Critical Evaluation of Indices Used to Assess β-Cell Function.

The assessment of β-cell function, defined as the relationship between insulin secretion rate (ISR) and plasma glucose, is not standardized and often involves any of a number of β-cell function indices. We compared β-cell function by using popular indices obtained during basal conditions and after glucose ingestion, including the HOMA-B index, the basal ISR (or plasma insulin)-to-plasma glucose concentration ratio, the insulinogenic and ISRogenic indices, the ISR (or plasma insulin)-to-plasma glucose concentration areas (or incremental areas) under the curve ratio, and the disposition index, which integrates a specific β-cell function index value with an estimate of insulin sensitivity, between lean people with normal fasting glucose (NFG) and normal glucose tolerance (NGT) (n = 50) and four groups of people with obesity (n = 188) with 1) NFG-NGT, 2) NFG and impaired glucose tolerance (IGT), 3) impaired fasting glucose (IFG) and IGT, and 4) type 2 diabetes. We also plotted the ISR-plasma glucose relationship before and after glucose ingestion and used a statistical mixed-effects model to evaluate group differences in this relationship (i.

Exercise Training to Improve Brain Health in Older People Living With HIV: Study Protocol for a Randomized Controlled Trial.

Background: With the advent of antiretrovirals, people living with HIV are living near-normal lifespans. However, people living with HIV are at greater risk of experiencing cognitive impairment and reduced brain integrity despite well-controlled viremia. A robust literature supports exercise interventions as a method of improving cognition and structural brain integrity in older individuals without HIV.

Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research.

Worksite-based intensive lifestyle therapy has profound cardiometabolic benefits in people with obesity and type 2 diabetes.

Lifestyle therapy (energy restriction and exercise) is the cornerstone of therapy for people with type 2 diabetes (T2D) but is difficult to implement. We conducted an 8-month randomized controlled trial in persons with obesity and T2D (17 women and 1 man) to determine the therapeutic effects and potential mechanisms of intensive lifestyle therapy on cardiometabolic function. Intensive lifestyle therapy was conducted at the worksite to enhance compliance and resulted in marked (17%) weight loss and beneficial changes in body fat mass, intrahepatic triglyceride content, cardiorespiratory fitness, muscle strength, glycemic control, β cell function, and multi-organ insulin sensitivity, which were associated with changes in muscle NAD biosynthesis, sirtuin signaling, and mitochondrial function and in adipose tissue remodeling.

Evolution of the diagnostic value of "the sugar of the blood": hitting the sweet spot to identify alterations in glucose dynamics.

In this paper, we provide an overview of the evolution of the definition of hyperglycemia during the past century and the alterations in glucose dynamics that cause fasting and postprandial hyperglycemia. We discuss how extensive mechanistic, physiological research into the factors and pathways that regulate the appearance of glucose in the circulation and its uptake and metabolism by tissues and organs has contributed knowledge that has advanced our understanding of different types of hyperglycemia, namely prediabetes and diabetes and their subtypes (impaired fasting plasma glucose, impaired glucose tolerance, combined impaired fasting plasma glucose, impaired glucose tolerance, type 1 diabetes, type 2 diabetes, gestational diabetes mellitus), their relationships with medical complications, and how to prevent and treat hyperglycemia.

Increased plasma fatty acid clearance, not fatty acid concentration, is associated with muscle insulin resistance in people with obesity.

Background: Although it is well-accepted that increased plasma free fatty acid (FFA) concentration causes lipid overload and muscle insulin resistance in people with obesity, plasma FFA concentration poorly predicts insulin-resistant glucose metabolism. It has been proposed that hyperinsulinemia in people with obesity sufficiently inhibits adipose tissue triglyceride lipolysis to prevent FFA-induced insulin resistance. However, we hypothesized enhanced FFA clearance in people with obesity, compared with lean people, prevents a marked increase in plasma FFA even when FFA appearance is high.

High rates of undiagnosed and uncontrolled hypertension upon a screening campaign in rural Rwanda: a cross-sectional study.

Background: Hypertension remains the major risk factor for cardiovascular diseases (CVDs) worldwide with a prevalence and mortality in low- and middle-income countries (LMICs) among the highest. The early detection of hypertension risk factors is a crucial pillar for CVD prevention.

