Composite Insulin Sensitivity Index Research Articles

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 < 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 < 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 < 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

A Single Sauna Session Does Not Improve Postprandial Blood Glucose Handling in Individuals with Type 2 Diabetes Mellitus: A Cross-Over, Randomized, Controlled Trial.

Passive heat treatment has been suggested to improve glycemic control in individuals with type 2 diabetes mellitus (T2DM). Previous studies have focused predominantly on hot water immersion and traditional sauna bathing, as opposed to the more novel method of infrared-based sauna bathing. Here, the impact of a single infrared sauna session on post-prandial glycemic control was assessed in older individuals with T2DM. In this randomized controlled crossover trial, 12 participants with T2DM (male/female: 10/2, age: 69±7 y, BMI: 27.5±2.9 kg/m2) rested in an infrared sauna twice: once in a heated (60°C) and once in a thermoneutral (21°C) condition for 40 min, immediately followed by a 2-h oral glucose tolerance test (OGTT). Venous blood samples were obtained to assess plasma glucose and insulin concentrations and to determine the whole-body composite insulin sensitivity index. Body core and leg skin temperature were higher following the heated condition compared to the thermoneutral condition (38.0±0.3 vs. 36.6±0.2°C and 39.4±0.8 vs. 31.3±0.8°C, respectively; P<0.001 for both). The incremental area under the curve (iAUC) of plasma glucose concentrations during the OGTT was higher after the heated condition compared to the thermoneutral condition (17.7±3.1 vs. 14.8±2.8 mmol/L/120 min; P<0.001). No differences were observed in plasma insulin concentrations (heated: 380±194 vs. thermoneutral: 376±210 pmol/L/120 min; P=0.93) or whole-body composite insulin sensitivity indexes (4.5±2.8 vs. 4.5±2.1; P=0.67). A single infrared sauna session does not improve postprandial blood glucose handling in individuals with T2DM. Future studies should assess the effect of more prolonged application of infrared sauna bathing on daily glycemic control.

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.

Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers

AimsWe explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. MethodsWe retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). ResultsAt baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (β: 0.045, p < 0.001; β: −0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9–2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. ConclusionsThe TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.

Exposure to perfluroalkyl substances is associated with impaired glucose homeostasis in Hispanic youth

Background: Animal studies show that perfluoroalkyl substances contribute to type 2 diabetes pathogenesis, even at low levels of exposure. However, evidence from human studies is inconclusive and largely based on cross-sectional studies in adults. We examined the associations between exposure to perfluorooctanoic acid (PFOA) and measures of glucose metabolism among Hispanic children at risk for type 2 diabetes. Methods: Overweight and obese Hispanic children were recruited from urban Los Angeles (N=312, age 7-15 years). All children underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT). Insulin sensitivity was assessed by the Composite Insulin Sensitivity Index (ISIcomposite), and insulin resistance was assessed by the homeostatic model of insulin resistance (HOMA-IR). Plasma levels of PFOA were measured using high resolution mass spectrometry. Multiple linear regression models were used to assess the association between PFOA plasma concentrations and measures of insulin sensitivity and resistance after adjusting for covariates including age, sex, socioeconomic status, pubertal status, and body mass index. Results: Each two-fold increase in plasma PFOA was associated with 19.0% increase in HOMA-IR (95% CI: 9.2, 29.8%; p&lt;0.001) and a 13.1% decrease in ISIcomposite (95% CI: -19.8, -5.7%). Plasma PFOA concentrations were also positively associated with fasting glucose and fasting insulin as well as two-hour post OGTT glucose and insulin measures. The effects of PFOA on HOMA-IR and ISIcomposite were similar among boys and girls (both p &gt; 0.2). Conclusion: Our results indicated that childhood exposure to PFOA is associated with impaired glucose metabolism in overweight and obese Hispanic youth. Future work is required to elucidate underlying biological mechanisms between PFOA and glucose metabolism.

