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OBJECTIVE: Alleviation of unrecognized glucotoxicity, with resultant recovery of β-cell function, could amplify the glucose-lowering effect of pharmacotherapy and contribute to the variable therapeutic response observed among patients with type 2 diabetes (T2D). However, clinical evidence supporting this concept is lacking. Short-term intensive insulin therapy (IIT) can ameliorate glucotoxicity and improve β-cell function in early T2D. Thus, for evidence of recovery of glucotoxicity-associated β-cell dysfunction, we sought to determine whether there exists a baseline fasting glucose threshold above which the post-IIT improvement in both β-cell function and glycemia is amplified. RESEARCH DESIGN AND METHODS: IIT (glargine, lispro) was administered for 3 weeks to 108 adults with T2D (mean duration 1.8 ± 1.4 years). Oral glucose tolerance tests before and after IIT enabled assessment of β-cell function by Insulin Secretion-Sensitivity Index-2 and insulinogenic index/HOMA-insulin resistance. For each level of baseline fasting glycemia from 6.0 to 10.5 mmol/L, we modeled the difference in IIT-induced percentage change in β-cell function between those at/above the indicated glucose level and those below it. RESULTS: The relationship between baseline fasting glucose and the differential change in β-cell function was nonlinear. Instead, this relationship was best fit by a cubic regression model with inflection (amplification) at fasting glucose at 9.3 mmol/L. Moreover, baseline fasting glucose at 9.3 mmol/L also identified the inflection point at which nonlinear reductions in fasting glucose and 2-h glucose, respectively, were both amplified. CONCLUSIONS: The respective improvements in β-cell function and glycemia in response to short-term IIT are amplified in those in whom baseline fasting glucose exceeds a defined threshold, consistent with reversal of glucotoxicity. [ABSTRACT FROM AUTHOR]

The maternal-offspring relationship, such as whether fetal sex influences maternal health, is essential to explore to advance prenatal and maternal health. While associations exist between fetal sex and maternal health outcomes, it is unclear whether these reflect a causal relationship. To demonstrate that fetal sex can be randomly assigned to test the causal effect of fetal sex on maternal outcomes. Holstein dairy cows were stratified and randomized using sealed opaque envelopes to be artificially inseminated with either X- or Y-sorted bull semen until 40 cows became pregnant. Monthly body weight measurements were recorded, and an intravenous glucose tolerance test was performed 30 days before the expected calving day. The primary outcome was insulin area under the curve (AUC), and secondary outcomes were clearance rate, half-life, and AUC for glucose, insulin, and non-esterified fatty acid concentrations. An intention-to-treat (ITT) approach using multiple imputation was employed for primary analysis, and an as-treated (AT) approach was used for secondary analysis. We demonstrated that we could successfully randomize the assignment of fetal sex to dams and test for causal effects of fetal sex on glucoregulatory outcomes using dairy cows as a model. Insulin AUC was not statistically different between groups (ITT p = 0.857, AT p = 0.874), and other outcomes were also not statistically different (p > 0.05). We demonstrated that causal effects of fetal sex on maternal outcomes can be causally tested in dairy cows. Our study did not provide statistical evidence to support an effect of fetal sex on maternal glucose-related outcomes. • Dairy cows are a suitable model to test the relationship between fetal sex and maternal health outcomes. • We demonstrate that fetal sex can be randomized using sex-sorted semen to assess causality. • Our results do not provide statistical evidence to support an effect of fetal sex on maternal glucoregulatory outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Hyperglycemia is affected by lifestyle and genetic factors. We investigated if dietary patterns associate with glycemia in individuals with high or low genetic risk for type 2 diabetes (T2D). Methods: Men (n = 1577, 51–81 years) without T2D from the Metabolic Syndrome in Men (METSIM) cohort filled a food-frequency questionnaire and participated in a 2-hour oral glucose tolerance test. Polygenetic risk score (PRS) including 76 genetic variants was used to stratify participants into low or high T2D risk groups. We established two data-driven dietary patterns, termed healthy and unhealthy, and investigated their association with plasma glucose concentrations and hyperglycemia risk. Results: Healthy dietary pattern was associated with lower fasting and 2-hour plasma glucose, glucose area under the curve, and better insulin sensitivity (Matsuda insulin sensitivity index) and insulin secretion (disposition index) in unadjusted and adjusted models, whereas the unhealthy pattern was not. No interaction was observed between the patterns and PRS on glycemic measures. Healthy dietary pattern was negatively associated with the risk for hyperglycemia in an adjusted model (OR 0.69, 95% CI 0.51–0.95, in the highest tertile), whereas unhealthy pattern was not (OR 1.08, 95% CI 0.79–1.47, in the highest tertile). No interaction was found between diet and PRS on the risk for hyperglycemia (p = 0.69 for healthy diet, p = 0.54 for unhealthy diet). Conclusion: Our findings suggest that healthy diet is associated with lower glucose concentrations and lower risk for hyperglycemia in men with no interaction with the genetic risk. [ABSTRACT FROM AUTHOR]

Our purpose was to determine how age affects metabolic flexibility and underlying glucose kinetics in healthy young and older adults. Therefore, glucose and lactate tracers along with pulmonary gas exchange data were used to determine glucose kinetics and respiratory exchange ratios [RER = carbon dioxide production (V̇ co 2)/oxygen consumption (V̇ o 2)] during a 2-h 75-g oral glucose tolerance test (OGTT). After an 12-h overnight fast, 28 participants, 15 young (21–35 yr; 7 men and 8 women) and 13 older (60–80 yr; 7 men and 6 women), received venous primed-continuous infusions of [6,6-2H]glucose and [3-13C]lactate with a H 13 C O 3 − bolus. After a 90-min metabolic stabilization and tracer equilibration period, volunteers underwent an OGTT. Arterialized glucose concentrations ([glucose]) started to rise 15 min post glucose consumption, peaked at 60 min, and remained elevated. As assessed by rates of appearance (Ra) and disposal (Rd) and metabolic clearance rate (MCR), glucose kinetics were suppressed in older compared to young individuals. As well, unlike in young individuals, fractional gluconeogenesis (fGNG) remained elevated in the older population after the oral glucose challenge. Finally, there were no differences in 12-h fasting baseline or peak RER values following an oral glucose challenge in older compared to young men and women, making RER an incomplete measure of metabolic flexibility in the volunteers we evaluated. Our study revealed that glucose kinetics are significantly altered in a healthy aged population after a glucose challenge. Furthermore, those physiological deficits are not detected from changes in RER during an OGTT. NEW & NOTEWORTHY: To determine metabolic flexibility in response to an OGTT, we studied healthy young and older men and women to determine glucose kinetics and changes in RER. Compared to young subjects, glucose kinetics were suppressed in older healthy individuals during an OGTT. Surprisingly, the age-related changes in glucose flux were not reflected in RER measurements; thus, RER measurements do not give a complete view of metabolic flexibility in healthy individuals. [ABSTRACT FROM AUTHOR]

Our previous study revealed that over 50% of recipients with pretransplant impaired glucose tolerance (IGT) improved to normal glucose tolerance after kidney transplantation. However, the mechanism is unclear. We aimed to investigate whether the changes in glucose tolerance are associated with β-cell function and insulin resistance in Japanese kidney transplant recipients with pretransplant IGT. Of the 265 recipients who received kidney transplantation, 54 with pretransplant IGT were included. We divided the recipients into improvement and nonimprovement groups according to the change in the area under the curve for glucose obtained from the oral glucose tolerance test (OGTT). β-Cell function was estimated by the insulin secretion sensitivity index-2 (ISSI-2) and the disposition index (DI). Insulin resistance was estimated by the Matsuda index (MI) and the homeostasis model assessment of insulin resistance (HOMA-IR). ISSI-2 and DI increased significantly after transplantation in the improved group (P < 0.01, P < 0.05, respectively), but not in the nonimproved group. ΔISSI-2 and ΔDI were significantly and positively associated with pretransplant 60-min OGTT plasma glucose levels (both P < 0.01). There were no differences in MI or HOMA-IR between these two groups after transplantation. In recipients not on pretransplant dialysis, a significant negative association was found between Δblood urea nitrogen (BUN) and ΔDI (correlation coefficient = −0.48, P < 0.05). In pretransplant IGT recipients, improvements in glucose tolerance after kidney transplantation were linked to improvements in β-cell function. The higher the 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Improvements in BUN after transplantation were associated with improvements in β-cell function. NEW & NOTEWORTHY: In recipients with pretransplant impaired glucose tolerance, improvements in glucose tolerance after kidney transplantation were associated with improvements in β-cell function. The higher the pretransplant 60-min OGTT plasma glucose level, the greater the improvement in posttransplant β-cell function. Although glucose tolerance is known to be impaired after transplantation, the present study focused on the reason for the improvement in glucose tolerance rather than the development of posttransplantation diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background Nephrin is a transmembrane protein with well-established signaling roles in kidney podocytes, and a smaller set of secretory functions in pancreatic β cells are implicated in diabetes. Nephrin signaling is mediated in part through its 3 cytoplasmic YDxV motifs, which can be tyrosine phosphorylated by high glucose and β cell injuries. Although in vitro studies demonstrate these phosphorylated motifs can regulate β cell vesicle trafficking and insulin release, in vivo evidence of their role in this cell type remains to be determined. Methods To further explore the role of nephrin YDxV phosphorylation in β cells, we used a mouse line with tyrosine to phenylalanine substitutions at each YDxV motif (nephrin-Y3F) to inhibit phosphorylation. We assessed islet function via primary islet glucose-stimulated insulin secretion assays and oral glucose tolerance tests. Results Nephrin-Y3F mice successfully developed pancreatic endocrine and exocrine tissues with minimal structural differences. Unexpectedly, male and female nephrin-Y3F mice showed elevated insulin secretion, with a stronger increase observed in male mice. At 8 months of age, no differences in glucose tolerance were observed between wild-type (WT) and nephrin-Y3F mice. However, aged nephrin-Y3F mice (16 months of age) demonstrated more rapid glucose clearance compared to WT controls. Conclusion Taken together, loss of nephrin YDxV phosphorylation does not alter baseline islet function. Instead, our data suggest a mechanism linking impaired nephrin YDxV phosphorylation to improved islet secretory ability with age. Targeting nephrin phosphorylation could provide novel therapeutic opportunities to improve β cell function. [ABSTRACT FROM AUTHOR]

