Controversy remains as to which obesity measures better predict type 2 diabetes (T2D) risk in overweight or obese individuals. The objective of this study is to determine which commonly used obesity measures better reflect beta cell function and predict T2D risk in participants with overweight or obesity and to validate the findings using prospective cohort data.

Cross-sectional data from the Obesity Clinic of the Xiangya Hospital of the Central South University and prospective cohort from UK Biobank. BMI, waist circumference (WC), waist-to-hip ratio (WHpR), and waist-to-height ratio (WHtR) were measured. Primary outcomes included beta cell function indices in the cross-sectional study and the occurrence of diabetes obtained from UK Biobank data.

One thousand four hundred and ninety-seven participants with overweight or obesity (median age 29 years, 41% males) and 322,023 UK Biobank participants without diabetes at baseline (mean age 56.83 years, 50.4% males) were studied. WHpR had a stronger association with beta cell function and central body fat distribution than the other three obesity measures irrespective of glucometabolic states. WHpR associated positively with diabetes risk in participants using the hazard ratio scale (HR per SD increase of WHpR, 2.311, 95% CI 2.250-2.374).

WHpR is a superior index in reflecting central body obesity, estimating beta cell function, and predicting T2D risk in people with overweight or obesity compared to BMI, WC, and WHtR.

Adverse social contexts, such as lockdowns and disasters during pregnancy, can significantly impact maternal and neonatal outcomes. However, the specific effects on different populations remain unclear. This study aimed to investigate the variations in pregnancy outcomes resulting from the pandemic lockdown and to identify distinct populations in need of targeted intervention.

Women who delivered at our institution spanning from 2017 to 2019 (pre-pandemic) and from 2020 to 2022 (during the pandemic lockdown) were included in this study. A comparison was conducted on maternal and neonatal outcomes across a total of 19,382 singleton pregnancies, with a specific focus on those affected by gestational diabetes mellitus (GDM).

As a total of 19,382 singleton pregnant women were included, this study found a significant increase in the incidence rates of GDM with an odds ratio of 1.194 (95%CI: 1.109-1.286, p < .001). Additionally, following the pandemic lockdown, there was an increase in rates of premature birth, premature rupture of membranes, and intrahepatic cholestasis of pregnancy. Further analysis of the GDM cohort revealed a notable rise in the risk of Group B Streptococcus infection and neonatal small for gestational age (SGA). Specifically, GDM patients with a body mass index (BMI) less than 18.5 kg/m2 exhibited an increased risk of fetal growth restriction and SGA.

The pandemic lockdown adversely affected pregnancy outcomes. Therefore, targeted screening and clinical management for specific populations should be prioritized.

Rare mutations of the ESR1 gene, encoding the estrogen receptor alpha (ERα), have been shown to cause estrogen resistance in humans. Phenotypic features include impaired maturation of epiphyseal cartilage, osteoporosis, and infertility. Clinical phenotype is not well described and the available data reflect inconsistency. To date, there are no effective therapeutic options.

This retrospective study provides a detailed description of bone and metabolic phenotype and 8-year follow-up data of a female with a novel p.Met543Thr missense variant in the homozygous state, localized in the ligand-binding domain.

The patient, first seen at the age of 21.3 years, presented with a tall stature (+2.2 SD), a delayed bone age (13 years). She had no breast development, normal axillary and pubic pilosity and bilateral axillary acanthosis nigricans. The metabolic phenotype included insulin resistance, decreased insulin sensitivity and increased leptinemia. The patient presented a continuous linear growth (height + 3SD at the age of 28.6 years). She had a severe osteoporosis of the lumbar spine (Z-score -3.9) and osteopenia of the femoral neck (Z-score -1.8). Osteoporosis worsened (Z-score -5.6 at the lumbar spine; Z-score -4.4 at the femoral neck) despite successive treatments with ethinyl-estradiol and tamoxifen (selective estrogen modulator). Markers of bone turnover were increased and unresponsive to treatment. Treatment with ethinyl-estradiol improved insulin sensitivity, lowered leptinemia, increased some estrogen-regulated liver proteins and the E2/T ratio.

This report brings new insights to the estrogen resistance syndrome and improves our understanding of the skeletal and tissue specific roles of ERα in humans.

Although the contribution of the circadian clock to metabolic regulation is widely recognized, the role of eating timing in glucose metabolism and diabetes risk remains insufficiently studied. This study aimed (i) to investigate the link between the eating timing pattern relative to individual clock and glucose homoeostasis and (ii) to explore the contribution of genetic and environmental factors to eating timing parameters.

In 92 adult twins (NCT01631123), glycaemic traits were assessed using the oral glucose tolerance test. Parameters of eating timing pattern (eating timing itself, daily calorie distribution, and eating frequency) were extracted from five-day food records. Caloric midpoint defined as the time point at which 50% of daily calories are consumed. Circadian timing of eating was determined as a time interval between the clock time of eating and a corrected midpoint of sleep, a chronotype marker. Heritability of eating timing components was estimated by comparing correlations within monozygotic and dizygotic twin pairs and fitting genetic structural equation models.

Among components of eating timing, the most associations were found for the circadian time of caloric midpoint (CCM). Later CCM was significantly associated with poorer insulin sensitivity, i.e. with lower ISI Stumvoll (β = 0.304, p = 5.9 × 10-4) and higher HOMA-IR (β = -0.258, p = 0.011) indices, as well as with higher fasting insulin levels (β = -0.259, p = 0.013), even after the model adjustment for sex, age, daily energy intake, and sleep duration. Later CCM also demonstrated robust associations with higher BMI and waist circumference. All eating timing components showed high or moderate heritability and were strongly related to individual sleep timing.

Later eating timing in relation to an individual internal clock is associated with lower insulin sensitivity. Shifting the main calorie intake to earlier circadian times may improve glucose metabolism, but genetic factors could influence the feasibility and effectiveness of eating-timing based interventions. The findings should be investigated in a larger cohort.

This work was supported by the German Research Foundation (DFG RA 3340/4-1 to OP-R, project number 530918029), by the European Association for the Study of Diabetes (Morgagni Prize 2020 to OP-R), and by the German Federal Ministry of Education and Research (BMBF NUGAT 0315424 to AFHP). The DZD is funded by the German Federal Ministry for Education and Research (01GI0925).

