Postchallenge Glucose Research Articles

Is there a genetic relationship between blood glucose and osteoarthritis? A mendelian randomization study

ObjectiveThe relationship between blood glucose levels and osteoarthritis (OA) is unclear. This study aimed to investigate the genetic causal relationship between blood glucose-related traits and OA.MethodsWe first performed univariate Mendelian randomization (UVMR) analyses using published genome-wide association study (GWAS) datasets with fasting glucose (FG), 2 h-glucose post-challenge glucose (2hGlu), and glycosylated hemoglobin (HbA1c) as exposures, and hip osteoarthritis (HOA) and knee osteoarthritis (KOA) as outcomes; then, we performed inverse analyses of them. We used Inverse-variance weighted (IVW) analysis as the primary analysis, and sensitivity analyses were performed. Moreover, we performed multivariate Mendelian randomization (MVMR) to estimate the independent effect of exposure on outcome after adjusting for body mass index (BMI). Summarized data for blood glucose-related traits were obtained from the MAGIC Consortium study of the glucose trait genome and for OA from the UK Biobank and arcOGEN. Summarized data for BMI were obtained from the GIANT Consortium meta-analysis of individuals of European ancestry. A two-sided p value < 0.05 in UVMR was considered suggestive of significance when p < 0.0167 (Bonferroni correction p = 0.05/3 exposures) was considered statistically significant.ResultsWe found significant negative genetic causality of FG for HOA and KOA, and these associations remained significant after we adjusted for the effect of BMI [odds ratios (ORs) of 0.829 (0.687–0.999, p = 0.049) and 0.741 (0.570–0.964, p = 0.025)]. HbA1c also had an independent negative genetic causal effect on HOA after adjustment for BMI [0.665 (0.463–0.954, p = 0.027)]. At the same time, there was no evidence of reverse genetic causality of OA on blood glucose-related traits.ConclusionWe further elucidated the relationship between blood glucose-related traits and OA by adjusting for the effect of BMI from a genetic causal perspective. This study provides new insights to further clarify the relationship between blood glucose levels and OA, as well as the pathogenesis, etiology and genetics of OA.

12596 Characterizing Glycemic Variability In Novel Subphenotypes Of Individuals At Elevated Risk For Type 2 Diabetes Using Continuous Glucose Monitoring

Abstract Disclosure: A.J. Kretowski: None. P. Konopka: None. A. Janucik: None. A. Citko: None. A. Paszko: None. M. Klak: None. A. Golonko: None. A. Szklaruk: None. L. Szczerbinski: None. Background: The heterogeneity among individuals at elevated risk for Type 2 Diabetes (T2D) recently has led to the identification of six subphenotypes, each with distinct risks for developing T2D, its complications, and mortality. Our study leveraged Continuous Glucose Monitoring (CGM) to offer a detailed characterization of these subphenotypes, aiming to uncover differences in glycemic variability and control. Methods: CGM data from 616 individuals without diabetes, from the Polish Registry of Diabetes (PolReD) study, classified into six clusters, were analyzed. The PolReD used Freestyle Libre 2 (Abbott) as the CGM device. CGM-derived measures of glucose control and glucose variability were calculated using the iglu R package. We utilized Analysis of Variance (ANOVA) and Analysis of Covariance (ANCOVA), adjusting for age and sex, to identify significant differences in CGM parameters across the clusters. Results: Our analysis identified significant differences in several CGM-derived parameters among the clusters, notably in the Glycemic Risk Assessment Diabetes Equation (GRADE), Standard Deviation of weekly glucose values (SDw), Mean Amplitude of Glycemic Excursions (MAGE), Maximum glucose value, Glucose range, and Mean Absolute Glucose (MAG). Clusters 3 and 5, characterized by beta-cell dysfunction and high insulin resistance respectively, and associated with the highest risk of T2D, exhibited the greatest glucose variability, with elevated risk for glycemic excursions. In contrast, Cluster 4, indicative of a metabolically healthy obesity profile with a low risk of T2D, demonstrated the most stable glycemic control and the lowest variability among the clusters. Conclusions: This study shows that subtypes of patients at elevated risk for T2D exhibit distinct patterns in CGM-derived parameters, indicating variations in glucose control and stability that extend beyond traditional fasting and post-challenge glucose assessments. Notably, we found that subtypes facing the highest T2D risk display increased glycemic variability, despite their differing underlying mechanisms of dysglycemia. These findings highlight the utility of CGM as a tool for identifying individuals at an increased risk of T2D, reducing the need for extensive phenotyping typically required for cluster assignment. Presentation: 6/1/2024

