Comparison of Various Indices in Identifying Insulin Resistance and Diabetes in Chronic Spinal Cord Injury

The purpose of this screening and diagnostic study was to examine the accord among indices of glucose metabolism, including the Homeostatic Model Assessment for Insulin Resistance (HOMA), HOMA2, Matsuda Index, Quantitative Insulin-sensitivity Check Index (QUICKI), hemoglobin A1C (HbA1C), and fasting plasma glucose (FPG) against intravenous glucose tolerance test-measured insulin sensitivity (Si) in individuals with chronic motor complete SCI. Persons with chronic (≥12-months post-injury) SCI (n = 29; 79% men; age 42.2 ± 11.4; body mass index 28.6 ± 6.4 kg/m2; C4-T10) were included. Measures were compared using adjusted R2 from linear regression models with Akaike information criterion (AIC, a measure of error). QUCKI had the greatest agreement with Si (adjusted R2 = 0.463, AIC = 91.1, p = 0.0001), followed by HOMA (adjusted R2 = 0.378, AIC = 95.4, p = 0.0008), HOMA2 (adjusted R2 = 0.256, AIC = 99.7, p = 0.0030), and the Matsuda Index (adjusted R2 = 0.356, AIC = 95.5, p = 0.0004). FPG (adjusted R2 = 0.056, AIC = 107.5, p = 0.1799) and HbA1C (adjusted R2 = 0.1, AIC = 106.1, p = 0.0975) had poor agreement with Si. While HbA1C and FPG are commonly used for evaluating disorders of glucose metabolism, QUICKI demonstrates the best accord with Si compared to the other measures.

Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity

BackgroundStatins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans.MethodsA prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a β3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated.ResultsTwo weeks of fluvastatin treatment led to a significant increase in glucose area under the curve (AUC) during oGTT (p=0.02), reduction in total cholesterol and LDL cholesterol (both p<0.0001). Insulin AUC (p=0.26), resting energy expenditure (REE) (p=0.44) and diet induced thermogenesis (DIT) (p=0.27) did not change significantly. The Matsuda index, as an indicator of insulin sensitivity, was lower after fluvastatin intake, but the difference was not statistically significant (p=0.09). As parameters of BAT activity, mean standard uptake value (SUVmean) (p=0.12), volume (p=0.49) and total glycolysis (p=0.74) did not change significantly during the intervention. Matsuda index, was inversely related to SUVmean and the respiratory exchange ratio (RER) (both R2 = 0.44, p=0.005) at baseline, but not after administration of fluvastatin (R2 = 0.08, p=0.29, and R2 = 0.14, p=0.16, respectively).ConclusionsTreatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.

Effects of Coffee Consumption on Insulin Resistance and Sensitivity: A Meta-Analysis

Coffee is widely consumed worldwide and impacts glucose metabolism. After a previous meta-analysis that evaluated the effects of coffee consumption on insulin resistance and sensitivity, additional randomized controlled trials (RCTs) were conducted. This meta-analysis aimed to evaluate the effects of coffee consumption on insulin resistance or sensitivity. We selected RCTs that evaluated the effects of coffee consumption for seven days or more on insulin sensitivity or resistance using surrogate indices (homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda index). The fixed-effects or random-effects model was used according to heterogeneity. Four studies with 268 participants were analyzed in this meta-analysis. Coffee consumption significantly decreased HOMA-IR compared to control (mean difference (MD) = −0.13; 95% CI = −0.24–−0.03; p-value = 0.01). However, the significance was not maintained in the sensitivity analysis (MD = −0.04; 95% CI = −0.18–0.10; p-value = 0.55) after excluding data from the healthy, young, normal-weight group. Matsuda index was not significantly different between coffee and control groups (standardized mean difference (SMD) = −0.33; 95% CI = −0.70–0.03; p-value = 0.08). In conclusion, long-term coffee consumption has a nonsignificant effect on insulin resistance and sensitivity. More studies evaluating the effects of coffee consumption in the healthy, young, and normal-weight individuals are needed.