Associations Between Metabolic Profiles and Target-Organ Damage in Chinese Individuals With Primary Aldosteronism

Purpose: Patients with primary aldosteronism (PA) have an increased risk of target-organ damage (TOD), but whether metabolic syndrome (MetS) is more prevalent and contributes to TOD in PA patients remains unresolved. We aimed to evaluate the associations between MetS profiles and TOD in Chinese PA individuals.Methods: Metabolic parameters and pre-clinical TOD including left ventricular hypertrophy, estimated glomerular filtration, and microalbuminuria; insulin sensitivity or resistance; and islet β-cell function were assessed by the homeostasis models (HOMA-IR, HOMA-β) and the other surrogate indexes [composite insulin sensitivity index (ISI), modified β-cell function index (MBCI)] determined from the oral glucose tolerance test were compared in PA vs. matched essential hypertension (EH) patients.Results: A total of 109 PA patients and 109 essential hypertension (EH) controls individually matched for sex, age, and office systolic blood pressure and duration of hypertension were studied. The prevalence of MetS and its individual components in PA was significantly lower than in EH [MetS: 28 (25.6%) vs. 54 (49.5%), P < 0.001]. PA patients had a higher composite ISI but a lower HOMA-IR, HOMA-β, and MBCI than EH controls (all P < 0.05). Concerning TOD, PA patients had significantly higher prevalence of microalbuminuria and left ventricular hypertrophy (LVH), and lower levels of estimated glomerular filtration (eGFR) than EH controls (all P < 0.05). On multivariate logistic regression analysis, female gender and elevated plasma aldosterone levels were significantly associated with TOD in PA. However, there were no significant associations between MetS and its individual components and TOD in PA patients.Conclusions: PA patients had a lower MetS prevalence but exhibited more severe TOD than matched EH controls. The study highlights the deleterious effects of aldosterone excess on the development of TOD, whereas MetS or its individual components might be less influential in PA.

Pathophysiology of gestational diabetes mellitus in lean Japanese pregnant women in relation to insulin secretion or insulin resistance

To determine the pathophysiology of gestational diabetes (GDM) in lean Japanese pregnant women in relation to insulin secretion or insulin resistance. The 75-g oral glucose tolerance test (OGTT) was performed in case of positive results of universal screening of a 50-g glucose challenge test at 24-28weeks' gestation in Japanese pregnant women. These women were treated in our hospital between 2012 and 2016. Among these women, 30 with a body mass index of < 18.5kg/m2 were selected as lean subjects. Nine women were diagnosed with GDM (GDM group) and the remaining 21 had normal glucose tolerance (control group). For evaluating insulin secretion or resistance, the following parameters were compared between the two groups together with a family history of diabetes mellitus (DM) among first-degree relatives: (1) plasma glucose and immnunoreactive insulin (IRI) levels after glucose loading, (2) insulinogenic index (I.I), (3) homeostasis model assessment of β-cell function (HOMA-β), (4) homeostasis model assessment of insulin resistance (HOMA-IR), and (5) insulin sensitivity index (ISI) composite. The percentage of having a family history of DM was significantly higher in the GDM group (3/9, 33.3%) than in the control group (0/21, 0.0%, P < 0.001). Serum glucose levels at 30, 60, and 120min after glucose loading were significantly higher in the GDM group than in the control group (all P < 0.05). IRI levels at 60 and 120min were significantly higher in the GDM group than in the control group (both P < 0.05), and they showed persistent insulin secretion patterns. Values of the I.I. and ISI composite were significantly lower in the GDM group than in the control group (both P < 0.05), with no differences in HOMA-β, HOMA-IR and HbA1c levels between the groups. Lean Japanese pregnant women with GDM have impaired β-cell function, which is in part associated with hereditary traits.

A Simple and Improved Predictor of Insulin Resistance Extracted From the Oral Glucose Tolerance Test: The I0*G60.

