Higher fasting glucose is associated with poorer survival in non-diabetic subjects having ischemia with non-obstructive coronary arteries.

Subjects who have ischemia with non-obstructive coronary arteries (INOCA) experience angina pectoris with evidence of myocardial ischemia but without coronary stenosis. Few studies have investigated factors associated with its survival, especially insulin resistance. In this study, subjects with angina pectoris, without known diabetes mellites (DM), and with non-invasive tests showing myocardial ischemia were admitted for coronary angiography (CAG). Those whose CAG did not reveal stenosis and agreed to receive an oral glucose tolerance test (OGTT) 2 weeks after hospital discharge were enrolled for analysis. All-cause mortality was recorded, which served as the outcome of the study. A total of 587 subjects with INOCA, without known DM, and with OGTT data were analyzed. After OGTT and HbA1c tests, 86 subjects (14.7%) were newly diagnosed with DM and 59.8% had pre-DM. The median duration of follow-up was 7.03 years. Thirty-nine subjects died during the follow-up period. The incidence rate of mortality was 9.9 /1000 person-year. Those who died had a higher fasting glucose (101 ± 17 vs. 94 ± 13 mg/dl, p = 0.003) but a lower estimated glomerular filtration rate (eGFR) (54 ± 22 vs. 87 ± 30 ml/min, p < 0.001). In the Cox survival analysis, a higher fasting glucose (hazard ratio 1.053, p = 0.007) was associated with worse mortality for INOCA without DM (N = 501). On the contrary, a higher eGFR (hazard ratio 0.967, p = 0.012) was protective of better survival for non-diabetic INOCA (N = 501). In conclusion, for non-diabetic INOCA, higher fasting glucose was associated with worse mortality and higher eGFR was protective for better survival.

Evidence of a bi-directional relationship between heart failure and diabetes: a strategy for the detection of glucose abnormalities and diabetes prevention in patients with heart failure.

Prevalence of heart failure (HF) and diabetes are markedly increasing globally. In a population of HF patients, approximately 40% have diabetes which is associated with a more severe HF, poorer cardiovascular outcomes and higher hospitalization rates for HF than HF patients without diabetes. Similar trends were shown in HF patients with prediabetes. In addition, the association between HF and renal function decline was demonstrated in patients with or without diabetes. However, the exact prevalence of dysglycemia in HF patients requires further investigation aiming to clarify the most accurate test to detect dysglycemia in this population. The relationship between HF and diabetes is complex and probably bidirectional. In one way, patients with diabetes have a more than two-fold risk of developing incident HF with reduced or preserved ejection fraction than those without diabetes. In the other way, patients with HF, when compared with those without HF, show an increased risk for the onset of diabetes due to several mechanisms including insulin resistance (IR), which makes HF emerging as a precursor for diabetes development. This article provides epidemiological evidence of undetected dysglycemia (prediabetes or diabetes) in HF patients and reviews the pathophysiological mechanisms which favor the development of IR and the risks associated with these disorders in HF patients. This review also offers a discussion of various strategies for the prevention of diabetes in HF patients, based first on fasting plasma glucose and HbA1c measurement and if normal on an oral glucose tolerance test as diagnostic tools for prediabetes and unknown diabetes that should be performed more extensively in those patients. It discusses the implementation of diabetes prevention measures and well-structured management programs for HF patients who are generally overweight or obese, as well as current pharmacotherapeutic options for prediabetes, including sodium-glucose cotransporter 2 inhibitors which are among the pillars of HF treatment and which recently showed a benefit in the reduction of incident diabetes in HF patients. Thus, there is an urgent need of routine screening for dysglycemia in all HF patients, which should contribute to reduce the incidence of diabetes and to treat earlier diabetes when already present.

Evaluation of the Antihyperglycemic efficacy of the roots of Ferula orientalis L.: An in vitro to in vivo assessment.