The identification of mothers at risk for gestational diabetes mellitus (GDM) at start of pregnancy may be beneficial to improve perinatal outcomes. This study aims evaluating the predictive performance of fasting and dynamic indices of glucose metabolism at first trimester and their association with later GDM development. A cohort of 198 women received detailed metabolic assessment at median gestational age (13 weeks) including 75-g oral glucose tolerance test (OGTT) with assessment of glucose, insulin and C-peptide, and biochemical markers (including triglycerides) to calculate different indices of insulin sensitivity either at fasting and in the OGTT dynamic conditions. Moreover, parameters of β-cell function were assessed. A second OGTT was performed between 24 and 28 gestational weeks (GW) to identify women with GDM. We found that 28 women developed GDM, and, in univariable analysis, this was fairly predicted by several first trimester indices, both at fasting and in dynamic conditions. However, fasting indices containing maternal triglycerides showed better accuracy as compared to traditional indices (even the dynamic ones). In multivariable analysis, the best predictive model of GDM development included fasting and OGTT glucose values, HbA1c, and an insulin sensitivity marker that includes triglycerides (e.g. the improved triglyceride-glucose index, TyGIS). β-Cell function was not included in such predictive model, but at 24-28 GW it showed remarkable impairment in women with GDM. In conclusion, both fasting and dynamic parameters of glucose homeostasis at early pregnancy showed fair predictive accuracy for later GDM, with TyGIS showing excellent performance. β-Cell dysfunction role needs being further elucidated.

Precision medicine approaches to gestational diabetes mellitus (GDM) have categorised patients according to disease pathophysiology (insulin resistance, insulin insufficiency or both), and demonstrated associations with clinical outcomes. We aimed to assess whether using enhanced processing to determine indices of insulin secretion and sensitivity is analytically robust, reproducible in a different population, and useful diagnostically and prognostically in clinical practice.

A total of 1308 pregnant women with one or more risk factors for GDM who underwent a 75 g OGTT at one of nine hospital sites were recruited to this observational study. Specimens were collected for determination of glucose levels using standard and enhanced procedures, HbA1c and insulin analysis. GDM diagnosis and management followed National Institute for Health and Care Excellence guidance. We categorised women into pathophysiological subtypes: insulin-resistant GDM (HOMA2-S < 25th centile of the population with normal glucose tolerance [NGT]), insulin-insufficient GDM (HOMA2-B < 25th centile), both or neither. We assessed associations with pregnancy outcomes using logistic regression.

Using enhanced specimen handling, 1027/1308 (78.5%) women had NGT, with 281/1308 (21.5%) being classified as having GDM. Of this group, 135/281 (48.0%) had insulin-resistant GDM, 73/281 (26.0%) had insulin-insufficient GDM and 2/281 (0.7%) had both insulin-resistant and insulin-insufficient GDM. Unexpectedly, 71 patients (25.3%) had GDM with both HOMA2-S and HOMA2-B ≥ 25th centile (GDM-neither). This novel subgroup appeared to be relatively insulin-sensitive in the fasting state but developed marked post-load hyperglycaemia and hyperinsulinaemia, suggesting an isolated postprandial defect in insulin sensitivity that was not captured by HOMA2-B or HOMA2-S. Women within most GDM subgroups had comparable pregnancy outcomes to those of normoglycaemic women, and HOMA2-B and HOMA2-S were weak predictors of pregnancy outcomes. Maternal BMI predicted a similar number of outcomes to HOMA2-S, suggesting that there was no additional predictive value in adding HOMA2-S. Similar findings were obtained when using different indices and standard specimen handling techniques.

Precision categorisation of GDM using HOMA2-S and HOMA2-B does not provide useful diagnostic or prognostic information, but did distinguish a novel subgroup of patients with GDM, characterised by an isolated postprandial defect in insulin sensitivity.

Hypoxia stimulates glucose uptake independently from the action of insulin. The purpose of this study was to determine the effect of intermittent hypoxia, consisting of alternating short bouts of breathing hypoxic and room air, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Nine adults with type 2 diabetes (2 women, HbA1c: 7.3 ± 1.5%, age: 52 ± 13 yr) and nine adults with normal glycemic control (4 women, HbA1c: 5.4 ± 0.1%, age: 24 ± 4 yr) performed a 2-h oral glucose tolerance test on two separate visits to the laboratory. Following ingestion of the glucose drink, participants were exposed to either an intermittent hypoxia protocol, consisting of eight 4-min hypoxic cycles at a targeted oxygen saturation of 80% interspersed with breathing room air to resaturation, or a sham protocol consisting of eight 4-min normoxic cycles interspersed with breathing room air. Intermittent hypoxia did not attenuate the increase in glucose concentration but attenuated the increase in insulin concentration in response to an oral glucose tolerance test in comparison with the sham protocol in adults with type 2 diabetes. Insulin sensitivity was greater during intermittent hypoxia in comparison with the sham protocol in adults with type 2 diabetes (0.043 ± 0.036 vs. 0.032 ± 0.046 μmol/kg/min/pmol, P = 0.01), but did not change in the control group (0.122 ± 0.015 vs. 0.128 ± 0.008 μmol/kg/min/pmol, P = 0.12). In conclusion, intermittent hypoxia improved insulin sensitivity in adults with type 2 diabetes.NEW & NOTEWORTHY The aim of this study was to determine the effect of short bouts of hypoxia, which stimulates glucose uptake, on glucose concentration, insulin concentration, and insulin sensitivity during an oral glucose tolerance test in adults with type 2 diabetes and adults with normal glycemic control. Intermittent hypoxia acutely improved insulin sensitivity in adults with type 2 diabetes.