ObjectiveTo evaluate the diagnostic performance of several biochemical predictors of insulin resistance (IR).DesignA total of 90 nondiabetic subjects were tested with both the pancreatic suppression test (PST) and the oral glucose tolerance test (OGTT). Of them, 53 were non–insulin-resistant (NIR) subjects and the remaining 37 were insulin resistant subjects.ResultsAll glucose and insulin values from the OGTT were positively correlated with the steady-state plasma glucose (SSPG) value of the PST. Among the OGTT values, basal insulin (I0) displayed a stronger correlation with SSPG (r = 0.604). Receiver operating characteristic analysis of the OGTT data demonstrated that I0 exhibited the highest area under the receiver operating characteristic curve (AUROC), compared with the rest of the OGTT data. However, the reduced sensitivity of this predictor precluded its clinical use.We then tested six potential predictors of IR derived from the OGTT values. Of them, the I0*G60 had a correlation coefficient of 0.697 with the SSPG and an AUROC of 0.867, surpassing the respective values of the traditional biochemical predictors of IR. Its cutoff predicting IR was >1110 mg/dL*μΙU/mL (>428 nM*pM), its sensitivity was 0.865, and its global accuracy was 0.822. We then selected the six best biochemical predictors of IR according to their posttest probability ratio. The order was as follows: I0*G60, ISI composite, AUC-Gl*In/′, quantitative insulin sensitivity check index, homeostatic model assessment 1 (HOMA1), and HOMA2.ConclusionWe conclude that the I0*G60 is a promising, inexpensive, and easily calculable predictor of IR that outperforms the predictive power of the traditional predictors of IR, including the insulin sensitivity index composite.

Insulin Resistance Index from Oral Glucose Tolerance Test Predicts Ischemic Stroke Outcomes in Non-Diabetic Patients with Different Estimated Glomerular Filtration Rate Strata

Background: Insulin resistance is associated with cardiovascular morbidity and mortality in the general population. However, the relationship between insulin resistance and health outcomes is controversial in patients with impaired renal function. Our study aimed to investigate the association between insulin resistance and prognosis in a cohort of non-diabetic stroke patients with different estimated glomerular filtration rate (eGFR) strata. Methods: Data were derived from Abnormal Glucose Regulation in Patients with Acute Stroke across China (ACROSS-China) registry. Ischemic stroke patients without history of diabetes were included. Fasting and oral glucose tolerance test (OGTT)-derived measures of insulin resistance were calculated along with homeostasis model assessment of insulin resistance (HOMA-IR) and composite insulin sensitivity index (ISI). Insulin resistance was defined by the highest HOMA-IR quartile (Q4) and the lowest composite ISI quartile (Q1). Results: Among 1,196 patients, HOMA-IR Q4 (insulin resistance) vs. Q1–3 was associated with increased 1-year mortality (adjusted hazards ratio [HR] 1.83, 95% CI 1.07–3.13) and poor functional outcome (adjusted OR 1.97, 95% CI 1.32–2.95) only in participants with an eGFR ≥90 mL/min/1.73 m². By comparison, composite ISI Q1 (insulin resistance) vs. Q2–4 was associated with higher risks of 1-year mortality (adjusted HR 3.64, 0.90–14.78; 2.50, 1.19–5.26; and 1.99, 1.17–3.39, respectively) and poor functional outcome (adjusted OR 3.62, 1.08–12.19; 1.51, 0.85–2.70; and 2.25, 1.42–3.57, respectively) in all 3 subgroups with eGFR < 60, 60–89, and ≥90 mL/min/1.73 m². Conclusions: An OGTT-derived estimate of insulin resistance with the composite ISI, but not HOMA-IR, was independently associated with increased risks of 1-year mortality and poor functional outcome in non-diabetic ischemic stroke patients with different eGFR strata.

Difference in Visceral Adipose Tissue in Pregnancy and Postpartum and Related Changes in Maternal Insulin Resistance.