Diabetes-associated Genetic Variation in MTNR1B and Its Effect on Islet Function.

Multiple common genetic variants have been associated with type 2 diabetes, but the mechanism by which they predispose to diabetes is incompletely understood. One such example is variation in MTNR1B, which implicates melatonin and its receptor in the pathogenesis of type 2 diabetes. To characterize the effect of diabetes-associated genetic variation at rs10830963 in the MTNR1B locus on islet function in people without type 2 diabetes. The association of genetic variation at rs10830963 with glucose, insulin, C-peptide, glucagon, and indices of insulin secretion and action were tested in a cohort of 294 individuals who had previously undergone an oral glucose tolerance test (OGTT). Insulin sensitivity, β-cell responsivity to glucose, and Disposition Indices were measured using the oral minimal model. The Clinical Research and Translation Unit at Mayo Clinic, Rochester, MN. Two cohorts were utilized for this analysis: 1 cohort was recruited on the basis of prior participation in a population-based study in Olmsted County. The other cohort was recruited on the basis of TCF7L2 genotype at rs7903146 from the Mayo Biobank. Two-hour, 7-sample OGTT. Fasting, nadir, and integrated glucagon concentrations. One or 2 copies of the G-allele at rs10830963 were associated with increased postchallenge glucose and glucagon concentrations compared to subjects with the CC genotype. The effects of rs10830963 on glucose homeostasis and predisposition to type 2 diabetes are likely to be partially mediated through changes in α-cell function.

Assessing the causal association of pregnancy complications with diabetes and cardiovascular disease.

To the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases. A two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot. Genetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1-1.01, P<0.0001), yet correlated with lower 2-hour post-challenge glucose levels (OR=0.89, 95% CI=0.82-0.97, P=0.006). Genetic liability for pregnancy with abortive outcomes indicated decreased fasting insulin levels (OR=0.97, 95% CI=0.95-0.99, P=0.02), but potentially elevated glycated hemoglobin levels (OR=1.02, 95% CI=1.01-1.04, P=0.01). Additionally, hypertensive disorders in pregnancy was tentatively linked to increased risks of stroke (OR=1.11, 95% CI=1.04-1.18, P=0.002) and CHD (OR=1.3, 95% CI=1.2-1.4, P=3.11E-11). Gestational hypertension might have a potential causal association with CHD (OR=1.11, 95% CI=1.01-1.22, P=0.04). No causal associations were observed between preterm birth and diabetes, stroke, or CHD. The findings of this study provide genetic evidence that gestational diabetes, pregnancy with abortive outcomes, and hypertensive disorders in pregnancy may serve as early indicators for metabolic and cardiovascular risks. These insights are pivotal for the development of targeted screening and preventive strategies.

One-hour post-challenge plasma glucose for the diagnosis of diabetes and intermediate hyperglycaemia

One-hour post-challenge plasma glucose for the diagnosis of diabetes and intermediate hyperglycaemia

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study

BackgroundElevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels.MethodsThis prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value.ResultsDuring a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01–1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04–1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95–1.46) in normoglycemic and 1.32 (95% CI: 0.98–1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12–1.64) and 1.57 (95% CI: 1.22–2.03), respectively.ConclusionsThe difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Postprandial Metabolite Profiles and Risk of Prediabetes in Young People: A Longitudinal Multicohort Study.

Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery and validation cohorts using logistic regression. Two metabolites (allylphenol sulfate and caprylic acid) were found to predict prediabetes beyond known risk factors, including sex, BMI, age, ethnicity, fasting/2-h glucose, total cholesterol, and triglycerides. In the discovery cohort, the area under the receiver operator characteristic curve (AUC) of the model with metabolites and known risk factors was 0.80 (95% CI 0.72-0.87), which was higher than the risk factor-only model (AUC 0.63 [0.53-0.73]; P = 0.001). When the predictive models developed in the discovery cohort were applied to the replication cohort, the model with metabolites and risk factors predicted prediabetes more accurately (AUC 0.70 [95% CI 40.55-0.86]) than the same model without metabolites (AUC 0.62 [0.46-0.79]). Metabolite profiles may help improve prediabetes prediction compared with traditional risk factors. Findings suggest that medium-chain fatty acids and phytochemicals are early indicators of prediabetes in high-risk youth.

Can earlier biomarker measurements explain a treatment effect on diabetes incidence? A robust comparison of five surrogate markers

IntroductionWe measured and compared five individual surrogate markers—change from baseline to 1 year after randomization in hemoglobin A1c (HbA1c), fasting glucose, 2-hour postchallenge glucose, triglyceride–glucose index (TyG) index, and homeostatic...

Association between VDR genetic polymorphisms and risk of gestational diabetes mellitus in the Chinese population.

Abnormal metabolism of vitamin D was the primary mechanism in many pregnancy diseases. Our study was the first to examine the hypothesis that VDR gene polymorphisms contribute to the risk of gestational diabetes mellitus (GDM) in the Chinese population at high altitudes. One hundred and eighteen women with GDM and 104 women with normal glucose tolerance (NGT) were included in this study using a case-control design. Four single nucleotide polymorphisms (g.47879112G>A, g.47846052C>T, g.47844974A>G, and g.47845054C>A) of mother and fetus were genotyped. Maternal and fetal frequency of the A allele of g.47879112G>A was significantly increased in women with GDM than in those with NGT (p<.05). A correlation between the AA homozygous genotype of g.47879112G>A and GDM was noted. Compared with non-carriers, A allele carriers showed higher fasting plasma insulin and two-hour post-challenge plasma glucose (2h-PPG), and lower levels of vitamin D. Furthermore, both maternal and fetal 4-marker haplotype ACCG were found to be significantly associated with GDM (p<.05). Association and haplotype analysis indicated that the A allele of g.47879112G>A could be a risk factor for GDM development in the Chinese population at high altitudes. Additionally, the VDR gene polymorphism of the fetus and mother may have a synergistic effect. The VDR polymorphism is associated with an increased risk of GDM and may be useful for predicting the development of the disease.

Rare Variant in Metallothionein 1E Increases the Risk of Type 2 Diabetes in a Chinese Population.

To uncover novel targets for the treatment of type 2 diabetes (T2D) by investigating rare variants with large effects in monogenic forms of the disease. We performed whole-exome sequencing in a family with diabetes. We validated the identified gene using Sanger sequencing in additional families and diabetes- and community-based cohorts. Wild-type and variant gene transgenic mouse models were used to study the gene function. Our analysis revealed a rare variant of the metallothionein 1E (MT1E) gene, p.C36Y, in a three-generation family with diabetes. This risk allele was associated with T2D or prediabetes in a community-based cohort. MT1E p.C36 carriers had higher HbA1c levels and greater BMI than those carrying the wild-type allele. Mice with forced expression of MT1E p.C36Y demonstrated increased weight gain, elevated postchallenge serum glucose and liver enzyme levels, and hepatic steatosis, similar to the phenotypes observed in human carriers of MT1E p.C36Y. In contrast, mice with forced expression of MT1E p.C36C displayed reduced weight and lower serum glucose and serum triglyceride levels. Forced expression of wild-type and variant MT1E demonstrated differential expression of genes related to lipid metabolism. Our results suggest that MT1E could be a promising target for drug development, because forced expression of MT1E p.C36C stabilized glucose metabolism and reduced body weight, whereas MT1E p.C36Y expression had the opposite effect. These findings highlight the importance of considering the impact of rare variants in the development of new T2D treatments.

