Oral Glucose Insulin Sensitivity Research Articles

The Mediterranean Diet: Effects on Insulin Resistance and Secretion in Individuals with Overweight or Obesity.

High adherence to the Mediterranean Diet (MD) is associated with a lower risk of type 2 diabetes. However, it is less clear whether the different MD food items might influence specific biological functions related to glucose tolerance, i.e., insulin resistance (IR) and/or secretion (IS). Thus, this cross-sectional study aimed to investigate the relationship between adherence to MD and IR, insulin sensitivity, and IS in individuals with overweight/obesity. Participants (62 individuals; 7M/55F; mean age 49 ± 15 years; mean BMI 35.8 ± 6.7 kg/m²) underwent a 75 g oral glucose tolerance test (OGTT) to assess plasma glucose and insulin concentrations. These parameters were used for the calculation of validated IR indices (Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for β-cell function (HOMA-β)), as well as insulin sensitivity indices (insulin sensitivity index (ISI), oral glucose insulin sensitivity (OGIS)). MD adherence was gauged using the PREDIMED questionnaire. Bivariate correlations were used to highlight the association between OGTT-derived indices and MD adherence (PREDIMED score) or specific foodstuffs related to MD. Despite there being no significant differences in BMI, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT), the high MD adherence group presented lower HOMA-IR (p = 0.022) and higher ISI (p = 0.033) compared to other groups. High MD adherence was inversely correlated with HOMA-IR (r = -0.400; p = 0.004) and directly correlated with ISI (r = 0.296, p = 0.039). Fish consumption, a key component of MD, exhibited significant associations: it was directly correlated to ISI (r = 0.394, p = 0.005) and inversely related to HOMA-IR (r = -0.327, p = 0.019) and β-cell function (r = -0.489, p < 0.001). In conclusion, a high MD adherence, and in particular the consumption of fish, is associated with a decreased IR in individuals with overweight/obesity.

Duodenal mucosal resurfacing with photodynamic therapy using methylene blue in a mouse model

BackgroundThe duodenum has emerged as a key player in metabolic diseases. The objective was to evaluate the safety and efficacy of intra-duodenal PDT using methylene blue in managing glycemic control and weight reduction. MethodsOptimal concentration of methylene blue and conditions for intra-duodenal PDT were determined through in vitro experiments. After injecting methylene blue into the duodenum, we performed intra-duodenal PDT. High-fat diet rats were used to assess the efficacy of intra-duodenal PDT through measures of oral glucose tolerance, insulin sensitivity, and weight change. Immunohistochemical staining was also conducted to examine GLP-1 and GIP-producing cells in the ileum and duodenum, respectively. ResultsIntroduodenal PDT reduced villous height of duodenum at 48 h, which was fully recovered at 30 days without complications. Rats treated with PDT showed significantly lower blood glucose levels with glucose loading and improved insulin sensitivity than rats in the sham-treatment group. The PDT group also had a significant reduction in body weight compared to the sham-treatment group at 30 days after intervention, although food intake was not significantly different between the two groups. Numbers of GLP-1 and GIP producing cells in the ileum and irradiated area were significantly higher in the PDT group than in the sham-treatment group. ConclusionsIntra-duodenal PDT using methylene blue showed a feasible therapeutic modality in improving metabolic parameters. However, large animal experiments and mechanism studies are needed to determine the clinical relevance. The possibility of repeating this treatment every 30 days and its accompanying complications should be further studied.

Improved Insulin Secretion Response and Beta-cell Function Correlated with Increased Prolactin Levels After Laparoscopic Sleeve Gastrectomy in Morbidly Obese Patients with Acanthosis Nigricans.

To explore insulin secretion patterns, β-cell function, and serum prolactin (PRL) concentrations in Chinese morbidly obese patients with Acanthosis nigricans (AN) and their alterations after laparoscopic sleeve gastrectomy (LSG). A total of 138 morbidly obese subjects undergoing LSG were categorized as simple obesity without AN (OB group, n = 55) and obesity with AN (AN group, n = 83). Oral glucose tolerance test (OGTT), PRL, and related metabolic indices were performed pre- and 12 months post-LSG. Insulin secretion patterns were derived from insulin secretion peak time during OGTT: type I (peak at 30 or 60 min) and type II (peak at 120 or 180 min). Preoperatively, AN group showed significantly higher proportions of type II insulin secretion pattern, fasting insulin (FINS), and homeostatic model assessment of insulin resistance (HOMA-IR) whereas lower oral glucose insulin sensitivity (OGIS), insulinogenic index (IGI), and disposition index (DI) than OB group, which were improved significantly at 12 months postoperatively in both groups, more pronounced in AN group. Intriguingly, serum PRL declined substantially in AN group than OB group at baseline whereas elevated only in the AN group post-LSG. After adjusting for confounding factors, elevated PRL correlated significantly with increased IGI and DI, and decreased HOMA-IR in both genders, as well as increased OGIS in females, which was detected only in the AN group CONCLUSION: Morbidly obese patients with AN presented delayed insulin secretion response, impaired insulin secretion, and β-cell dysfunction, which were significantly improved by LSG and might benefit from elevated PRL.