Decoctions of Ferula orientalis L. (Apiaceae), have been traditionally used to lower blood glucose levels (BGLs). After in vitro enzyme inhibition tests on the dichloromethane extracts of the roots (FOD) and the methanol extract of the roots (FOM), isolation studies were carried out on the FOD extract. The anti-hyperglycemic effects of the FOD extract and the pure compounds were studied in mice using the Oral Glucose Tolerance Test (OGTT) and streptozotocin (STZ)-induced diabetes mellitus (DM) models. Molecular docking studies were performed on potent compounds in the binding pockets of enzymes α-glucosidase and α-amylase. The isolations of 11 compounds were isolated from the FOD extract, which comprised teferidine (1), ferutinin (FT) (2), teferin (3), epoxy-jaeschkeanadiol-p-hydroxybenzoate (4), epoxy-jaeschkeanadiol-6-vanillate (5), tovarol-8-angelate (6), leucoferin (7), tovarol-8-p-hydroxybenzoate (8), tovarol-8-vanillate (9), 6-ß-p-hydroxybenzoyloxy-germacra-1(10),4-diene (10), and chimgin (11). Compounds 2 and 8-11 exhibited a higher inhibitory activity on α-glucosidase. In the OGTT, pretreatment with the FOD extract or compound 2 did not alter the BGLs after administration of the glucose solution compared to the control. In the STZ-induced diabetic mice model, no significant difference in the BGLs was observed with the FOD extract (200 mg/kg) or compound 2 (100 mg/kg)-treated diabetic mice compared to the diabetic control mice. The experimental studies all showed that the F. orientalis extract had significant effects on the enzyme systems involved in DM, and it would be appropriate to plan further studies on possible problems of bioavailability of the compound FT and the FOD extract, inadequate dose, and duration of administration.

Risk factors for cardiometabolic health in Ghana: Cardiometabolic Risks Study Protocol-APTI Project.

Introduction: Cardiometabolic diseases are rapidly becoming primary causes of death in developing countries, including Ghana. However, risk factors for these diseases, including obesity phenotype, and availability of cost-effective diagnostic criteria are poorly documented in an African-ancestry populations in their native locations. The extent to which the environment, occupation, geography, stress, and sleep habits contribute to the development of Cardiometabolic disorders should be examined. Purpose: The overall goal of this study is to determine the prevalence of undiagnosed diabetes, prediabetes, and associated cardiovascular risks using a multi-sampled oral glucose tolerance test. The study will also investigate the phenotype and ocular characteristics of diabetes and prediabetes subgroups, as well as determine if lifestyle changes over a one-year period will impact the progression of diabetes and prediabetes. Methods and analysis: The study employs a community-based quasi-experimental design, making use of pre- and post-intervention data, as well as a questionnaire survey of 1200 individuals residing in the Cape Coast metropolis to ascertain the prevalence and risk factors for undiagnosed diabetes and prediabetes. Physical activity, dietary habits, stress levels, sleep patterns, body image perception, and demographic characteristics will be assessed. Glucose dysregulation will be detected using oral glucose tolerance test, fasting plasma glucose, and glycated hemoglobin. Liver and kidney function will also be assessed. Diabetes and prediabetes will be classified using the American Diabetes Association criteria. Descriptive statistics, including percentages, will be used to determine the prevalence of undiagnosed diabetes and cardiovascular risks. Inferential statistics, including ANOVA, t-tests, chi-square tests, ROC curves, logistic regression, and linear mixed model regression will be used to analyze the phenotypic variations in the population, ocular characteristics, glycemic levels, sensitivity levels of diagnostic tests, etiological cause of diabetes in the population, and effects of lifestyle modifications, respectively. Additionally, t-tests will be used to assess changes in glucose regulation biomarkers after lifestyle modifications. Ethics and dissemination: Ethics approval was granted by the Institutional Review Board of the University of Cape Coast, Ghana (UCCIRB/EXT/2022/27). The findings will be disseminated in community workshops, online learning platforms, academic conferences and submitted to peer-reviewed journals for publication.

Implementing care for women with gestational diabetes after delivery-the challenges ahead.