Low-carbohydrate diets and intermittent energy restriction may offer metabolic advantages in fuel utilisation, that are independent of weight loss. The underlying mechanisms for these effects are unclear but may involve extensions of the catabolic phase and/or attenuation of insulin secretion. To address this gap, we aimed to investigate the independent acute metabolic effect of carbohydrate restriction at varying energy levels. Twelve, (six female) healthy overweight/obese participants (27.3 ± 1.8 years; 25.2 ± 1.6 kg/m2) completed this three-way study. Volunteers followed three diets for one day (36 h, covering the intervention day and overnight fasting), separated by 5-day washout: a normal carbohydrate, energy-balanced diet (nEB, 55% CHO), a low-carbohydrate, energy-balanced diet (LCEB, 50 g/day CHO), and a low-carbohydrate, energy-restricted diet (LC25, 50 g/day CHO with 75% energy restriction). Fasting and serial postprandial (360 min) measurements to a mixed test meal were collected the following morning. Additionally, subjective appetite responses and two-day subsequent ad libitum food intake was assessed. Both low-carbohydrate with and without energy restriction diets induced comparable decrease in triacylglycerol iAUC (p = 0.02, p = 0.04, respectively), and respiratory quotient (both p < 0.01) along with increase in non-esterified fatty acids (both p < 0.01) and 3-hydroxybutyrate (p = 0.001, p = 0.01, respectively) levels. Compared to a non-restricted carbohydrate, energy-balanced diet, postprandial glucose levels significantly increased in the LCEB arm (p = 0.024) and showed a rising trend in the LC25 arm (p = 0.07). Neither insulin responses nor resting, and diet-induced thermogenesis were significantly altered by variations in energy or carbohydrate content. These findings demonstrate that carbohydrate restriction, without altering energy intake, can elicit effects similar to those observed in short-term fasting. As such we propose a strategy of repeated carbohydrate restriction cycles alone may be an emerging alternative approach for the enhancement of cardiometabolic health, warranting further investigation.

During the COVID-19 pandemic, the Health Service Executive (HSE) and Royal College of Obstetricians and Gynaecologists (RCOG) recommended fasting and random plasma glucose (FPG/RPG) alongside glycated haemoglobin (HbA1c) to replace the oral glucose tolerance test (OGTT) for diagnosing Gestational Diabetes Mellitus (GDM).

The study compared testing patterns and diagnostic rates for GDM before and after implementing the RCOG guidelines (01/05/2020) in pregnancies beginning 01/11/2018 to 31/03/2021. Trends were inspected using Cochrane-Armitage tests. Differences between General Practice (GP) and Secondary Care (SCare) were assessed by chi-square analysis. A significance level of p < 0.05 was used for all analyses. Information on maternal and pregnancy characteristics was accessed where available.

Data indicated a significant reduction in OGTTs requested by GPs and SCare. Conversely, HbA1c, FPG and RPG test requests increased significantly in both locations. The overall GDM positivity rate increased significantly from 7.4% to 22.0% in GP and 16.9% to 39.0% in SCare following RCOG guideline implementation.

The RCOG guidelines appear to have been well adopted by GPs and SCare, with greater adherence in SCare. Using FPG, RPG and HbA1c to a greater extent than the OGTT corresponded with increased GDM diagnostic rates. Given the difficulties with interpreting HbA1c in pregnancy, its routine use in diagnosing GDM requires further careful consideration. Relaying changes in diagnostic protocol during pandemics requires strong communication with all requesting clinicians, including GPs. Comparisons between GP and SCare indicated significant differences in test-requesting practices and GDM positivity rates.

Subtypes of gestational diabetes mellitus (GDM) based on insulin sensitivity and secretion have been described. We addressed the hypothesis that GDM subtypes are differentially associated with newborn and child anthropometric and glycemic outcomes.

Newborn and child (age 11-14 years) outcomes were examined in 7,970 and 4,160 mother-offspring dyads, respectively, who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study and HAPO Follow-Up Study. GDM was classified as insulin-deficient GDM (insulin secretion <25th percentile with preserved insulin sensitivity), insulin-resistant GDM (insulin sensitivity <25th percentile with preserved insulin secretion), or mixed-defect GDM (both <25th percentile). Regression models for newborn and child outcomes included adjustment for field center, maternal BMI, and other pregnancy covariates. Child models also included adjustment for child age, sex, and family history of diabetes.

Compared with mothers with normal glucose tolerance, all three GDM subtypes were associated with birth weight and sum of skinfolds >90th percentile. Insulin-resistant and mixed-defect GDM were associated with higher risk of cord C-peptide levels >90th percentile. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia. Insulin-resistant GDM was associated with higher risk of neonatal hypoglycemia and childhood obesity (odds ratio [OR] 1.53, 95% CI 1.127-2.08). The risk of childhood impaired glucose tolerance was higher with insulin-resistant GDM (OR 2.21, 95% CI 1.50-3.25) and mixed-defect GDM (OR 3.01, 95% CI 1.47-6.19).

GDM subtypes are differentially associated with newborn and childhood outcomes. Better characterizing individuals with GDM could help identify at-risk offspring to offer targeted, preventative interventions early in life.

Standard lifestyle interventions have shown limited efficacy in preventing type 2 diabetes among individuals with isolated impaired fasting glucose (i-IFG). Hence, tailored intervention approaches are necessary for this high-risk group.

This study aims to (1) assess the feasibility of conducting a high-intensity interval training (HIIT) study and the intervention acceptability among individuals with i-IFG, and (2) investigate the preliminary efficacy of HIIT in reducing fasting plasma glucose levels and addressing the underlying pathophysiology of i-IFG.

This study is a 1:1 proof-of-concept randomized controlled trial involving 34 physically inactive individuals (aged 35-65 years) who are overweight or obese and have i-IFG. Individuals will undergo a 3-step screening procedure to determine their eligibility: step 1 involves obtaining clinical information from electronic health records, step 2 consists of completing questionnaires, and step 3 includes blood tests. All participants will be fitted with continuous glucose monitoring devices for approximately 80 days, including 10 days prior to the intervention, the 8-week intervention period, and 10 days following the intervention. Intervention participants will engage in supervised HIIT sessions using stationary "spin" cycle ergometers in groups of 5 or fewer. The intervention will take place 3 times a week for 8 weeks at the Aerobic Exercise Laboratory in the Rehabilitation Hospital at Emory University. Control participants will be instructed to refrain from engaging in intense physical activities during the study period. All participants will receive instructions to maintain a eucaloric diet throughout the study. Baseline and 8-week assessments will include measurements of weight, blood pressure, body composition, waist and hip circumferences, as well as levels of fasting plasma glucose, 2-hour plasma glucose, and fasting insulin. Primary outcomes include feasibility parameters, intervention acceptability, and participants' experiences, perceptions, and satisfaction with the HIIT intervention, as well as facilitators and barriers to participation. Secondary outcomes comprise between-group differences in changes in clinical measures and continuous glucose monitoring metrics from baseline to 8 weeks. Quantitative data analysis will include descriptive statistics, correlation, and regression analyses. Qualitative data will be analyzed using framework-driven and thematic analyses.

