Maternal glucose and fatty acid kinetics and infant birth weight in obese women with type 2 diabetes

The objectives of this study were 1) to describe maternal glucose and lipid kinetics and 2) to examine the relationships with infant birth weight in obese women with pregestational type 2 diabetes during late pregnancy. Using stable isotope tracer methodology and mass spectrometry, maternal glucose and lipid kinetic rates during the basal condition were compared in three groups: lean women without diabetes (Lean, n = 25), obese women without diabetes (OB, n = 26), and obese women with pregestational type 2 diabetes (OB+DM, n = 28; total n = 79). Glucose and lipid kinetics during hyperinsulinemia were also measured in a subset of participants (n = 56). Relationships between maternal glucose and lipid kinetics during both conditions and infant birth weight were examined. Maternal endogenous glucose production (EGP) rate was higher in OB+DM than OB and Lean during hyperinsulinemia. Maternal insulin value at 50% palmitate R(a) suppression (IC50) for palmitate suppression with insulinemia was higher in OB+DM than OB and Lean. Maternal EGP per unit insulin and plasma free fatty acid concentration during hyperinsulinemia most strongly predicted infant birth weight. Our findings suggest maternal fatty acid and glucose kinetics are altered during late pregnancy and might suggest a mechanism for higher birth weight in obese women with pregestational diabetes

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. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations

Effect of dietary n‐3 PUFA supplementation on the muscle transcriptome in older adults

Dietary fish oil‐derived n‐3 PUFA supplementation can increase muscle mass, reduce oxygen demand during physical activity, and improve physical function (muscle strength and power, and endurance) in people. The results from several studies conducted in animals suggest that the anabolic and performance‐enhancing effects of n‐3 PUFA are at least in part transcriptionally regulated. The effect of n‐3 PUFA therapy on the muscle transcriptome in people is unknown. In this study, we used muscle biopsy samples collected during a recently completed randomized controlled trial that found that n‐3 PUFA therapy increased muscle mass and function in older adults to provide a comprehensive assessment of the effect of n‐3 PUFA therapy on the skeletal muscle gene expression profile in these people. Using the microarray technique, we found that several pathways involved in regulating mitochondrial function and extracellular matrix organization were increased and pathways related to calpain‐ and ubiquitin‐mediated proteolysis and inhibition of the key anabolic regulator mTOR were decreased by n‐3 PUFA therapy. However, the effect of n‐3 PUFA therapy on the expression of individual genes involved in regulating mitochondrial function and muscle growth, assessed by quantitative RT‐PCR, was very small. These data suggest that n‐3 PUFA therapy results in small but coordinated changes in the muscle transcriptome that may help explain the n‐3 PUFA‐induced improvements in muscle mass and function

Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction

BACKGROUND AND AIMS: We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate diet or a low-carbohydrate diet on hepatic and skeletal muscle insulin sensitivity. METHODS: Twenty-two obese subjects (body-mass index, 36.5±0.8kg/m(2)) were randomized to a high-carbohydrate (>180g/d) or low-carbohydrate (<60g/d) energy-deficit diet. A euglycemic–hyperinsulinemic clamp, muscle biopsies, and magnetic resonance spectroscopy were used to determine insulin action, cellular insulin signaling and intrahepatic triglyceride content before, after 48 h, and after ~11 wks (7% weight loss) of diet therapy. RESULTS: At 48 h, intrahepatic triglyceride content decreased more in the low-carbohydrate than the high-carbohydrate diet group (29.6±4.8% vs. 8.9±1.4%; P<0.05), but was similar in both groups after 7% weight loss (low-carbohydrate diet, 38.0±4.5% vs. high-carbohydrate diet, 44.5±13.5%). Basal glucose production rate decreased more in the low-carbohydrate than the high-carbohydrate diet group at 48 h (23.4±2.2% vs. 7.2±1.4%, P<0.05) and after 7% weight loss (20.0±2.4% vs. 7.9±1.2%, P<0.05). Insulin-mediated glucose uptake did not change at 48 h, but increased similarly in both groups after 7% weight loss (48.4±14.3%, P<0.05). In both groups, insulin-stimulated phosphorylation of Jun N-terminal kinase decreased by 29±13% and phosphorylation of Akt and insulin receptor substrate -1 increased by 35±9% and 36±9%, respectively, after 7% weight loss (all p<0.05). CONCLUSION: Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 h of calorie restriction affects the liver (intrahepatic triglyceride content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling)

Sexually dimorphic effect of aging on skeletal muscle protein synthesis

BACKGROUND: Although there appear to be no differences in muscle protein turnover in young and middle aged men and women, we have reported significant differences in the rate of muscle protein synthesis between older adult men and women. This suggests that aging may affect muscle protein turnover differently in men and women. METHODS: We measured the skeletal muscle protein fractional synthesis rate (FSR) by using stable isotope-labeled tracer methods during basal postabsorptive conditions and during a hyperaminoacidemic-hyperinsulinemic-euglycemic clamp in eight young men (25–45 y), ten young women (25–45 y), ten old men (65–85 y) and ten old women (65–85 y). RESULTS: The basal muscle protein FSR was not different in young and old men (0.040 ± 0.004 and 0.043 ± 0.005%·h(-1), respectively) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR both in young (to 0.063 ± 0.006%·h(-1)) and old (to 0.051 ± 0.008%·h(-1)) men but the increase (0.023 ± 0.004 vs. 0.009 ± 0.004%·h(-1), respectively) was ~60% less in the old men (P = 0.03). In contrast, the basal muscle protein FSR was ~30% greater in old than young women (0.060 ± 0.003 vs. 0.046 ± 0.004%·h(-1), respectively; P < 0.05) and combined insulin, glucose and amino acid infusion significantly increased the muscle protein FSR in young (P < 0.01) but not in old women (P = 0.10) so that the FSR was not different between young and old women during the clamp (0.074 ± 0.006%·h(-1) vs. 0.072 ± 0.006%·h(-1), respectively). CONCLUSIONS: There is sexual dimorphism in the age-related changes in muscle protein synthesis and thus the metabolic processes responsible for the age-related decline in muscle mass