Gestational diabetes (GDM), defined as glucose intolerance during pregnancy, affects one in six pregnancies globally and significantly increases a woman's lifetime risk of type 2 diabetes mellitus (T2DM). Being a relatively young group, women with GDM are also at higher risk of developing diabetes related complications (e.g., cardiovascular disease, non-alcoholic fatty liver disease) later in life. Children of women with GDM are also likely to develop GDM and this perpetuates a cycle of diabetes, escalating our current pandemic of metabolic disease. The global prevalence of GDM has now risen by more than 30% over the last two decades, making it an emerging public health concern. Antepartum management of maternal glucose is unable to fully mitigate the associated lifetime cardiometabolic risk. Thus, efforts may need to focus on improving care for women with GDM during the postpartum period where prevention or therapeutic strategies could be implemented to attenuate progression of GDM to DM and its associated vascular complications. However, strategies to provide care for women in the postpartum period often showed disappointing results. This has led to a missed opportunity to halt the progression of impaired glucose tolerance/impaired fasting glucose to DM in women with GDM. In this review, we examined the challenges in the management of women with GDM after delivery and considered how each of these challenges are defined and could present as a gap in translating evidence to clinical care. We highlighted challenges related to postpartum surveillance, postpartum glucose testing strategies, postpartum risk factor modification, and problems encountered in engagement of patients/providers to implement interventions strategies in women with GDM after delivery. We reasoned that a multisystem approach is needed to address these challenges and to retard progression to DM and cardiovascular disease (CVD) in women with GDM pregnancies. This is very much needed to pave way for an improved, precise, culturally sensitive and wholistic care for women with GDM.

Aging delays the suppression of lipolysis in the postprandial period.

Plasma glycerol and free fatty acid concentrations decrease following oral glucose consumption, but changes in the rate of lipolysis during an oral glucose tolerance test (OGTT) have not been documented in conjunction with changes in fatty acid (FA) oxidation or reesterification rates in healthy individuals. After a 12-hr overnight fast, 15 young (21-35 yr; 7 men and 8 women) and 14 older (60-80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-2H]glycerol. A contralateral hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and carbohydrate (CHO) oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g OGTT. Glycerol rate of appearance (Ra), an index of lipolysis, decreased significantly from baseline 5 min post-challenge in young participants and 30 min in older participants. At 60 min, FA Rox decreased in both groups, but was significantly higher in older participants. Between 5-90 min, CHO Rox was significantly lower in older participants. Additionally, FA Rs was significantly lower in older participants at 60 and 90 min. The AUC for FA Rox was greater than that for FA Rs in older, but not young participants. Our results indicate that, in aging, the postprandial suppression of lipolysis and FA oxidation are delayed such that FA oxidation is favored over CHO oxidation and FA reesterification.

The predictive ability of the triglyceride glucose index, fasting glucose and oral glucose tolerance test for postpartum hyperglycemia in women with a GDM history.

OBJECTIVE: This study aimed to determine the likelihood of hyperglycemia postpartum in women with gestational diabetes mellitus (GDM) and to identify the predictors. METHODS: The retrospective cohort study involved 1 527 GDM patients who delivered at Peking University First Hospital from 1 January 2021, to 31 December 2021. According to the blood glucose level of postpartum oral glucose tolerance test (OGTT), women were divided into a normal glucose tolerance (NGT) group and a hyperglycemia group, and their characteristics and risk factors of hyperglycemia were compared. RESULTS: The prevalence of hyperglycemia was 33.9% (184/543) at 6-12 weeks postpartum. Compared with the NGT group, the fasting plasma glucose (FPG) of hyperglycemia group increased significantly during pregnancy and postpartum, the OGTT 1h postprandial glucose (PG) and 2hPG increased in the second trimester of pregnancy, the triglyceride (TG) increased in the first trimester of pregnancy and postpartum, the triglyceride glucose (TyG) index increased in the first trimester of pregnancy and postpartum, and the total cholesterol (TCHO) and low density lipoprotein cholesterol (LDL-C) decreased in the second trimester (p < 0.05). Fasting plasma glucose (FPG) in the first trimester [odds ratio (OR) = 3.583, p < 0.001], OGTT 2hPG in the second trimester (OR = 1.604, p < 0.001), the TyG index in the first trimester (OR = 1.863, p = 0.045) and FPG in third trimester (OR = 1.985, p = 0.024) were independent risk factors for postpartum hyperglycemia. CONCLUSIONS: Approximately one-third of women with GDM have hyperglycemia 6-12 weeks after delivery. FPG and the TyG index in the first trimester, OGTT 2hPG in the second trimester and FPG in third trimester are risk factors for postpartum hyperglycemia.