To measure the difference between first-trimester and postpartum visceral adipose tissue (VAT), the agreement of this difference with change in body mass index, and whether a difference in VAT is associated with insulin resistance or glucose mishandling. Prospective study of 93 women with singleton pregnancies without a history of diabetes. Visceral adipose tissue depth was sonographically assessed at 11 to 14 weeks and at 6 to 12 weeks postpartum. Metabolic measures, sampled at 24 to 28 weeks and 6 to 12 weeks postpartum, included homeostatic model assessment of insulin resistance, insulin sensitivity index composite, and area under the 75-g oral glucose tolerance test curve. First-trimester VAT depth explained only 37% (95% confidence interval [CI], 22-52) of the variation in postpartum VAT depth. There was limited agreement between the net change in postpartum minus first-trimester VAT depth and that same net change for body mass index (Cohen's kappa, 0.26; 95% CI, 0.05-0.47). Those with a net gain in VAT depth demonstrated poorer insulin sensitivity index postpartum than women with a net regression in VAT depth-a difference of -2.0 (95% CI, -3.3 to -0.69). Sonographic assessment of postpartum VAT is feasible and may provide insight to metabolic changes between pregnancy and postpartum, beyond body mass index.

Factors associated with regression from prediabetes to normal glucose tolerance in a Korean general population: A community-based 10-year prospective cohort study.

A proportion of people with prediabetes convert back to normal glucose tolerance. We sought to determine the clinical variables associated with conversion from prediabetes to normal glucose tolerance, with a focus on insulin secretory capacity, insulin sensitivity and body composition. We followed 1731 people with prediabetes at baseline from the Korean Genome and Epidemiology Study every 2years for 10years. Oral glucose tolerance tests (OGTT) were performed, and muscle and fat mass were estimated using bioelectrical impedance analysis. During 10years of follow-up, 36% (623/1731) of people with prediabetes converted to normal glucose tolerance. Higher baseline fasting glucose, 2-h OGTT glucose and triglyceride levels were inversely associated with this conversion. Higher 60-min insulinogenic index (IGI60 ) at baseline was independently associated with this conversion [HR per sd (95% CI) 1.09 (1.02-1.17); P=0.01]. However, other indices reflecting insulin sensitivity, including the composite insulin sensitivity index, were not associated with this conversion. In addition, a higher baseline muscle to fat ratio was independently associated with conversion to normal glucose tolerance [HR per sd (95% CI) 1.15 (1.04-1.26); P=0.005]. People with conversion to normal glucose tolerance showed a greater increase in the 60-min insulinogenic index and disposition index and a smaller decrease in the composite insulin sensitivity index compared with people without conversion during 10years of follow-up (all p-values <0.001). A higher insulin secretory capacity at baseline and during follow-up and higher baseline muscle to fat ratio were independently associated with an improvement in glucose tolerance in Korean adults with prediabetes.

Artificially Sweetened Vitamin Drink Consumption Reduces Insulin Sensitivity and Alters One‐Carbon, B‐Vitamin Dependent Metabolism in Adolescents

