Insulin Sensitivity Index Research Articles

Association Between Zinc Status and Insulin Resistance/Sensitivity Check Indexes in Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is considered the most common metabolic disorder of the pregnancy period. It is characterized by pancreatic beta-cell dysfunction in the setting of chronic insulin resistance. Zinc is a nutrient involved in numerous metabolic processes and shows a relationship with glycometabolic disorders and GDM. The latest data have demonstrated the association of zinc with insulin sensitivity and resistance. The exact role of zinc in the connection with indexes of insulin resistance and insulin sensitivity is still not fully clarified. The aim of the study is to analyze the newly calculated indexes Glu/Zn, Ins/Zn, and HOMA-IR/Zn as surrogate markers to explore the correlation between serum zinc status and some indexes of insulin sensitivity and insulin resistance. The possible role of these indexes as markers of insulin resistance in pregnant women was analyzed too. An ROC analysis demonstrated that HOMA-IR/Zn with AUC 0.989, p < 0.001 (95% CI 0.967–1.000) and Ins/Zn with AUC 0.947, p < 0.001 (95% CI 0.889–1.000) in the GDM group, and only HOMA-IR/Zn index with AUC 0.953, p < 0.001 (95% CI 0.877–1.000) in healthy pregnant women, have good power as markers of insulin resistance in both groups. We speculate that these new ratios could be suitable for the assessment of pregnant women at high risk of insulin resistance development and, probably, for the evaluation of the specific pathophysiologic characteristics of women with GDM.

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

BackgroundPrevious studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk.MethodsThis retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ResultsA total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31–30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09–13.92; all-cause mortality, HR 4.56, 95% CI 2.97–7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ConclusionsThe classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.Graphical abstract

Association and mediation pathways of maternal hyperglycaemia and liability to gestational diabetes with neonatal outcomes: A two-sample Mendelian randomization study.

Maternal hyperglycemia is linked to adverse neonatal outcomes. However, current evidence was insufficient for mechanistic pathways. We aim to use two-sample Mendelian randomization (MR) to obtain a comprehensive understanding of the causal association and mediation pathways. Genetic variants of fasting glucose (FG), insulin sensitivity index (ISI), glycated haemoglobin (HbA1c), gestational diabetes mellitus (GDM) and type 2 diabetes (T2D) were used as instruments (N = 50 404-898 130). The associations with offspring birthweight, gestational duration, spontaneous preterm and post-term birth were assessed by the inverse-variance weighted method, using summary statistics of European genome-wide association studies (N = 131 279-210 248). Sensitivity analyses, including multivariable MR removing pleiotropic effect from maternal body mass index (BMI), assessed the robustness. Mediation via placental weight and maternal hypertension were assessed via a two-step MR design. FG (0.46 SD per mmol/L, 95% confidence interval [95% CI]: 0.32, 0.61) and GDM liability (0.18 SD per log odds, 95% CI: 0.08, 0.18) were positively associated with birthweight, with consistent findings for HbA1c, T2D liability and ISI. These associations were mediated by placental weight (proportion mediated: 32.8% to 77.7%). Higher HbA1c, GDM and T2D liability were associated with preterm birth (odds ratios for GDM: 1.07, 95% CI: 1.01, 1.14) and shorter gestational duration, whilst the association for T2D attenuated after adjusted for maternal BMI and gestational hypertension. Maternal hyperglycemia is associated with higher birthweight (possibly indicating macrosomia), mediated via increased placental growth. GDM and T2D liability are related to preterm birth, whilst the association for T2D liability is driven by maternal adiposity.

Causal association between insulin sensitivity index and Alzheimer's disease.

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.

Decreased neutrophils are associated with reduced risk of Type 2 Diabetes Incidence: Results from the CORDIOPREV study.