Predicting Type 2 Diabetes Metabolic Phenotypes Using Continuous Glucose Monitoring and a Machine Learning Framework.

Type 2 diabetes (T2D) and prediabetes are classically defined by the level of fasting glucose or surrogates such as hemoglobin HbA1c. This classification does not take into account the heterogeneity in the pathophysiology of glucose dysregulation, the identification of which could inform targeted approaches to diabetes treatment and prevention and/or predict clinical outcomes. We performed gold-standard metabolic tests in a cohort of individuals with early glucose dysregulation and quantified four distinct metabolic subphenotypes known to contribute to glucose dysregulation and T2D: muscle insulin resistance, ß-cell dysfunction, impaired incretin action, and hepatic insulin resistance. We revealed substantial inter-individual heterogeneity, with 34% of individuals exhibiting dominance or co-dominance in muscle and/or liver IR, and 40% exhibiting dominance or co-dominance in ß-cell and/or incretin deficiency. Further, with a frequently-sampled oral glucose tolerance test (OGTT), we developed a novel machine learning framework to predict metabolic subphenotypes using features from the dynamic patterns of the glucose time-series ("shape of the glucose curve"). The glucose time-series features identified insulin resistance, ß-cell deficiency, and incretin defect with auROCs of 95%, 89%, and 88%, respectively. These figures are superior to currently-used estimates. The prediction of muscle insulin resistance and ß-cell deficiency were validated using an independent cohort. We then tested the ability of glucose curves generated by a continuous glucose monitor (CGM) worn during at-home OGTTs to predict insulin resistance and ß-cell deficiency, yielding auROC of 88% and 84%, respectively. We thus demonstrate that the prediabetic state is characterized by metabolic heterogeneity, which can be defined by the shape of the glucose curve during standardized OGTT, performed in a clinical research unit or at-home setting using CGM. The use of at-home CGM to identify muscle insulin resistance and ß-cell deficiency constitutes a practical and scalable method by which to risk stratify individuals with early glucose dysregulation and inform targeted treatment to prevent T2D.

Delayed and diminished postprandial lactate shuttling in healthy older men and women.

Lactate, a product of glycolysis, is formed under aerobic conditions. Extensive work has shown lactate flux in young and exercising humans; however, the effect of age is not known. We tested the hypothesis that postprandial lactate shuttling (PLS) would be diminished in older adults. We used [3-13C]lactate and [6,6-2H]glucose tracers, an oral glucose tolerance test (OGTT), and arterialized blood sampling to determine postprandial lactate rates of appearance (Ra), disappearance (Rd), and oxidation (Rox) in 15 young (28.1 ± 1.4 yr) and 13 older (70.6 ± 2.4 yr) healthy men and women. In young participants, fasting blood [lactate] (≈0.5 mM) rose after the glucose challenge, peaked at 15 min, dipped to a nadir at 30 min, and rose again peaking at 60 min (≈1.0 mM). Initial responses in lactate Ra of older participants were delayed and diminished until 90 min rising by 0.83 mg·kg-1·min-1. Lactate Rox was higher throughout the entire trial in young participants by a difference of ∼0.5 mg·kg-1·min-1. Initial peaks in lactate Ra and concentration in all volunteers demonstrated the presence of an enteric PLS following an OGTT. Notably, in the systemic, but not enteric, PLS phase, lactate Ra correlated highly with glucose Rd (r2 = 0.92). Correspondence of second peaks in lactate Ra and concentration and glucose Rd shows dependence of lactate Ra on glucose Rd. Although results show both enteric and systemic PLS phases in young and older study cohorts, metabolic responses were delayed and diminished in healthy older individuals.NEW & NOTEWORTHY We used isotope tracers, an oral glucose tolerance test, and arterialized blood sampling to determine postprandial lactate flux rates in healthy young and older men and women. Lactate rates of appearance and oxidation and the lactate-pyruvate exchange were delayed and diminished in both enteric and systemic postprandial lactate shuttle phases in older participants.