Insulin-Like Growth Factor -1 (IGF-1) and Glucose Dysregulation in Young Adult Patients with β-Thalassemia Major: Causality or Potential Link?

Insulin-like growth factor-1 (IGF-1) has been shown to lower blood glucose through stimulating glucose transport to fat and muscle and inhibiting hepatic glucose output. Although previous cross-sectional reports reported an association between low circulating concentrations of IGF-1 and glucose dysregulation (GD), its role is still debated. The present retrospective study was designed to assess the circulating IGF-1 levels in β-thalassemia major (β -TM) patients with normal oral glucose tolerance test (NGT-OGTT) and (GD) referred for an endocrine evaluation to explore the potential link between low IGF-1 and GD. Our study included 34 young adult patients with β-TM; 12 patients with NGT after OGTT, 7 with impaired glucose tolerance (IGT), 9 with impaired fasting glucose (IFG) plus IGT, and 6 patients with β-TM-related diabetes mellitus (β-TM- DM). Twenty-two β-TM patients with GD or β-TM- DM and 1 patient with NGT had IGF-1 levels below the 2.5th percentile. Correlation of IGF-1 with fasting plasma glucose, HOMA-IR (homeostatic model assessment for insulin resistance) and OGIS (oral glucose insulin sensitivity) was found. Moreover, a negative correlation was documented between ALT and the Insulinogenic Index (IGI) and a positive correlation between serum ferritin and PG 2-h after OGTT. This study reports for the first time an association between low levels of IGF-1 and GD in β-TM patients. Despite some limitations, our study can serve to generate proposals for more convenient and efficient methods to identify and treat early GD in patients with β-TM, and to conduct more extensive studies. www.actabiomedica.it).

PSUN299 GLP-1 Contribution to Insulin Secretory Response to Protein Ingestion and Insulin Kinetics Following Gastric Bypass and Sleeve Gastrectomy

Abstract Rapid passage of ingested nutrients to the gut after Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) results in hyperinsulinemia after glucose ingestion, in part due to an enhanced glucagon-like peptide-1 (GLP-1)-induced insulin secretory response (ISR) and reduced metabolic clearance rate of insulin (MCRI). The effect of endogenous GLP-1 on insulin kinetics is unknown, and so is GLP-1 contribution to insulin secretory response to non-glucose nutrient ingestion. In non-surgical subjects, protein ingestion enhances insulin secretion and reduces MCRI. We hypothesized that protein ingestion enhances GLP-1-induced ISR and alters MCRI in proportion to changes in nutrient influx after GB and SG. To test this hypothesis ISR, β-cell sensitivity to glucose (BGS), MCRI, and oral glucose insulin sensitivity (OGIS) were measured on 3 days during 50 g glucose ingestion as well as 50 g protein ingestion with and without GLP-1R antagonist, exendin (9-39) [Ex-9] infusion. Ten GB-treated subjects, 9 SG-treated, and 7 non-operated controls (CN) were enrolled. The 3 non-diabetic groups were matched for age, BMI, fat-free mass, HbA1c; surgical groups were matched for weight loss and time post-surgery. Fasting glucose, insulin, and ISR were similar among the 3 groups and among the 3 studies but fasting MCRI was greater in surgical groups than CN (p&amp;lt;0.05). Compared to glucose, protein ingestion led to larger BGS in 3 groups despite smaller overall ISR response (AUCISR3h) (p&amp;lt;0.05). Blocking GLP-1R during protein ingestion decreased AUCISR3h only in surgical subjects (p&amp;lt;0.05 for interaction), whereas BGS was reduced similarly in 3 groups during Ex-9 infusion (p&amp;lt;0.05). OGIS was smaller during protein than glucose ingestion in 3 groups (p&amp;lt;0.05). GLP-1R blockade did not affect insulin sensitivity. Following nutrient ingestion in parallel with increase in insulin secretion MCRI was reduced to nadir values at 40 minutes, but then gradually increased approaching premeal values at different pace among surgical and non-surgical subjects (p&amp;lt;0.05). The slope of MCRI: Insulin (0-40 min) was smaller after protein ingestion than glucose, and after protein with Ex-9 infusion than without in 3 groups (p&amp;lt;0.05). Blocking GLP-1R had no effect on MCRI values in the latter phase of protein ingestion when insulin secretion reduced approaching premeal values. There was no association between parameters of insulin sensitivity and insulin clearance during glucose or protein ingestion. Our findings indicate that the regulation of insulin secretion and clearance during protein ingestion is altered after GB and SG. Further, endogenous GLP-1 contribution to insulin secretory response to protein ingestion after GB and SG is enhanced, but GLP-1 effect on insulin kinetics is trivial. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Antidiabetic effects of Brugmansia aurea leaf extract by modulating the glucose levels, insulin resistance, and oxidative stress mechanism.