Numerous studies have reported an association between neutrophils and T2DM, although this relationship remains unclear. This study aims to investigate the interaction of neutrophils and a dietary intervention on T2DM incidence after 60 months of follow-up. A comprehensive analysis was conducted on the framework of the CORDIOPREV study, which included 462 patients without T2DM at the beginning of the study. They were randomly assigned to either a Mediterranean or a low-fat diet, of whom 107 developed T2DM. Absolute neutrophil counts and other related-ratio, were measured. Kaplan-Meier curves showed that the lowest tertile of basal neutrophils was associated with a reduced likelihood of T2DM incidence when compared to the middle [HR=0.499 (95%CI, 0.287-0.866)] and the highest tertiles [HR=0.442 (95%CI, 0.255-0.768)] in overall population, after adjusting for clinical variables. This association only remained significant in patients who follow a Mediterranean diet when compared the lowest to the middle [HR=0.423 (95% CI, 0.213-0.842)] and the highest tertiles [HR=0.371 (95% CI, 0.182-0.762)]. The predictive capacity yielded an AUC of 0.711 (95%CI: 0.652-0.769), being neutrophils the most important variable in the in the model. Decrease in neutrophils over the 60 months were associated with increased insulin sensitivity index (ISI) (R=-0.31; p=0.019), particularly in patients who followed the Mediterranean diet. These findings suggest that monitoring neutrophils can help prevent the development of T2DM, as a reduction in neutrophil counts could be associated with improved insulin sensitivity. Following a Mediterranean diet might be a potential strategy to reduce the incidence of T2DM by lowering neutrophil levels. Further research is necessary to gain a deeper understanding regarding this mechanism.

Relationship of Plasma Apolipoprotein C-I Truncation With Risk of Diabetes in the Multi-Ethnic Study of Atherosclerosis and the Actos Now for the Prevention of Diabetes Study.

Higher truncated-to-native apolipoprotein (apo) C-I proteoform ratios (C-I'/C-I) are associated with favorable cardiometabolic risk profiles, but their relationship with longitudinal changes in insulin resistance (IR) and incident diabetes is unknown. Plasma apoC-I proteoforms were measured by mass spectrometry immunoassay at baseline in 4,742 nondiabetic participants in the Multi-Ethnic Study of Atherosclerosis (MESA) and 524 participants with prediabetes in the Actos Now for Prevention of Diabetes (ACT NOW) study. The primary outcome was incident diabetes (fasting glucose [FG] ≥7.0 mmol/L or hypoglycemic medication use in MESA; FG ≥7.0 mmol/L or 2-h glucose ≥11.1 mmol/L in an oral glucose tolerance test [OGTT] in ACT NOW). Secondary outcomes were changes in FG and HOMA-IR in MESA, and OGTT-glucose area under the curve (AUCglucose) and Matsuda insulin sensitivity index (ISI) in ACT NOW. In MESA, a higher C-I'/C-I was associated with lower risk of diabetes (n = 564 events; HR 0.87 [95% CI 0.79, 0.95] per SD; P = 0.0036; median follow-up, 9 years), and smaller increases (follow-up adjusted for baseline) in FG (-0.5%; P < 0.0001) and HOMA-IR (-2.9%; P = 0.011) after adjusting for baseline clinical and demographic covariates, including plasma triglycerides and HDL cholesterol. Total apoC-I concentrations were not associated with changes in FG, HOMA-IR, or incident diabetes. In ACT NOW, higher C-I'/C-I was associated with smaller increases in AUCglucose (-1.8%; P = 0.0052), greater increases in ISI (7.2%; P = 0.0095), and lower risk of diabetes (n = 59 events; 0.66 [95% CI 0.48, 0.91]; P = 0.004; median follow-up, 2.5 years) after adjusting for treatment group and diabetes risk factors, including plasma lipids. Our results indicate that apoC-I truncation may contribute to changes in glucose levels, IR, and risk of diabetes.