Incidence of overt diabetes in pregnancy among women with 50-g glucose challenge test ≥ 200 mg/dL.

Objectives: To determine the incidence of overt diabetes in pregnancy (ODIP) among women with 50-g GCT results ≥ 200 mg/dL and compare characteristics and pregnancy outcomes between women with and without gestational diabetes (GDM). Methods: A retrospective cohort study was conducted in 212 pregnant women whose 50-g GCT results ≥ 200 mg/dL. ODIP was diagnosed from 75-g OGTT if fasting plasma glucose ≥ 126 and/or 2-h plasma glucose ≥ 200 mg/dL. Various characteristics and pregnancy outcomes were compared between ODIP and those with and without GDM. Results: Incidence of ODIP was 1.9% of all pregnant women and 23.6% of women with 50-g GCT ≥ 200 mg/dL. Women with ODIP and GDM were more likely to be overweight or obese than those without GDM (52%, 39.6%, and 18.2%, p < 0.001). Women with ODIP had significantly higher 50-g GCT results, lower gestational weight gain, and were less likely to deliver vaginally. Insulin therapy was significantly more common in women with ODIP compared to GDM (70.2% vs. 15.4%, p < 0.001). Rates of LGA, macrosomia, and other neonatal outcomes were comparable. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of any abnormal glucose tolerance [adjusted OR 3.22 (95% CI 1.55-6.70) and 2.28 (95% CI 1.14-4.58)] and ODIP [adjusted OR 9.43 (95% CI 2.15-41.38) and 6.36 (95% CI 2.85-14.18)], respectively. Conclusion: Incidence of ODIP was 23.6% of women with 50-g GCT ≥ 200 mg/dL. BMI ≥ 25 kg/m2 and 50-g GCT ≥ 240 mg/dL independently increased the risk of GDM and ODIP. Neonatal complications were comparable between ODIP and those with and without GDM.

Fasting or 2-hour postprandial plasma glycemic criteria for gestational diabetes mellitus are aassociated with distinct adverse outcomes.

OBJECTIVE: We aimed to evaluate the heterogeneity of gestational diabetes mellitus (GDM) patients diagnosed with various screening criteria. METHODS: We stratified pregnant women using consecutive fasting plasma glucose (FPG) and 2-hour postprandial plasma glucose (2hPPG) intervals of 0.2 mmol/L. The incidence of abnormal neonatal birthweight and birth-related adverse outcomes was compared with that of pregnant women without GDM. RESULTS: The study included 39,988 pregnant women (18-45 years, mean [SD], 31.5 [4.7] years) in Ningbo, China. The means (SDs) of FPG and 2hPPG within 24-28 weeks of gestation were 4.5 (0.5) and 6.8 (1.3) mmol/L, respectively. A total of 3025 (7.6%) women had 5.1-6.9 mmol/L FPG and 4560 (11.4%) had 8.5-11.0 mmol/L 2hPPG. The incidence of GDM according to the two combination criteria was 17.3% (6908 cases). The relative risk (RR) for < 10th percentile birthweight (< 10th WT) was 0.82 (95% CI, 0.74-0.91, p < 0.001) by 5.1 mmol/L FPG criterion and 1.14 (95% CI, 1.06-1.23, p < 0.001) by 8.5 mmol/L 2hPPG criterion, while the RRs for > 90th percentile birthweight (> 90th WT) were 1.48 (95% CI, 1.35-1.63, p < 0.001) and 0.95 (95% CI, 0.86-1.04, p = 0.29) according to the corresponding criteria. The FPG criterion was more strongly associated with maternal hypertension than the 2hPPG criterion. Both criteria did not show a distinct association with other composite adverse outcomes. CONCLUSION: High FPG is significantly associated with high birth weight, whereas high 2hPPG is slightly associated with low birth weight. Our findings highlight the heterogeneity of patients with GDM diagnosed by different criteria.

Sex hormone-binding globulin is a valuable diagnostic indicator of gestational diabetes mellitus.