Recruitment for the study is scheduled to begin in February 2025, with follow-up expected to be completed by the end of September 2025. We plan to publish the study findings by the end of 2025.

The study findings are expected to guide the design and execution of an adequately powered randomized controlled trial for evaluating HIIT efficacy in preventing type 2 diabetes among individuals with i-IFG.

Clinicaltrials.gov NCT06143345; https://clinicaltrials.gov/study/NCT06143345.

PRR1-10.2196/59842.

Physical exercise is a key component in the treatment of type 2 diabetes and plays an important role in maintaining a healthy glucose metabolism even in healthy subjects. To date, no studies have investigated the effect of a single bout of aerobic physical exercise on glucose metabolism in young, moderately active, healthy adults.

We performed an OGTT 7 days before and 24 h after a single bout of physical exercise, to evaluate 1-hour post-load plasma glucose and surrogate indexes of insulin sensitivity and insulin secretion.

Glucose levels were significantly reduced after exercise at baseline and one hour after glucose load; similarly, insulin was significantly lower 1 h after glucose load. We found a significant increase in the Matsuda index, confirmed by OGIS index, QUICKI index, and by significant reduction in HOMA-IR. Conversely, we observed a trend to increase in HOMA-B.

This is the first study to evaluate the effect of a single bout of exercise on 1-hour glucose levels following OGTT. We found a significant reduction in 1-hour glucose levels following OGTT together with an increased insulin sensitivity. A single 30-minute bout of aerobic exercise also seemed to improve the insulin secretion pattern. Modifications in beta cell secretory capacity during exercise are likely secondary to an improvement in insulin action in insulin dependent tissues.

Evidence from observational and Mendelian randomization (MR) studies suggested that insulin resistance (IR) was associated with Alzheimer's disease (AD). However, the causal effects of different indicators of IR on AD remain inconsistent. Here, we aim to assess the causal association between the insulin sensitivity index (ISI), a measure of post-prandial IR, and the risk of AD. We first conducted primary and secondary univariable MR analyses. We selected 8 independent genome-wide significant (p < 5E-08, primary analyses) and 61 suggestive (p < 1E-05, secondary analyses) ISI genetic variants from large-scale genome-wide association studies (GWAS; N = 53 657), respectively, and extracted their corresponding GWAS summary statistics from AD GWAS, including IGAP2019 (N = 63 926) and FinnGen_G6_AD_WIDE (N = 412 181). We selected five univariable MR methods and used heterogeneity, horizontal pleiotropy test, and leave-one-out sensitivity analysis to confirm the stability of MR estimates. Finally, we conducted a meta-analysis to combine MR estimates from two non-overlapping AD GWAS datasets. We further performed multivariable MR (MVMR) to assess the potential mediating role of type 2 diabetes (T2D) on the association between ISI and AD using two MVMR methods. In univariable MR, utilizing 8 genetic variants in primary analyses, we found a significant causal association of genetically increased ISI with decreased risk of AD (OR = 0.79, 95% CI: 0.68-0.92, p = 0.003). Utilizing 61 genetic variants in secondary analyses, we found consistent findings of a causal effect of genetically increased ISI on the decreased risk of AD (OR = 0.89, 95% CI: 0.82-0.96, p = 0.003). Heterogeneity, horizontal pleiotropy test, and leave-one-out sensitivity analysis ensured the reliability of the MR estimates. In MVMR, we found no causal relationship between ISI and AD after adjusting for T2D (p > 0.05). We provide genetic evidence that increased ISI is significantly and causally associated with reduced risk of AD, which is mediated by T2D. These findings may inform prevention strategies directed toward IR-associated T2D and AD.

Introduction: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. Materials and Methods: Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis. Weighted Gene Co-Expression Network Analysis (WGCNA) and mediation analysis were used to explore the clinical impacts of metabolomic biomarkers. Results: Visual separations of the metabolic profiles were observed between three bone mineral density (BMD) groups in both genders. According to the iENA approach, several metabolites had significant abundance and association changes in osteopenia participants, confirming that osteopenia is a critical stage in the development of osteoporosis. Metabolites were further selected to identify osteopenia (nine metabolites in females; eight metabolites in males), and their ability to discriminate osteopenia was improved significantly compared to traditional bone turnover markers (BTMs) (female AUC = 0.717, 95% CI 0.547-0.882, versus BTMs: p = 0.036; male AUC = 0.801, 95% CI 0.636-0.966, versus BTMs: p = 0.007). The roles of the identified key metabolites were involved in the association between total fat-free mass (TFFM) and osteopenia in females. Conclusion: Osteopenia was identified as a tipping point during the development of osteoporosis with metabolomic characteristics. A few metabolites were identified as candidate early-warning biomarkers by machine learning analysis, which could indicate bone loss and provide new prevention guidance for osteoporosis.

Increased adiposity has been directly associated with insulin resistance (IR), and cytokines released by adipose tissue seem to link adiposity to IR in youth. We used an antibody-based array to investigate the differential levels of serum cytokines according to insulin status in a cohort of overweight/obese and inactive adolescents and evaluated their potential associations with clinical and metabolic characteristics.

We performed a cross-sectional data analysis from 122 adolescents (11-17 years of age). We assessed body composition, cardiometabolic risk factors, biochemical variables, and physical fitness. The concentration of 55 cytokines was quantified in blood samples. The homeostasis model assessment insulin resistance (HOMA-IR) and AST/ALT and TG/HDL ratios were calculated. IR adolescents as defined as HOMA-IR >2.5. The number of adolescents with IR in the study was 91 (66 % girls). In the IS group, after controlling for confounders, higher IL-15 levels were significantly associated with higher alanine aminotransferase levels and lower AST/ALT ratio, respectively (Ps<0.05). In the same line, there were significantly higher alanine aminotransferase levels and lower AST/ALT ratio, respectively, with FGF-9 (Ps<0.05). Likewise, higher alanine aminotransferase levels were significantly associated positively with HGF (p=0.045). Additionally, leptin levels are associated with six adiposity indexes (i.e., fat mass/height index, body fat, body mass index, android fat mass and gynoid fat mass) in overweight/obese adolescents with IR (Ps<0.05).

These data may provide novel insights into the pathogenic mechanisms underlying IR in youth, offering new targets for prevention.

