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Introduction and Objectives: Data on the prevalence of non-alcoholic fatty liver disease (NAFLD) in subgroups of the United States (US) population are limited. This study was conducted to estimate NAFLD prevalence overall and by subgroups, and prevalence of NAFLD with advanced fibrosis. Materials and Methods: Using the National Health and Nutrition Examination Survey (NHANES) 2011-2018 data, a cross-sectional study was conducted. NAFLD was defined as having a US Fatty Liver Index (USFLI) = 30 in the absence of other causes of liver disease, including excessive alcohol intake, chronic hepatitis B, and chronic hepatitis C. Likelihood for having advanced fibrosis was determined by the calculated NAFLD fibrosis score (NFS; high = 0.676; low < -1.445) and fibrosis-4 index (FIB-4; high = 2.67; low < 1.30). Results: The weighted national prevalence of NAFLD in US adults was 26.7% (95% confidence interval: 25.3%-28.1%). Prevalence was higher among those aged = 65 years, males, Mexican Americans, with BMI = 35 kg/m2 (class 2 and 3 obesity) and with type 2 diabetes (T2D). Of those meeting the USFLI criterion for NAFLD, 18.1% and 3.7% were determined as having a high probability of advanced fibrosis based on NFS = 0.676 and FIB-4 = 2.67 cut-off values, respectively. Conclusions: This study supports an increased prevalence of NAFLD in specific subpopulations (aged = 65 years, males, Mexican Americans, obese population, and patients with T2D). The observed difference in the prevalence of advanced fibrosis as estimated by NFS and FIB-4 highlights the challenge of choosing optimal cut-off values. [ABSTRACT FROM AUTHOR]

Improving glycemic control generally improves β-cell function in T2DM but the predictors for this effect are unclear. SGLT2 inhibitors improve glycemia and have no known direct effects on β-cell function. Therefore, we aimed to identify predictors of β-cell function changes by treatment with the SGLT2 inhibitor ertugliflozin (ERTU). Data of patients (pts) randomized to ERTU (5 or 15 mg) only or placebo (PBO) only from four phase 3 ERTU studies of the VERTIS clinical program were pooled and analyzed. Change from baseline in β-cell function (fasting homeostatic model assessment beta [HOMA-β] and C-peptide Insulinogenic Index [IGI] at 30 min of a mixed meal tolerance test) at Week 26 was assessed, followed by linear regression analyses to examine the relationship between change in β-cell function versus metabolic and demographic characteristics. ERTU compared with PBO improved β-cell function when assessed by the changes from baseline (95% CIs) in HOMA-β (14.7 [12.3,17.1] versus −0.4 [−3.4, 2.5]) but not IGI. Change in HOMA-β correlated negatively and similarly with change in A1C in both groups (ERTU: r=−0.29; PBO: r=−0.36, both P<0.001). In the ERTU group, change in HOMA-β correlated positively with baseline fasting plasma glucose (FPG; r=0.23, P<0.001) and baseline A1C (r=0.14, P<0.001) but negatively with baseline HOMA-β (r=−0.32, P<0.001) in simple linear regression analyses; no significant correlations were found with age, sex, ethnicity, diabetes duration, baseline serum triglycerides, creatinine, weight or systolic blood pressure. Correlations between change in HOMA-β and baseline FPG, A1C and HOMA-β remained significant in multiple regression analyses. ERTU improves fasting HOMA-β but not the postprandial IGI in pts with T2DM. Pts with high baseline FPG and A1C values but low baseline HOMA-β may derive greater benefit than those with low baseline FPG, A1C and high HOMA-β with ertugliflozin treatment in terms of fasting HOMA-β. Disclosure: S. Gallo: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. A. Raji: Employee; Self; Merck & Co., Inc. Stock/Shareholder; Self; Merck & Co., Inc. R.A. Calle: Employee; Self; Pfizer Inc. Stock/Shareholder; Self; Pfizer Inc. M.C. Ellison: Employee; Self; Merck & Co., Inc. C. Meyer: Employee; Self; Merck & Co., Inc. Funding: Merck Sharp & Dohme Corp; Pfizer Inc. [ABSTRACT FROM AUTHOR]

