in TRE interventions in adolescents, or the expected changes in glycemic profiles in response to changes in meal-timing. As part of a pilot trial of TRE in adolescents with obesity, this study aimed to 1) assess the feasibility of CGM use, 2) describe baseline glycemic profiles in adolescents with obesity, without diabetes, and 3) compare the difference between glycemic profiles in groups practicing TRE versus control.MethodsThis study leverages data from a 12-week pilot trial (ClinicalTrials.gov Identifier: NCT03954223) of late TRE in adolescents with obesity compared to a prolonged eating window. Feasibility of CGM use was assessed by monitoring 1) the percent wear time of the CGM and 2) responses to satisfaction questionnaires. A computation of summary measures of all glycemic data prior to randomization was done using EasyGV and R. Repeat measures analysis was conducted to assess the change in glycemic variability over time between groups. Review of CGM tracings during periods of 24-hour dietary recall was utilized to describe glycemic excursions.ResultsFifty participants were enrolled in the study and 43 had CGM and dietary recall data available (16.4 + 1.3 years, 64% female, 64% Hispanic, 74% public insurance). There was high adherence to daily CGM wear (96.4%) without negative impacts on daily functioning. There was no significant change in the glycemic variability as measured by standard deviation, mean amplitude glycemic excursion, and glucose area under the curve over the study period between groups.ConclusionsCGM use appears to be a feasible and acceptable tool to monitor glycemic profiles in adolescents with obesity and may be a helpful strategy to confirm TRE dosage by capturing glycemic excursions compared to self-reported meal timing. There was no effect of TRE on glucose profiles in this study. Further research is needed to investigate how TRE impacts glycemic variability in this age group and to explore if timing of eating window effects these findings.

One Bout of Resistance Training Does Not Enhance Metformin Actions in Prediabetic and Diabetic Individuals.

This study aimed to determine the separated and combined effects of metformin and resistance exercise on glycemic control, insulin sensitivity, and insulin-like growth factor 1 (IGF-1) in overweight/obese individuals with prediabetes and type 2 diabetes mellitus. Fourteen adults with a body mass index of 32.1 ± 4.1 kg·m-2, insulin resistance (HOMA-2 1.6 ± 0.6), and poor glycemic control (glycated hemoglobin, 6.9% ± 0.9%; 51.9 ± 10.7 mmol·mol-1) while taking metformin (1561 ± 470 g·d-1) were recruited. Participants underwent four 72-h long experimental trials in a randomized counterbalanced order, either 1) taking metformin (MET), 2) replacing metformin by placebo pills (PLAC), 3) taking placebo and undergoing a resistance training bout (RT + PLAC), and 4) taking metformin and undergoing the same RT bout (RT + MET). Interstitial fluid glucose concentration was frequently sampled to obtain 72-h glucose area under the curve (GAUC) and the percentage hyperglycemic glucose readings (>180 mg·dL-1; GPEAKS). Insulin sensitivity (i.e., HOMA-2) and IGF-1 were also assessed. HOMA-2 was not affected by treatments. GAUC and GPEAKS were similarly reduced below PLAC during RT + MET and MET (all P < 0.05). In contrast, RT + PLAC did not affect glucose concentration. Metformin decreased serum IGF-1 concentrations (P = 0.006), and RT did not reverse this reduction. A bout of full-body RT does not interfere or aid on metformin's blood glucose-lowering actions in individuals with prediabetes and type 2 diabetes mellitus.

Dietary Advanced Glycation End Products Shift the Gut Microbiota Composition and Induce Insulin Resistance in Mice.