ImportanceDiscretionary fortified beverages contain several ingredients such as vitamins and minerals in excess amounts, yet their consumption and sales have been burgeoning. Marketed as providing a unique health benefits to consumers, concerns have been raised about the overconsumption of some nutrients, especially in children and adolescents.ObjectiveTo evaluate the impact of discretionary fortified beverage consumption on energy metabolism, gut hormones and metabolic profiles of adolescents.DesignA double blind, randomized, placebo‐controlled crossover trial examined the metabolic effects of a concentrated, small format B‐vitamin fortified beverage. Healthy adolescents (10 males, 10 females, 13–19y) completed two trials separated by at least 1 week, consuming either water as placebo (PL) or an artificially sweetened discretionary fortified beverage (FB, 1.5ml/kg), which were given 40min prior to an oral glucose tolerance test (OGTT).MethodBlood samples were collected at baseline and at different time‐points throughout the OGTT for insulin, gut hormones and 1H‐NMR spectroscopy‐based metabolomics analyses. To evaluate gene‐metabolic interactions, a group of the most common single nucleotide polymorphisms (SNPs) linked to B‐vitamin metabolism was also assessed.ResultsPlasma glucose was not different between the treatment groups (p=0.111). However, plasma insulin was significantly higher in the FB group (p=0.003) and accompanied by a 28% decrease in insulin sensitivity in FB compared to PL as indicated by the composite Insulin Sensitivity Index (ISI). Gut hormone secretion was also differentially modulated by the consumption of FB. We found a significant increase in AUC of GLP‐1 (p&lt;0.001), glucagon (p=0.015), PYY (p=0.001) and C‐peptide (p=0.017) in FB compared to the PL group. Employing 1H‐NMR metabolomics, we also show perturbations to one carbon, B‐vitamin linked sulfur amino acid metabolism with FB consumption. This metabolic response was dependent on genotypic variance at rs651852 (Betaine Homocysteine methyltransferase, BHMT, p&lt;0.05).ConclusionCurrent data provide evidence that FB are not inert, but may promote insulin resistance, perturb one carbon, B‐vitamin‐linked metabolism and differentially modulate gut hormone secretion in adolescent consumers. Results may warrant reconsideration of regular, artificially sweetened FB consumption for adolescents at risk for obesity and metabolic disease.Support or Funding InformationThe research was funded by the Alberta Children's Hospital Research Institute and the National Science and Engineering Council of Canada (JS). SM is funded through an Eyes High Postdoctoral Fellowship and an Alberta Innovates Health Solutions Postdoctoral Fellowship.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Impact of Exercise on Cardiometabolic Component Risks in Spinal Cord-injured Humans.

ABSTRACTPurposeSpinal cord injury (SCI) creates a complex pathology, characterized by low levels of habitual physical activity and an increased risk of cardiometabolic disease. This study aimed to assess the effect of a moderate-intensity upper-body exercise training intervention on biomarkers of cardiometabolic component risks, adipose tissue metabolism, and cardiorespiratory fitness in persons with SCI.MethodsTwenty-one inactive men and women with chronic (>1 yr) SCI (all paraplegic injuries) 47 ± 8 yr of age (mean ± SD) were randomly allocated to either a 6-wk prescribed home-based exercise intervention (INT; n = 13) or control group (CON; n = 8). Participants assigned to the exercise group completed 4 × 45-min moderate-intensity (60%–65% peak oxygen uptake (V˙O2peak)) arm-crank exercise sessions per week. At baseline and follow-up, fasted and postload blood samples (collected during oral glucose tolerance tests) were obtained to measure metabolic regulation and biomarkers of cardiovascular disease. Abdominal subcutaneous adipose tissue biopsies were also obtained, and cardiorespiratory fitness was assessed.ResultsCompared with CON, INT significantly decreased (P = 0.04) serum fasting insulin (Δ, 3.1 ± 10.7 pmol·L−1 for CON and −12.7 ± 18.7 pmol·L−1 for INT) and homeostasis model assessment of insulin resistance (HOMA2-IR; Δ, 0.06 ± 0.20 for CON and −0.23 ± 0.36 for INT). The exercise group also increased V˙O2peak (Δ, 3.4 mL·kg−1·min−1; P ≤ 0.001). Adipose tissue metabolism, composite insulin sensitivity index (C-ISIMatsuda), and other cardiovascular disease risk biomarkers were not different between groups.ConclusionsModerate-intensity upper-body exercise improved aspects of metabolic regulation and cardiorespiratory fitness. Changes in fasting insulin and HOMA2-IR, but not C-ISIMatsuda, suggest improved hepatic but not peripheral insulin sensitivity after 6 wk of exercise training in persons with chronic paraplegia.