Objective: To assess the performance of the Sex Hormone-Binding Globulin (SHBG) assay as a diagnostic indicator of Gestational Diabetes Mellitus (GDM) in the study population. Design: Analytical cross-sectional study. Setting: Hospital-based, Benue State University Teaching Hospital (BSUTH), Makurdi, Nigeria. Participants: Women with singleton pregnancies at 24 to 28 weeks gestational age attending Antenatal care at BSUTH, Makurdi. Intervention: Serum SHBG levels were assayed by ELISA during a diagnostic 75-gram Oral Glucose Tolerance Test (OGTT) for assessment of GDM in the cohort of consecutively selected participants who met the inclusion criteria. Main Outcome Measures: Serum levels of SHBG and presence of GDM in the participants. Result: Serum SHBG was significantly negatively correlated (rpb = - 0.534, p-value < 0.001) with the presence of GDM. It had an area under the ROC curve of 0.897 (95% Confidence Interval = 0.858-0.935; p-value < 0.001). A cut-off value of 452.0 nmol/L indicative of GDM had a diagnostic odds ratio of 21.4 in the study population. Conclusion: SHBG is a valuable diagnostic indicator for GDM in the study population. Funding: None declared.

Analysis of early-pregnancy metabolome in early- and late-onset gestational diabetes reveals distinct associations with maternal overweight.

AIMS/HYPOTHESIS: It is not known whether the early-pregnancy metabolome differs in patients with early- vs late-onset gestational diabetes mellitus (GDM) stratified by maternal overweight. The aims of this study were to analyse correlations between early-pregnancy metabolites and maternal glycaemic and anthropometric characteristics, and to identify early-pregnancy metabolomic alterations that characterise lean women (BMI <25 kg/m2) and women with overweight (BMI ≥25 kg/m2) with early-onset GDM (E-GDM) or late-onset GDM (L-GDM). METHODS: We performed a nested case-control study within the population-based prospective Early Diagnosis of Diabetes in Pregnancy cohort, comprising 210 participants with GDM (126 early-onset, 84 late-onset) and 209 normoglycaemic control participants matched according to maternal age, BMI class and primiparity. Maternal weight, height and waist circumference were measured at 8-14 weeks' gestation. A 2 h 75 g OGTT was performed at 12-16 weeks' gestation (OGTT1), and women with normal results underwent repeat testing at 24-28 weeks' gestation (OGTT2). Comprehensive metabolomic profiling of fasting serum samples, collected at OGTT1, was performed by untargeted ultra-HPLC-MS. Linear models were applied to study correlations between early-pregnancy metabolites and maternal glucose concentrations during OGTT1, fasting insulin, HOMA-IR, BMI and waist circumference. Early-pregnancy metabolomic features for GDM subtypes (participants stratified by maternal overweight and gestational timepoint at GDM onset) were studied using linear and multivariate models. The false discovery rate was controlled using the Benjamini-Hochberg method. RESULTS: In the total cohort (n=419), the clearest correlation patterns were observed between (1) maternal glucose concentrations and long-chain fatty acids and medium- and long-chain acylcarnitines; (2) maternal BMI and/or waist circumference and long-chain fatty acids, medium- and long-chain acylcarnitines, phospholipids, and aromatic and branched-chain amino acids; and (3) HOMA-IR and/or fasting insulin and L-tyrosine, certain long-chain fatty acids and phospholipids (q<0.001). Univariate analyses of GDM subtypes revealed significant differences (q<0.05) for seven non-glucose metabolites only in overweight women with E-GDM compared with control participants: linolenic acid, oleic acid, docosapentaenoic acid, docosatetraenoic acid and lysophosphatidylcholine 20:4/0:0 abundances were higher, whereas levels of specific phosphatidylcholines (P-16:0/18:2 and 15:0/18:2) were lower. However, multivariate analyses exploring the early-pregnancy metabolome of GDM subtypes showed differential clustering of acylcarnitines and long-chain fatty acids between normal-weight and overweight women with E- and L-GDM. CONCLUSIONS/INTERPRETATION: GDM subtypes show distinct early-pregnancy metabolomic features that correlate with maternal glycaemic and anthropometric characteristics. The patterns identified suggest early-pregnancy disturbances of maternal lipid metabolism, with most alterations observed in overweight women with E-GDM. Our findings highlight the importance of maternal adiposity as the primary target for prevention and treatment.