Improvements in glycemic control following acute exercise are typically attributed to improved postexercise insulin sensitivity (IS) with comparatively little known about how acute exercise impacts β cell function, especially in postmenopausal females. We determined how two high-intensity interval training (HIIT) protocols, matched for total estimated energy expenditure, impact β cell function in postmenopausal females with type 2 diabetes. Thirteen postmenopausal females (70 ± 5 yr; 12 ± 7 yr since diagnosis, 80.9 ± 13.8 kg, 32.4 ± 5.6 kg·m2; HbA1c-49.8 ± 10.3 mmol/mol [6.7 ± 1.0]) living with type 2 diabetes were included in this semirandomized crossover trial. The trial involved an initial resting control condition followed by two HIIT conditions [4 × 4-min HIIT (HIIT4) and 10 × 1-min HIIT (HIIT10)] completed in a randomized order 2-4 days apart. β cell function (glucose sensitivity) and insulin sensitivity were determined from a 2-h mixed-meal tolerance test performed 2 h after rest or HIIT. Both HIIT4 and HIIT10 significantly improved β cell glucose sensitivity compared with control (15 pmol/min/m2/[mmol/L], [95% confidence interval (CI) 6, 23]; P = 0.002 and 16 pmol/min/m2/[mmol/L], [95% CI 7, 25]; P = 0.002, respectively), with no difference between HIIT protocols (1 [-8, 10], P = 0.79). There were no significant differences in IS metrics (Matsuda index, OGIS, Stumvoli, and QUICKI) between the conditions. An acute bout of 4 × 4-min or 10 × 1-min HIIT improves β cell glucose sensitivity in postmenopausal females living with type 2 diabetes. ClinicalTrials.gov: NCT04986345.NEW & NOTEWORTHY This is the first study to explore the effects of acute high-intensity interval training (HIIT) on β cell function in postmenopausal women with type 2 diabetes. Our crossover trial compares two HIIT protocols, matched for total estimated energy expenditure, examining their impacts on β cell function and insulin sensitivity. Despite the absence of an insulin-sensitizing effect, we show robust effects of HIIT on β-cell function, including an improvement in β-cell glucose sensitivity.

The classification of type 2 diabetes and prediabetes does not consider heterogeneity in the pathophysiology of glucose dysregulation. Here we show that prediabetes is characterized by metabolic heterogeneity, and that metabolic subphenotypes can be predicted by the shape of the glucose curve measured via a continuous glucose monitor (CGM) during standardized oral glucose-tolerance tests (OGTTs) performed in at-home settings. Gold-standard metabolic tests in 32 individuals with early glucose dysregulation revealed dominant or co-dominant subphenotypes (muscle or hepatic insulin-resistance phenotypes in 34% of the individuals, and β-cell-dysfunction or impaired-incretin-action phenotypes in 40% of them). Machine-learning models trained with glucose time series from OGTTs from the 32 individuals predicted the subphenotypes with areas under the curve (AUCs) of 95% for muscle insulin resistance, 89% for β-cell deficiency and 88% for impaired incretin action. With CGM-generated glucose curves obtained during at-home OGTTs, the models predicted the muscle-insulin-resistance and β-cell-deficiency subphenotypes of 29 individuals with AUCs of 88% and 84%, respectively. At-home identification of metabolic subphenotypes via a CGM may aid the risk stratification of individuals with early glucose dysregulation.

Insulin resistance (IR) contributes substantially to the development of cardiovascular disease (CVD) and metabolic disorders, particularly obesity. The homeostatic model assessment of IR is a prevalent IR indicator, but insulin measurement is quite impractical for widely use. Given its convenience and accessibility, the triglyceride-glucose (TyG) index, along with modified indices such as the triglyceride-glucose-waist circumference (TyG-WC) and triglyceride-glucose-waist-height ratio (TyG-WHtR), are gaining recognition as practical tools for assessing IR. This study aimed to investigate the specific correlation between the TyG index and its modified indices with arterial stiffness in an overweight or obese population and to explore novel, self-defined modified TyG indices for identifying individuals at elevated risk for such conditions.

This retrospective study included 1,143 overweight or obese individuals from 2021 to 2023. Medical data, including brachial-ankle pulse wave velocity (baPWV), were collected. Two novel modified TyG indices, TyG-1h and TyG-2h, were defined by substituting the fasting glucose level in the TyG formula with 1-hour and 2-hour post-load plasma glucose levels, respectively. Multivariate logistic regression analyses were conducted to identify parameters that demonstrated a statistically significant correlation with arterial stiffness, defined as a baPWV threshold of ≥ 1400 cm/s. Additionally, restricted cubic spline (RCS) modelling was employed to further explore these relationships in a visually interpretable manner. To evaluate and compare the diagnostic accuracy of the conventional TyG index and its novel modified versions, receiver operating characteristic (ROC) curve analyses were performed.

Our findings revealed that individuals with arterial stiffness presented significantly elevated TyG index and all its modified versions (P< 0.05). By utilizing a binary logistic regression model and adjusting for potential confounders, we determined that all TyG-related parameters independently correlated with an increased risk of developing arterial stiffness. Moreover, TyG-WHtR displayed the best correlation (OR 3.071, 95% CI 1.496-6.303) when stratified by quartiles, followed by TyG-1h (OR 2.298, 95% CI 1.248-4.234) and TyG-2h (OR 2.115, 95% CI 1.175-3.807). ROC curves suggested that TyG-1h and TyG-2h demonstrated superior diagnostic performance compared to TyG, with AUCs of 0.685, 0.679 and 0.673, respectively.

The modified TyG indices exhibited strong effectiveness in identifying arterial stiffness in Chinese overweight or obese individuals.

In a clinical study, tirzepatide, a glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA), provided superior glycemic control vs the GLP-1RA semaglutide. The physiologic mechanisms are incompletely understood.

This work aimed to evaluate treatment effects by model-based analyses of mixed-meal tolerance test (MMTT) data.

A 28-week double-blind, randomized, placebo-controlled trial of patients with type 2 diabetes treated with metformin was conducted at 2 clinical research centers in Germany. Interventions included tirzepatide 15 mg, semaglutide 1 mg, and placebo. Main outcome measures included glycemic control, model-derived β-cell function indices including insulin secretion rate (ISR) at 7.2-mmol/L glucose (ISR7.2), β-cell glucose sensitivity (β-CGS), insulin sensitivity, and estimated hepatic insulin-to-glucagon ratio.