ObjectiveThis study aimed to explore the associations between gut microbiota characteristics and glycometabolic profiles in mice fed diets high in advanced glycation end products (AGEs).MethodsC57BL/6 mice were exposed to a heat-treated diet or exogenous AGEs for 24 weeks, and glucose metabolism was assessed via the intraperitoneal glucose-tolerance test (IPGTT). Serum AGE and lipopolysaccharide-binding protein (LBP) levels were quantified using ELISA kits. 16S rDNA sequencing was performed to analyze the changes in gut microbiota according to α- and β-diversity. Key operational taxonomic units (OTUs) were evaluated, and co-abundance groups (CAGs) were delineated using weighted correlation network analysis. Associations between CAGs and clinical parameters were analyzed using Spearman correlation; predictive functional analysis of gut microbiota was performed using Kyoto Encyclopedia of Genes and Genomes data.ResultsWe identified significant increases in fasting blood glucose (FBG) and fasting insulin levels, as well as homeostatic model assessment insulin resistance (HOMA-IR) and glucose area under the receiver operating characteristic curve from IPGTT, in the high-AGE diet groups relative to controls at week 24. Serum AGE and LBP levels were elevated, and the α- and β-diversity of gut microbiota reduced in high-AGE diet groups. We identified 92 key OTUs that clustered into six CAGs, revealing positive correlations between CAG2/3/5 and insulin levels and mice weight and negative correlations between CAG1/3/4/5 and AGE, FBG, and LBP levels and HOMA-IR in mice fed high-AGE diets. We observed a reduced abundance of butyrate-producing bacteria, including Bacteroidales_S24-7, Ruminococcaceae, and Lachnospiraceae, in mice fed high-AGE diets, with pathway analysis of gut microbiota revealing significantly enriched fructose and mannose metabolism.ConclusionHigh-AGE diets altered the gut microbiota composition and structure, and induced insulin resistance in mice. In the pathogenesis of insulin resistance, the loss of butyrate-producing bacteria might impair the colonic epithelial barrier, thereby triggering chronic low-grade inflammation.

Effects of Resistant Starch Interventions on Metabolic Biomarkers in Pre-Diabetes and Diabetes Adults.

Simple lifestyle changes can prevent or delay the onset of type 2 diabetes mellitus (T2DM). In addition to maintaining a physically active way of life, the diet has become one of the bases in managing TD2M. Due to many studies linking the ability of resistant starch (RS) to a substantial role in enhancing the nutritional quality of food and disease prevention, the challenge of incorporating RS into the diet and increasing its intake remains. Therefore, we conducted this review to assess the potential benefits of RS on metabolic biomarkers in pre-diabetes and diabetes adults based on available intervention studies over the last decade. Based on the conducted review, we observed that RS intake correlates directly to minimize possible effects through different mechanisms for better control of pre-diabetic and diabetic conditions. In most studies, significant changes were evident in the postprandial glucose and insulin incremental area under the curve (iAUC). Comparative evaluation of RS consumption and control groups also showed differences with inflammatory markers such as TNF-α, IL-1β, MCP-1, and E-selectin. Only RS2 and RS3 were extensively investigated and widely reported among the five reported RS types. However, a proper comparison and conclusion are deemed inappropriate considering the variations observed with the study duration, sample size, subjects and their metabolic conditions, intervention doses, and the intervention base products. In conclusion, this result provides interesting insights into the potential use of RS as part of a sustainable diet in diabetes management and should be further explored in terms of the mechanism involved.

Interplay of Dinner Timing and MTNR1B Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial.

We tested whether the concurrence of food intake and elevated concentrations of endogenous melatonin, as occurs with late eating, results in impaired glucose control, in particular in carriers of the type 2 diabetes-associated G allele in the melatonin receptor-1B gene (MTNR1B). In a Spanish natural late-eating population, a randomized, crossover study was performed. Each participant (n = 845) underwent two evening 2-h 75-g oral glucose tolerance tests following an 8-h fast: an early condition scheduled 4 h prior to habitual bedtime ("early dinner timing") and a late condition scheduled 1 h prior to habitual bedtime ("late dinner timing"), simulating an early and a late dinner timing, respectively. Differences in postprandial glucose and insulin responses between early and late dinner timing were determined using incremental area under the curve (AUC) calculated by the trapezoidal method. Melatonin serum levels were 3.5-fold higher in the late versus early condition, with late dinner timing resulting in 6.7% lower insulin AUC and 8.3% higher glucose AUC. The effect of late eating impairing glucose tolerance was stronger in the MTNR1B G-allele carriers than in noncarriers. Genotype differences in glucose tolerance were attributed to reductions in β-cell function (P for interaction, Pint glucose area under the curve = 0.009, Pint corrected insulin response = 0.022, and Pint disposition index = 0.018). Concurrently high endogenous melatonin and carbohydrate intake, as typical for late eating, impairs glucose tolerance, especially in MTNR1B G-risk allele carriers, attributable to insulin secretion defects.