18FDG PET-CT imaging detects arterial inflammation and early atherosclerosis in HIV-infected adults with cardiovascular disease risk factors

BACKGROUND: Persistent vascular inflammation has been implicated as an important cause for a higher prevalence of cardiovascular disease (CVD) in HIV-infected adults. In several populations at high risk for CVD, vascular (18)Fluorodeoxyglucose ((18)FDG) uptake quantified using 3D-positron emission-computed tomography (PET-CT) has been used as a molecular level biomarker for the presence of metabolically active proinflammatory macrophages in rupture-prone early atherosclerotic plaques. We hypothesized that (18)FDG PET-CT imaging would detect arterial inflammation and early atherosclerosis in HIV-infected adults with modest CVD risk. METHODS: We studied 9 HIV-infected participants with fully suppressed HIV viremia on antiretroviral therapy (8 men, median age 52 yrs, median BMI 29 kg/m(2), median CD4 count 655 cells/μL, 33% current smokers) and 5 HIV-negative participants (4 men, median age 44 yrs, median BMI 25 kg/m(2), no current smokers). Mean Framingham Risk Scores were higher for HIV-infected persons (9% vs. 2%, p < 0.01). (18)FDG (370 MBq) was administered intravenously. 3D-PET-CT images were obtained 3.5 hrs later. (18)FDG uptake into both carotid arteries and the aorta was compared between the two groups. RESULTS: Right and left carotid (18)FDG uptake was greater (P < 0.03) in the HIV group (1.77 ±0.26, 1.33 ±0.09 target to background ratio (TBR)) than the control group (1.05 ± 0.10, 1.03 ± 0.05 TBR). (18)FDG uptake in the aorta was greater in HIV (1.50 ±0.16 TBR) vs control group (1.24 ± 0.05 TBR), but did not reach statistical significance (P = 0.18). CONCLUSIONS: Carotid artery (18)FDG PET-CT imaging detected differences in vascular inflammation and early atherosclerosis between HIV-infected adults with CVD risk factors and healthy HIV-seronegative controls. These findings confirm the utility of this molecular level imaging approach for detecting and quantifying glucose uptake into inflammatory macrophages present in metabolically active, rupture-prone atherosclerotic plaques in HIV infected adults; a population with increased CVD risk

High-Protein Intake during Weight Loss Therapy Eliminates the Weight-Loss-Induced Improvement in Insulin Action in Obese Postmenopausal Women

SummaryHigh-protein (HP) intake during weight loss (WL) therapy is often recommended because it reduces the loss of lean tissue mass. However, HP intake could have adverse effects on metabolic function, because protein ingestion reduces postprandial insulin sensitivity. In this study, we compared the effects of ∼10% WL with a hypocaloric diet containing 0.8 g protein/kg/day and a hypocaloric diet containing 1.2 g protein/kg/day on muscle insulin action in postmenopausal women with obesity. We found that HP intake reduced the WL-induced decline in lean tissue mass by ∼45%. However, HP intake also prevented the WL-induced improvements in muscle insulin signaling and insulin-stimulated glucose uptake, as well as the WL-induced adaptations in oxidative stress and cell structural biology pathways. Our data demonstrate that the protein content of a WL diet can have profound effects on metabolic function and underscore the importance of considering dietary macronutrient composition during WL therapy for people with obesity

Review of measures of worksite environmental and policy supports for physical activity and healthy eating

INTRODUCTION: Obesity prevention strategies are needed that target multiple settings, including the worksite. The objective of this study was to assess the state of science concerning available measures of worksite environmental and policy supports for physical activity (PA) and healthy eating (HE). METHODS: We searched multiple databases for instruments used to assess worksite environments and policies. Two commonly cited instruments developed by state public health departments were also included. Studies that were published from 1991 through 2013 in peer-reviewed publications and gray literature that discussed the development or use of these instruments were analyzed. Instrument administration mode and measurement properties were documented. Items were classified by general health topic, 5 domains of general worksite strategy, and 19 subdomains of worksite strategy specific to PA or HE. Characteristics of worksite measures were described including measurement properties, length, and administration mode, as well as frequencies of items by domain and subdomain. RESULTS: Seventeen instruments met inclusion criteria (9 employee surveys, 5 manager surveys, 1 observational assessment, and 2 studies that used multiple administration modes). Fourteen instruments included reliability testing. More items were related to PA than HE. Most instruments (n = 10) lacked items in the internal social environment domain. The most common PA subdomains were exercise facilities and lockers/showers; the most common HE subdomain was healthy options/vending. CONCLUSION: This review highlights gaps in measurement of the worksite social environment. The findings provide a useful resource for researchers and practitioners and should inform future instrument development