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We set out to examine the genetics of variation in concentrations of postprandial metabolites (t=150 min) in response to a liquid mixed meal through genome-wide association studies (GWAS) performed in the Netherlands Epidemiology of Obesity study (N=5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (beta (SE): -0.23 (0.03), P-value: 2.15×10^-19). In addition, <i>ANKRD55</i> locus led by rs458741:C showed strong associations to extremely large VLDL particle (XXLVLDL) response (with XXLVLDLC: beta (SE): 0.17 (0.03) P-value: 5.76×10^-10and with XXLVLDLCE: beta (SE): 0.17 (0.03), P-value: 9.74×10^-10), which also revealed strong associations to body composition and diabetes in the UK Biobank (p-values<5×10^-8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, ISI matsuda index and HbA1c in the NEO study further implied the role of chylomicron synthesis in diabetes (with FDR corrected q-value<0.05). To conclude, genetic studies of metabolomics change after a liquid meal illuminate novel pathways for glucose and lipid metabolism. Further studies are warranted to corroborate biological pathways of <i>ANKRD55</i> locus underlying diabetes.

Genetic Studies of Metabolomics Change After a Liquid Meal Illuminate Novel Pathways for Glucose and Lipid Metabolism

Humans spend the greater part of the day in a postprandial state. However, the genetic basis of postprandial blood measures is relatively uncharted territory. We set out to examine the genetics of variation in concentrations of postprandial metabolites (t=150 min) in response to a liquid mixed meal through genome-wide association studies (GWAS) performed in the Netherlands Epidemiology of Obesity study (N=5,705). The metabolite response GWAS identified an association between glucose change and rs10830963:G in the melatonin receptor 1B (beta (SE): -0.23 (0.03), P-value: 2.15×10^-19). In addition, <i>ANKRD55</i> locus led by rs458741:C showed strong associations to extremely large VLDL particle (XXLVLDL) response (with XXLVLDLC: beta (SE): 0.17 (0.03) P-value: 5.76×10^-10and with XXLVLDLCE: beta (SE): 0.17 (0.03), P-value: 9.74×10^-10), which also revealed strong associations to body composition and diabetes in the UK Biobank (p-values<5×10^-8). Furthermore, the associations between XXLVLDL response and insulinogenic index, HOMA-β, ISI matsuda index and HbA1c in the NEO study further implied the role of chylomicron synthesis in diabetes (with FDR corrected q-value<0.05). To conclude, genetic studies of metabolomics change after a liquid meal illuminate novel pathways for glucose and lipid metabolism. Further studies are warranted to corroborate biological pathways of <i>ANKRD55</i> locus underlying diabetes.

Effect of Direct Acting Anti-Viral Drugs on Insulin Resistance and sensitivity Among Egyptian Chronic HCV Infected Patients

Background Hepatitis C virus (HCV) infection is a worldwide infection, affecting up to 185 million people across the world. It carries a high risk for developing liver cirrhosis, hepatocellular carcinoma (HCC) and liver-related deaths. Aim of the Work to assess the impact of direct acting anti-viral drugs on the status of insulin resistance and sensitivity in non-diabetic chronic HCV infection patients Patients and Methods study included 100 treatment naive patients with chronic infection of HCV attending the out-patient clinic at Gastro-enterology and Hepatology Department, Ain shams University and Kobry El Kobba Military Hospital between September 2017 till June 2019. Patients were diagnosed by HCV antibodies & HCV RNA by PCR. Results The fasting blood glucose, seum insulin and HbA1c were significantly decreased between the baseline and after SVR12. The 2Hrs PP was significantly increased between the baseline and after SVR12. The HOMA-IR showed significant decrease between the baseline and SVR12. The QUICKI and Matsuda Index showed significant increase at SVR12. Conclusion HOMA-IR, QUICKI and Matsuda index showed significant improvement between the baseline and after SVR12.

245Comparison of methods for classifying heterogeneity in gestational diabetes (GDM) and association with outcomes