Enhanced external counterpulsation (EECP) improves biomarkers of glycemic control in patients with non-insulin-dependent type II diabetes mellitus for up to 3months following treatment.

The purpose of the present study was to evaluate the potential clinical benefits of EECP on glycemic parameters [fasting plasma glucose (FPG), postprandial glucose (PPG120), glycosylated hemoglobin (HbA1c)] in patients with a clinical diagnosis of type II diabetes mellitus (T2DM). Thirty subjects (60.7±1.9years) with T2DM were randomly assigned (2:1 ratio) to receive either 35 1-h sessions of EECP (n=20) or time-matched control of standard care (n=10). FPG, PPG120, and HbA1c were evaluated before and at 48h, 2weeks, 3 and 6months following EECP treatment or time-matched control. EECP significantly decreased FPG (-14.6 and -12.0%), PPG120 (-14.6 and -13.5%), and HbA1c (-11.5 and -19.6%) 48h following EECP and 2weeks following EECP, respectively. HbA1c remained significantly reduced at 3months following EECP (-14.3%). The homeostasis model assessment of insulin resistance (-31.1%) and whole-body composite insulin sensitivity index (+54.2%) were significantly improved 48h following EECP. Nitrite/nitrate (NO x ) was significantly increased 48h following EECP (+48.4%) and 2weeks (+51.9%) following EECP treatment. Our findings provide novel evidence that EECP improves glycemic control in patients with T2DM that persist for up to 3months following treatment.

Insulin-Like Growth Factor Binding Protein 1 Predicts Insulin Sensitivity And Insulin Area-Under-The-Curve In Obese, Nondiabetic Adolescents

To compare fasting insulin-like growth factor binding protein 1 (IGFBP-1) to other fasting indices as a surrogate marker of insulin sensitivity and resistance calculated from a 3-hour oral glucose tolerance test (oGTT). Fasting IGFBP-1 and oGTT were performed at 0 (n = 77), 52 (n = 54), and 100 (n = 38) weeks in a study investigating metformin treatment of obesity in adolescents. Insulin area-under-the-curve (IAUC) and the composite insulin sensitivity index (CISI) calculated from the oGTT were compared to fasting IGFBP-1, homeostasis model assessment-insulin resistance, and corrected insulin release at the glucose peak (CIRgp). IGFBP-1 and the ratio of IGFBP-1 to fasting insulin were significantly correlated with indices based on timed sampling, including IAUC, CISI, and CIRgp. In addition, a significant effect of IGFBP-1, but not IGFBP-1 to insulin at time zero, was observed for IAUC and CISI. Our results indicate that fasting IGFBP-1 may be a useful marker of insulin sensitivity and secretion.

10-year trajectory of β-cell function and insulin sensitivity in the development of type 2 diabetes: a community-based prospective cohort study