Tirzepatide significantly reduced fasting glucose and MMTT total glucose area under the curve (AUC) vs semaglutide (P < .01). Incremental glucose AUC did not differ significantly between treatments; therefore, greater total glucose AUC reduction with tirzepatide was mainly attributable to greater suppression of fasting glucose. A greater reduction in total ISR AUC was achieved with tirzepatide vs semaglutide (P < .01), in the context of greater improvement in insulin sensitivity with tirzepatide (P < .01). ISR7.2 was significantly increased with tirzepatide vs semaglutide (P < .05), showing improved β-CGS. MMTT-derived β-CGS was increased but not significantly different between treatments. Both treatments reduced fasting glucagon and total glucagon AUC, with glucagon AUC significantly reduced with tirzepatide vs semaglutide (P < .01). The estimated hepatic insulin-to-glucagon ratio did not change substantially with either treatment.

These results suggest that the greater glycemic control observed for tirzepatide manifests as improved fasting glucose and glucose excursion control, due to improvements in ISR, insulin sensitivity, and glucagon suppression.

To examine longitudinal and dose-d ependent associations between dietary fiber intake and various clinical outcomes over 48 weeks of pharmacological treatment in T2DM patients.

In this secondary analysis, we used data from the MARCH trial, which was designed to compare the efficacy of acarbose or metformin monotherapy as the initial therapy in Chinese patients newly diagnosed with T2DM. Dietary data were obtained using a 24-h dietary recall method to evaluate the intakes of dietary fiber from different sources as well as the carbohydrate-to-fiber ratio.

A total of 551 newly-diagnosed patients with T2DM complete dietary records (286 in the acarbose group and 265 in the metformin group) were included. Higher intake of total fiber and whole grain fiber was positively associated with better β-cell function, insulin sensitivity and postprandial glycemic control under acarbose treatment. Higher intake of legume fiber was associated with better glycemic control under both acarbose and metformin treatment but with better weight loss only under metformin treatment. A high-carbohydrate-low-fiber diet was associated with worse glycemic control and lower HDL-C under acarbose treatment but with higher insulin sensitivity and better weight loss under metformin treatment.

The notable effects of various dietary fibers when combined with different oral glucose-lowering medications should be considered to maximize therapeutic benefit.

The genetics of β-cell function (BCF) offer valuable insights into the aetiology of type 2 diabetes (T2D)1,2. Previous studies have expanded the catalogue of BCF genetic associations through candidate gene studies3-7, large-scale genome-wide association studies (GWAS) of fasting BCF8,9 or functional islet studies on T2D risk variants10-14. Nonetheless, GWAS focused on BCF traits derived from oral glucose tolerance test (OGTT) data have been limited in sample size15,16 and have often overlooked the potential for related traits to capture distinct genetic features of insulin-producing β-cells17,18. We reasoned that investigating the genetic basis of multiple BCF estimates could provide a broader understanding of β-cell physiology. Here, we aggregate GWAS data of eight OGTT-based BCF traits from ~26,000 individuals of European descent, identifying 55 independent genetic associations at 44 loci. By examining the effects of BCF genetic signals on related phenotypes, we uncover diverse disease mechanisms whereby genetic regulation of BCF may influence T2D risk. Integrating BCF-GWAS data with pancreatic islet transcriptomic and epigenomic datasets reveals 92 candidate effector genes. Gene silencing in β-cell models highlights ACSL1 and FAM46C as key regulators of insulin secretion. Overall, our findings yield insights into the biology of insulin release and the molecular processes linking BCF to T2D risk, shedding light on the heterogeneity of T2D pathophysiology.

Metabolic characteristics and outcomes were compared among pregnant individuals with varying levels of glucose intolerance.

827 participants from a randomized clinical trial comparing the IADPSG and Carpenter Coustan Criteria were grouped as follows: normal glucose tolerance, mild glucose intolerance (100 g OGTT with one abnormal value) and treated GDM (diagnosed by Carpenter Coustan or IADPSG criteria). Differences in metabolic characteristics and perinatal outcomes were assessed using inverse probability of treatment weighting.

Mild glucose intolerance had lower insulin sensitivity and beta cell response than normal glucose tolerance, and similar findings to treated GDM. Small for gestational age (SGA) (OR 0.13, 95% CI 0.08-0.24) and neonatal composite morbidity were lower (OR 0.53, 95% CI 0.38-0.74), and maternal composite morbidity higher (OR 2.03, 95% CI 1.57-2.62) when comparing mild intolerance to normal glucose tolerance. Large for gestational age (OR 3.42 95% CI 1.39-8.41) was higher while SGA (OR 0.21, 95% CI 0.05-0.81) and neonatal composite morbidity (OR 0.31, 95% CI 0.17-0.57) were lower with mild glucose intolerance compared to treated GDM.

Mild glucose intolerance has a similar metabolic profile to treated GDM, and outcome differences are likely related to knowledge of diagnosis and treatment.

NCT02309138.

Background: Identifying β-cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet β-cell function in individuals with T2DM remains insufficiently investigated. Methods: This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual-energy X-ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C-peptide, and glucose levels were assessed concurrently following a glucose load. β-cell function included insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA-β and C-peptidogenic index (CGI). Results: Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA-IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA-IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (ΔBMI) and ΔMI, while positive associations were observed in both ΔHOMA-IR and ΔCGI. Among body composition indexes, ΔFMI exhibited the strongest correlation with ΔHOMA-IR (r = 0.255, p < 0.001), and ΔASMI was positively associated with ΔMI and ΔCGI (r = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Conclusions: Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM.

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, β-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 β-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, β-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 β-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 β-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 β-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.