Impact of lifestyle intervention on vitamin D, Adiponectin, Insulin-like growth factor 1 and Proneurotensin in overweight individuals from the Middle East

BackgroundImmigrants from the Middle East (ME) have a higher prevalence of type 2 diabetes (T2D) compared to the native-born Swedish population. In individuals free from T2D, ME immigrants are more insulin resistant and have lower levels of adjusted insulin secretion (Disposition index, DIo) compared to Swedish-born individuals. The ethnic differences are not fully explained by traditional risk factors. This has raised the question as to whether hormonal factors other than insulin are involved, contributing to higher T2D risk in ME immigrants. AimsIn ME immigrants at high risk of developing T2D, we aimed to study the effect of a randomized culturally adapted lifestyle intervention on the levels of Vitamin D (25(OH)D), insulin-like growth factor 1 (IGF-1), Pro-neurotensin (Pro-NT) and Adiponectin. Furthermore, we aimed to study if the effect of the intervention was associated to these hormones, or if a direct effect of the intervention remained after accounting for these. MethodsIn this culturally adapted randomized controlled trial of four months duration, eligible ME immigrants at high risk of developing T2D identified in the MEDIM cohort were invited to participate. The intervention group (N= 35) received a culturally adapted lifestyle intervention program consisting of seven group sessions and cooking classes. The control group (N= 32) were given treatment as usual with oral and written information to improve their lifestyle habits. Using mixed models’ linear regression analysis, the changes in the levels of 25(OH)D, IGF-1, Adiponectin and Pro-NT were assessed by comparing the groups and we further studied the effects of the changes on insulin action and secretion. ResultsThe adjusted levels of 25(OH)D significantly increased in the intervention group compared to the control group (β for the effect of the intervention on 25(OH)D: 0.061, 95% CI 0.009-0.113, P = 0.023). The increase in insulin sensitivity index (ISI) observed in the intervention compared to the control group was altered after adjusting for 25(OH)D: 0.129, 95% CI -0.016-0.274, P = 0.078). IGF-1, Adiponectin and Pro-NT did not significantly influence the change over time concerning insulin secretion. ConclusionLifestyle intervention increases the adjusted levels of 25(OH)D. Moreover, the effect of the lifestyle intervention on insulin action and secretion was altered when adjusting for 25(OH)D.

Fasting as an intervention to alter the impact of simulated night-shift work on glucose metabolism in healthy adults: a cluster randomised controlled trial.

Night-shift work causes circadian misalignment and impairs glucose metabolism. We hypothesise that food intake during night shifts may contribute to this phenomenon. This open-label, multi-arm, single-site, parallel-group controlled trial involved a 6 day stay at the University of South Australia's sleep laboratory (Adelaide, SA, Australia). Healthy, non-shift-working adults without obesity (N=55; age 24.5 ± 4.8 years; BMI 24.8 ± 2.8 kg/m2) were assigned to the next available run date and cluster randomised (1:1:1) to fasting-at-night (N=20), snack-at-night (N=17), or meal-at-night (N=18) conditions. One participant withdrew from each group, prior to starting the study. Due to study design, neither participants nor people collecting their measurements could be blinded. Statistical and laboratory staff were concealed to study allocation. Participants were fed at calculated energy balance, with the macronutrient composition of meals being similar across conditions. The primary outcomes were a linear mixed-effects model of glucose, insulin and NEFA AUC in response to a 75 g OGTT that was conducted prior to and after 4 consecutive nights of shift work plus 1 night of recovery sleep. Insulin sensitivity, insulinogenic and disposition indexes were also calculated. Night-shift work impaired insulin sensitivity, as measured by insulin AUC (p=0.035) and the insulin sensitivity index (p=0.016) across all conditions. Insulin secretion, as measured by the insulinogenic index, was increased in the fasting-at-night condition only (p=0.030), resulting in a day×condition interaction in glucose AUC (p<0.001) such that glucose tolerance was impaired in the meal-at night (+2.00 [95% CI 1.45, 2.56], p<0.001) and snack at-night (+0.96 [0.36, 1.56], p=0.022) conditions vs the fasting-at-night (+0.34 [-0.21, 0.89]) condition. A day×condition interaction was also observed in NEFA AUC (p<0.001), being higher in the meal-at-night (+0.07 [0.03, 0.10]. p=0.001) and snack-at-night (0.01 [-0.03, 0.05], p=0.045) conditions vs the fasting-at-night condition (-0.02 [-0.06, 0.01]). No adverse events occurred. The timing of food intake has a critical effect on glucose metabolism during simulated night-shift work, which was readily amendable to a meal re-timing intervention. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001556437 FUNDING: This work was funded by the National Health and Medical Research Council (NHMRC), APP1099077.