Background: The association between years of non-diabetes status after diagnosis of impaired glucose tolerance (IGT) and the risk of long-term death and cardiovascular outcomes needed to be clarified. Methods and findings: In this post hoc analysis, we included 540 individuals with IGT who participated in the original Da Qing Diabetes Prevention Study (DQDPS). In the DQDPS, all participants were diagnosed with IGT by a 75 g oral glucose tolerance test and randomized to intervention or control groups with a 6-year lifestyle intervention trial. After the completion of the trial, death, cardiovascular events, and microvascular complications were monitored over a 30-year follow-up. In this post hoc analysis, the Cox analysis assessed the extended risk of these outcomes in individuals who either remained non-diabetes status or progressed to diabetes at the end of 2, 4, and 6 years after diagnosis of IGT. In all participants, the difference in the cumulative incidence rate of the outcomes between the diabetes and non-diabetes group gradually increased over 30 years. Compared with the diabetes group, a significantly lower risk of all-cause death (hazard ratio [HR]: 0.74; 95% confidence interval [CI]: 0.57 to 0.97, p = 0.026), cardiovascular events (HR: 0.63; 95% CI: 0.49 to 0.82, p < 0.001), and microvascular complications (HR: 0.62; 95% CI: 0.45 to 0.86, p = 0.004) first emerged in individuals who remained non-diabetes at the 4 years visit, whereas the significant risk reduction in cardiovascular death was first observed at the end of 6 years (HR: 0.56; 95% CI: 0.39 to 0.81, p = 0.002) after adjustment for age, sex, smoking status, BMI, systolic blood pressure, blood glucose, total cholesterol, intervention, and medications (including insulin plus oral hypoglycaemics, antihypertensives, and lipid-lowering agents). The results in the original intervention group alone were similar to the whole group. The main limitations of our study are the limited number of participants and the sole ethnicity of the Chinese population. Conclusions: In this study, we observed that maintaining several years of non-diabetes status after IGT diagnosis was associated with a significant reduction in long-term risk of death and vascular complications, and for most of these outcomes, maintaining at least 4 years of non-diabetes status may be needed to achieve a significant risk reduction. Xin Qian and co-authors explore how the duration of a lifestyle intervention for diabetes prevention influences length of time spent in non-diabetes status after a diagnosis of impaired glucose tolerance and, the impact on long term outcomes. Author summary: Why was this study done?: Lifestyle intervention can reduce or delay the incidence of diabetes in people with impaired glucose tolerance (IGT). Major lifestyle intervention trials have shown that lifestyle intervention can improve microvascular complications and some cardiovascular risk factors. To the best of our knowledge, no study has reported the relationship between long-term outcomes and duration of maintaining non-diabetes status after a diagnosis of IGT which may be influenced by the duration of lifestyle intervention, after IGT diagnosis. What did the researchers do and find?: We conducted a post hoc analysis of the China Da Qing Diabetes Prevention Study (DQDPS), a 6-year lifestyle intervention trial in people with IGT. In this study, we included 540 individuals with IGT and assessed the long-term risk of mortality, macro- and microvascular diseases between those who remained non-diabetes status or not at the end of 2, 4, and 6 years visit after diagnosis of IGT. Our analyses showed that individuals who remained non-diabetic for at least 4 years after being diagnosed with IGT had a significantly lower risk of all-cause death, cardiovascular events, and microvascular complications compared with those who progressed to diabetes. However, this effect was not observed in individuals who remained non-diabetic for a shorter period. What do these findings mean?: This post hoc analysis suggests that a longer duration of non-diabetes status in those with IGT has beneficial health outcomes and reduces mortality. The implementation of effective interventions targeting those with IGT should be considered as part of preventative management for diabetes and diabetes-related vascular complications. The main limitations of this study are the limited number of participants and the sole ethnicity of the Chinese population. [ABSTRACT FROM AUTHOR]

Exercise has long been known for its beneficial effects on insulin sensitivity (IS) and glucose handling with both moderate-intensity continuous (MIC) exercise and resistance exercise (RE) inducing beneficial effects. In recent years, low-load, high-repetition (LLHR) RE has emerged as a strategy to increase muscle mass and strength to levels similar to traditional RE; however, the effects of LLHR RE on glucose handling has yet to be investigated. The purpose of this trial was to compare the acute effects of LLHR RE to MIC exercise on post-exercise glycemic control and insulin sensitivity in males and females. Twenty-four (n = 12/sex) participants completed acute bouts of MIC exercise (30 min at 65% V̇O₂peak) and LLHR (3 circuits, 6 exercises/circuit, 25–35 repetitions/exercise/circuit) matched for time with muscle biopsies immediately pre and post exercise and an oral glucose tolerance test (OGTT) 90 min following exercise. Blood glucose concentrations (p = 0.002, ηp2 = 0.37), glucose AUC (p = 0.002, ηp2 = 0.35) and max glucose concentration (p = 0.003, ηp2 = 0.34) were lower during the post exercise OGTT following LLHR RE compared to MIC exercise. There was a main effect of trial on TBC1D1 Ser237 phosphorylation (p = 0.04, ηp2 = 0.19) such that it was greater following MIC exercise compared to LLHR RE. Furthermore, phosphorylated ACC Ser79 increased following MIC exercise with no change following LLHR RE (p < 0.001, ηp2 = 0.50). Phosphorylation of PTEN Ser380 was greater in males than females during LLHR RE (p = 0.01, ηp2 = 0.27). These findings suggest that LLHR RE is a feasible exercise modality to improve post-exercise glycemic control in both males and females. Trial registration number: NCT06217679. [ABSTRACT FROM AUTHOR]

• Abnormal glucose tolerance affects every third child with cystic fibrosis. • Prediabetes frequently presents before 10 years of age in cystic fibrosis. • Regular screening for abnormal glucose tolerance should be started at 5 years of age. • Abnormal glucose tolerance affects every second adult with cystic fibrosis. Despite translational evidences suggesting that cystic fibrosis-related abnormal glucose tolerance (CF-related AGT) may begin early in life and is known to be associated with increased morbidity and mortality, current guidelines recommend screening for AGT only from 10 years of age, thus missing the opportunity for early detection and intervention. A systematic review and meta-analysis (PROSPERO number: CRD42021282516) was conducted on studies that reported data on the prevalence of AGT or its subtypes in CF populations. Pooled proportions, risk, and odds ratios with 95 % confidence intervals (CI) were calculated. One-stage dose-response random-effect meta-analysis was used to assess the effect of age on CF-related diabetes (CFRD). The quantitative analysis included 457 studies and data from 520,544 patients. Every third child with CF (chwCF) (0.31 [95 % CI 0.25–0.37]) and every second adult with CF (awCF) (0.51 [95 % CI 0.45–0.57]) were affected by AGT. Even in the 5–10 years of age subgroup, the proportion of AGT was 0.42 [95 % CI 0.34–0.51]. The prevalence of prediabetes remained unchanged (impaired glucose tolerance in chwCF:0.14 [95 % CI 0.10–0.18]) vs. awCF:0.19 [95 % CI 0.14–0.25]), whereas the proportion of CFRD increased with age (0–5: 0.005 [95 % CI 0.0001–0.15]; 5–10: 0.05 [95 % CI 0.01–0.27]; 10–18: 0.11 [95 % CI 0.08–0.14]; >18 years of age: 0.27 [95 % CI 0.24–0.30]). CF-related AGT is common under 10 years of age. Our study suggests considering earlier AGT screening, starting from 5 years of age. This highlights the imperative for additional research for guideline adjustments and provides the opportunity for early intervention. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction: Diabetes mellitus is a clinical syndrome characterized by hyperglycemia due to absolute or relative deficiency of insulin. In the oral cavity, yeasts commonly colonize the tongue, palate, and buccal mucosa. Aside from oral mucosa, recent research have revealed the existence of C. albicans in other oral sites such as root canal, including persistent infection, carious lesions, and periodontal pockets.[5] The main aim of the study is to evaluate and compare Candidal colonization and species variation in healthy individuals and Diabetic patients. Material and Methods: Study includes 60 samples which are divided into Group -I consist of 30 Diabetic patients & Group II consists of 30 healthy individuals. Blood samples were collected to estimate the glucose levels using Glucose Tolerance Test & HbA1C. Saliva Sample was collected to estimate the candida using VITEK_2 Procedure. The absorbance values were measured on a digital calorimeter for Glucose Tolerance Test & HbA1C levels using the standard protocol. Results: Statistical Analysis was done using SPS software. Anova test & Paired t -test were done to estimate the comparison of Candidal positivity to HbA1C and VITEK_2 Procedure showed a mean of 97.33 and SD of 11.02 and with that of HbA1C, showed a mean of 4.93 and SD of 1.00. Comparison of study & control groups with VITEK2 status showed (46%) Candida albicans, followed by (16.67%) Candida famata and (10%) Candida tropicalis. Conclusion: The patients with diabetes mellitus are at a higher risk of developing oral Candidiasis. These members of the normal flora probably acquire invasiveness and become pathogenic leading to change in disease progression and develop resistance to the existing drug regime. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) is a non-invasive indicator of the activity of the autonomic nervous system, which regulates many physiological functions including metabolism. The purpose of this study was to quantify the relationship between resting markers of HRV and oral glucose tolerance test (OGTT) response. Eighteen healthy individuals (10 males, 8 females, (23.8±2.9 years) underwent a 10-minute resting HRV recording. The final five minutes were evaluated via Kubios HRV Standard for: root mean square of successive differences (RMSSD), standard deviation of normal-to-normal sinus beats (SDNN), high frequency (HF), and low frequency (LF). A standard 2-hour OGTT was then administered. Glucose was measured via finger stick before, 30-minutes post, 1-hour post, and 2-hours post OGTT. Pearson correlations demonstrated that RMSSD, SDNN, HF and LF were strongly correlated to fasting blood glucose (FBG) for the group (p<0.05) but not for glucose area under the curve (AUC). When analyzed by sex, only males demonstrated significant correlations between AUC and RMSSD, SDNN, and LF (p<0.05). An independent samples t-test revealed no sex differences for FBG, AUC, RMSSD, SDNN, HF and LF. These findings provide new and interesting insights into the relationship of autonomic activity and glucose uptake, highlighting sex-based relationships. [ABSTRACT FROM AUTHOR]