BackgroundEthnopharmacological relevance: Brugmansia, a genus of the Solanaceae family, has historically been utilized in many different parts of the world as an anti-inflammatory for treating skin infections, wounds, and bodily aches and pains. The current study aimed to investigate the potential benefits of a methanolic extract of Brugmansia aurea in the management of diabetes and underlying complications in alloxanized-induced diabetic rats.Materials and methodsAnimals were divided into nine groups (n = 6). Four groups received different standard oral hypoglycemic agents; three groups received 100, 200, and 400 mg/kg of B. aurea leaf extract for six consecutive weeks, and the remaining two were normal and disease control groups. All groups received alloxan (150 mg/kg) except for the normal control. Only those animals whose glucose levels were raised to 200 mg/dl were selected for the study. After a 6-week dosage period, various biochemical parameters, as well as HbA1c, antioxidant profile, oral glucose tolerance test (OGTT), insulin sensitivity, histopathology, and insulin resistance, were measured and compared with the untreated diabetic group.ResultsBrugmansia aurea leaf extract at a dose of 400 mg/kg showed potent antidiabetic activity by reducing blood glucose levels (p < 0.001) after 6 weeks of treatment. OGTT data showed that B. aurea exhibited significant (p < 0.001) glucose tolerance by significantly reducing blood glucose levels in just 2 h post-treatment. Other tests showed that plant extract significantly increased (p < 0.001) insulin sensitivity and decreased (p < 0.001) insulin resistance. The biochemical profile showed reduced triglyceride and cholesterol, while the antioxidant profile showed restoration of antioxidant enzymes in the pancreas, kidney, and liver tissues of treated rats.ConclusionThe present study indicated that crude extracts of B. aurea increase insulin sensitivity and reduce hyperlipidemia in diabetic rats, which rationalizes the traditional medicinal use of this plant as an antidiabetic agent.

Effects of the Seed Oil of Carica papaya Linn on Food Consumption, Adiposity, Metabolic and Inflammatory Profile of Mice Using Hyperlipidic Diet.

Background: Studies indicate that different parts of Carica papaya Linn have nutritional properties that mean it can be used as an adjuvant for the treatment of various pathologies. Methods: The fatty acid composition of the oil extracted from the seeds of Carica papaya Linn was evaluated by gas chromatography, and an acute toxicity test was performed. For the experiment, Swiss mice were fed a balanced or high-fat diet and supplemented with saline, soybean oil, olive oil, or papaya seed oil. Oral glucose tolerance and insulin sensitivity tests were performed. After euthanasia, adiposity, glycemia, total cholesterol and fractions, insulin, resistin, leptin, MCP-1, TNF-α, and IL-6 and the histology of the liver, pancreas, and adipose tissue were evaluated. Results: Papaya seed oil showed predominance of monounsaturated fatty acids in its composition. No changes were observed in the acute toxicity test. Had lower food intake in grams, and caloric intake and in the area of adipocytes without minimizing weight gain or adiposity and impacting the liver or pancreas. Reductions in total and non-HDL-c, LDL-c, and VLDL-c were also observed. The treatment had a hypoglycemic and protective effect on insulin resistance. Supplementation also resulted in higher leptin and lower insulin and cytokine resistance. Conclusions: Under these experimental conditions, papaya seed oil led to higher amounts of monounsaturated fatty acids and had hypocholesterolemic, hypotriglyceridemic, and hypoglycemic effects.

Contribution of RAS, ROS and COX-1-derived prostanoids to the contractile profile of perivascular adipose tissue in cafeteria diet-induced obesity

AimsObesity can lead to the loss of the anticontractile properties of perivascular adipose tissue (PVAT). Given that cafeteria (CAF) diet reflects the variety of highly calorie and easily accessible foods in Western societies, contributing to obesity and metabolic disorders, we sought to investigate the impact of CAF diet on PVAT vasoactive profile and the involvement of renin-angiotensin system, oxidative stress, and cyclooxygenase pathway. Main methodsMale Balb/c mice received standard or CAF diet for 4 weeks. Oral glucose tolerance and insulin sensitivity tests were performed, and fasting serum glucose, cholesterol and triglyceride parameters were determined. Vascular reactivity, fluorescence and immunofluorescence analyzes were carried out in intact thoracic aorta in the presence or absence of PVAT. Key findingsCAF diet was effective in inducing obesity and metabolic disorders, as demonstrated by increased body weight gain and adiposity index, hyperlipidemia, hyperglycemia, glucose intolerance and insulin insensitivity. Importantly, CAF diet led to a significant decrease in aortic contractility which was restored in the presence of PVAT, exhibiting therefore a contractile profile. The contractile effect of PVAT was associated with the activation of AT1 receptor, reactive oxygen species, cyclooxygenase-1, thromboxane A2 and prostaglandin E2 receptors. SignificanceThese findings suggest that the contractile profile of PVAT involving the renin-angiotensin system activation, reactive oxygen species and cyclooxygenase-1 metabolites may be a protective compensatory adaptive response during early stage of CAF diet-induced obesity as an attempt to restore the impaired vascular contraction observed in the absence of PVAT, contributing to the maintenance of vascular tone.