8413 Skeletal Muscle Mass, Insulin Sensitivity, And Beta-Cell Function In The Development Of Type 2 Diabetes: A 16-Year Prospective Cohort Study

Abstract Disclosure: H. Mun: None. S. Lee: None. S. Kim: None. S. Yoo: None. J. Son: None. Background: The relationship of relative muscle mass with beta-cell dysfunction and insulin resistance in the development of type 2 diabetes is unclear. We therefore aimed to evaluate longitudinal changes in glycemia, insulin sensitivity, and beta-cell function according to muscle mass. Methods: We prospectively evaluated 7090 middle-aged and older participants without diabetes at baseline every 2 years with oral glucose tolerance tests for 16 years in the Korean Genome Epidemiology Study. Weight-adjusted appendicular skeletal muscle mass was used to derive the muscle mass index (MMI). Using linear mixed-effect models, we assessed trajectories of fasting and 2-hour post-load glucose (2hPG), the composite insulin sensitivity index (ISIcomp), the 60-minute insulinogenic index (IGI60), and the disposition index (DI) according to sex-specific MMI tertiles before diagnosis with type 2 diabetes or the completion of follow-up. Results: During a median follow-up of 13.9 years, 1742 (24.5%) participants were diagnosed with type 2 diabetes. The risk of developing type 2 diabetes gradually increased as MMI decreased (multivariable-adjusted hazard ratio 1.36; 95% CI 1.29; 1.44 per SD decline in MMI). After age- and sex adjustment, significant differences were found in fasting and 2hPG trajectories between low and high MMI tertiles during follow-up (p &amp;lt; 0.001 for group-by-time interaction). The low MMI tertile showed significantly lower ISIcomp and DI at baseline compared to the high MMI tertile. The rate of increase in IGI60 was significantly lower in the low MMI tertile than in the high MMI tertile (0.0021 vs. 0.0191; p &amp;lt; 0.001) despite a progressive decline in ISIcomp during follow-up. The rate of decrease in DI was significantly greater in the low MMI tertile than in the high MMI tertile (-0.0228 vs. -0.006; p &amp;lt; 0.001). Conclusion: Sufficient muscle mass in middle-aged and older adults could protect against incident type 2 diabetes by preserving beta-cell function to compensate for aging-induced reductions in insulin action, independent of obesity. Presentation: 6/1/2024

Antidiabetic and hypolipidemic activities of Sanghuangporus vaninii compounds in streptozotocin‐induced diabetic mice via modulation of intestinal microbiota

AbstractSanghuangporus vaninii is a traditional edible and medicinal fungi with a long history in China. Recent studies have focused on its potential in treating diabetes, although the underlying mechanism remains unclear. This study aimed to investigate the antidiabetic and hypolipidemic effects of the formula of S. vaninii compounds (SVC) in diabetic mice and explore the potential improvement in the intestinal microbiota. Oral administration of SVC significantly reduced fasting blood glucose and improved insulin sensitivity and lipid indexes. In addition to its direct effects on glucose levels and insulin sensitivity, SVC was found to have an impact on the intestinal microbiota. The levels of short‐chain fatty acids receiving SVC intervention increased, and 16S rRNA sequencing revealed changes in the abundances of certain bacteria, such as Harryflintia, Helicobacter, Candidatus_Soleaferrea, Klebsiella, and Candidatus_Stoquefichus. These bacteria were found to be negatively associated with glucose and lipid indexes and positively related to body weight and insulin sensitivity. Overall, this study highlights the potential of SVC in treating diabetes and provides a novel perspective for understanding its antidiabetic mechanism through modulation of the intestinal microbiota.