Insulin enhances blood flow to human skeletal muscle, but the relationship between total blood flow, capillary recruitment, and rate of glucose uptake is not clearly established. To address this question, we measured total brachial artery blood flow and microvascular volume in the forearm deep flexor muscle in 7 healthy volunteers (mean ± SD age = 25±4 yrs, BMI = 22±3 kg/m², FPG = 87±6 mg/dl) at baseline and at the end of a 2 hr euglycemic hyperinsulinemic clamp (1 mU/kg/min). Contrast enhanced ultrasound (HDI 5000, ATL Ultrasound) assessment of microvascular volume and brachial artery flow were obtained during continuous infusion of microbubble contrast (Definity) with images acquired at pulsing intervals of 0.2 to 15 sec. The video intensity of background-subtracted images at each pulsing interval was quantified, and plateau video intensity during infusion used as an index of microvascular volume. Brachial artery velocity and diameter were obtained using an L 12-5 linear array probe (Philips) to calculate total flow into the forearm. At the end of the clamp, mean rate of glucose uptake (M) was 8.9±0.8 mg/kg/min. Significant increases from baseline were observed for brachial artery blood flow (39±10 to 67±13 ml/min, p=0.02) and microvascular volume (71±10 to 1004±8 video intensity units, p=0.01). Insulin-mediated glucose uptake was positively correlated with both brachial artery blood flow (r=0.80, p<0.05) and microvascular volume (r=0.62). Triglycerides correlated negatively with insulin sensitivity (r=-0.75) and brachial artery blood flow (r=-0.67). In conclusion, physiologic hyperinsulinemia enhances both microvascular volume in forearm skeletal muscle and total brachial artery blood flow. The close relationship between these hemodynamic measures and insulin sensitivity suggests that insulin-mediated glucose uptake in muscle may be largely mediated by an increase in capillary recruitment and subsequent augmentation of total blood flow. Ongoing studies are examining the temporal and dose-response effects of insulin on microvascular perfusion (capillary recruitment) and blood flow. [ABSTRACT FROM AUTHOR]

Asian Indians (AI) are insulin resistant and have a higher risk of diabetes compared to Caucasians (C). However, potential abnormalities in insulin secretion and their relationship to the severity of insulin resistance in AI have not been carefully studied. To address this question we examined l) first (0-10 min) and second (l0-120 min) phase insulin secretion during a 2-hr hyperglycemic clamp at +90 mg/dl, 2) insulin secretion in response to a non-glucose secretagogue (arginine, 5 gm IV) at euglycemia and at the end of the hyperglycemic clamp, and 3) insulin sensitivity (M) during a 1 mU/kg⋅min hyperinsulinemic euglycemic clamp. Four healthy AI and 6 C of similar age (29±2 vs 38±6 yrs) and BMI (25.3±2.3 vs 24.7±1.3 kg/msup2;) were studied. AI and C had similar FPG (94±2 vs 90±2. mg/dl), but AI had higher fasting insulin levels (9.1±2.2 vs 3.4±0.6 µU/ml, p<0.05) and were very insulin resistant during the euglycemic clamp (M = 4.0±0.5 vs 9.7±0.6 mg/kg/min, p<0.001). During the hyperglycemic clamp, first phase (321±106 vs 102±22 µU/ml⋅0 min, p<0.05) and second phase (4920±959 vs 1340±174 pU/ml. 110 min, p<0.01) insulin secretion were significantly increased in AI vs C. The insulin responses to arginine at euglycemia (314±43 vs 145±9 µU/ml. l0 min, p<0.01) and hyperglycemia (2399±415 vs 1203±235 #U/ml. 10 min, p<0.05) also were significantly higher in AI. All measures of insulin secretion were inversely correlated with M (r = -0.69 to -0.82, p<0.05 to 0.005). The glucose disposition index (M x first phase insulin secretion) was increased moderately (by 29%), but not significantly, in AI vs C. Conclusion: Non-diabetic AI are characterized by l) marked insulin resistance, 2) enhanced first- and second-phase insulin responses to hyperglycemia, 3) increased insulin response to arginine at euglycemia and hyperglycemia, and 4) a moderate increase in the glucose disposition index. These data suggest that beta cell function remains intact in non-diabetic AI despite the presence of significant insulin resistance. [ABSTRACT FROM AUTHOR]