The Role of Fatty Acid Signaling in Islet Beta-Cell Adaptation to Normal Pregnancy

BackgroundMaintenance of a normal fetal nutrient supply requires major adaptations in maternal metabolic physiology, including of the islet beta-cell. The role of lipid signaling processes in the mechanisms of islet beta-cell adaptation to pregnancy has been minimally investigated.ObjectiveTo determine the effects of pregnancy on islet fatty acid (FA) metabolic partitioning and FA augmentation of glucose-stimulated insulin secretion (GSIS).MethodsAge matched virgin, early pregnant (gestational day-11, G11) and late pregnant (G19) Sprague-Dawley rats were studied. Fasted and fed state biochemistry, oral glucose tolerance tests (OGTT), and fasted and post-OGTT liver glycogen, were determined to assess in vivo metabolic characteristics. In isolated islets, FA (BSA-bound palmitate 0.25 mmol/l) augmentation of GSIS, FA partitioning into esterification and oxidation processes using metabolic tracer techniques, lipolysis by glycerol release, triacylglycerols (TG) content, and the expression of key beta-cell genes were determined.ResultsPlasma glucose in pregnancy was lower, including during the OGTT (glucose area under the curve 0-120 min (AUC0-120); 655±24 versus 849±13 mmol.l-1.min; G19 vs virgin; P<0.0001), with plasma insulin concentrations equivalent to those of virgin rats (insulin AUC0-120; 97±7 versus 83±7 ng.ml-1.min; G19 vs virgin; not significant). Liver glycogen was depleted in fasted G19 rats with full recovery after oral glucose. Serum TG increased during pregnancy (4.4±0.4, 6.7±0.5; 17.1±1.5 mmol/l; virgin, G11, G19, P<0.0001), and islet TG content decreased (147±42, 172±27, 73±13 ng/µg protein; virgin, G11, G19; P<0.01). GSIS in isolated islets was increased in G19 compared to virgin rats, and this effect was augmented in the presence of FA. FA esterification into phospholipids, monoacylglycerols and TG were increased, whereas FA oxidation was reduced, in islets of pregnant compared to virgin rats, with variable effects on lipolysis dependent on gestational age. Expression of Ppargc1a, a key regulator of mitochondrial metabolism, was reduced by 51% in G11 and 64% in G19 pregnant rat islets compared to virgin rat islets (P<0.001).ConclusionA lowered set-point for islet and hepatic glucose homeostasis in the pregnant rat has been confirmed. Islet adaptation to pregnancy includes increased FA esterification, reduced FA oxidation, and enhanced FA augmentation of glucose-stimulated insulin secretion.

Time-restricted eating improves glycemic control and dampens energy-consuming pathways in human adipose tissue

ObjectiveWe sought to examine the effects of 8 wk of time-restricted eating (TRE) on glucose metabolism and the adipose tissue transcriptome during a metabolic ward stay in men with obesity. MethodsIn a single-arm, pre-post trial, 15 men (ages 63 ± 4 y, body mass index = 30.5 ± 2.4 kg/m2, waist circumference = 113 ± 4 cm) with obesity but no history of diabetes were enrolled and underwent 2 wk of baseline monitoring before they were instructed to eat their regular diets within a contiguous 10-h time frame each day for 8 wk. Metabolic testing was performed at baseline and week 8 during a 35-h metabolic ward stay, during which all food intake was strictly timed and controlled. Identical meal-tolerance tests were performed at breakfast and dinner. Blood glucose, glucoregulatory hormones, and subjective appetite score were measured. Subcutaneous adipose tissue biopsies were performed and the transcriptome was assessed. ResultsThe primary outcome, plasma glucose area under the curve, was altered by TRE, being unchanged at breakfast but increased at dinner. However, TRE reduced fasting glucose, glycated hemoglobin, body weight, and body fat, and increased glucose-dependent insulinotropic peptide area under the curve at dinner. In subcutaneous adipose tissue, 117 genes were up-regulated and 202 genes down-regulated by TRE. Pathway analysis revealed down-regulation of genes involved in proteasome function and mitochondrial regulation. ConclusionsTRE had a net effect of reducing glycemia and dampening energy-consuming pathways in adipose tissue.