An Application Study of the Simple Insulin Sensitivity Index for the Assessment of the Level of Insulin Resistance in People with Different Kidney Function

An Application Study of the Simple Insulin Sensitivity Index for the Assessment of the Level of Insulin Resistance in People with Different Kidney Function

Flaxseed extract: A potential therapeutic intervention for type-2 diabetes mellitus and cardiovascular risk reduction in Wistar rats

Introduction: Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, highlighting the importance of dietary interventions. Flaxseed (Linum usitatissimum L.) has shown promise in treating chronic metabolic diseases. This study investigates the therapeutic potential of flaxseed as an antidiabetic agent and its protective effect on cardiovascular diseases. Methods: Rats were randomly divided into five groups: normal fed with drug carrier group (N), diabetes with drug carrier group (D), diabetes with metformin (M) group (D+M), and diabetes with flaxseed extract doses of 100 and 200 mg/kg (D+F1 and D+F2) groups. The diabetic rat model was established by administration of drinking water containing 25% fructose and a single intraperitoneal injection of 100 mg/kg alloxan. After a six-week intervention, the rats were sacrificed to assess the antidiabetic and cardiovascular effects. Results: The doses of 100 and 200 mg/kg flaxseed extract significantly reduced body weight and fasting glucose levels and increased insulin sensitivity index (KITT) compared to the diabetes group (P&lt;0.05). In addition, histological analysis showed a significant improvement and increase in pancreatic beta cells in the treatment group compared to the diabetes group (P&lt;0.05). Flaxseed extract doses of 100 and 200 mg/kg significantly reduced weight gain and insulin resistance, contributing to decreased arterial stiffness and atherogenic index compared to the diabetic group (P&lt;0.05). The hypoglycemic effect suggested a dose-dependent response. Conclusion: Flaxseed extract regulates blood glucose levels probably by enhancing insulin sensitivity and revitalizing damaged pancreatic beta cells. It mitigates cardiovascular risk, by reducing arterial stiffness and atherogenicity.

A single bout of physical exercise improves 1-hour post-load plasma glucose in healthy young adults.

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 24h 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 1h 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.

The Association of the HEPAKID Index with Insulin Sensitivity Index in Obese Adolescents with Metabolic Syndrome.

Objective: The HEPAKID index, a novel diagnostic tool with a sensitivity of 82% and specificity of 62% for detecting nonalcoholic fatty liver disease in obese adolescents. Our study aimed to explore the potential relationship between the HEPAKID index and risk factors contributing to the development of cardiovascular disease in obese adolescents with metabolic syndrome. Methods: This prospective cross-sectional study, conducted at two medical centers from December 2023 to March 2024, included 208 obese adolescents, with a median age of 14.5 years and an average body mass index (BMI) of 30.57 kg/m2. Results: Elevated HEPAKID index values were found in obese adolescents with metabolic syndrome, showing positive associations with BMI, waist and hip circumferences, alanine aminotransferase level, fasting insulin, and homeostasis model assessment for insulin resistance. In those with metabolic syndrome, waist circumference (WC) and homeostasis model assessment for insulin resistance were significant independent variables linked to the HEPAKID index, while WC was the sole influencer in the nonmetabolic syndrome group. Multivariate logistic regression highlighted systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and the HEPAKID index as reliable predictors of metabolic syndrome. A predictive cutoff value of 60.84 for the HEPAKID index showed 61.7% sensitivity and 59.1% specificity in identifying metabolic syndrome. Conclusions: Our study highlighted the potential value of the HEPAKID index in combination with other clinical parameters for predicting metabolic syndrome in obese adolescents, underscoring its role as a valuable screening tool. Furthermore, our findings revealed a correlation between the HEPAKID index and insulin sensitivity in this high-risk population.

Adipose tissue insulin resistance in young Japanese women is associated with metabolic abnormalities and dehydroepiandrosterone-sulfate.

The proportion of young Japanese women who are underweight is exceptionally high. We previously showed that the prevalence of impaired glucose tolerance (IGT) was high in underweight young Japanese women, and that IGT was characterized by high free fatty acid levels and adipose tissue insulin resistance (ATIR). As the next step, this study aimed to explore factors associated with elevated ATIR in this population. Ninety-eight young, healthy, underweight women participated in this study. To investigate the relationship between ATIR and metabolic parameters, participants were divided into three groups (Low, Medium, and High) according to ATIR level. Body composition examination, oral glucose tolerance testing, and blood biochemical analysis were performed; Adipo-IR and the Matsuda index were used as indices of ATIR and systemic insulin sensitivity, respectively. Participants in the High ATIR group had the highest prevalence of IGT (25%), and significantly higher body fat percentage, whole-body insulin resistance, and levels of insulin-like growth factor-1 and dehydroepiandrosterone sulfate (DHEA-S) than the other two groups. They were also significantly younger and had higher systolic blood pressure than the Low ATIR group. Multiple regression analysis showed that DHEA-S, which is known to enhance lipolysis in adipose tissue, was an independent correlate of ATIR. Underweight Japanese women with high ATIR had impaired metabolism, a higher prevalence of IGT, higher systemic insulin resistance, and higher systolic blood pressure. DHEA-S was a determinant of high ATIR levels.