Design And Method: This cross-sectional study included 4284 subjects, mean age 46 ± 16SD, 56.

Effect of obstructive sleep apnea on glucose metabolism.

Background: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, β-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown.

Design And Methods: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA.

Insulin sensitivity and kinetics in African American and White people with obesity: Insights from different study protocols.

Objective: Studies that used an intravenous glucose tolerance test (IVGTT) have suggested that race is an important modulator of insulin sensitivity, β-cell function, and insulin clearance. However, the validity of the IVGTT has been challenged.

Methods: This study assessed insulin sensitivity and insulin kinetics in non-Hispanic White (NHW, n = 29) and African American (AA, n = 14) people with obesity by using a hyperinsulinemic-euglycemic pancreatic clamp with glucose tracer infusion, an oral glucose tolerance test (OGTT), and an IVGTT.

Cardiorespiratory Fitness Is Associated With Better White Matter Integrity in Persons Living With HIV.

Background: Despite improved survival rates, neurocognitive impairment persists in persons living with HIV (PLWH). An active lifestyle is linked to improved cognition among PLWH, yet the neural substrates remain unclear. Diffusion tensor imaging and diffusion basis spectrum imaging measure HIV-related changes in brain white matter integrity.

Resistance exercise training with protein supplementation improves skeletal muscle strength and improves quality of life in late adolescents and young adults with Barth syndrome: A pilot study.

Background: Muscle weakness and exercise intolerance contribute to reduced quality of life (QOL) in Barth syndrome (BTHS). Our group previously found that 12 weeks of resistance exercise training (RET) improved muscle strength, however, did not increase muscle (lean) mass or QOL in n = 3 young adults with BTHS. The overall objective of this pilot study was to examine the safety and effectiveness of RET plus daily protein supplementation (RET + protein) on muscle strength, skeletal muscle mass, exercise tolerance, cardiac function, and QOL in late adolescents/young adults with BTHS.

Exploring contextual factors influencing the implementation of evidence-based care for hypertension in Rwanda: a cross-sectional study using the COACH questionnaire.

Importance: Hypertension is the largest contributor to the Global Burden of Disease. In Rwanda, as in most low-income and middle-income countries, an increasing prevalence of hypertension and its associated morbidity and mortality is causing major healthcare and economic impact. Understanding healthcare systems context in hypertension care is necessary.

Bictegravir-Based Antiretroviral Therapy-Associated Accelerated Hyperglycemia and Diabetes Mellitus.

Integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) is first line for treatment of people with human immunodeficiency virus (PWH). Emerging data suggest the possibility of adverse metabolic effects of these medications. We describe 3 cases in which PWH developed hyperglycemia and ketoacidosis within months of being switched to bictegravir-based ART.

Comparison of the Ekblom-Bak Submaximal Test to a Maximal Test in a Cohort of Healthy Younger and Older Adults in the United States.

Cardiorespiratory fitness (CRF) is routinely investigated in diverse populations, including in older adults of varying physical activity levels. Commonly performed maximal exercise testing protocols might be contraindicated and/or inadequate for older individuals who have physical or cognitive impairment. Moreover, early termination of an attempted maximal exercise test could result in underestimation of CRF in this population.

Arginine kinetics are altered in a pilot sample of adolescents and young adults with Barth syndrome.

Barth syndrome (BTHS) is a rare, X-linked cardiomyopathy that is characterized by abnormalities in glucose and lipid metabolism, with less known regarding amino acid metabolism. This pilot study characterized whole-body arginine kinetics and found lower arginine rate of appearance into plasma (0.69 ± 0.

A Single Bout of Premeal Resistance Exercise Improves Postprandial Glucose Metabolism in Obese Men with Prediabetes.

Introduction: Prediabetes is a major risk factor for type 2 diabetes and cardiovascular diseases. Although resistance exercise (RE) is recommended for individuals with prediabetes, the effects of RE on postprandial glucose metabolism in this population are poorly understood. Therefore, the purpose of this study was to elucidate how RE affects postprandial glucose kinetics, insulin sensitivity, beta cell function, and glucose oxidation during the subsequent meal in sedentary men with obesity and prediabetes.

No independent or combined effects of vitamin D and conjugated linoleic acids on muscle protein synthesis in older adults: a randomized, double-blind, placebo-controlled clinical trial.