The postprandial glucose response is an independent risk factor for type 2 diabetes. Observationally, early glucose response after an oral glucose challenge has been linked to intestinal glucose absorption, largely influenced by the expression of sodium–glucose cotransporter 1 (SGLT1). This study uses Mendelian randomization (MR) to estimate the causal effect of intestinal SGLT1 expression on early glucose response. Involving 1,547 subjects with class II/III obesity from the Atlas Biologique de l'Obésité Sévère cohort, the study uses SGLT1 genotyping, oral glucose tolerance tests, and jejunal biopsies to measure SGLT1 expression. A loss-of-function SGLT1 haplotype serves as the instrumental variable, with intestinal SGLT1 expression as the exposure and the change in 30-min postload glycemia from fasting glycemia (Δ30 glucose) as the outcome. Results show that 12.8% of the 1,342 genotyped patients carried the SGLT1 loss-of-function haplotype, associated with a mean Δ30 glucose reduction of −0.41 mmol/L and a significant decrease in intestinal SGLT1 expression. The observational study links a 1-SD decrease in SGLT1 expression to a Δ30 glucose reduction of −0.097 mmol/L. MR analysis parallels these findings, associating a statistically significant reduction in genetically instrumented intestinal SGLT1 expression with a Δ30 glucose decrease of −0.353. In conclusion, the MR analysis provides genetic evidence that reducing intestinal SGLT1 expression causally lowers early postload glucose response. This finding has a potential translational impact on managing early glucose response to prevent or treat type 2 diabetes Article Highlights: Loss-of-function variant of SGLT1 is associated with reduced intestinal SGLT1 expression and early postload glucose response. Mendelian randomization supports the causal relationship between intestinal glucose absorption and postprandial glucose. Modulating intestinal SGLT1 expression/function is a promising avenue for the prevention and treatment of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Metformin has attracted increasing interest for its potential benefits in extending healthspan and longevity. This study examined the effects of early-life metformin treatment on the development and metabolism of C57BL/6 J (B6) mice, with metformin administered to juvenile mice from 15 to 56 days of age. Metformin treatment led to decreased body weight in both sexes (P < 0.05, t-test). At 9 weeks of age, mice were euthanized and organ weights were recorded. The relative weight of retroperitoneal fat was decreased in females, while relative weights of perigonadal and retroperitoneal fat were decreased, and relative liver weight was increased in males (P < 0.05, t-test). Glucose and insulin tolerance tests (GTT and ITT) were conducted at the age of 7 weeks. ANOVA revealed a significant impairment in insulin sensitivity by the treatment, and a significantly interactive effect on glucose tolerance between sex and treatment, underscoring a disparity in GTT between sexes in response to the treatment. Metformin treatment reduced circulating insulin levels in fasting and non-fasting conditions for male mice, with no significant alterations observed in female mice. qRT-PCR analysis of glucose metabolism-related genes (Akt2, Glut2, Glut4, Irs1, Nrip1, Pi3k, Pi3kca, Pkca) in the liver and skeletal muscle reveals metformin-induced sex- and organ-specific effects on gene expression. Comparison with previous studies in heterogeneous UM-HET3 mice receiving the same treatment suggests that genetic differences may contribute to variability in the effects of metformin treatment on development and metabolism. These findings indicate that early-life metformin treatment affects development and metabolism in both sex- and genetics-dependent manners. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM), a chronic condition leading to glucose intolerance during pregnancy, is common in low- and middle-income countries, posing health risks to both the mother and fetus. Limited studies have been done in Ethiopia, especially using WHO's 2013 universal screening criteria. Therefore, this study aimed to evaluate the risk factors linked to GDM in women attending antenatal (ANC) clinics in Hawassa town public health institutions, located in the Sidama regional state of Ethiopia. Methods: An Unmatched case-control study was carried out in Ethiopia's Sidama Region from April 1st to June 10th, 2023, involving 510 pregnant women. The Oral Glucose Tolerance Test (OGTT) was utilized for universal screening and diagnosing GDM based on the updated 2013 WHO diagnostic criteria. Data analysis included descriptive and analytical statistics, with variables having p-values below 0.1 deemed suitable for bivariate analysis. Statistical significance was assessed using the adjusted odds ratio (AOR) with a 95% confidence interval and a p-value < 0.05. Results: The study involved 633 participants (255 cases and 378 controls), resulting in a 100% response rate, with women having an average age of 29.03 years.Variables such as: age at first conception (AOR=0.97, P=0.01, 95% CI (0.95,0.99)), urban residency (AOR=1.66, P< 0.01, 95% CI(01.14,2.40)), widowed marital status (AOR=0.30, P=0.02, 95% CI (0.30,0.90)), parity (AOR=1.10, P< 0.01, 95% CI (1.03,1.17)), history of stillbirth (AOR=1.15, P=0.03, 95% CI(1.04,2.30)), and previous cesarean section (AOR=1.86, P=0.01, 95% CI (1.13,2.66)) were identified as independent factors associated with GDM. Conclusion: The study concluded that factors like age at first conception, place of residence, marital status, parity, history of Caesarian section, and stillbirth were independently associated with GDM. Surprisingly, upper arm circumference (MUAC), a proxy for pre-gestational BMI, was not identified as a risk factor for GDM. It is recommended that healthcare providers conduct comprehensive GDM risk assessments in pregnant women to identify and address risk factors, and propose specific screening and intervention strategies. [ABSTRACT FROM AUTHOR]

The article discusses a study which compared continuous positive airway pressure (CPAP) treatment with nasal dilator strip (NDS) control in pregnant individuals with gestational diabetes mellitus (GDM). Topics include assessment of adherence to CPAP by downloading CPAP usage reports every two weeks, analysis of glucose profiles, and primary analysis of CGM data using multiple imputation.