Exercise mode influences post-exercise glucose sensitivity and insulin clearance in young, healthy males and females in a sex-dependent manner: A randomized control trial.

Type 2 diabetes (T2D) risk is lower in females than males. It has been reported that females have greater pancreatic 𝛽‐cell function than males, which may at least in part contribute to the T2D risk in females. 𝛽‐cell function is influenced by exercise training; however, previous trials comparing 𝛽‐cell function between the sexes have not included participants matched for training status. Furthermore, the acute effects of different modes of exercise on 𝛽‐cell function, and whether sex inherently influences these effects, are largely unexamined. Males and females (12/sex) completed a 120‐min oral glucose tolerance test (OGTT) at rest (CON) and following acute bouts of high‐intensity interval exercise (HIIE), moderate intensity continuous (MIC) exercise, and low‐load high‐repetition (LLHR) resistance exercise to assess whether sex inherently influences baseline and/or post‐exercise pancreatic function in the absence of pathology. We found no sex differences in basal pancreatic 𝛽‐cell function. Females had greater basal insulin clearance following MIC exercise compared to males (p = 0.01) and males tended to have a higher potentiation ratio following HIIE (p = 0.07). Females also had lower glucose sensitivity following MIC exercise compared to HIIE (p = 0.007) and LLHR (p = 0.003). Insulin clearance during the OGTT was greater following HIIE as compared with CON and MIC exercise (p = 0.02). 2‐H oral glucose insulin sensitivity was greater following LLHR compared to CON (p = 0.01). Acute bouts of different modes of exercise do not differentially influence 𝛽‐cell function but do influence insulin clearance and insulin sensitivity. Therefore, sex and exercise mode interact to differentially influence insulin clearance and glucose sensitivity.

Glomerular hyperfiltration in morbid obesity: Role of the inflammasome signalling.

Obesity is associated with glomerular hyperfiltration which may precede the development of overt renal damage. Few studies evaluated the link between inflammasome signalling and hyperfiltration. The aim is to evaluate the relationship between IL1-β/Caspase-1, insulin sensitivity and hyperfiltration in subjects with severe obesity, before and after weight loss. Forty-six patients with BMI > 35 kg/m2 , without type-2-diabetes or hypertension, were evaluated at baseline and 6months after bariatric surgery with oral glucose tollerance test, bioimpedance analysis and blood tests. The eGFR was calculated according to EPIcr-cys formula and insulin sensitivity by Oral Glucose Insulin Sensitivity. IL-1β/Caspase-1 were measured with the ELISA-kit. HF was defined as eGFR ≥ 140 ml/min (non-indexed for BSA). Sixteen subjects at baseline had hyperfiltration, with a higher insulin resistance, BMI, lean mass and plasma levels of IL-1β/Caspase-1. After surgery, there was a reduction in BMI and improvement in insulin resistance in all patients. However, in 8 of 16 patients hyperfiltration persisted and IL-1β/Caspase-1 levels did not decrease (3.22 ± 0.79 vs. 3.13 ± 1.03 and 23.7± 12.1 vs. 20.6± 9.1, pre vs. post, pg/ml), while cytokines normalized in all the other patients in parallel with the eGFR. In a logistic regression model, correcting for the main covariates, lean mass and IL-1β before surgery (p= .01 and p= .03, respectively), were the only predictors of hyperfiltration. Weight loss is effective in reducing hyperfiltration in most, but not all patients. Hyperfiltration remains unchanged in subjects who do not have a reduction in IL-1β/Caspase-1, suggesting a pathogenetic role of the inflammasome signalling in the early stages of nephropathy.

Diabetic family history in young Japanese persons with normal glucose tolerance associates with k-means clustering of glucose response to oral glucose load, insulinogenic index and Matsuda index

AimsThe present study aimed to clarify the relationships between diabetic family history (FH), and dysglycemic response to the oral glucose tolerance test (OGTT), insulin secretion, and insulin sensitivity in young Japanese persons with normal glucose tolerance (NGT). MethodsWe measured plasma glucose (PG) and immunoreactive insulin levels in 1,309 young Japanese persons (age <40 years) with NGT before and at 30, 60, and 120 min during a 75-g OGTT. Dysglycemia during OGTT was analyzed by k-means clustering analysis. Body mass index (BMI), blood pressure (BP), and lipids were measured. Insulin secretion and sensitivity indices were calculated. ResultsPG levels during OGTT were classified by k-means clustering analysis into three groups with stepwise decreases in glucose tolerance even among individuals with NGT. In these clusters, proportion of males, BMI, BP and frequency of FH were higher, and lipid levels were worse, together with decreasing glucose tolerance. Subjects with a diabetic FH showed increases in PG after glucose loading and decreases in insulinogenic index and Matsuda index. ConclusionsDysglycemic response to OGTT by k-means clustering analysis was associated with FH in young Japanese persons with NGT. FH was also associated with post-loading glucose, insulinogenic index, and Matsuda index.