Can the postload-fasting glucose gap be used to determine risk of developing diabetes in chinese adults: A prospective cohort study.

OBJECTIVE: To evaluate the relationship between fasting plasma glucose (FPG) and 2-hour postload plasma glucose (2hPG) measured during an oral glucose tolerance test, and the risk of developing diabetes in Chinese adults. METHODS: We followed 3,094 participants without diabetes, categorizing them based on their oral glucose tolerance test (OGTT) results into low post load (2hPG ≤ FPG) and high post load (2hPG > FPG) at baseline. We monitored the incidence of diabetes, incidence of prediabetes, disease progression from prediabetes to diabetes and disease reversal from prediabetes to normal glucose tolerance (NGT) over an average of 3.2 years of follow-up. After the Schoenfeld residual test, Cox's time-varying covariate (Cox-TVC) models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CI) to compare the different clinical events between low and high post load groups. RESULTS: In the cohort study, of the 3,094 participants, 702 (22.7 %) had low post load (2hPG ≤ FPG, mean postload-fasting gap: -0.8 ± 0.7 mmol/L) and 2,392 (77.3 %) had high post load (2hPG > FPG, mean postload-fasting gap: 1.8 ± 1.2 mmol/L). Over 3.2 ± 0.2 years of follow-up, 282 (9.1 %) developed diabetes. In the low post load group, the incidence rates per 1,000 person-years were: diabetes was 7.9, prediabetes was 70.0, disease progression from prediabetes to diabetes was 23.4 and disease reversal to NGT was 327.2. For the high post load group, incidence rates for diabetes was 13.9, prediabetes was 124.3, disease progression was 59.5 and disease reversal was 238.6 per 1,000 person-years. Participants with high post load showed higher incidence rates of diabetes, prediabetes, and progression from prediabetes to diabetes compared to those with low post load. HRs were significantly higher for incident diabetes and prediabetes, and disease progression from prediabetes to diabetes, whereas disease reversal was lower. CONCLUSION: The risk of developing prediabetes/diabetes after 3.2 years of follow-up was higher in the participants with high post load. It suggested that postload-fasting gap may be a simple tool to predict the risk of developing prediabetes, diabetes or reversal to NGT.

Rise in fasting and dynamic glucagon levels in children and adolescents with obesity is moderate in subjects with impaired fasting glucose but accentuated in subjects with impaired glucose tolerance or type 2 diabetes.

Background: Fasting levels of glucagon are known to be elevated in youth and adults with type 2 diabetes mellitus (T2D). Children and adolescents with obesity were previously reported to show increasing fasting and post-glucose-challenge hyperglucagonemia across the spectrum of glucose tolerance, while no data are available in those with impaired fasting glucose (IFG). Materials and methods: Individuals from the Beta-JUDO study population (Uppsala and Salzburg 2010-2016) (n=101, age 13.3 ± 2.8, m/f =50/51) were included (90 with overweight or obesity, 11 with normal weight). Standardized OGTT were performed and plasma glucose, glucagon and insulin concentrations assessed at baseline, 5, 10, 15, 30, 60, 90 and 120 minutes. Patients were grouped according to their glycemic state in six groups with normal glucose metabolism (NGM) and normal weight (NG-NW), NGM with obesity or overweight (NG-O), impaired glucose tolerance (IGT), impaired fasting glucose (IFG), IGT+IFG and T2D, and in two groups with NGM and impaired glucose metabolism (IGM), for statistical analysis. Results and conclusion: Glucagon concentrations were elevated in young normoglycemic individuals with overweight or obesity (NG-O) compared to normoglycemic individuals with normal weight. Glucagon levels, fasting and dynamic, increased with progressing glycemic deterioration, except in IFG, where levels were comparable to those in NG-O. All glycemic groups showed an overall suppression of glucagon during OGTT. An initial increase of glucagon could be observed in T2D. In T2D, glucagon showed a strong direct linear correlation with plasma glucose levels during OGTT. Glucagon in adolescents, as in adults, may play a role in the disease progression of T2D.