Large-scale exome array summary statistics resources for glycemic traits to aid effector gene prioritization.

Genome-wide association studies for glycemic traits have identified hundreds of loci associated with these biomarkers of glucose homeostasis. Despite this success, the challenge remains to link variant associations to genes, and underlying biological pathways. To identify coding variant associations which may pinpoint effector genes at both novel and previously established genome-wide association loci, we performed meta-analyses of exome-array studies for four glycemic traits: glycated hemoglobin (HbA1c, up to 144,060 participants), fasting glucose (FG, up to 129,665 participants), fasting insulin (FI, up to 104,140) and 2hr glucose post-oral glucose challenge (2hGlu, up to 57,878). In addition, we performed network and pathway analyses. Single-variant and gene-based association analyses identified coding variant associations at more than 60 genes, which when combined with other datasets may be useful to nominate effector genes. Network and pathway analyses identified pathways related to insulin secretion, zinc transport and fatty acid metabolism. HbA1c associations were strongly enriched in pathways related to blood cell biology. Our results provided novel glycemic trait associations and highlighted pathways implicated in glycemic regulation. Exome-array summary statistic results are being made available to the scientific community to enable further discoveries.

Insulin Clearance at the Pubertal Transition in Youth with Obesity and Steatosis Liver Disease.

No data are available on insulin clearance (ClI) trends during the pubertal transition. The aim of this study was to investigate in 973 youths with obesity whether ClI in fasting and post-oral glucose challenge (OGTT) conditions varies at the pubertal transition in relation to the severity of obesity and the presence of steatosis liver disease (SLD). The severity of obesity was graded according to the Centers for Disease Control. SLD was graded as absent, mild and severe based on alanine amino transferase levels. ClI was defined as the molar ratio of fasting C-peptide to insulin and of the areas under the insulin to glucose curves during an OGTT. In total, 35% of participants were prepubertal, 72.6% had obesity class II, and 52.6% had mild SLD. Fasting ClI (nmol/pmol × 10-2) was significantly lower in pubertal [0.11 (0.08-0.14)] than in prepubertal individuals [0.12 (0.09-0.16)] and higher in class III [0.15 (0.11-0.16)] than in class I obesity [0.11 (0.09-0.14)]. OGTT ClI was higher in boys [0.08 (0.06-0.10)] than in girls [0.07 (0.06-0.09)]; in prepubertal [0.08 (0.06-0.11)] than in pubertal individuals [0.07 (0.05-0.09)]; in class III [0.14 (0.08-0.17)] than in class I obesity [0.07 (0.05-0.10)]; and in severe SLD [0.09 (0.04-0.14)] than in no steatosis [0.06 (0.04-0.17)]. It was lower in participants with prediabetes [0.06 (0.04-0.07)]. OGTT ClI was lower in youths with obesity at puberty along with insulin sensitivity and greater secretion. The findings suggest that the initial increase in ClI in youth with severe obesity and SLD is likely to compensate for hyperinsulinemia and its subsequent decrease at the onset of prediabetes and other metabolic abnormalities.