198-OR: Altered Prandial Glucose Metabolism in Nondiabetic Subjects with Spinal Cord Injury Is Associated with Impaired Insulin Secretion and Clearance

Patients with spinal cord injury (SCI) develop type 2 diabetes earlier and at 2-3 times higher frequency compared to the matched able-bodied persons (AB) . The difference in glucose abnormalities among SCI and AB cohorts remains after adjusting for known risk factors for DM, such as decreased physical activity, or lower body lean mass, or larger visceral fat mass. The mechanism for this dramatic effect of SCI on glucose metabolism is unknown but is consistent with endocrine-neurological alterations after injury. We hypothesized that SCI is associated with abnormalities in prandial glucose metabolism and β-cell function. To test this hypothesis glucose, insulin, and C-peptide levels were measured during 3-hr mixed meal tolerance test in 4 non-diabetic SCI (3M/1F, ages 33-61 years) and 6 age-matched AB with normal glucose tolerance test (2M/4F, ages 37-57 years) . SCI subjects had lower BMI (p=0.05) and A1C (p&amp;lt;0.05) than AB (SCI vs. AB; BMI range: 19-29 vs. 25-39 kg/m2; A1C range: 5.0-5.3 vs. 5.3-5.9%) . Fasting values of glucose, insulin, C-peptide, insulin sensitivity (HOMA-IR) , and insulin clearance (CP/insulin) were similar between SCI and AB. Prandial glucose (AUCGlucose3h) and insulin (AUCInsulin3h) responses, however, were greater in SCI than AB (p&amp;lt;0.01) . Despite larger prandial insulinemia β-cell output (AUCC-peptide3h) did not differ among 2 groups. This was consistent with a diminished insulin clearance (Total AUCC-peptide3h / Total AUCInsulin3h) in SCI compared to AB by 3-fold (p&amp;lt;0.05) . Oral glucose insulin sensitivity (OGIS) was similar between 2 groups while β-cell glucose sensitivity and disposition index were smaller in SCI than AB by 2-fold (p=0.08) . These findings indicate that among subjects with normal glucose tolerance, those with SCI have larger prandial glycemic concentration despite lower BMI and A1C. This glycemic effect of SCI is associated with impaired β-cell function as well as insulin clearance. Disclosure M.Trbovich: None. R.Dimas: None. M.Salehi: None.

Plasma FGF-21 and Sclerostin Levels, Glycemia, Adiposity, and Insulin Sensitivity in Normoglycemic Black and White Adults.

Increased circulating fibroblast growth factor (FGF)-21 and sclerostin levels have been reported in patients with type 2 diabetes (T2D). We assessed the association of FGF-21 and sclerostin with adiposity, glycemia, and glucoregulatory measures in healthy subjects. We studied 20 normoglycemic Black and White offspring of parents with T2D. Assessments included oral glucose tolerance test, insulin sensitivity (Si-clamp), insulin secretion (homeostasis model assessment index of b-cell function [HOMA-B]), and body fat (dual-energy X-ray absorptiometry). Fasting plasma FGF-21 and sclerostin levels were measured with enzyme-linked immunosorbent assays. The participants’ mean (+SD) age was 50.4 ± 5.97 years; body mass index (BMI) 32.5 ± 5.86 kg/m2; fasting plasma glucose (FPG) 96.1 ± 5.21 mg/dL, and 2-hour postload glucose 116 ± 5.45 mg/dL. FGF-21 levels were similar in Black people vs White people (0.36 ± 0.15 ng/mL vs 0.39 ± 0.25 ng/mL), men vs women (0.45 ± 0.14 vs 0.44 ± 0.07 ng/mL), correlated positively with BMI (r = 0.23, P = .05) and waist circumference (r = 0.27, P = .04), and inversely with FPG (r = –0.26, P = .05). Sclerostin levels also were similar in Black people (33.5 ± 17.1 pmol/L) vs White people (34.2 ± 6.41 pmol/L), men vs women (35.3 ± 9.01 pmol/L vs 32.3 ± 15.8 pmol/L), and correlated inversely with FPG (r = –0.11 to –0.44) but not adiposity measures. The correlation coefficient between Si-clamp values and FGF-21 levels was –0.31 (P = .09) compared with 0.04 (P = .89) for sclerostin levels. FGF-21 and sclerostin levels were not correlated with each other or HOMA-B. Among healthy Black and White subjects, plasma FGF-21 and sclerostin showed differential associations with adiposity but concordant association with FPG levels.