Characteristics and pregnancy outcomesofsubtypes of gestational diabetes mellitusbased on HOMA-IR and BMI.

To identify the characteristics and pregnancy outcomes across different subgroups of gestational diabetes mellitus (GDM) categorized by insulin resistance index and body mass index (BMI) in early pregnancy. This retrospective study included 1804 women who underwent a 75g-OGTT during 22-28weeks of gestation, categorized into normal glucose tolerance (NGT) (1487) and GDM (317 [17.57%] of the total cohort). Metabolic parameters were assessed, and equation of homeostatic model assessment (HOMA) were utilized to compute indices of insulin resistance (HOMA-IR), β-cell secretory (HOMA-B), and insulin sensitivity (HOMA-%S) in early and mid-pregnancy. The cut-off value of HOMA-IR (1.61) in early pregnancy was determined via ROC curve analysis. This value, combined with pre-pregnancy BMI, further categorized NGT and GDM into six subgroups respectively, based on HOMA-IR levels (≥ 1.61 or < 1.61) and BMI categories (< 18.5kg/m2, 18.5-25kg/m2, or ≥ 25kg/m2). In comparison to women with NGT, those with GDM were notably older, had higher pre-BMI, fasting plasma glucose (FPG), insulin, and lipid levels in early pregnancy. They also exhibited more pronounced insulin resistance in both early and mid-pregnancy, leading to poorer outcomes. Following an oral glucose load, the peaks of glucose and insulin were out of sync in GDM and its subgroups, accompanied by further increases in HOMA-IR, HOMA-B, and a decrease in HOMA-%S, except for the GDM subgroup with HOMA-IR < 1.61/BMI < 18.5kg/m2. Conversely, glucose and insulin secretion in NGT and its subgroups peaked synchronously at 60min. GDM women with HOMA-IR ≥ 1.61/18.5kg/m2 ≤ BMI < 25kg/m2 had higher rates of neonatal jaundice (34.5% vs 13.9%, p < 0.0001), LGA (28.9% vs 13.2%, p = 0.001), macrosomia (9.8% vs 3.7%, p = 0.025) compared to peers, while in GDM women with HOMA-IR ≥ 1.61/BMI ≥ 25kg/m2, the rates of LGA and macrosomia were 26.6% and 8.4%, respectively. The GDM subgroup with HOMA-IR < 1.61/BMI < 18.5kg/m2 exhibited the highest rates of premature rupture of membrane (46.7%) and postpartum hemorrhage (20%), predominantly with vaginal delivery and a 1min Apgar score of 4.5% in GDM women with HOMA-IR < 1.61/18.5kg/m2 ≤ BMI < 25kg/m2. GDM and its subgroups displayed severe insulin resistance and poorer insulin sensitivity, leading to an increased risk of adverse pregnancy outcomes. GDM women with higher IR and normal or over weight were more likely to experience LGA and macrosomia, while those with lower IR and underweight were prone to premature rupture of membrane and postpartum hemorrhage during vaginal delivery.

1-Hour Post-Load Glucose: Early Screening for High Risk of Type 2 Diabetes in Koreans with Normal Fasting Glucose.

