Relationship Between Average Glucose Levels and HbA1c Differs Across Racial Groups: A Substudy of the GRADE Randomized Trial.

Objective: To determine whether the relationship between average glucose (AG) levels and hemoglobin A1c (HbA1c) differs across racial/ethnic groups.

Research Design And Methods: We performed a prospective substudy of GRADE, a comparative effectiveness randomized trial conducted in 36 centers in the U.S.

Considerations for the design and conduct of pediatric obesity pharmacotherapy clinical trials: Proceedings of expert roundtable meetings.

Anti-obesity medications (AOMs) have emerged as one element of comprehensive obesity clinical care intended to improve long-term health outcomes for children and adolescents. The number of pediatric AOM clinical trials has burgeoned in recent years as new pharmacotherapeutics have been developed. Factors related to growth and development in children and adolescents can present unique challenges in terms of designing and conducting clinical trials investigating the safety and efficacy of AOMs.

From pre-clinical efficacy to promising clinical trials that delay Type 1 diabetes.

Recent advancements in immunology and islet biology have unveiled remarkable prospects for the postponement of Type 1 diabetes (T1D) through the strategic modulation of the immune system. In this Perspective, we discuss the pharmaceutical strides achieved, traversing from pre-clinical validation to the execution of impactful clinical trials. We begin with the initial investigations involving cyclosporine and glucocorticoids in rodent models, such as the non-obese diabetic (NOD) mouse, which guided early clinical trials.

Association of Age at Menarche with Inflammation and Glucose Metabolism Biomarkers in U.S. Adult Women: NHANES 1999-2018.

Context: Early age at menarche (AAM) is a risk factor for type 2 diabetes later in life, but the pathogenic pathways that confer increased risk remain unknown.

Objective: We examined the associations between AAM and inflammatory and glucose metabolism biomarkers among U.S.

The glucosylamine oxidation pathway of vitamin C recycling.

The proposed glucosylamine oxidation pathway (GOP) is a two-step, intraerythrocyte, thermodynamically favorable nonenzymatic reaction that first binds glucose to the N-terminal valine of beta globin (βVal1) to form a closed-chain glucosylamine that can spontaneously reduce oxidized vitamin C to its antioxidant form. This review summarizes analytical, biochemical and clinical research supporting the existence of the GOP and the surprising hypothesis that βVal1 glucosylamine is a reducing agent that works cooperatively with reduced glutathione to dynamically regulate vitamin C recycling during naturally occurring periods of transiently or chronically elevated blood glucose and oxidant production. Rationale for the existence of the GOP is presented from the perspective of the hemoglobin glycation index, a clinically practical biomarker of risk for chronic vascular disease that we propose is mechanistically explained by person-to-person variation in GOP activity.

Researching COVID to enhance recovery (RECOVER) pediatric study protocol: Rationale, objectives and design.

Importance: The prevalence, pathophysiology, and long-term outcomes of COVID-19 (post-acute sequelae of SARS-CoV-2 [PASC] or "Long COVID") in children and young adults remain unknown. Studies must address the urgent need to define PASC, its mechanisms, and potential treatment targets in children and young adults.

Observations: We describe the protocol for the Pediatric Observational Cohort Study of the NIH's REsearching COVID to Enhance Recovery (RECOVER) Initiative.

The incidence of retinopathy in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness study (GRADE).

Based on self-report in the GRADE diabetes study, cumulative incidence of retinopathy was low over 5 years (3.7 %; 184 of 4098 participants) and did not differ among the 4 treatment groups (glargine 4.0 %, glimepiride 3.

Racial differences in measures of glycemia in the Vitamin D and Type 2 Diabetes (D2d) Study: a secondary analysis of a randomized trial.

Introduction: Understanding how race may influence the association between A1c and glycemia can improve diabetes screening. We sought to determine whether, for a given A1c level, glucose levels during an oral glucose tolerance test (OGTT) differed by race.

Research Design And Methods: From data collected at 22 US clinical sites, we conducted a cross-sectional study of concurrently measured A1c and OGTT and observational longitudinal follow-up of the subset with high-risk pre-diabetes.

Effects of phentermine / topiramate extended-release, phentermine, and placebo on ambulatory blood pressure monitoring in adults with overweight or obesity: A randomized, multicenter, double-blind study.

Background: A fixed-dose combination of phentermine and extended-release topiramate (PHEN/TPM - approved for weight management) has demonstrated in-clinic reduction of blood pressure (BP). Ambulatory BP monitoring (ABPM) may be a better predictor of cardiovascular disease risk than in-clinic BP.

Methods: This randomized, multicenter, double-blind study enrolled 565 adults with overweight/obesity.

Comparative Effects of Randomized Second-line Therapy for Type 2 Diabetes on a Composite Outcome Incorporating Glycemic Control, Body Weight, and Hypoglycemia: An Analysis of the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

Objective: In Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) (5,047 participants, mean follow-up 5.0 years), differences in glycemic control were demonstrated over time among four randomized therapies added to metformin. Weight gain and hypoglycemia are also important outcomes for people with type 2 diabetes.

Effects of Episodic Food Insecurity on Psychological and Physiological Responses in African American Women With Obesity (RESPONSES): Protocol for a Longitudinal Observational Cohort Study.