Aims: This study aimed to establish a decisive threshold for the Glucose Tolerance peak (GTp) parameter in diagnosing Gestational Diabetes Mellitus (GDM) and to assess its diagnostic efficacy in comparison with other commonly employed indexes in clinical practice. Materials and methods: Conducted as a prospective observational cohort, the study enrolled 92 pregnant women between 24–28 weeks of gestation, who underwent an Oral glucose Tolerance Test (OGTT) 100 gr. following a positive O'Sullivan screening at La Paz University Hospital. An additional 30-min sample was incorporated to assess the insulin response dynamics during hyperglycaemia. Basal indices and those derived from the OGTT 100 gr. test were computed. Receiver Operating Characteristic (ROC) curves were utilized to determine the optimal cut-off points for the indexes derived from the OGTT. Informed written consent was obtained from all participants. Results: Significantly greater glucose tolerance, as indicated by GTp, was observed in the Non-Gestational Diabetes (NTG) pregnant group (p < 0.01). The GTp emerged as the parameter with the highest positive predictive value for GDM diagnosis. A cut-off of < 0.36 demonstrated 100% specificity and 75% sensitivity in diagnosing GDM. Conclusions: GTp, an index derived exclusively from the OGTT peak glycaemia, proves valuable in confirming the presence of GDM. The GTp could be used to confirm the presence of GDM under necessity of a second OGTT as test confirmation in pregnant woman. A cut-off of < 0. 36 has a specificity of 100% and a sensitivity of 75% for the diagnosis of GDM. Highlights: The correlation between the GT peak and the Insulin resistance and sensitivity indixes included in the study was evaluated. It's obtained that the GTp is the parameter with the highest positive predictive value for the diagnosis of GDM. A cut-off of < 0. 36 has a specificity of 100% and a sensitivity of 75% for the diagnosis of GDM. The GTp could be used to confirm the presence of GDM under necessity of a second OGTT or test confirmation in pregnant woman. [ABSTRACT FROM AUTHOR]

Introduction The German Diabetes Association recommends using sampling tubes with citrate and fluoride additives to diagnose diabetes by oral glucose tolerance test to inhibit glycolysis. The effect of different tubes on measurement results was assessed. Materials and Methods In a first study, an oral glucose tolerance test was performed on 41 participants without anamnestically known diabetes. Venous blood was sampled in two different tubes with citrate/fluoride additives from different manufacturers and one with only lithium-heparin additive. A second study with 42 participants was performed to verify the initial results with an adapted design, in which a third tube with citrate buffer was used, and glucose measurements were performed on two additional devices of another analyser model. Samples were centrifuged either immediately (<5 min incubation time) or after 20 min or 4 h. All glucose measurements were performed in plasma. Glucose concentrations in lithium-heparin tubes with<5 min incubation time served as baseline concentrations. Results In the first study, glucose concentrations in one of the citrate/fluoride tubes were similar to the baseline. In the other citrate/fluoride tube, markedly lower concentrations (approximately − 5 mg/dL (− 0.28 mmol/L)) were measured. This was reproduced in the verification study for the same analyser, but not with the other analyser model. Lithium-heparin tubes centrifuged after 20 and 240 min showed systematically lower glucose concentrations. Conclusions The results confirm that glycolysis can be effectively inhibited in citrate/fluoride-containing sampling tubes. However, glucose measurement results of one analyser showed a relevant negative bias in tubes containing liquid citrate buffer. [ABSTRACT FROM AUTHOR]

We investigated if a bout of exercise in a hot environment (HEAT) would reduce the postprandial hyperglycemia induced by glucose ingestion. The hypothesis was that HEAT stimulating carbohydrate oxidation and glycogen use would increase the disposal of an ingested glucose load [i.e., oral glucose tolerance test (OGTT); 75 g of glucose]. Separated by at least 1 wk, nine young healthy individuals underwent three trials after an overnight fast in a randomized order. Two trials included 50 min of pedaling at 58 ± 5% V̇ o 2max either in a thermoneutral (21 ± 1°C; NEUTRAL) or in a hot environment (33 ± 1°C; HEAT) eliciting similar energy expenditure (503 ± 101 kcal). These two trials were compared with a no-exercise trial (NO EXER). Twenty minutes after exercise (or rest), subjects underwent an OGTT, while carbohydrate oxidation (CHOxid, using indirect calorimetry) plasma blood glucose, insulin concentrations (i.e., [glucose], [insulin]), and double tracer glucose kinetics ([U-13C] glucose ingestion and [6,6-2H2] glucose infusion) were monitored for 120 min. At rest, [glucose], [insulin], and rates of appearance/disappearance of glucose in plasma (glucose Ra/Rd) were similar among trials. During exercise, heart rate, tympanic temperature, [glucose], glycogen oxidation, and total CHOxid were higher during HEAT than NEUTRAL (i.e., 149 ± 35 vs. 124 ± 31 µmol·kg−1·min−1, P = 0.010). However, during the following OGTT, glucose Rd was similar in HEAT and NEUTRAL trials (i.e., 25.1 ± 3.6 vs. 25.2 ± 5.3 µmol·kg−1·min−1, P = 0.981). Insulin sensitivity (i.e., ISIndexMATSUDA) only improved in NEUTRAL compared with NO EXER (10.1 ± 4.6 vs. 8.8 ± 3.7 au; P = 0.044). In summary, stimulating carbohydrate use with exercise in a hot environment does not improve postprandial plasma glucose disposal or insulin sensitivity in a subsequent OGTT. NEW & NOTEWORTHY: Exercise in the heat increases estimated muscle glycogen use. Reduced muscle glycogen after exercise in the heat could increase insulin-mediated glucose uptake during a subsequent oral glucose tolerance test (OGTT). However, plasma glucose kinetics are not improved during the OGTT in response to a bout of exercise in the heat, and insulin sensitivity worsens. Heat stress activates glucose counterregulatory hormones whose actions may linger during the OGTT, preventing increased glucose uptake. [ABSTRACT FROM AUTHOR]

Aim: Myo‐inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at‐risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo‐inositol‐containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. Methods: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo‐inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. Results: Higher 7‐week myo‐inositol, but not 28‐week myo‐inositol, associated with higher 1 h PG [βadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge μmol/L, p =.022] and 2 h PG [0.08 (0.03, 0.12), p =.001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7‐week myo‐inositol increase of 23.4 μmol/L with myo‐inositol supplementation. Higher 7‐week myo‐inositol associated with a lower 28‐week Stumvoll index (first phase), an approximation of insulin secretion [−0.08 (−0.15, −0.01), p =.020] but not with 28‐week Matsuda insulin sensitivity index. However, the clinical significance of a 7‐week myo‐inositol‐related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C‐peptide levels. In‐silico modelling found higher 28‐week myo‐inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7‐week myo‐inositol effects. Conclusion: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo‐inositol may slightly exacerbate later pregnancy post‐challenge glycaemia, indicating that the optimal timing for starting prenatal myo‐inositol supplementation needs further investigation. [ABSTRACT FROM AUTHOR]

The sweet taste receptor, TAS1R2-TAS1R3, is expressed in taste bud cells, where it conveys sweetness, and also in intestinal enteroendocrine cells, where it may facilitate glucose absorption and assimilation. In the present study, our objective was to determine whether TAS1R2-TAS1R3 influences glucose metabolism bidirectionally via hyperactivation with 5 mM sucralose (n = 12) and inhibition with 2 mM sodium lactisole (n = 10) in mixture with 75 g glucose loads during oral glucose tolerance tests (OGTTs) in healthy humans. Plasma glucose, insulin, and glucagon were measured before, during, and after OGTTs up to 120 minutes post-prandially. We also assessed individual participants' sweet taste responses to sucralose and their sensitivities to lactisole sweetness inhibition. The addition of sucralose to glucose elevated plasma insulin responses to the OGTT (F(1, 11) = 4.55, p = 0.056). Sucralose sweetness ratings were correlated with early increases in plasma glucose (R2 = 0.41, p<0.05), as well as increases in plasma insulin (R2 = 0.38, p<0.05) when sucralose was added to the OGTT (15 minute AUC). Sensitivity to lactisole sweetness inhibition was correlated with decreased plasma glucose (R2 = 0.84, p<0.01) when lactisole was added to the OGTT over the whole test (120 minute AUC). In summary, stimulation and inhibition of the TAS1R2-TAS1R3 receptor demonstrates that TAS1R2-TAS1R3 helps regulate glucose metabolism in humans and may have translational implications for metabolic disease risk. [ABSTRACT FROM AUTHOR]

• The 1-hour glucose in the 3 point OGTT, contributes only small numbers of GDM cases and a high number needed to screen (67 for 1 additional case in a selective high risk GDM screening strategy). • Omitting the 1 and/or 2-hour glucose measurements from the mid-trimester OGTT may reduce costs and burdens on pregnant women and the healthcare system, with only a marginal reduction in diagnostic yield. • The 2-hour and 1-hour glucose concentrations contributed only 7.4 % and 4.7 % to GDM diagnoses. The WHO 2013 guidelines recommend screening for gestational diabetes mellitus (GDM) by 3-point oral glucose tolerance test (OGTT). The objective of this retrospective cohort study was to evaluate GDM diagnosed by an isolated high glucose. We included pregnant women deemed at risk for GDM were offered GDM screening. We examined the records of 1939 consecutively screened pregnancies at two teaching hospitals in Amsterdam during 2016–2020. Using the WHO 2013 diagnostic criteria, we calculated the proportion of GDM cases diagnosed by isolated abnormal glucose values. Among those screened in our high risk cohort, GDM incidence was 31.5%. Of the GDM diagnoses, 57.0% were based on an isolated fasting glucose value, 30.9% based on multiple raised glucose measurements, 7.4% on an isolated raised 2-hour glucose and 4.7% on an isolated raised 1-hour glucose. For 1-hour glucose, the number needed to screen was 67 persons for one additional GDM case. The 1-hour glucose in the 3 point OGTT, as suggested by the WHO 2013 guidelines for GDM, contributes only small numbers of GDM cases and a high number needed to screen (67 for 1 additional case in a selective high risk GDM screening strategy), and is likely even less effective in universally screened populations. [ABSTRACT FROM AUTHOR]