Reproducibility and discrimination of different indices of insulin sensitivity and insulin secretion.

AimsInsulin sensitivity and insulin secretion can be estimated by multiple indices from fasting blood samples or blood samples obtained during oral glucose tolerance tests. The test-retest reliability of these indices in repeated measurements within the same individuals can strongly vary.MethodsWe analyzed data of persons without diabetes who underwent two repeated OGTTs. For each measurement pair, we calculated multiple commonly used indices for the assessment of insulin secretion and insulin sensitivity. We then evaluated the coefficient of variation (standard deviation/mean) and discriminant ratio for each index.Results89 persons underwent two OGTTs with a median interval of 86 days (IQR 64–249). Among indices of insulin sensitivity derived from fasting blood samples, the revised quantitative insulin sensitivity check index had the smallest coefficient of variation (2.8 ± 2.1%) whereas the C-peptide based homeostasis model assessment 2 had the highest discriminant ratio (1.97 (1.65–2.39)). As for insulin sensitivity indices that are based on OGTT, the oral glucose insulin sensitivity index had the smallest coefficient of variation (6.5 ± 5.1%). The highest discriminant ratio was found for the non-esterified fatty acids-based insulin sensitivity index (NEFA-ISI, 2.70 (2.30–3.22)). For the assessment of insulin secretion from fasting variables, the lowest mean coefficient of variation was found for C-peptide based homeostasis model assessment 2 beta with 10.8 ± 8% and the highest discriminant ratio for the C-peptide / Glucose-Ratio (2.18 (1.84–2.63)). Among indices assessing insulin secretion from an OGTT, the lowest coefficient of variation was found for the ratio of the areas under the C-peptide and glucose curves from 0 to 120 minutes with 11.3 ± 9.7%.ConclusionThe data reveal large differences in the reproducibility and the discrimination capability of different indices that assess insulin sensitivity or insulin secretion. Our findings can aid the selection of an appropriate index in clinical studies.

Shift of Glucose Peak Time During Oral Glucose Tolerance Test is Associated with Changes in Insulin Secretion and Insulin Sensitivity After Therapy with Antidiabetic Drugs in Patients with Type2 Diabetes.

IntroductionDelay in peak blood glucose during an oral glucose tolerance test (OGTT) predicts declining β-cell function and poor ability to regulate glucose metabolism. Glucose peak time has not been used as a comparative indicator of the improvement in islet function after treatment with exenatide, insulin, or oral antidiabetic drugs (OADs). We evaluated the efficacy of three types of antidiabetic drugs on the basis of blood glucose peak time in patients with non-newly diagnosed type 2 diabetes.MethodsThe data from 100 patients with diabetes who completed two OGTTs within 6 months were collected. Thirty-seven of them with type 2 diabetes were treated with Humalog Mix25, 28 patients with OADs (metformin, acarbose, and gliclazide), and 35 patients with exenatide.ResultsGlycated hemoglobin improved in all three groups after treatment (P < 0.05). Subcutaneous adipose tissue (P < 0.01) and visceral adipose tissue (P < 0.0001) significantly decreased in the exenatide group. The insulinogenic index (IGI) (P = 0.01) and IGI × oral glucose insulin sensitivity (OGIS) (P = 0.01) improved in the exenatide group only. Homeostatic assessment of β-cell function (HOMA-β) and OGIS were greater in the exenatide and OAD groups than in the Humalog Mix25 group (all P < 0.05). A shift to an earlier peak was observed in 57.1%, 35.7%, and 27.0% of patients in the exenatide, OAD, and Humalog Mix25 groups, respectively (P = 0.029). OGIS (odds ratio [OR] 0.54, 95% confidence interval [CI] 0.33–0.89, P = 0.026) and IGI × OGIS (OR 1.72, 95% CI 0.44–6.68, P = 0.012) were independently related to shifts in glucose peak time.ConclusionExenatide, Humalog Mix25, and OADs improved glycemic metabolism. However, exenatide exhibited superior efficacy in shifting blood glucose peak time to an earlier point, while it improved insulin secretion and insulin sensitivity. Hence, the shift of glucose peak time may be considered an indicator for the evaluation of the effect of hypoglycemic drugs.