Background: Food insecurity is a risk factor for multiple chronic diseases, including obesity. Importantly, both food insecurity and obesity are more prevalent in African American women than in other groups. Furthermore, food insecurity is considered a cyclic phenomenon, with episodes of food adequacy (ie, enough food to eat) and food shortage (ie, not enough food to eat).

Sex Differences in Branched-chain Amino Acid and Tryptophan Metabolism and Pathogenesis of Youth-onset Type 2 Diabetes.

Objectives: Insulin resistance is associated with elevations in plasma branched-chain amino acids (BCAAs). BCAAs compete with aromatic amino acids including tryptophan for uptake into β cells. To explore relationships between BCAAs and tryptophan metabolism, adiposity, and glucose tolerance, we compared urine metabolites in overweight/obese youth with type 2 diabetes (T2D) with those in nondiabetic overweight/obese and lean youth.

Exercise-induced Changes in Central Adiposity During an RCT: Effect of Exercise Dose and Associations With Compensation.

Context: Exercise can decrease central adiposity, but the effect of exercise dose and the relationship between central adiposity and exercise-induced compensation is unclear.

Objective: Test the effect of exercise dose on central adiposity change and the association between central adiposity and exercise-induced weight compensation.

Methods: In this ancillary analysis of a 6-month randomized controlled trial, 170 participants with overweight or obesity (mean ± SD body mass index: 31.

Impact of a Nutrient Formulation on Longitudinal Myelination, Cognition, and Behavior from Birth to 2 Years: A Randomized Clinical Trial.

Observation studies suggest differences in myelination in relation to differences in early life nutrition. This two-center randomized controlled trial investigates the effect of a 12-month nutritional intervention on longitudinal changes in myelination, cognition, and behavior. Eighty-one full-term, neurotypical infants were randomized into an investigational (N = 42) or a control group (N = 39), receiving higher versus lower levels of a blend of nutrients.

Effect of biological variation in HbA1c and blood glucose on the diagnosis of prediabetes.

Introduction: People with a low or high haemoglobin glycation index (HGI) have lower or higher HbA1c than other people with the same FPG. This study compared the prevalence of prediabetes based on FPG, 2hOGTT and HbA1c in people with low, moderate or high HGI.

Methods: Prediabetes was diagnosed based on ADA cutpoints in 10,488 NHANES participants without self-reported diabetes.

Effect of vitamin D on regression to normal glucose regulation and individual glycemic measures: A secondary analysis among participants adherent to the trial protocol in the randomized clinical trial vitamin D and type 2 diabetes (D2d) study.

Aims: To examine the effect of vitamin D on regression to normal glucose regulation (NGR) and individual glycemic measures in the D2d study.

Methods: In per-protocol analyses, we examined time to new-onset diabetes; time to new-onset NGR defined as first occurrence of: 2-or-3 glycemic criteria in the normal range (NGR-1) or fasting plasma glucose (FPG) and 2-hour post-load-glucose (2hPG) in the normal range (NGR-2); proportion meeting NGR at the last study visit; and change in FPG, 2hPG, and HbA1c.

Results: Among 2423 participants, hazard ratio [HR] for diabetes was 0.

Harmonized Multisite MRI-Based Quantification of Human Liver Fat and Stiffness: A Pilot Study.

Background: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of end-stage liver disease. NAFLD diagnosis and follow-up relies on a combination of clinical data, liver imaging, and/or liver biopsy. However, intersite imaging differences impede diagnostic consistency and reduce the repeatability of the multisite clinical trials necessary to develop effective treatments.

New-Onset Diabetes After COVID-19.

There is evidence suggesting that infection with SARS-CoV-2 can lead to several long-term sequelae including diabetes. This mini-review examines the rapidly evolving and conflicting literature on new-onset diabetes after COVID-19, which we term NODAC. We searched PubMed, MEDLINE, and medRxiv from inception until December 1, 2022, using Medical Subject Headings (MeSH) terms and free text words including "COVID-19," "SARS-CoV-2," "diabetes," "hyperglycemia," "insulin resistance," and "pancreatic β-cell.

Phentermine/Topiramate for the Treatment of Adolescent Obesity.

Background: Antiobesity medication may be useful for the treatment of pediatric obesity, yet few safe and effective options exist. We evaluated phentermine/topiramate (PHEN/TPM) for weight management in adolescents with obesity.

Methods: This 56-week, randomized, double-blind trial enrolled adolescents 12 to less than 17 years of age with obesity.

Disrupted Circadian Rhythm of Epinephrine in Males With Youth-Onset Type 2 Diabetes.

Context: Blood pressure and plasma catecholamines normally decline during sleep and rapidly increase in early morning. This is blunted in adults with type 2 diabetes (T2D).

Objective: We hypothesize that increased sympatho-adrenal activity during sleep differentiates youth with T2D from nondiabetic obese youth and lean youth.

Association between Sleep, Sedentary Time, Physical Activity, and Adiposity in Adolescents: A Prospective Observational Study.

Purpose: This study aimed to examine the effects of substituting sedentary time with sleep or physical activity on adiposity in a longitudinal sample of adolescents.

Methods: Adolescents (10-16 yr) were recruited for a prospective observational cohort. Parents and adolescents reported demographic characteristics and pubertal development.