Background: Previous studies showed that residents of higher elevations have lower glucose levels. Our objective in this study is to determine the basal and postprandial glucose levels in apparently healthy permanent residents of the miner population center of La Rinconada located 5100 meters (m) above sea level. Method: Forty male permanent residents of the Rinconada miner population center were studied. The oral glucose tolerance test was used to evaluate basal and postprandial glycemia levels at 1, 2, and 3 h. Results: The individuals had a mean age of 43.95 ± 8.54 years. Basal glycemia in subjects without excessive erythrocytosis (EE) was 73.3 ± 7.9 mg/dL, while levels in patients with EE were 57.98 ± 7.38 mg/dL. In the postprandial period, at 1 h after oral glucose overload, a mean value of 76.35 ± 13.53 mg/dL was observed in subjects with EE compared to 94.68 ± 9.98 mg/dL in subjects without EE. After 2 h, subjects with EE had a glycemia level of 72.91 ± 9.17 mg/dL EE compared to 90.73 ± 13.86 mg/dL without EE. At 3 h, the average glycemia level in subjects with EE was 70.77 ± 8.73 mg/dL compared to 87.79 ± 14.16 mg/dL in those without EE. Conclusion: These findings suggest that under hypoxic conditions, glycemia levels are lower in both subjects with and without EE, having obtained lower levels in subjects with EE in relation to those with normal values of Hb and Hct. The results of this study indicate that in the conditions of severe hypoxia, blood glucose levels are below the values considered normal for sea level. [ABSTRACT FROM AUTHOR]

Background: Mild hyperglycaemia is associated with increased birth weight but association with other neonatal outcomes is controversial. We aimed to study neonatal outcomes in untreated mild hyperglycaemia using different oral glucose tolerance test (OGTT) thresholds. Methods: This register-based study included all (n = 4,939) singleton pregnant women participating a 75 g 2-h OGTT in six delivery hospitals in Finland in 2009. Finnish diagnostic cut-offs for GDM were fasting ≥ 5.3, 1 h ≥ 10.0 or 2-h glucose ≥ 8.6 mmol/L. Women who did not meet these criteria but met the International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria (fasting 5.1–5.2 mmol/L and/or 2-h glucose 8.5 mmol/L, n = 509) or the National Institute for Health and Clinical Excellence (NICE) criteria (2-h glucose 7.8–8.5 mmol/L, n = 166) were considered as mild untreated hyperglycaemia. Women who met both the Finnish criteria and the IADPSG or the NICE criteria were considered as treated GDM groups (n = 1292 and n = 612, respectively). Controls were normoglycaemic according to all criteria (fasting glucose < 5.1 mmol/L, 1-h glucose < 10.0 mmol/L and 2-h glucose < 8.5 mmol/L, n = 3031). Untreated mild hyperglycemia groups were compared to controls and treated GDM groups. The primary outcome – a composite of adverse neonatal outcomes, including neonatal hypoglycaemia, hyperbilirubinaemia, birth trauma or perinatal mortality – was analysed using multivariate logistic regression. Results: The risk for the adverse neonatal outcome in untreated mild hyperglycemia was not increased compared to controls (adjusted odds ratio [aOR]: 1.01, 95% confidence interval [CI]: 0.71–1.44, using the IADPSG criteria; aOR: 1.05, 95% CI: 0.60–1.85, using the NICE criteria). The risk was lower compared to the treated IADPSG (aOR 0.38, 95% CI 0.27–0.53) or the treated NICE group (aOR 0.32, 95% CI 0.18–0.57). Discussion: The risk of adverse neonatal outcomes was not increased in mild untreated hyperglycaemia compared to normoglycaemic controls and was lower than in the treated GDM groups. The OGTT cut-offs of 5.3 mmol/L at fasting and 8.6 mmol/L at 2 h seem to sufficiently identify clinically relevant GDM, without excluding neonates with a risk of adverse outcomes. [ABSTRACT FROM AUTHOR]

Background: Hypothyroidism is associated with metabolic syndrome. Several studies have shown that hypothyroidism is linked to dysglycemia and dyslipidemia that leads to diabetes mellitus and atherosclerosis with clinical manifestations. Aim: To determine the relationship of dyslipidemia and dysglycemia with the thyroid status in patients with hypothyroidism. Methodology: 100 subjects were included, 50 hypothyroid patients and 50 controls were selected in the age group of 20-50yrs. the parameters determined were waist circumference, fasting serum glucose, oral glucose tolerance test, thyroid profile, lipid profile, fasting serum insulin, and HOMA-IR. Results: In this study it was found that hypothyroidism was associated with obesity. Waist circumference (p=0.004) was significantly increased in hypothyroid patients when compared to controls. The mean value of triglycerides in test group was 159.22 ± 19.88 mg/dl compared to the mean of the control group which was 143.14 ± 28.97 mg/dl and was highly significant (p<0.001). The mean value of LDL in test group was 184.26±24.75 mg/dl compared to the mean of the control group which was 148.08±41.57 mg/dl and was statistically significant p<0.001. The mean value of HDL in test group was 39.74±5.67 mg/dl compared to the mean of HDL in the control group which was 44.06±8.83 mg/dl and was statistically significant p=0.003. The mean of HOMA-IR in test group was 9.10 ± 3.73 when compared to the mean in the control group which was 4.95 ± 2.08 and was found to be statistically significant (p<0.001). TSH correlated positively with insulin (0.64) and HOMA-IR (0.69) and it was statistically significant p<0.001. Conclusion: Central obesity in hypothyroidism is well established in this study with elevated waist circumference. Hypercholesterolemia is a constant feature of hypothyroidism with elevated LDL-cholesterol and decreased level of HDL-cholesterol. Impaired glucose tolerance was found to be more prevalent in hypothyroid patients, they are also found to have elevated insulin resistance. Together impaired glucose tolerance and elevated insulin resistance imply that hypothyroid patients are more prone to develop type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed. [ABSTRACT FROM AUTHOR]

Purpose: Understanding factors that influence blood glucose levels in patients with type 2 diabetes mellitus (T2DM) is crucial for managing hyperglycemia. Currently, there is no standardized interpretation method for glucagon levels in oral glucose tolerance test (OGTT). This study aims to assess the relationship between the lowest glucagon/highest C-peptide ratio (Lglc/Hcp) in OGTT and glucose control levels in T2DM. Patients and Methods: Clinical data from 120 patients with T2DM were examined to compare the correlations of Lglc/Hcp and other pancreatic islet function-associated indices with fasting blood glucose (G0), glucose at 120 minutes in OGTT (G120), hemoglobin A1c (HbA1c), and the area under the glucose curve in OGTT (AUCglu). Additionally, the study investigated difference in Lglc/Hcp between patient groups based on the highest blood glucose levels (Hglu) in OGTT (Hglu ≥ 16.7 mmol/L vs Hglu < 16.7 mmol/L). Results: The generalized linear model suggested that Lglc/Hcp significantly correlated with G0 (B = 0.85, P < 0.001), G120(B = 1.46, P < 0.001), HbA1c (B = 0.67, P < 0.001), and AUCglu (B = 3.46, P < 0.001). This correlation surpassed C-peptide and glucagon-related parameters, even after adjusting for confounding factors. Furthermore, Lglc/Hcp was notably higher in patients with Hglu ≥ 16.7 mmol/L compared to those with Hglu < 16.7 mmol/L (Z = − 3.71, p < 0.001). Conclusion: Lglc/Hcp in OGTT closely relates to blood glucose control in patients with T2DM, potentially reflecting the overall pancreatic islet function in regulating glucose levels. Moreover, inhibiting glucagon secretion may be a crucial consideration for patients requiring insulin treatment. [ABSTRACT FROM AUTHOR]

Context It is not clear if the risk of abnormal glucose tolerance (AGT) is attenuated in the long-term in women diagnosed with gestational diabetes (GDM) using the World Health Organization (WHO) 2013 criteria and who have received appropriate treatment during pregnancy. Objective We aimed to assess the long-term prevalence of AGT and other cardiovascular disease (CVD) risk factors in this cohort. Methods A retrospective cohort follow-up study was conducted of 37 and 107 women diagnosed with and without GDM respectively using the WHO 2013 criteria between June 2010 and December 2010. Women were invited to attend our center, where they underwent a 75-g oral glucose tolerance test, blood and urine collection, body measurements, and electrocardiography. Main outcome measure included the development of AGT using the American Diabetes Association criteria. Results Sixteen (43.2%) women with GDM compared to 5 (4.7%) women with normal glucose tolerance (NGT) at index pregnancy had AGT (P <.001). In the GDM group, 10 (27.0%), 7 (18.9%), and 4 (10.8%) women had impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM), respectively. In the NGT group, 2 (1.9%), 3 (2.8%), and 1 (0.9%) woman had IFG, IGT, and T2DM, respectively. Women with AGT also had an unfavorable metabolic profile including obesity, hypertension, insulin resistance, and dyslipidemia. Conclusion Women treated for GDM (WHO 2013 criteria) remain at increased risk for developing AGT and adverse CVD risk factors as early as a decade after diagnosis. Continued efforts are needed to accurately follow this population to address modifiable risk factors. [ABSTRACT FROM AUTHOR]

N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, MNAM supplementation reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. The NAD+/sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was diminished in placenta by MNAM. In addition, weight of placenta, fetus weight, and litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of glucose tolerance tests by MNAM. Our data provide evidence for the careful usage of MNAM in treatment of GDM. [ABSTRACT FROM AUTHOR]