Oral Glucose Tolerance Test for Universal screening for Gestational Diabetes Mellitus.

BACKGROUND: Gestational Diabetes Mellitus increased almost 30% in many countries, including underdeveloped countries and same in Nepal. Hospital-based studies in Nepal reported Gestational Diabetes Mellitus cases, with prevalence 2.48% in 2010 to 4.47% in 2019 emphasising on necessity of universal screening for Gestational Diabetes Mellitus. METHODS: As part of implementation of Electronic Decision support System for Antenatal Care, in formative study clinical vignettes on Gestational Diabetes Mellitus case presented to six healthcare providers ( Incharges, Auxiliary Nurse, Midwives and Lab Assistants) from 3 primary healthcare facilities in Kavre and Dolakha districts, Nepal from October-December 2019. 19 Auxiliary Nurse, Midwives from 19 HCF of 4 districts (Kavre, Dolakha, Sindhuli, and Sindhupalchok, including where clinical vignette were applied trained to perform Oral Glucose Tolerance Test for 4 hours. In-depth Interviews conducted with 16 Auxiliary Nurse, Midwives (8 trained and 8 peer coached from selected 4 HCF to explore their perception and experiences of conducting Oral Glucose Tolerance Test and continuing it for future. Clinical vigenttes compared with PEN protocol and IDIs analyzed thematically. RESULTS: Only 4/6 HCPs made probable diagnosis of Gestational Diabetes Mellitus. 217 Oral Glucose Tolerance Test performed, 24 found to have Gestational Diabetes Mellitus. In-depth Interviews showed Auxiliary Nurse, Midwives enthusiasts on implementing tests for Gestational Diabetes Mellitus and to continue what has been learnt in training. Some challenges; clients hesitate to stay 2 hours at facilities due to unavailability of transport and household work. Oral Glucose Tolerance Test trained Auxiliary Nurse, Midwives seem more confident in counselling and conducting Oral Glucose Tolerance Test than those peer coached. CONCLUSIONS: Administering Oral Glucose Tolerance Test seemed feasible in HCF settings despite some challenges. Training and continuing logistics supply from municipality level seems promising.

Altered glucose kinetics occurs with aging: a new outlook on metabolic flexibility.

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 (V̇co2)/oxygen consumption (V̇o2)] 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 [Formula: see text] 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.

The Preoperative Paradoxical GH Response to Oral Glucose Load Predicts a low Risk of Recurrence in Acromegaly.

CONTEXT: a paradoxical growth hormone (GH) response to oral glucose load (OGTT) in acromegaly is associated with a milder phenotype. OBJECTIVE: To study whether the GH response to OGTT predicts the risk of recurrence after initial surgical cure. DESIGN: Retrospective, observational study. SETTING: Two tertiary care centers. PATIENTS: We investigated 254 patients with acromegaly who were cured by surgery. INTERVENTION: All patients underwent OGTT at diagnosis before pituitary surgery. A peak-to-basal GH ratio ≥ 120% within 90 minutes was used to distinguish paradoxical (GH-Par) from non-paradoxical acromegalic patients (GH-NPar). MAIN OUTCOME MEASURE: Cox analysis was used to investigate whether the paradoxical GH response to OGTT was associated with the risk of disease recurrence. RESULTS: A paradoxical GH response to OGTT occurred in 87 patients (34.3%, termed GH-Par group). Recurrence of acromegaly occurred in three patients of the GH-Par group (3.4%) and in 20 patients in the GH-NPar group (12.0%). In the multivariate analysis, the paradoxical GH response to OGTT was significantly associated with the risk of recurrence (HR 0.18, 95% CI, 0.05-0.63; P = 0.007). Basal GH level at diagnosis was the only other variable associated with the risk of disease recurrence (HR 1.58, 95% CI, 1.01-2.47; P = 0.04). CONCLUSIONS: our study demonstrates that a paradoxical GH response to OGTT in the preoperative setting predicts a lower risk of disease recurrence after initial surgical cure. The pattern of GH responsiveness to OGTT is, therefore, useful to predict the long-term outcome of patients with acromegaly.