THU265 A U-Shaped Relationship Between Undiagnosed Diabetes And Thyroid Function

Abstract Disclosure: Z.Z. Alvi: None. R. Karnchanasorn: None. H. Ou: None. L. Chuang: None. A.G. Gianoukakis: None. K.C. Chiu: None. Thyroid dysfunction is present in about 20 million people in the United States, with about 60% percent unaware of their condition. Thyroid hormone is one of the key hormone regulators of energy metabolism, while diabetes mellitus (DM) is a disorder of dysregulated fuel metabolism. Thus, thyroid hormone can affect glucose metabolism. Unfortunately, this area has received little attention over the past few decades. This study investigates the rate of undiagnosed DM in relation to thyroid function. A representative and noninstitutionalized US adult (aged 20 years or older with BMI available) population from the National Health and Nutrition Examination Survey 2007-2012 was used for this study. Subjects with known thyroid diseases and/or diabetes were excluded. This study only included subjects with available TSH, free T4 (FT4), and free T3 (FT3) levels and the defined status of glucose tolerance by HbA1c, fasting, and/or 2-hour post-challenge plasma glucose concentrations (n=6,843). The rates of previously undiagnosed DM were determined for each quintile of TSH, FT4, and FT3 with sample-weighted analysis. The adjusted odds ratio (AOD) with a 95% confidence interval (95%CI) for DM was calculated with the lowest quintile as a reference after consideration of age, gender, BMI, and racial/ethnic groups. Amongst 6,834 subjects in this study, DM was found in 488 subjects. The rates of DM from quintile 1 to quintile 5 were 3.37%, 3.95%, 3.84%, 6.42%, and 7.26 % for TSH quintiles (P&amp;lt;0.0001 by ANOVA); 5.69%, 4.27%, 5.05%, 4.74%, and 6.46% for FT4 quintiles (P&amp;lt;0.0001 by ANOVA); and 4.82%, 4.63%, 5.33%, 5.33%, and 4.93% for FT3 quintiles (P&amp;lt;0.0001 by ANOVA). Although the correlations were imperfect among TSH, FT4, and FT3 quintiles, the U-shaped relationship of DM with thyroid function was confirmed by the lowest AOD of 0.80 (95%CI: 0.80 - 0.80, P&amp;lt;0.0001) for the 3rd quintile of TSH (TSH: 1.321 - 1.771 mIU/L). The association of DM with low thyroid function was confirmed by the AOD of 1.31 (95%CI: 1.30 - 1.32, P&amp;lt;0.0001) for the 5th quintile of TSH (TSH: 2.519 - 80.968 mIU/L). The association of DM with high thyroid function was confirmed by AOD of 2.45 (95%CI: 2.44 - 2.46, P&amp;lt;0.0001) for the 5th quintile of FT3 (FT3: 3.51 - 28.82 pg/mL). FT4 confirmed the U-shaped relationship with the highest AOD of 1.07 (95%CI: 1.07 - 1.08, P&amp;lt;0.0001) for the 5th quintile of FT4 (FT4: 0.91 - 4.80 ng/mL) and the lowest AOD of 0.82 (95%CI: 0.82 - 0.82, P&amp;lt;0.001) for the 2nd quintile of FT4 (FT4: 0.91 - 4.80 ng/mL). Our study revealed a U-shaped relationship between the rates of undiagnosed DM with thyroid function in a representative and noninstitutionalized US adult population without a prior diagnosis of thyroid dysfunction and diabetes. Different underlying mechanisms may be responsible for the association of DM with high and low thyroid function. Further studies are required to elucidate the underlying mechanisms. Presentation: Thursday, June 15, 2023

The Glucose Challenge Test in Pregnancy Identifies Future Risk of Diabetes.

Women with gestational diabetes (GDM) have an increased future risk of type 2 diabetes but, in practice, their recommended postpartum glucose tolerance testing is often missed or substituted with measurement of A1c instead. We hypothesized that the antenatal screening glucose challenge test (GCT) should predict future diabetes risk and, if so, would have thresholds that identify the same degree of risk as the diagnosis of prediabetes on postpartum measurement of A1c. With population-based administrative databases, we identified all women in Ontario, Canada, who had a GCT in pregnancy with delivery between January 2007 and December 2017, followed by measurement of A1c and fasting glucose within 2 years postpartum (n = 141 858, including 19 034 with GDM). Women were followed over a median of 3.5 years for the development of diabetes. Under the assumption of a linear exposure effect, the 1-hour post-challenge glucose concentration on the GCT was associated with an increased likelihood of developing diabetes (hazard ratio 1.39; 95% CI, 1.38-1.40). A GCT threshold of 8.0 mmol/L predicted the same 5-year risk of diabetes (6.0%; 95% CI, 5.8-6.2) as postpartum A1c 5.7% (identifying prediabetes). Moreover, in women with GDM, a GCT threshold of 9.8 mmol/L equaled prediabetes on postpartum A1c in predicting a 5-year risk of diabetes of 16.5% (14.8-18.2). The GCT offers predictive capacity for future diabetes in pregnant women. In women with GDM, this insight could identify those at highest risk of diabetes, toward whom postpartum screening efforts should be most strongly directed.

Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life.

Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.

The Triglycerides and Glucose (TyG) Index Is Associated with 1-Hour Glucose Levels during an OGTT.

Among individuals with normal glucose tolerance (NGT), subjects with high levels of plasma glucose (≥155 mg/dL) at sixty minutes during an oral glucose tolerance test (1h-OGTT) are at an increased risk of developing type 2 diabetes. We investigated the association between the triglycerides and glucose (TyG) index, a novel marker of insulin resistance, with 1h-OGTT glucose plasma concentrations. 1474 non-diabetic Caucasian subjects underwent a 75 g OGTT and were divided into two groups according to the cutoff 1h-OGTT plasma glucose &lt; 155 mg/dL (NGT-1h-low) and ≥ 155 mg/dL (NGT-1h-high). The TyG index was calculated as ln [fasting triglycerides (milligrams per deciliter) × fasting blood glucose (milligrams per deciliter)/2]. Multivariable linear and logistic regression analyses were used to establish the contribution of the TyG index to the variability of 1h-OGTT glucose, and how the former affected the risk of being NGT-1h-high. 1004 individuals were NGT-1h-low and 470 were NGT-1h-high. The TyG index was higher for NGT-1h-high (p = 0.001) individuals, and it was an independent factor influencing 1h-OGTT glycemia (β = 0.191, p &lt; 0.001) after correcting for age, sex, and BMI. The TyG index was the strongest marker associated with the risk of being NGT-1h-high (OR = 1.703, CI 95% 1.34-2.17, p &lt; 0.001) when compared with FPG (OR = 1.054, CI 95% 1.04-1.07, p &lt; 0.001) and the HOMA-IR (OR = 1.156, CI 95% 1.08-1.23, p &lt; 0.001). Our study demonstrated that the TyG index, an efficient and cost-effective marker of insulin resistance, is associated with the variability of early post-challenge glucose levels and is an independent marker of being NGT-1h-high.

Macronutrient Recommendations for Remission and Prevention of Diabetes in Asian Indians Based on a Data-Driven Optimization Model: The ICMR-INDIAB National Study.

To derive macronutrient recommendations for remission and prevention of type 2 diabetes (T2D) in Asian Indians using a data-driven optimization approach. Dietary, behavioral, and demographic assessments were performed on 18,090 adults participating in the nationally representative, population-based Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. Fasting and 2-h postglucose challenge capillary blood glucose and glycosylated hemoglobin (HbA1c) were estimated. With HbA1c as the outcome, a linear regression model was first obtained for various glycemic categories: newly diagnosed diabetes (NDD), prediabetes (PD), and normal glucose tolerance (NGT). Macronutrient recommendations were formulated as a constrained quadratic programming problem (QPP) to compute optimal macronutrient compositions that would reduce the sum of the difference between the estimated HbA1c from the linear regression model and the targets for remission (6.4% for NDD and 5.6% for PD) and prevention of progression in T2D in PD and NGT groups. Four macronutrient recommendations (%E- Energy) emerged for 1) diabetes remission in NDD: carbohydrate, 49-54%; protein, 19-20%; and fat, 21-26%; 2) PD remission to NGT: carbohydrate, 50-56%; protein,18-20%; fat, 21-27%; 3 and 4) prevention of progression to T2D in PD and NGT: carbohydrate, 54-57% and 56-60%; protein, 16-20% and 14-17%, respectively; and fat 20-24% for PD and NGT. We recommend reduction in carbohydrates (%E) and an increase in protein (%E) for both T2D remission and for prevention of progression to T2D in PD and NGT groups. Our results underline the need for new dietary guidelines that recommend appropriate changes in macronutrient composition for reducing the burden due to diabetes in South Asia.

Breastfeeding effect on glucose tolerance assessment in women with previous gestational diabetes mellitus: A randomized controlled trial.