Aim: To determine whether glucose volume of distribution (VdGLUCOSE) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). Methods: Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2·kg−1·min−1; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time‐response curve. Results: VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg−1; p < 0.001). VdGLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = −0.548 and −0.555, respectively; p < 0.001). Conclusions: Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat‐free mass rather than body weight for a more accurate diagnosis of impaired IS. [ABSTRACT FROM AUTHOR]

This study focused on Stevia rebaudiana, a plant known for its sweet taste and unique medicinal properties in managing diabetes complications. The research aimed to evaluate the antihyperglycemic potential of crude ethanolic and aqueous extracts from Stevia rebaudiana leaves, utilizing the Oral Glucose Tolerance Test (OGTT) on albino rats subjected to glucose loading. Additionally, a thorough phytochemical analysis was conducted to identify essential secondary metabolites present in the extracts. The study involved five groups, each comprising equal number of male Wistar albino rats. Groups II, III, IV, and V received an oral solution of 8 gm/kg glucose. Group IV was administered a 2 gm/kg ethanolic extract, while Group V received a 2 gm/kg aqueous extract. Blood glucose levels (BGL) were monitored at specified intervals of 30, 60, 90, and 120 minutes. Phytochemical screening confirmed the presence of various phytoconstituents in the extracts. The ethanolic extract demonstrated a 39.49% reduction in blood glucose levels, and the aqueous extract exhibited a 35.39% reduction. Both extracts from Stevia rebaudiana leaves displayed significant antihyperglycemic effects in glucose-loaded rats after 120 minutes. [ABSTRACT FROM AUTHOR]

Background: 5′‐adenosine monophosphate‐activated protein kinase (AMPK) agonists, particularly resveratrol (RES), have not been extensively evaluated for their effect on insulin dysregulation (ID) in horses. Objectives: Evaluate the effects of treatment with RES (10 mg/kg PO q12h), metformin (MET; 30 mg/kg PO q12h), and aspirin (ASP; 20 mg/kg PO q24h) on experimentally induced ID. Animals: Thirty‐three healthy, adult, light‐breed horses. Methods: Unblinded, placebo‐controlled, experimental trial evaluating effects of AMPK agonists (RES, MET, and ASP) on experimentally induced ID. Horses were randomly assigned to a treatment group (RES, MET/ASP, RES/ASP, RES/MET/ASP, or placebo [CON]) after induction of ID with dexamethasone (0.08 mg/kg PO q24h for 7 days). Frequently sampled insulin‐modified IV glucose tolerance tests (FSIGTT) and oral sugar tests (OST) were performed at baseline, 7 days after ID, and ID plus 7 days of treatment. Minimal model and OST variables were compared between (1‐way ANOVA) and within (1‐way ANOVA for repeated measures) groups over time to determine effects of treatment on ID. Results: Administration of dexamethasone for 14 days resulted in significantly altered insulin and glucose dynamics (SI, DI, basal [glucose], and [insulin]) and produced clinical signs of laminitis in 5 out of 33 (15%) of horses included in the study. Combination therapy with RES, MET, and ASP did not significantly improve insulin and glucose dynamics in horses with experimentally induced ID. Conclusions and Clinical Importance: Metabolic testing before glucocorticoid administration should be considered in horses with clinical signs of metabolic syndrome. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is well-recognised as a continuum heralded by the development of islet autoantibodies, progression to islet autoimmunity causing beta cell destruction, culminating in insulin deficiency and clinical disease. Abnormalities of glucose homeostasis are known to exist well before the onset of typical symptoms. Laboratory-based tests such as the oral glucose tolerance test (OGTT) and glycated haemoglobin (HbA1c) have been used to stage T1D and assess the risk of progression to clinical T1D. Continuous glucose monitoring (CGM) can detect early glycaemic abnormalities and can therefore be used to monitor for metabolic deterioration in pre-symptomatic, islet autoantibody positive, at-risk individuals. Early identification of these children can not only reduce the risk of presentation with diabetic ketoacidosis (DKA), but also determine eligibility for prevention trials, which aim to prevent or delay progression to clinical T1D. Here, we describe the current state with regard to the use of the OGTT, HbA1c, fructosamine and glycated albumin in pre-symptomatic T1D. Using illustrative cases, we present our clinical experience with the use of CGM, and advocate for an increased role of this diabetes technology, for monitoring metabolic deterioration and disease progression in children with pre-symptomatic T1D. [ABSTRACT FROM AUTHOR]

Objective: The mechanisms behind the diminished incretin effect in type 2 diabetes are uncertain, but impaired vagal transmission has been suggested. We aimed to investigate the association between the incretin effect and autonomic neuropathy, and the degree of dysglycaemia and duration of diabetes. Design and Methods: For a cross‐sectional study, we included participants with either longstanding type 2 diabetes, recent onset, untreated diabetes and controls without diabetes matched for age, sex and body mass index. Autonomic nerve function was assessed with cardiovascular reflex tests, heart rate variability and sudomotor function. Visceral afferent nerves in the gut were tested performing rapid rectal balloon distention. An oral glucose tolerance test and an intravenous isoglycaemic glucose infusion were performed to calculate the incretin effect and gastrointestinal‐mediated glucose disposal (GIGD). Results: Sixty‐five participants were recruited. Participants with diabetes had rectal hyposensitivity for earliest sensation (3.7 ± 1.1 kPa in longstanding, 4.0 ± 1.3 in early), compared to controls (3.0 ± 0.9 kPa), p =.005. Rectal hyposensitivity for earliest sensation was not associated with the incretin effect (rho = −0.204, p =.106), but an association was found with GIGD (rho −0.341, p =.005). Incretin effect and GIGD were correlated with all glucose values, HbA1c and duration of diabetes. Conclusions: Rectal hyposensitivity was uncovered in both longstanding and early type 2 diabetes, and was not associated with the incretin effect, but with GIGD, implying a potential link between visceral neuropathy and gastrointestinal handling of glucose. Both the incretin effect and GIGD were associated with the degree of dysglycaemia and the duration of diabetes. Previously Published: Some of the data have previously been published and presented as a poster on the American Diabetes Association 83rd Scientific Sessions: Meling et al; 1658‐P: Rectal Hyposensitivity, a Potential Marker of Enteric Autonomic Nerve Dysfunction, Is Significantly Associated with Gastrointestinally Mediated Glucose Disposal in Persons with Type 2 Diabetes. Diabetes 20 June 2023; 72 (Supplement_1): 1658–P. https://doi.org/10.2337/db23‐1658‐P. [ABSTRACT FROM AUTHOR]

The heterogeneity of oral glucose tolerance test (OGTT) patterns during pregnancy remains unclear. This study aims to identify latent OGTT patterns in pregnant women and investigate the high-risk population for late-onset gestational diabetes mellitus (GDM). This study including 17,723 participants was conducted from 2018 to 2021. Latent mixture modeling was used to identify subgroups. Modified Poisson regression was performed to explore the relationship between OGTT patterns and late-onset GDM or adverse perinatal outcomes. Three distinct glucose patterns, high, medium, and low glucose levels (HG, MG, and LG patterns) were identified. The HG pattern represented 28.5% of the participants and 5.5% of them developed late-onset GDM. A five-fold higher risk of late-onset GDM was found in HG pattern than in LG pattern (relative risk [RR]: 5.17, 95% confidence interval [CI]: 3.38-7.92) after adjustment. Participants in HG pattern were more likely to have macrosomia, large for gestational age, preterm birth, and cesarean deliveries, with RRs of 1.59 (1.31-1.93), 1.55 (1.33-1.82), 1.30 (1.02-1.64) and 1.15 (1.08-1.23), respectively. Three distinct OGTT patterns presented different risks of late-onset GDM and adverse perinatal outcomes, indicating that timely monitoring of glucose levels after OGTT should be performed in pregnant women with HG pattern. [ABSTRACT FROM AUTHOR]

Background: The heart has metabolic flexibility, which is influenced by fed/fasting states, and pathologies such as myocardial ischemia and hypertrophic cardiomyopathy (HCM). Hyperpolarized (HP) 13C-pyruvate MRI is a promising new tool for non-invasive quantification of myocardial glycolytic and Krebs cycle flux. However, human studies of HP 13C-MRI have yet to demonstrate regional quantification of metabolism, which is important in regional ischemia and HCM patients with asymmetric septal/apical hypertrophy. Methods: We developed and applied methods for whole-heart imaging of 13C-pyruvate, 13C-lactate and 13C-bicarbonate, following intravenous administration of [1-13C]-pyruvate. The image acquisition used an autonomous scanning method including bolus tracking, real-time magnetic field calibrations and metabolite-specific imaging. For quantification of metabolism, we evaluated 13C metabolite images, ratio metrics, and pharmacokinetic modeling to provide measurements of myocardial lactate dehydrogenase (LDH) and pyruvate dehydrogenase (PDH) mediated metabolic conversion in 5 healthy volunteers (fasting & 30 min following oral glucose load). Results: We demonstrate whole heart coverage for dynamic measurement of pyruvate-to-lactate conversion via LDH and pyruvate-to-bicarbonate conversion via PDH at a resolution of 6 × 6 × 21 mm3 (13C-pyruvate) and 12 × 12 × 21 mm3 (13C-lactate, 13C-bicarbonate). 13C-pyruvate and 13C-lactate were detected simultaneously in the RV blood pool, immediately after intravenous injection, reflecting LDH activity in blood. In healthy volunteers, myocardial 13C-pyruvate-SNR, 13C-lactate-SNR, 13C-bicarbonate-SNR, 13C-lactate/pyruvate ratio, 13C-pyruvate-to-lactate conversion rate, kPL, and 13C-pyruvate-to-bicarbonate conversion rate, kPB, all had statistically significant increases following oral glucose challenge. kPB, reflecting PDH activity and pyruvate entering the Krebs Cycle, had the highest correlation with blood glucose levels and was statistically significant. Conclusions: We demonstrate first-in-human regional quantifications of cardiac metabolism by HP 13C-pyruvate MRI that aims to reflect LDH and PDH activity. [ABSTRACT FROM AUTHOR]