With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Pathophysiological characteristics of subjects with intermediate hyperglycemia and type 2 diabetes identified by 1-hour plasma glucose during an oral glucose tolerance test

AimsThe International Diabetes Federation (IDF) has recently recommended determination of 1-hour plasma glucose (1-hPG) during an oral glucose tolerance test (OGTT) to diagnose intermediate hyperglycemia (IH) and type 2 diabetes (T2DM). Herein, we investigated the cardiometabolic characteristics of individuals with IH and T2DM according to IDF criteria. MethodsWe studied 3086 individuals stratified on the basis of fasting, 1-hPG and 2-hPG in four groups: 1) normal glucose tolerance (NGT), 2) isolated impaired fasting glucose (iIFG,), 3) IH (fasting glucose < 126 mg/dL, 1-hPG 155–208 mg/dL, and/or 2-hPG 140–199 mg/dL, and 4) newly diagnosed T2DM (fasting glucose, 1-hPG and/or 2-hPG≥126 mg/dL, 209 mg/dL and 200 mg/dL, respectively). ResultsIndividuals with IH and T2DM exhibited higher adiposity, blood pressure, uric acid, a worse lipid and inflammatory profile and a progressive reduction in Matsuda index of insulin sensitivity, insulinogenic index, and disposition index as compared to the NGT group. Moreover, individuals with IH and T2DM exhibited lower Matsuda, insulinogenic, and disposition indexes as compared to the iIFG group. Conclusions1-h PG-based criteria for diagnosis of IH and diabetes identify individuals having an unfavorable cardiometabolic risk profile with a progressive reduction in insulin sensitivity associated with impaired β cell function.

Glucose Variability in People with Type 1 Diabetes: Associations with Body Weight, Body Composition, and Insulin Sensitivity.

The prevalence of overweight and obesity increases in people with type 1 diabetes (T1D). However, the impact of fat accumulation on glucose dynamics in T1D is poorly understood. We assessed continuous glucose monitoring (CGM) parameters in patients with T1D depending on their body weight, body composition, and insulin sensitivity. In 547 patients, including 238 overweight/obese individuals, CGM-derived time in range (TIR) and glucose variability (GV) were estimated. Body composition was assessed by DXA. Estimated glucose disposal rate (eGDR) was used as an indicator of insulin sensitivity. Overweight/obese patients, when compared to normal-weight ones, have a lower time below range (TBR) (<3 mmol/L), GV, and experienced fewer episodes of low glucose. In men, lower TIR, higher time above range (TAR), and GV reduction were associated with central adiposity assessed by total, trunk, and android fat mass. In women, gynoid fat mass only was associated with a lower TIR and higher TAR. The eGDR was a positive predictor of TIR and a negative predictor of TAR, TBR, and GV in men and women. In conclusion, adiposity in people with T1D is associated with a lower risk of CGM-confirmed hypoglycemia, higher TAR, and reduced GV. These features of daily glucose dynamics may be mediated by insulin resistance.

Heterogeneous response of estimated insulin sensitivity indices to metformin in young individuals with type 1 diabetes and different phenotypes

AimsThis study aimed to investigate whether the response to adding metformin to insulin in young adults with type 1 diabetes (T1D) differs according to weight phenotype and insulin sensitivity index.MethodsA prospective pilot study was conducted over 26 weeks in which insulin plus metformin (2 g/day) was administered to 35 individuals, ranging from normal weight (NW) to overweight (OW) to obese (OB) T1D individuals, to correlate insulin sensitivity indices and other clinical variables.ResultsAt the end of the follow-up period, all groups showed an increase in the eGDR (NW: 7.37 vs 8.16, p = 0.002; OW: 7.28 vs 8.24, p < 0.001; OB: 6.33 vs 7.52 p < 0.001). KITT and SEARCH SCORE improved only in the OB group (2.15 vs 3.14, p < 0.001 and 5.26 vs 5.72, p = 0.007, respectively). Furthermore, HbA1c and BMI were significantly greater in the OB group (− 0.62%, p < 0.001; − 1.12 kg/m2, p = 0.031, respectively). Regression analysis revealed that the serum levels of triglycerides and uric acid were significantly (0.059, p = 0.013; 0.076, p = 0.001) associated with insulin sensitivity indices.ConclusionsThe study showed that eGDR improved independently of basal weight after metformin treatment. However, the KITT and SEARCH indices improved only in the obese group. Triglycerides and uric acid are associated with insulin sensitivity indices. These results highlight the heterogeneity of the mechanisms underlying insulin resistance and its response to metformin in individuals with T1D.