To test whether breastfeeding during the oral glucose tolerance test (OGTT) affects glucose and insulin outcomes (main outcome: 120 min plasma glucose). A randomized crossover trial was conducted in 20 women with prior gestational diabetes mellitus. Each woman undertook two OGTTs in the first 3 months after delivery, breastfeeding the infant in one and avoiding breastfeeding in the other. Glucose and insulin were measured at 0, 30, 60 and 120 min. Statistics included: T-test for paired data, general linear model (GLM) for repeated measures. Analysis of covariance (ANCOVA) was used to adjust for glucose and insulin values at 0 min. Statistical dispersion for GLM and ANCOVA outcomes is expressed as standard error. In the OGTTs with breastfeeding, higher values were observed for overall glucose and insulin concentrations, glucose and insulin peaks and individual time points of glucose (at 0, 30 and 60 min) and insulin (at 0 and 60 min) but without differences at 120 min (glucose 6.7 ± 0.3 vs. 6.9 ± 0.3 mmol/L, p= 0.506). The rate of abnormal tests was not different. ANCOVA confirmed higher postchallenge glucose values in the OGTT with breastfeeding and similar glucose values at 120 min. According to the results of this randomized trial, we conclude that breastfeeding during the OGTT resulted in similar 120 min glucose concentration and glycaemic status categorization. However, breastfeeding during the OGTT led to clear differences in glucose and insulin values in the first hour, that warrant further studies.

Gut Microbiota across Normal Gestation and Gestational Diabetes Mellitus: A Cohort Analysis.

The prevalence of gestational diabetes mellitus (GDM) is a global public health concern. The mechanism that leads to glucose tolerance beyond normal physiological levels to pathogenic conditions remains incompletely understood, and it is speculated that the maternal microbiome may play an important role. This study analyzes the gut microbiota composition in each trimester of weight-matched women with and without GDM and examines possible bacterial genera associations with GDM. This study followed 56 pregnant women with GDM and 59 without admitted to the outpatient clinic during their first/second or third trimester of gestation. They were submitted to a standardized questionnaire, dietary recalls, clinical examination, biological sample collection, and molecular profiling of fecal microbiota. Women with GDM were older and had a higher number of pregnancies than normal-tolerant ones. There was no difference in alpha diversity, and the groups did not differ regarding the overall microbiota structure. A higher abundance of Bacteroides in the GDM group was found. A positive correlation between Christensenellaceae and Intestinobacter abundances with one-hour post-challenge plasma glucose and a negative correlation between Enterococcus and two-hour plasma glucose levels were observed. Bifidobacterium and Peptococcus abundances were increased in the third gestational trimester for both groups. The gut microbiota composition was not dependent on the presence of GDM weight-matched women throughout gestation. However, some genera abundances showed associations with glucose metabolism. Our findings may therefore encourage a deeper understanding of physiological and pathophysiological changes in the microbiota throughout pregnancy, which could have further implications for diseases prevention.

Cardiometabolic profile of young women with hypoprolactinemia

PurposeUnlike hyperprolactinemia, clinical significance of prolactin deficiency remains poorly understood. The aim of this study was to assess the cardiometabolic profile of patients with low prolactin levels.MethodsThe study population consisted of three groups of young women. Two groups were chronically treated with cabergoline but differed in prolactin levels, which were either abnormally low (group A; n = 16) or within the reference range (group B, n = 23). Group C, serving as a control group, included 28 drug-naïve women with normal prolactin levels. The dose of cabergoline in group A was then tapered down. Glucose homeostasis markers, plasma lipids and circulating levels of hormones, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as the carotid intima-media thickness were assessed at baseline and 6 months later.ResultsCompared with subjects with normal prolactin levels, women with hypoprolactinemia had higher levels of 2-h postchallenge glucose, glycated hemoglobin, triglycerides, uric acid, hsCRP and fibrinogen, lower values of HDL-cholesterol, total testosterone and free androgen index, as well as reduced insulin sensitivity. No differences in these variables were observed between groups B and C. Apart from prolactin normalization, cabergoline dose reduction reversed all laboratory disturbances reported in group A.ConclusionThe obtained results suggest that hypoprolactinemia in women of reproductive age may increase cardiometabolic risk.