Background: It remains unclear how the condition of glucose metabolism during pregnancy affects fetal outcomes. This study aimed to investigate the associations of gestational diabetes mellitus (GDM) and elevated glucose levels at each time point during oral glucose tolerance test (OGTT) with congenital heart disease (CHD) risk in offspring. Methods: We conducted a retrospective cohort study of mothers with singleton pregnancies of 20 weeks or more registered at Maternal and Child Health Centers in Fujian Province, China. The OGTT results and offspring CHD occurrence were collected. We used logistic regression to analyse the association between elevated blood glucose at each time point during OGTT and CHD. Results: A total of 71,703 normal and 533 CHD fetuses were included. Compared to the corresponding normal group, women with GDM, elevated blood glucose at different time points in OGTT (0 h ≥ 5.1 mmol/L, 1 h ≥ 10 mmol/L, and 2 h ≥ 8.5 mmol/L) showed an increased risk of CHD in offspring (adjusted OR = 1.41, 1.36, 1.37, and 1.41, all P < 0.05, respectively). Compared to group 1 (normal OGTT 0 h, 1 h and 2 h), the risk of CHD was higher in group 3 (normal OGTT 0 h and abnormal OGTT 1 h or 2 h) and group 4 (abnormal OGTT 0 h, 1 h and 2 h), OR = 1.53 and 2.21, all P < 0.05, respectively. Moreover, we divided participants by advanced maternal age, multipara, assisted reproduction, fetal sex, and others, similar associations were observed in the subgroup analyses. Conclusion: Elevated blood glucose at different time points during OGTT was associated with CHD in offspring. Fetuses of pregnant women with GDM should be screened for a high risk of CHD. [ABSTRACT FROM AUTHOR]

Aims: Incretin hormones glucagon-like peptide 1 (GLP-1) and gastric inhibitory peptide (GIP) cause increased insulin secretion in non-pregnant adults, but their role in pregnancy, where there are additional metabolically-active hormones from the placenta, is less clear. The aim of the present study was to assess if fasting and post-load incretin concentrations were predictive of pregnancy insulin and glucose concentrations. Methods: Pregnant women (n = 394) with one or more risk factors for gestational diabetes were recruited at 28 weeks for a 75 g oral glucose tolerance test (OGTT). Glucose, insulin, GLP-1 and GIP were measured in the fasting state and 120 min after glucose ingestion. Results: Fasting plasma GLP-1 concentrations were associated with plasma insulin (standardised β' 0.393 (0.289–0.498), p = 1.3 × 10–12; n = 306), but not with glucose concentrations (p = 0.3). The association with insulin was still evident when adjusting for BMI (β' 0.271 (0.180–0.362), p = 1.1 × 10–8; n = 297). Likewise, at 120 min the OGTT GLP-1 concentrations were associated with plasma insulin concentrations (β' 0.216 (0.100–0.331), p = 2.7 × 10–4; n = 306) even after adjusting for BMI (β' 0.178 (0.061–0.294), p = 2.9 × 10–3; n = 296), but not with glucose (p = 0.9). GIP concentrations were not associated with insulin or glucose concentrations at either time point (all p > 0.2). In pregnancy plasma GLP-1, but not GIP, concentrations appear to be predictive of circulating insulin concentrations, independently of associations with BMIs. Conclusions: These results suggest that the relationship between insulin and incretins is preserved in pregnancy, but that other factors, such as placental hormones or counter-regulatory hormones, may be more important determinants of glycaemia and gestational diabetes aetiology. [ABSTRACT FROM AUTHOR]

Aim: Cluster of differentiation 81 (CD81) is a cell surface protein involved in cell development, activation, growth, and motility. Recent studies have suggested that CD81 is a marker of dedifferentiated β-cells under conditions of metabolic stress, such as progressive diabetes. However, the clinical significance of changes in soluble serum CD81 (sCD81) in diabetic individuals remains unknown. The aim of this study was to investigate whether serum sCD81 concentrations differ between subjects with diabetes and normal glucose tolerance (NGT), and whether sCD81 changes during a 75 g oral glucose tolerance test (OGTT). Materials and methods: We recruited 101 subjects who had completed an OGTT. According to the test results, the participants were divided into diabetes mellitus (DM) and NGT groups. Participants with prediabetes were excluded from the analysis. During the OGTT, sCD81 levels were measured at 0 and 120 min. We compared changes in sCD81 between the groups. Results: In the DM group, soluble sCD81 levels were significantly higher at baseline and 120 min in the OGTT compared with the normal group (0.59 (0.22–1.05) ng/mL vs. 0.25 (0.81–0.67) ng/mL, 0.55 (0.17–0.96) ng/mL vs. 0.21 (0.92–0.78) ng/mL, p = 0.006 and 0.029, respectively). The soluble sCD81 levels in the NGT group remained unchanged (p = 0.658), while those in the DM group were significantly decreased during the OGTT (p = 0.003). Conclusion: Soluble sCD81 levels were elevated in individuals with type 2 diabetes, such that changes in sCD81 were only observed during the OGTT in the DM group. Soluble sCD81 may have potential as a new diagnostic marker for type 2 diabetes. [ABSTRACT FROM AUTHOR]

Whether glucose concentration increases during heat exposure because of reduced peripheral tissue uptake or enhanced appearance is currently unknown. This study aimed to report glucose concentrations in both capillary and venous blood in response to a glucose challenge during passive heating (PH) to assess whether heat exposure affects glucose uptake in healthy males. Twelve healthy male participants completed two experimental sessions, where they were asked to undertake an oral glucose tolerance test (OGTT) whilst immersed in thermoneutral (CON, 35.9 (0.6) °C) and hot water (HWI, 40.3 (0.5) °C) for 120 min. Venous and capillary blood [glucose], rectal temperature, and heart rate were recorded. [Glucose] area under the curve for HWI venous (907 (104) AU) differed from CON venous (719 (88) AU, all P < 0.001). No other differences were noted (P > 0.05). Compared with CON, HWI resulted in greater rectal temperature (37.1 (0.3) °C versus 38.6 (0.4) °C, respectively) and heart rate (69 (12) bpm versus 108 (11) bpm, respectively) on cessation (P < 0.001). An OGTT results in similar capillary [glucose] during hot and thermoneutral water immersion, whereas venous [glucose] was greater during HWI when compared with CON. This indicates that peripheral tissue glucose uptake is acutely reduced in response to HWI. Abbreviations: AUC: Area under the curve; CON: Thermoneutral immersion trial; HWI: Hot water immersion trial; OGTT: Oral glucose tolerance test; PH: Passive heating; $${\bar T_{{\rm{msk}}}}$$ T ˉ m s k : Mean skin temperature; Trec: Rectal temperature [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus is a common medical disorder of pregnancy. Diabetic ketoacidosis is a complication that may affect both maternal and perinatal wellbeing adversely. It is rare, most often involving women with type 1 or type 2 diabetes, but occasionally can be seen in gestational diabetes mellitus. Here are two cases of ketoacidosis seemingly triggered by glucose ingestion for the oral glucose tolerance test in previously normoglycemic women, posing a diagnostic and therapeutic challenge. Prevention of such complications must be considered when treating high-risk pregnant women> 40 years of age, pregnant as a result of assisted reproductive techniques. Fasting blood glucose checked before ingestion of the glucose in a selected group of women may be one way of avoiding this complication. This suggestion may put women at risk of prolonged fasting and stretching services. Glucose tolerance test is a diagnostic test, and these cases demonstrate a rare complication. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF. Objective: To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF. Methods: We performed a population‐based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference. Results: The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p‐value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF. Conclusions/interpretation: The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF. [ABSTRACT FROM AUTHOR]

Background: Gestational Diabetes mellitus (GDM) is fast becoming an important cause of maternal and perinatal morbidity and mortality. The objective of this study is to assess the prevalence and the perinatal outcome of gestational diabetes in an antenatal population. Methodology: This was a cross-sectional study. The patients were pregnant women between 24-28 weeks of gestation without a prior diagnosis of diabetes mellitus. The consenting women were evaluated using fasting plasma glucose and oral glucose tolerance testing using 75 grams of glucose in 300ml of water orally. Results: Two hundred and fifteen women participated in the study and the prevalence of GDM was 9%. The mean fasting plasma glucose was 4.04mmol/l at the time of the Oral glucose tolerance test (OGTT) and 5.78mmol/l after the oral glucose load. When compared with pregnant normoglycaemic patients, GDM patients had significantly fewer vaginal deliveries (p=0.05), higher birth weight (3.71kg), and more neonatal admissions (50%). Conclusions. Gestational diabetes mellitus is an important disease entity, and it is a cause of maternal and perinatal morbidities. [ABSTRACT FROM AUTHOR]