Acosmium dasycarpum (Vog.) Yakovlev root bark reduces obesity induced by hypercaloric diet in mice

• Acosmium dasycarpum improved metabolic syndrome. • Acosmium dasycarpum root bark significantly reduces triglycerides. • Acosmium dasycarpum has a beneficial effect on weight reduction and adiposity. Acosmium dasycarpum (Vog.) Yakovlev, is a Brazilian medicinal plant, belonging to the Fabaceae family known as "Unha D'anta", exclusively found in the Cerrado (Brazilian Savanna) region, and has already shown tranquilizing, hypotensive, antineoplastic and antiseptic activities reported by traditional medicine and scientific evidences. Considering that overweight and obesity are an increasing worldwide health problem, the present study aimed to investigate the anti-obesity effect of bark powder and the dichloromethane extract of A. dasycarpum compared to the most abundant bioactive component (lupeol) using an obese mice model induced by a high-fat diet (HFD). The extracts derived from root bark of A. dasycarpum were characterized (phytochemical screening and GC–MS analysis) and their biological effects tested. After obesity inducement, Swiss male mice were treated with bark root powder or dichloromethane extract or lupeol (all treatments with 10 mg/1000 g/body weight dose) during 14 days. Oral glucose tolerance, insulin sensitivity, lipid profile, histology, ultrasound imaging and adipogenic genes expression were evaluated. The main results showed that A. dasycarpum root bark powder and dichloromethane extract reduced body weight and adiposity as evidenced by histology and ultrasound imaging. We also verified an improved glycemic and lipid profiles by reducing triglycerides, LDL and increasing HDL. The A. dasycarpum treatment suppressed the expression of CCAAT/enhancer-binding protein (C/EBPα), fatty acid translocase (FAT), and stearoyl coenzyme A desaturase-1 (SCD-1) adipogenic genes when compared to the obese control group. In conclusion, A. dasycarpum root bark showed a potential to be an accessible adjuvant treatment for obesity.

A Mediterranean Diet and Low-Fat Vegan Diet to Improve Body Weight and Cardiometabolic Risk Factors: A Randomized, Cross-over Trial

Objective: Evidence suggests that both Mediterranean and vegan diets improve body weight and cardiometabolic risk factors, but their relative efficacy has not been compared in a randomized trial. Methods: In a randomized crossover trial, 62 overweight adults were randomly assigned to a Mediterranean or vegan diet for a 16-week period. Body weight, plasma lipids, blood pressure, and body composition (dual X-ray absorptiometry) were measured. Secondary measures included insulin resistance (Homeostasis Model Assessment, HOMA-IR), oral glucose insulin sensitivity (OGIS), and predicted insulin sensitivity (PREDIM) indices. Thereafter, participants were asked to return to their baseline diets for 4 weeks, after which they began the opposite diet for 16 weeks. The same parameters were measured before and after this 2nd 16-week period. Results: Overall net weight changes were 0.0 (Mediterranean) and −6.0 kg (vegan), (treatment effect −6.0 kg [95% CI −7.5 to −4.5]; p < 0.001). HOMA-IR decreased and OGIS increased on the vegan diet with no significant change on the Mediterranean diet (treatment effect −0.7 [95% CI, −1.8 to +0.4]; p = 0.21; and +35.8 mL/min/m2 [95% CI, +13.2 to +58.3]; p = 0.003, respectively). PREDIM did not change significantly in either group. Among participants with no medication changes, total and LDL-cholesterol decreased 18.7 mg/dL (0.5 mmol/L) and 15.3 mg/dL (0.4 mmol/L), respectively, on the vegan diet, compared with no significant change on the Mediterranean diet (treatment effect −15.6 [-24.6 to −6.6]; p = 0.001 and −14.8 [-23.5 to −6.2]; p = 0.001, respectively); systolic and diastolic blood pressure decreased 9.3 and 7.3 mmHg on the Mediterranean diet, compared with 3.4 and 4.1 mmHg on the vegan diet (treatment effect +5.9 [95% CI +1.0 to +10.9]; p = 0.02; and +1.8 [95% CI −4.6 to +8.1]; p = 0.58, respectively). Conclusions: A low-fat vegan diet improved body weight, lipid concentrations, and insulin sensitivity, both from baseline and compared with a Mediterranean diet. Blood pressure decreased on both diets, more on the Mediterranean diet. Clinical trial registration: ClinicalTrials.gov number, NCT03698955 https://clinicaltrials.gov/ct2/show/NCT03698955?term=NCT03698955&draw=2&rank=1

Mifepristone Improves Adipose Tissue Insulin Sensitivity in Insulin Resistant Individuals.

