Composite Insulin Sensitivity Index Research Articles

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.

The independent and combined effects of exercise training and reducing sedentary behavior on cardiometabolic risk factors.

This pilot study examined if the combination of exercise training and reducing sedentary time (ST) results in greater changes to health markers than either intervention alone. Fifty-seven overweight/obese participants (19 males/39 females) (mean ± SD; age, 43.6 ± 9.9 years; body mass index (BMI), 35.1 ± 4.6 kg·m(-2)) completed the 12-week study and were randomly assigned to (i) EX: exercise 5 days·week(-1) for 40 min·session(-1) at moderate intensity; (ii) rST: reduce ST and increase nonexercise physical activity; (iii) EX-rST: combination of EX and rST; and (iv) CON: maintain behavior. Fasting lipids, blood pressure (BP), peak oxygen uptake, BMI, and 2-h oral glucose tolerance tests were completed pre- and post-intervention. EX and EX-rST increased peak oxygen uptake by ∼10% and decreased systolic BP (both p < 0.001). BMI decreased by -3.3% (95% confidence interval: -4.6% to -1.9%) for EX-rST and -2.2% (-3.5% to 0.0%) for EX. EX-rST significantly increased composite insulin-sensitivity index by 17.8% (2.8% to 32.8%) and decreased insulin area under the curve by 19.4% (-31.4% to -7.3%). No other groups improved in insulin action variables. rST group decreased ST by 7% (∼50 min·day(-1)); however, BP was the only health-related outcome that improved. EX and EX-rST improved peak oxygen uptake and BMI, providing further evidence that moderate-intensity exercise is beneficial. The within-group analysis provides preliminary evidence that exercising and reducing ST may result in improvements in metabolic biomarkers that are not seen with exercise alone, though between-group differences did not reach statistical significance. Future studies, with larger samples, should examine health-related outcomes resulting from greater reductions in ST over longer intervention periods.

Insulin Sensitivity and Secretion in Arab Americans with Glucose Intolerance

This study examined the pathophysiological abnormalities in Arab Americans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin secretion (HOMA-%β), and the Matsuda Insulin Sensitivity Index composite (ISIcomposite) were calculated from the fasting and stimulated glucose and insulin concentrations measured during the oral glucose tolerance test in a population-based, representative, cross-sectional sample of randomly selected Arab Americans. In total, 497 individuals (42±14 years old; 40% males; body mass index [BMI], 29±6 kg/m(2)) were studied. Multivariate linear regression models were performed to compare HOMA-IR, HOMA-%β, and ISIcomposite among individuals with normal glucose tolerance (NGT) (n=191) versus isolated IFG (n=136), isolated IGT (n=22), combined IFG/IGT (n=43), and diabetes (n=105). Compared with individuals with NGT (2.9±1.6), HOMA-IR progressively increased in individuals with isolated IFG (4.8±2.7, P<0.001), combined IFG/IGT (6.0±4.3, P<0.001), and diabetes (9.7±8.3, P<0.001) but not in those with isolated IGT (3.0±1.7, P=0.87). After adjustment for sex and BMI, these associations remained unchanged. Whole-body insulin sensitivity as measured by ISIcomposite was significantly lower in individuals with isolated IFG (3.9±2.3, P<0.001), isolated IGT (2.8±1.5, P<0.001), combined IFG/IGT (1.9±1.1, P<0.001), and diabetes (1.6±1.1, P<0.001) compared with those with NGT (6.1±3.5). HOMA-%β was significantly lower in diabetes (113.7±124.9, P<0.001) compared with NGT (161.3±92.0). After adjustment for age, sex, and BMI, isolated IFG (146.6±80.2) was also significantly associated with a decline in HOMA-%β relative to NGT (P=0.005). This study suggests that differences in the underlying metabolic defects leading to diabetes in Arab Americans with IFG and/or IGT exist and may require different strategies for the prevention of diabetes.

Comparison of insulin sensitivity measures in South Asians

ObjectiveSouth Asians have increased visceral adiposity, insulin resistance and greater prevalence of type 2 diabetes and cardiovascular disease when compared to Caucasians of European origin. Surrogate markers of insulin resistance such as the composite insulin sensitivity (Matsuda) index correlate with glucose clamps in other populations, but ethnicity can affect these indices. We compared the Matsuda index, homeostasis model assessment (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglyceride/HDL ratio to insulin sensitivity derived from euglycemic clamps in healthy South Asians and Caucasians. Materials/MethodsTwenty-three healthy South Asians and 18 Caucasians matched for age (mean±SE=33.6±2.1 vs. 36.0±3.0years) and BMI (25.2±1.1 vs. 24.6±0.9kg/m2) underwent 75g oral glucose tolerance test (OGTT), 2-h euglycemic hyperinsulinemic clamp (240 pmol·m−2·min−1), fasting lipid profile, and anthropometric measures. ResultsSouth Asians had higher fasting insulin (41±5 vs. 21±2 pmol/l; p=0.002) and lower HDL-C (1.25±0.06 vs. 1.56±0.10mmol/l; p=0.010), but similar fasting glucose (5.0±0.1 vs. 4.9±0.1mmol/l) levels vs. Caucasians. South Asians had significantly decreased measures of insulin sensitivity derived from both the euglycemic clamp (24.9±1.3 vs. 41.4±1.9μmol·kg−1·min−1; p<0.0001) and OGTT (Matsuda Index 7.60±0.99 vs. 13.60±1.79; p=0.004). The Matsuda index correlated highly with clamp insulin sensitivity in South Asians (r=0.50; p=0.014) and Caucasians (r=0.47; p=0.046). HOMA-IR, QUICKI, and triglyceride/HDL ratio correlated with clamp values in South Asians, but not in Caucasians. ConclusionsIn South Asians, Matsuda index, HOMA-IR, QUICKI, and triglyceride/HDL ratio offer simple and valid surrogate measures of insulin sensitivity that can be employed in larger clinical or epidemiological studies in this ethnic group.