The ability to perform accurate continuous glucose monitoring without blood sampling has revolutionised the management of diabetes. Newer methods that can allow measurements during longer periods are necessary to substantially improve patients' quality of life. This paper presents an alternative method for glucose monitoring which is based on electrical impedance spectroscopy. A battery-less implantable bioimpedance spectroscope was designed, built, and used in an in vivo study on pigs. After a recovery period of 14 days post surgery, a total of 236 subcutaneous bioimpedance measurements obtained from intravenous glucose tolerance tests, with glucose concentration ranges between 77.4 and 523.8 mg/dL, were analyzed. The results show that glucose concentrations estimated by subcutaneous bioimpedance measurements correlate very well to the blood glucose reference values. The pigs were clinically healthy throughout the study, and the postmortem examinations revealed no signs of adverse effects related to the sensor. The implantation of the sensor requires minor surgery. The implant, being externally powered, could in principle last indefinitely. These encouraging results demonstrate the potential of the bioimpedance method to be used in future continuous glucose monitoring systems. [ABSTRACT FROM AUTHOR]

The potential interaction between metformin and exercise on glucose-lowering effects remains controversial. We studied the separated and combined effects of metformin and/or exercise on fasting and postprandial insulin sensitivity in individuals with pre-diabetes and type 2 diabetes (T2D). Eight T2D adults (60 ± 4 yr) with overweight/obesity (32 ± 4 kg·m-2) under chronic metformin treatment (9 ± 6 yr; 1281 ± 524 mg·day-1) underwent four trials; 1) taking their habitual metformin treatment (MET), 2) substituting during 96 h their metformin medication by placebo (PLAC), 3) placebo combined with 50 min bout of high-intensity interval exercise (PLAC þ EX), and 4) metformin combined with exercise (MET þ EX). Plasma glucose kinetics using stable isotopes (6,6-2H2 and [U-13C] glucose), and glucose oxidation by indirect calorimetry, were assessed at rest, during exercise, and in a subsequent oral glucose tolerance test (OGTT). Postprandial glucose and insulin concentrations were analyzed as mean and incremental area under the curve (iAUC), and insulin sensitivity was calculated (i.e., MATSUDAindex and OGISindex). During OGTT, metformin reduced glucose iAUC (i.e., MET and MET þ EX lower than PLAC and PLAC þ EX, respectively; P = 0.023). MET þ EX increased MATSUDAindex above PLAC (4.8 ± 1.4 vs. 3.3 ± 1.0, respectively; P = 0.018) and OGISindex above PLAC (358 ± 52 vs. 306 ± 46 mL·min-1·m-2, respectively; P = 0.006). Metformin decreased the plasma appearance of the ingested glucose (Ra OGTT; MET vs. PLAC, -3.5; 95% CI -0.1 to -6.8 lmol·kg-1·min-1; P = 0.043). Metformin combined with exercise potentiates insulin sensitivity during an OGTT in individuals with pre-diabetes and type 2 diabetes. Metformin's blood glucose-lowering effect seems mediated by decreased oral glucose entering the circulation (gut-liver effect) an effect partially blunted after exercise. [ABSTRACT FROM AUTHOR]

Aim: Evidence from mouse models suggests that brain serotonergic pathways control blood glucose. We hypothesized that sumatriptan (5HT1B‐receptor agonist) would alter glucose homeostasis in humans. Materials and Methods: We conducted a two‐visit random‐order double‐blinded placebo‐controlled cross‐over trial in 10 overweight adults that were otherwise healthy. Participants received sumatriptan (single dose, 100 mg) or placebo before undergoing a 60‐min intravenous glucose tolerance test, followed by a 120‐min hyperinsulinaemic euglycaemic clamp. Results: Glucose excursion was greater during intravenous glucose tolerance test with sumatriptan compared with placebo [iAUC0‐60 min 316 (268‐333) vs. 251 (197‐319) min/mmol/L p =.047]. This was probably explained by a combination of reduced circulating insulin levels [iAUC0‐10 min 1626 (1103‐2733) vs. 2336 (1702‐3269) min/pmol/L, p =.005], reduced insulin sensitivity [M/I‐value 2.11 (1.15, 4.05) vs. 3.03 (1.14, 4.90) mg/kg/min per pmol/L, p =.010] and glucose effectiveness [SG 0.17 (0.12, 0.21) vs. 0.22 (0.18, 0.65)/min, p =.027]. Conclusions: 5HT1B receptors have a glucoregulatory role in humans, probably acting on insulin secretion, insulin sensitivity and glucose effectiveness. [ABSTRACT FROM AUTHOR]

Allium hookeri (AH) has been used as a nutritional and medicinal food in Asia for many years. Our previous studies have described its anti-diabetic, anti-obesity, and anti-inflammatory activities in animal models and prediabetes. This study investigated whether AH could improve glycemia by modulating insulin secretion in prediabetic subjects through an in-depth study. Eighty prediabetic subjects (100 ≤ fasting plasma glucose < 140 mg/dL) were randomly assigned to a placebo (n = 40) group or an ethanol AH extract (500 mg/day, n = 40) group for 12 weeks. Dietary intake and physical activity, blood glucose (an oral glucose tolerance test for 120 min), insulin (insulin response to oral glucose for 120 min), area under the curve (AUC) of glucose or insulin after oral glucose intake, insulin sensitivity markers, C-peptide, adiponectin, glycated hemoglobin A1c (HbA1c) levels, hematological tests (WBC, RBC, hemoglobin, hematocrit, and platelet count), blood biochemical parameters (ALP, AST, total bilirubin, total protein, albumin, gamma-GT, BUN, creatinine, LD, CK, and hs-CRP), and urine parameters (specific gravity and pH) were examined at both baseline and 12 weeks after supplementation with placebo or AH capsules. Fifty-eight participants (placebo group: 20 men and 10 women; AH group: 13 men and 15 women) completed the study. AH supplementation moderately reduced postprandial blood glucose at 60 min (−6.14 mg/dL, p = 0.061), postprandial insulin levels at 90 min (−16.69 µU/mL, p = 0.017), the glucose AUC at 90 min (−412.52 mg*min/dL, p = 0.021), as well as the insulin AUC at 90 min (−978.77 µU*min/mL, p = 0.021) and 120 min (−1426.41 µU*min/mL, p = 0.015) when compared with the placebo group. However, there were no effects of AH on dietary intake and physical activity; HOMA index; HbAlc; C-peptide; or adiponectin, hematological-, blood biochemical-, and urinary markers. To confirm the effects of AH extract on blood glucose insulin sensitivity, C57BL/6J or C57BL/KsJ-db/db mice were used (n = 8/group). Body weight, fasting plasma glucose level, lipid profiles, liver and renal function, pancreatic histology, and insulin immunoreactivity were assessed. In the diabetic db/db mice, hyperglycemia, which was accompanied by an increase in insulin secretion in diabetic mice, was significantly reduced by AH treatment, resulting in the alleviation of β-cell overcompensation and insulin resistance. We confirmed that AH supplementation can effectively control blood glucose and insulin levels by improving insulin sensitivity and may be a potential agent for glycemic control in subjects with prediabetes and type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Rotational night shift work has been shown to be associated with increased risk of diabetes. However, the exact mechanism is not clear. The present study aimed to investigate the expression of TCF7L2 and PPAR-γ genes in healthcare workers with normal glucose tolerance performing rotational night shift duties. Methods: The expression of TCF7L2 and PPAR-γ genes in peripheral blood was compared in two groups (n = 20 each group) of healthcare workers with normal glucose tolerance (NGT). The first group included NGT healthcare workers performing rotational night shift duties. The second group included NGT healthcare workers performing regular day shifts. Blood samples in the study group were collected 1 week after the last night shift to document the long-term effects of night shift work on the expression of TCF7L2 and PPAR-γ genes. Results: The age of study participants in the first group was 29.7 ± 3.92 and in the second group was 29.7 ± 2.23 years. Body mass index was 23.69 ± 2.59 and 24.35 ± 2.82 kg/m2 in both groups, respectively (p = 0.4). The expression of TCF7L2 gene was found to be 4.6-fold increased in NGT healthcare workers performing rotational night shift duties compared to those performing day shift duties (p = 0.02). The expression of PPAR-γ gene was found to be 3.7-fold decreased in NGT healthcare workers performing rotational night shift duties compared to those performing day shift duties (p = 0.04). The mean duration of exposure to rotational night shift work was 4.6 years. Conclusion: Rotational night shift work adversely affects the expression of common diabetogenic genes TCF7L2 and PPAR-γ in healthcare workers with normal glucose tolerance. This suggests a possible role for the dysregulation of these genes in shift work associated diabetes risk. [ABSTRACT FROM AUTHOR]