Increased tissue cortisol availability has been implicated in abnormal glucose and fat metabolism in patients with obesity, metabolic syndrome, and type 2 diabetes (T2DM). Our objective was to evaluate whether blockade of glucocorticoid receptor (GR) with mifepristone ameliorates insulin resistance (IR) in overweight/obese subjects with glucose intolerance. We conducted a randomized, double-blinded, placebo-controlled, crossover study in overweight/obese individuals (n = 16, 44% female) with prediabetes or mild T2DM but not clinical hypercortisolism. Mifepristone (50 mg every 6 h) or placebo was administered for 9 days, followed by crossover to the other treatment arm after a washout period of 6 to 8weeks. At baseline and following each treatment, oral glucose tolerance test (OGTT) and frequently sampled intravenous glucose tolerance test (FSIVGTT) were performed. Insulin sensitivity was measured using FSIVGTT [primary outcome: insulin sensitivity index (SI)] and OGTT [Matsuda index (MI) and oral glucose insulin sensitivity index (OGIS)]. Hepatic and adipose insulin resistance were assessed using hepatic insulin resistance index (HIRI), and adipose tissue insulin sensitivity index (Adipo-SI) and adipo-IR, derived from the FSIVGTT. Mifepristone administration did not alter whole-body glucose disposal indices of insulin sensitivity (SI, MI, and OGIS). GR blockade significantly improved Adipo-SI (61.7 ± 32.9 vs 42.8 ± 23.9; P = 0.002) and reduced adipo-IR (49.9 ± 45.9 vs 65.5 ± 43.8; P = 0.004), and HIRI (50.2 ± 38.7 vs 70.0 ± 44.3; P = 0.08). Mifepristone increased insulin clearance but did not affect insulin secretion or β-cell glucose sensitivity. Short-term mifepristone administration improves adipose and hepatic insulin sensitivity among obese individuals with hyperglycemia without hypercortisolism.

Impact of pre-exercise feeding status on metabolic adaptations to endurance-type exercise training.

Nutrition and exercise metabolism are vibrant physiological fields, yet at times it feels as if greater progress could be made by better integrating these disciplines. Exercise is advocated for improving metabolic health, in part by increasing peripheral insulin sensitivity and glycaemic control. However, when a modest-to-high carbohydrate load is consumed before and/or during each exercise bout within a training programme, increases in oral glucose insulin sensitivity can be blunted in both men of a healthy weight and those with overweight/obesity. Exercise training-induced adaptation in the energy sensing AMP-activated protein kinase (AMPK) and the insulin-sensitive glucose transporter GLUT4 protein levels are sensitive to pre-exercise feeding status in both healthy individuals and individuals classified as overweight or obese. Increased lipid oxidation may, in part, explain the enhanced adaptive responses to exercise training performed before (i.e. fasted-state exercise) versus after nutrient ingestion. Evidence in individuals with type 2 diabetes currently shows no effect of altering nutrient-exercise timing for measured markers of metabolic health, or greater reductions in glycated haemoglobin (HbA1c) concentrations with exercise performed after versus before nutrient provision. Since the metabolic inflexibility associated with type 2 diabetes diminishes differences in lipid oxidation between the fasted and fed states, it is plausible that pre-exercise feeding status does not alter adaptations to exercise when metabolic flexibility is already compromised. Current evidence suggests restricting carbohydrate intake before and during exercise can enhance some health benefits of exercise, but in order to establish clinical guidelines, further research is needed with hard outcomes and different populations.

Effect of Vitamin D3 Supplementation on Insulin Sensitivity in Prediabetes With Hypovitaminosis D: A Randomized Placebo-Controlled Trial.

IntroductionThe interplay of vitamin D and glucose metabolism is an area of ongoing research. The need for vitamin D supplementation trials in individuals with prediabetes and hypovitaminosis D has been stressed by earlier research studies. The objective of this study was to assess the effect of vitamin D3 supplementation on oral glucose insulin sensitivity (OGIS) index in patients with prediabetes and hypovitaminosis D.Methods We enrolled 120 individuals with prediabetes (ADA definition) and hypovitaminosis D (vitamin D < 30 ng/mL) and randomized them into the vitamin D supplementation (60,000 IU weekly) group and the placebo group. Primary outcome measure (i.e., 2-hour OGIS index) and secondary outcome measures (i.e., fasting and postprandial blood glucose, glycosylated hemoglobin, body mass index, and insulin sensitivity indices, i.e., quantitative insulin sensitivity check index [QUICKI] and homeostatic model assessment for insulin resistance [HOMA-IR]) were analyzed for change with the 12 weeks of intervention.Results A total of 52 subjects in the vitamin D group and 49 in the placebo group completed the study. Serum vitamin D levels (10.11 ± 2.73 to 52.2 ± 13.14 ng/mL; p < 0.0001) and OGIS index (376.4 ± 39.7 to 391.7 ± 40.7 mL/min/m2; p = 0.011) increased significantly on per-protocol analysis in the vitamin D group. There was no significant change observed in vitamin D levels and OGIS index in the placebo group. Between-group comparison showed a rise in OGIS index (15.3 ± 47.1 mL/min/m2) in the vitamin D group and decrease in OGIS index (-10.4 ± 44.7 mL/min/m2) in the placebo group, and the difference was statistically significant (p = 0.0029). The inter-group comparison showed relative fall in fasting glucose levels in the vitamin D group, with no significant change observed in the other secondary outcome measures.ConclusionsThe correction of hypovitaminosis D in subjects with prediabetes led to improved insulin sensitivity as assessed by OGIS index at 120 minutes, signifying the role of vitamin D in glucose homeostasis.