Background Clinical experience suggests that diverse clinical subtypes exist within the broader diagnosis of GDM. Analysis from a single centre recently outlined heterogeneity in GDM with respect to insulin secretion and sensitivity, defining four GDM subtypes: 1) GDMsecr (&lt;25th centile HOMA-β (Hb) for non-GDM); 2) GDMsens (&lt;25th centile Matsuda Index for non-GDM); 3) GDMmixed (both GDMsecr and GDMsens); 4) GDMND, no defect (neither GDMsecr and GDMsens). Classification using these subtypes is associated with adverse outcomes. Methods Following similar methodology, women with GDM were classified into four subtypes including comparison of Hb, insulinogenic index (II) and Stumvoll first-phase estimate (SV) for defining GDMsecr. Analyses compared neonatal outcomes with non-GDM women and between GDM groups using c2 tests and regression analyses adjusted for multiple confounders including maternal age, BMI and HAPO study centre. Results Hb, II and SV gave divergent results for GDMsecr, with only 19% concordance. In all analyses, GDMND (10% by Hb, 6% by II, 6% by SV) showed outcome frequencies similar to those of non-GDM women; groups 1-3 showed higher risks (p &lt; 0.01 vs non GDM). These results persisted in the fully adjusted model (aOR generally &gt;2.0). Conclusions Different clinical subtypes in GDM are associated with differing risks of adverse outcome. Key messages Determination of GDM subtype can assist in assessing GDM women at higher risk of adverse clinical outcome and help guide clinical practice.

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

IntroductionUncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America.Research design and methodsOral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan.ResultsThe prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group.ConclusionsBeta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ.Trial registration numberNCT00001853.

Pharmacokinetic Investigation of Commercially Available Edible Marijuana Products in Humans: Potential Influence of Body Composition and Influence on Glucose Control

The purpose of the study was to describe and compare the pharmacokinetics of five commercial edible marijuana products, determine the influence of body composition on pharmacokinetics, and, in light of epidemiology suggesting marijuana may offer diabetes protection, explore the influence of edible marijuana on glucose tolerance. Seven regular users of marijuana self-administered five edible products in a randomized crossover design; each product contained 10 mg of delta-9-tetrahydrocannabinol (THC). Thirty minutes following marijuana ingestion, participants imbibed a 75 g glucose beverage. Time-to-peak plasma THC concentration ranged between 35 and 90 min; maximal plasma THC concentration (Cmax) ranged between 3.2 and 5.5 ng/mL. Differences between products in plasma THC concentration during the first 20–30 min were detected (p = 0.019). Relations were identified between body composition and pharmacokinetic parameters for some products; however, none of these body composition characteristics were consistently related to pharmacokinetics across all five of the products. Edible marijuana had no effect on oral glucose tolerance compared with a marijuana-free control (Matsuda Index; p > 0.395). Commercially available edible marijuana products evoke different plasma THC concentrations shortly after ingestion, but do not appear to influence acute glucose regulation. These data may allow recreational marijuana users to make informed decisions pertaining to rates of edible marijuana ingestion and avoid overdose.

Association between insulin resistance and cardinal rheological parameters in young healthy Japanese individuals during 75 g oral glucose tolerance test

Background: Insulin resistance is a well-known predictor and risk factor for Type 2 Diabetes Mellitus (T2DM). Higher hematocrit induced by higher insulin resistance affects blood rheology. Objective: This study intended to reveal the association between indices of insulin resistance and hemorheological parameters during a 75 g oral glucose tolerance test (75-g OGTT). Methods: A total of 575 healthy young Japanese participants took 75-g OGTT. We then analyzed the association between insulin resistance indices and hematological parameters. Results: The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) was significantly correlated with hematocrit (Ht), hemoglobin (Hb), Red Blood Cell (RBC), White Blood Cell (WBC), platelet count, lipid parameters, and Body Mass Index (BMI). The Matsuda index was negatively correlated with RBC count, WBC count, platelet count, Total Cholesterol (TC), Low-Density Lipoprotein-Cholesterol (LDL-C), triglyceride (TG), and positively correlated with High-Density Lipoprotein-Cholesterol (HDL-C). The disposition index was negatively correlated with Hb, RBC count, LDL-C, and BMI, while remaining positively correlated with HDL-C. The Homeostasis Model Assessment of beta cell (HOMA- IR ) was positively correlated with WBC count, platelet count, TC, LDL-C, and TG. The insulinogenic index was positively correlated with WBC count, platelet count, and TC. Multiple regression analysis revealed that HOMA-IR was independently associated with TG, and the Matsuda index was independently associated with TG, WBC count, and platelet count. The insulinogenic index was independently associated with WBC count. Conclusion: Cardinal rheological parameters reflected insulin resistance and were released even in the young, healthy Japanese individuals within the physiological range of glycemic control.