The relative contributions of β-cell function and insulin sensitivity in the pathogenesis of type 2 diabetes are not fully understood. We investigated the longitudinal change in β-cell function and insulin sensitivity in the development of diabetes and the role of genetic variants in deterioration of glucose tolerance. We followed up 4106 participants with normal glucose tolerance (NGT) from the Korean Genome and Epidemiology Study with oral glucose tolerance tests every 2 years for 10 years. We estimated pancreatic β-cell function with the 60 min insulinogenic index (IGI60) and insulin sensitivity with the composite (Matsuda) insulin sensitivity index (ISI). We investigated the association of 66 known type 2 diabetes genetic variants with risk of prediabetes or diabetes and impaired β-cell function and insulin sensitivity. During 10 years of follow-up, 1093 (27%) of 4106 participants developed prediabetes and 498 (12%) participants developed diabetes. Compared with participants who remained NGT, those who progressed to diabetes had a lower IGI60 (unadjusted data 5·1 μU/mmol [95% CI 0·5-56·1] vs 7·9 μU/mmol [0·5-113·8]; p<0·0001) and lower ISI (unadjusted data 8·2 [2·6-26·0] vs 10·0 [3·2-31·6]; p<0·0001) at baseline. Participants who had NGT at 10 years showed a decrease in ISI (adjusted data 10·1 [9·9-10·3] vs 7·4 [7·3-7·6]; p<0·0001) but a compensatory increase in IGI60 (adjusted data 6·9 μU/mmol [6·5-7·2] vs 11·7 μU/mmol [11·2-12·1]; p<0·0001) compared with baseline. By contrast, participants who developed diabetes showed a decrease in ISI (adjusted data 8·4 [8·0-8·7] vs 3·0 [2·8-3·2]; p<0·0001) but no significant compensatory increase (p=0·95) in IGI60. A genetic variant near the glucokinase gene (rs4607517) was significantly associated with progression to prediabetes or diabetes (hazard ratio 1·27, 1·16-1·38; p=1·70 × 10(-7)). Decreased β-cell function, which might be determined partly by genetic factors, and impaired β-cell compensation for progressive decline in insulin sensitivity are crucial factors in the deterioration of glucose tolerance. South Korean Ministry of Health & Welfare.

Alterations in carbohydrate metabolism in cirrhotic patients before and after liver transplant

AimThe main objective of this study is to demonstrate whether carbohydrate metabolism alterations identified in patients with advanced cirrhosis show any improvement after liver transplant. MethodsThe study included 86 patients who underwent liver transplant between March 2010 and February 2011. An oral glucose tolerance test was performed before the liver transplant, and 6 and 12 months after. Beta cell function and insulin resistance were also calculated, applying formulae that use basal plasma glycaemia and insulin, and plasma glycaemia and insulin during an oral glucose tolerance test. Risk factors for pre- and post-transplant diabetes were also studied. The diagnosis of diabetes was based on an OGTT. ResultsThe proportion of patients with diabetes before transplant, and at month 6 and 12 after transplant were 70.9%, 48.8% and 39.2%, respectively. Compared to baseline, at month 6 the odds ratio of having diabetes was 0.39 (IC 95% [0.21, 0.73]) and at month 12 it was 0.26 (IC 95% [0.14, 0.50]). The composite insulin sensitivity index values at 6 and 12 months were 1.72 units higher (IC 95% [0.84, 2.58]) and 1.58 units higher (IC 95% [0.68, 2.44)] than baseline. A statistically significant association was found between high MELD values and high body mass index, and risk of pre-transplant diabetes (p=0.001 and p=0.033, respectively). Cirrhosis aetiology did not influence the risk of diabetes. ConclusionsIn this study, we were able to ascertain that alterations in carbohydrate metabolism typical of advanced cirrhosis improve after liver transplant. This improvement is mainly due to an improvement in insulin resistance.

No Dose‐Response Relationship in the Effect of Commonly Consumer Sugars on Insulin Sensitivity Across a Range of Typical Human Consumption Levels

Questions have been raised as to whether dietary carbohydrate intake is directly related to the development of type 2 diabetes. Of particular importance, fructose‐induced insulin resistance has been previously shown in animals. However, the implications of such findings for humans are unclear as these models typically use very high doses of sugars and from sources not commonly consumed. Therefore, little is known about how the typical consumption of sugar in humans affects risk factors for diabetes.355 weight‐stable (weight change &lt;3% in previous 30 days) individuals aged 20‐60 years old drank sugar‐sweetened low fat milk every day for 10 weeks as part of their usual diet. Added sugar was provided in the milk as either high fructose corn syrup or sucrose at 8%, 18% or 30% of the calories required to maintain body weight. Insulin resistance was measured using the Homeostasis Model Assessment (HOMA IR) on fasting measures and a standard Oral Glucose Tolerance Test (OGTT) was used to measure insulin and glucose areas under the curve resistance (AUC30g * AUC30I) and whole body insulin sensitivity and hepatic insulin resistance using the Matsuda Composite Insulin Sensitivity Index (ISI).There was a small increase in weight in the entire cohort (169.1 ± 30.6 vs 171.6 ± 31.8lbs, p&lt;0.001), which was greater in the 30% level than in the 8% or 18% levels (p&lt;0.05). Glucose, insulin, HOMA, Glucose AUC, Insulin AUC, Matsuda Insulin Sensitivity Index, and hepatic insulin resistance did not vary by sugar level (p&gt;0.05) nor by sugar type (p&gt;0.05).These data show that risk factors for diabetes do not vary between the 8th % (25th percentile), and the 30% group (95th percentile). Importantly, the type of sugar (HFCS versus sucrose) had no effect on any response.