Background: Aging is associated with skeletal muscle anabolic resistance (i.e., reduced muscle protein synthesis during anabolic conditions such as hyperaminoacidemia).

Effects of Diet versus Gastric Bypass on Metabolic Function in Diabetes.

Background: Some studies have suggested that in people with type 2 diabetes, Roux-en-Y gastric bypass has therapeutic effects on metabolic function that are independent of weight loss.

Methods: We evaluated metabolic regulators of glucose homeostasis before and after matched (approximately 18%) weight loss induced by gastric bypass (surgery group) or diet alone (diet group) in 22 patients with obesity and diabetes. The primary outcome was the change in hepatic insulin sensitivity, assessed by infusion of insulin at low rates (stages 1 and 2 of a 3-stage hyperinsulinemic euglycemic pancreatic clamp).

The TDR MOOC training in implementation research: evaluation of feasibility and lessons learned in Rwanda.

Background: Hypertension (HTN) affects nearly 1 billion people globally and is a major cause of morbidity and mortality. In low- and middle-income countries (LMICs), HTN represents an unmet health care gap that can be addressed by strengthening national health care systems. The National Heart, Lung, and Blood Institute recently funded the T4 Translation Research Capacity Building Initiative in Low Income Countries (TREIN) program to build capacity in dissemination and implementation (D&I) research in HTN in LMICs.

A single bout of resistance exercise improves postprandial lipid metabolism in overweight/obese men with prediabetes.

Aims/hypothesis: Prediabetes is associated with postprandial hypertriacylglycerolaemia. Resistance exercise acutely lowers postprandial plasma triacylglycerol (TG); however, the changes in lipid metabolism that mediate this reduction are poorly understood. The aim of this study was to identify the constitutive metabolic mechanisms underlying the changes in postprandial lipid metabolism after resistance exercise in obese men with prediabetes.

Myocardial glucose and fatty acid metabolism is altered and associated with lower cardiac function in young adults with Barth syndrome.

Background: Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function.

Methods/results: Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of O-water and 1-C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging.

Dissemination and Implementation Program in Hypertension in Rwanda: Report on Initial Training and Evaluation.

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide and in low- and middle-income countries, and hypertension (HTN) is a major risk factor for CVD. Although effective evidence-based interventions for control of HTN in high-income countries exist, implementation of these in low- and middle-income countries has been challenging due to limited capacity and infrastructure for late-phase translational research. In Rwanda, the 2015 STEPS NCD (STEPwise Approach to Surveillance of Noncommunicable Diseases) risk survey reported an overall prevalence of HTN of 15% (95% confidence interval [CI]: 13.

Blunted fat oxidation upon submaximal exercise is partially compensated by enhanced glucose metabolism in children, adolescents, and young adults with Barth syndrome.

Barth syndrome (BTHS) is a rare X-linked condition resulting in abnormal mitochondria, cardioskeletal myopathy, and growth delay; however, the effects of BTHS on substrate metabolism regulation and their relationships with tissue function in humans are unknown. We sought to characterize glucose and fat metabolism during rest, submaximal exercise, and postexercise rest in children, adolescents, and young adults with BTHS and unaffected controls and examine their relationships with cardioskeletal energetics and function. Children/adolescents and young adults with BTHS (n = 29) and children/adolescent and young adult control participants (n = 28, total n = 57) underwent an infusion of 6'6'H2 glucose and U- C palmitate and indirect calorimetry during rest, 30-minutes of moderate exercise (50% ), and recovery.

The muscle anabolic effect of protein ingestion during a hyperinsulinaemic euglycaemic clamp in middle-aged women is not caused by leucine alone.

Key Points: It has been suggested that leucine is primarily responsible for the increase in muscle protein synthesis after protein ingestion because leucine uniquely activates the mTOR-p70S6K signalling cascade. We compared the effects of ingesting protein or an amount of leucine equal to that in the protein during a hyperinsulinaemic-euglycaemic clamp (to eliminate potential confounding as a result of differences in the insulinogenic effect of protein and leucine ingestion) on muscle anabolic signalling and protein turnover in 28 women. We found that protein, but not leucine, ingestion increased muscle p-mTOR and p-p70S6K , although only protein, and not leucine, ingestion decreased muscle p-eIF2α and increased muscle protein synthesis.