Continuous Glucose Monitoring (CGM) not only can be used for glycemic control in chronic diseases (e.g., diabetes), but is increasingly being utilized by individuals and athletes to monitor fluctuations in training and everyday life. However, it is not clear how accurately CGM reflects plasma glucose concentration in a healthy population in the absence of chronic diseases. In an oral glucose tolerance test (OGTT) with forty-four healthy male subjects (25.5 ± 4.5 years), the interstitial fluid glucose (ISFG) concentration obtained by a CGM sensor was compared against finger-prick capillary plasma glucose (CPG) concentration at fasting baseline (T0) and 30 (T30), 60 (T60), 90 (T90), and 120 (T120) min post OGTT to investigate differences in measurement accuracy. The overall mean absolute relative difference (MARD) was 12.9% (95%-CI: 11.8-14.0%). Approximately 100% of the ISFG values were within zones A and B in the Consensus Error Grid, indicating clinical accuracy. A paired t-test revealed statistically significant differences between CPG and ISFG at all time points (T0: 97.3 mg/dL vs. 89.7 mg/dL, T30: 159.9 mg/dL vs. 144.3 mg/dL, T60: 134.8 mg/dL vs. 126.2 mg/dL, T90: 113.7 mg/dL vs. 99.3 mg/dL, and T120: 91.8 mg/dL vs. 82.6 mg/dL; p < 0.001) with medium to large effect sizes (d = 0.57-1.02) and with ISFG systematically under-reporting the reference system CPG. CGM sensors provide a convenient and reliable method for monitoring blood glucose in the everyday lives of healthy adults. Nonetheless, their use in clinical settings wherein implications are drawn from CGM readings should be handled carefully.

Accurate measurements of glycaemic control and the underpinning regulatory mechanisms are vital in human physiology research. Glycaemic control is the maintenance of blood glucose concentrations within optimal levels and is governed by physiological variables including insulin sensitivity, glucose tolerance and β-cell function. These can be measured with a plethora of methods, all with their own benefits and limitations. Deciding on the best method to use is challenging and depends on the specific research question(s). This review therefore discusses the theory and procedure, validity and reliability and any special considerations of a range common methods used to measure glycaemic control, insulin sensitivity, glucose tolerance and β-cell function. Methods reviewed include glycosylated haemoglobin, continuous glucose monitors, the oral glucose tolerance test, mixed meal tolerance test, hyperinsulinaemic euglycaemic clamp, hyperglycaemic clamp, intravenous glucose tolerance test and indices derived from both fasting concentrations and the oral glucose tolerance test. This review aims to help direct understanding, assessment and decisions regarding which method to use based on specific physiology-related research questions.

We tested whether skeletal muscle mass is associated with insulin sensitivity, pancreatic β-cell function, and postglucose glycemia.

Appendicular skeletal muscle mass (ASM) (relative to body size, %ASM) by DXA, surrogate measures of insulin sensitivity, insulin secretion and the disposition index (insulin sensitivity adjusted insulin secretion: a product of the insulinogenic index and Matsuda insulin sensitivity index) inferred from serum insulin kinetics during a 75 g oral glucose tolerance test (OGTT) were evaluated in 168 young and 65 middle-aged women, whose BMI averaged <23.0 kg/m2 and HbA1c ≦ 5.5 %.

In two groups of women, %ASM was associated negatively with homeostasis model assessment insulin resistance (HOMA-IR) and 2-h insulin (both p < 0.01 or less). In middle-aged women not in young women, %ASM was associated inversely with the Matsuda index (p < 0.001). In middle-aged women only, it also showed a positive association with the disposition index (p = 0.02) and inverse associations with 1-h and 2-h glucose (both p < 0.01) and area under the glucose concentration curve during OGTT (p = 0.006). On multivariate linear regression analyses, 2-h insulin emerged as a determinant of %ASM independently of HOMA-IR in young women (standardized β: 0.287, p < 0.001, R2 = 0.077). In middle-aged women, the Matsuda index emerged as a determinant of %ASM (standardized β: 0.476, p < 0.001) independently of HOMA-IR, log ODI and AUCg and explained 21.3 % of %ASM variability. Post-glucose glycemia and AUCg were higher and log ODI was lower in middle-aged women with low compared with high %ASM.

Low skeletal muscle mass (relative to body size) was associated with low insulin sensitivity in young and middle-aged Japanese women who were neither obese nor diabetic. Middle-aged women with low muscle mass had low disposition index, an early marker of inadequate pancreatic β-cell compensation, and hence high glucose excursion. Low skeletal muscle mass may be associated with the development of type 2 diabetes at a much lower BMI in Japanese people.

The relationship of adipose tissue insulin resistance (AT-IR, a product of fasting insulin and free fatty acids) and homeostasis-model assessment-insulin resistance (HOMA-IR) to β-cell function was studied cross-sectionally in the setting of subtle glucose dysregulation. Associations of AT-IR and HOMA-IR with fasting and post-glucose glycemia and β-cell function inferred from serum insulin kinetics during a 75 g oral glucose tolerance test were studied in 168 young female Japanese students. β-cell function was evaluated by disposition index calculated as a product of the insulinogenic index (IGI) and Matsuda index. AT-IR, not HOMA-IR, showed positive associations with post-glucose glycemia and area under the glucose response curve although both indices were associated with fasting glycemia. HOMA-IR, not AT-IR, was associated positively with log IGI whereas both indices were inversely associated with Matsuda index. AT-IR, not HOMA-IR, showed inverse associations with log disposition index. Associations of adipose tissue insulin resistance with β-cell function (inverse) and glucose excursion in young Japanese women may suggest that lipotoxicity to pancreatic β-cells for decades may be associated with β cell dysfunction found in Japanese patients with type 2 diabetes. Positive association of HOMA-IR with insulinogenic index may be associated with compensatory increased insulin secretion.

Background and Objectives: Deep seawater has been shown to restore pancreatic function in obese diabetic mice and considerably improve the homeostatic model assessment for insulin resistance, total cholesterol, and low-density lipoprotein cholesterol concentrations in patients with impaired fasting glucose or glucose tolerance. In this study, the effect of 12-week daily consumption of magnesium (Mg2+)-containing deep seawater mineral extracts on blood glucose concentration and insulin metabolism-associated indicators was investigated in patients with impaired glucose tolerance. Materials and methods: In this 12-week randomized, double-blind trial, patients (n = 37) with impaired glucose tolerance consumed deep seawater mineral extracts. Changes in blood glucose concentration and related indicators were compared between the treatment group and placebo group (n = 38). Results: The fasting insulin, C-peptide, homeostatic model assessment for insulin resistance, quantitative insulin sensitivity check index, homeostatic model assessment of beta-cell function, and Stumvoll insulin sensitivity index values in the deep seawater mineral extract group showed improvements compared with the placebo group. However, no significant differences between groups were observed in fasting blood glucose, postprandial blood glucose, glycated hemoglobin, or incremental area under the curve values. Conclusions: Oral supplementation with deep seawater mineral extracts enriched in Mg2+ markedly improves insulin sensitivity in patients with pre-diabetes. This study illustrates the potential clinical application of natural Mg2+ from deep seawater to alleviate insulin resistance in patients with pre-diabetes. Trial registration: This trial was retrospectively registered with Clinical Research information Service (CRIS), No. KCT0008695, on 8 August 2023.