No Dose Response Relationship in the Effects of Commonly Consumed Sugars on Risk Factors for Diabetes across a Range of Typical Human Consumption Levels

Questions have been raised as to whether dietary carbohydrate intake is directly related to the development of type 2 diabetes. Of particular importance, fructose-induced insulin resistance has been previously shown in animals. However, the implications of such findings for humans are unclear as these models typically use very high doses of sugars and from sources not commonly consumed. Little is known about how the typical consumption of sugar in humans affects risk factors for diabetes. 355 weight-stable (weight change * AUC30 I) and whole body insulin sensitivity and hepatic insulin resistance using the Matsuda Composite Insulin Sensitivity Index (ISI). There was a small increase in weight in the entire cohort (169.1 ± 30.6 vs 171.6 ± 31.8 lbs, p 0.05) nor by sugar type (p > 0.05). In the entire cohort insulin sensitivity decreased as evidenced by an increase in HOMA IR (1.8 ± 1.3 vs 2.3 ± 3.4, p 0.05). Neither sugar level nor sugar type had any effect on any of these three measures (interaction p > 0.05). These data show that risk factors for diabetes do not vary between the 8% (25th percentile), and the 30% group (95th percentile) although insulin sensitivity may be affected by sugar consumption across a wide range of typical consumption levels. Importantly, the type of sugar (HFCS versus sucrose) had no effect on any response.

The [13C]Glucose Breath Test Is a Reliable Method to Identify Insulin Resistance in Mexican Adults Without Diabetes: Comparison with Other Insulin Resistance Surrogates

Insulin resistance (IR) precedes type 2 diabetes, but tests used to detect it in clinical settings reported poor reproducibility. We assessed the reliability of the [(13)C]glucose breath test ((13)C-GBT) in a sample of subjects without diabetes. Repeatability of the test was compared with that of other IR surrogates derived from the fasting or oral glucose tolerance test (OGTT). Eighty-six healthy volunteers received an oral load of 75 g of glucose in 150 mL of water followed by 1.5 mg/kg of [U-(13)C]glucose in 50 mL of water. Breath and blood samples were collected at baseline and at 10, 20, 30, 60, 90, 120, 150, and 180 min following the glucose load; the same procedure was repeated within 1 week. The enrichment of breath (13)CO2 was measured by ratio mass spectrometry and expressed as percentage oxidized dose at a given time period. Intrasubject variability was assessed with Bland-Altman plots and coefficients of variation (CVs). The overall CV of the (13)C-GBT was 12.99±11.61%, compared with 18.42% of fasting insulin, 19.44% for homeostasis model assessment, 17.06% of the composite insulin sensitivity index, and 29.99% for insulin in the 2-h oral glucose tolerance test. The variability of the (13)C-GBT tended to be higher in lean (17.40%) than in overweight (10.17%) and obese (12.61%) individuals. The variability of the (13)C-GBT is lower than that of other IR surrogates, making it a reproducible method to estimate insulin sensitivity in overweight and obese adults without diabetes. Because the individuals did not have diabetes but were within a high range of insulin sensitivity, the test should have application in clinical and population-based studies, given the evidence for the utility and limitations of this surrogate.