Our study aimed to analyze how hepatic insulin resistance (IR) influences the efficacy of 48 weeks of metformin treatment in newly diagnosed type 2 diabetes patients.

We chose 291 participants who were allocated to a 48-week metformin treatment in the "Metformin and Acarbose in Chinese as initial Hypoglycemic treatment" (MARCH) trial and calculated their hepatic insulin resistance indexes (HIRI). We equally grouped the subjects into tertiles: low, medium, and high HIRI groups based on baseline HIRI; Low, medium, and high ΔHIRI groups based on the decreasing extent of HIRI after a 48-week metformin treatment.

Multiple linear regression showed that baseline HIRI was positively associated with the rising degree of Matsuda index and the falling range of fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and HIRI. Furthermore, baseline fasting insulin, homeostatic model assessment of β cell function (HOMA-β), HOMA-IR, and HIRI were positively associated with the decreasing extent of HIRI, while baseline Matsuda index had a negative association with the falling extent of HIRI.

Patients with higher levels of hepatic IR obtained better curative effects from metformin in terms of glycemic control, insulin saving, insulin sensitivity enhancement, and IR improvement. Higher fasting blood glucose, fasting insulin, HOMA-β, IR, and lower Matsuda index were indicators of better hepatic IR improvement.

Despite some reported benefits, there is a low quality of evidence for resistance training (RT) improving metabolic health of individuals with overweight or obesity. We evaluated the impact of RT on body composition, cardiorespiratory fitness (CRF) and physical performance, lipid-lipoprotein profile, inflammation, and glucose-insulin homeostasis in 51 postmenopausal women versus 29 controls matched for age, obesity, and physical activity. Exercised women were further subdivided for comparison of RT effects into those presenting metabolically healthy obesity (MHO) and those with metabolically unhealthy obesity (MUHO) classified according to Karelis and Rabasa-Lhoret or an approach based on adipose tissue secretory dysfunction using the plasma adiponectin(A)/leptin (L) ratio. Participants followed a 4-month weekly RT program targeting major muscle groups (3 × 10 repetitions at 80% one repetition maximum (1-RM)). Percent fat marginally decreased and lean body mass increased (0.01 < p < 0.05) while CRF and muscular strength improved in all women, after RT (effect size (ES): 0.11-1.21 (trivial to large effects), p ˂ 0.01). Fasting plasma triacylglycerol and high-density lipoprotein-cholesterol levels slightly increased and decreased, respectively, in participants with MHO using the A/L ratio approach (ES: -0.47 to 1.07 (small to large effects), p ˂ 0.05). Circulating interleukin-6 soluble receptor decreased in both groups and soluble tumor necrosis factor receptor-1/soluble tumor necrosis factor receptor-2 in women with MUHO only, irrespective of definition (ES: -0.42 to -0.84 (small to large effects), p ˂ 0.05). Glucose-insulin homeostasis was unchanged regardless of group or definition. RT improved physical performance and body composition but had a lesser impact on cardiometabolic risk in women with obesity, irrespective of their metabolic phenotype.

Diabetes mellitus is a chronic metabolic disease that affects more than 10.5% of the world's adult population. Biochemical and hematological parameters, such as albumin (ALB) and red cell distribution width (RDW), have been shown to be altered in diabetic patients. This study aimed to correlate hematological and biochemical parameters with glycated hemoglobin (HbA1c). A total of 777 adults (372 women and 405 men, aged 19-85 years) were divided into three groups: 218 participants with HbA1c < 5.7% (group A: non-diabetic), 226 with HbA1c ≥ 5.7% and <6.5% (group B: prediabetic) and 333 with HbA1c ≥ 6.5% (group C: diabetic). Biochemical and hematological parameters were compared among the three groups. An analysis of variance was performed to determine the correlations of the parameters among the groups. The ALB and sodium (Na) levels were significantly lower in group C than in groups A (ALB: 3.8 g/dL vs. 4.1 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.3 mmol/L, p < 0.001) and B (ALB: 3.8 g/dL vs. 4.0 g/dL, p < 0.0001, Na: 138.4 mmol/L vs. 139.6 mmol/L, p < 0.0001), whereas the RDW-standard deviation (RDW-SD) and urea were increased in group C as compared to group A (RDW: 45.8 vs. 43.9 fL, p < 0.0001, urea: 55.6 mg/dL vs. 38.5 mg/dL, p < 0.0001). The mean platelet volume (MPV) was increased in group C as compared to group A (9.3 fL vs. 9.1 fL, p < 0.05, respectively). Τhe increase in RDW-SD in group A as compared to B and C demonstrates the impact of hyperglycemia on red blood cells. Albumin and RDW might improve risk assessment for the development of diabetes. These results highlight the potential role of these parameters as an indication for prediabetes that would alert for measurement of HbA1c.

Interindividual variations in postprandial metabolism and weight loss outcomes have been reported. The literature suggests links between postprandial metabolism and weight regulation. Therefore, the study aims to evaluate if postprandial glucose metabolism after a glucose load predicts anthropometric outcomes of a weight loss intervention.

Anthropometric data from adults with obesity (18-65 years, body mass index [BMI] 30.0-39.9 kg m-2) are collected pre- and post an 8-week formula-based weight loss intervention. An oral glucose tolerance test (OGTT) is performed at baseline, from which postprandial parameters are derived from glucose and insulin concentrations. Linear regression models explored associations between these parameters and anthropometric changes (∆) postintervention. A random forest model is applied to identify predictive parameters for anthropometric outcomes after intervention. Postprandial parameters after an OGTT of 158 participants (63.3% women, age 45 ± 12, BMI 34.9 ± 2.9 kg m-2) reveal nonsignificant associations with changes in anthropometric parameters after weight loss (p > 0.05). Baseline fat-free mass (FFM) and sex are primary predictors for ∆ FFM [kg].

Postprandial glucose metabolism after a glucose load does not predict anthropometric outcomes after short-term weight loss via a formula-based low-calorie diet in adults with obesity.

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.

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.

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.

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.