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Objective Insulin sensitivity is lower in African American (AA) versus Caucasian American (CA). We tested the hypothesis that lower insulin sensitivity in AA could be explained by mitochondrial respiratory rates, coupling efficiency, myofiber composition, or H2O2 emission. A secondary aim was to determine whether sex affected the results. Methods AA and CA men and women, 19–45 years, BMI 17–43 kg m2, were assessed for insulin sensitivity (SIClamp) using a euglycemic clamp at 120 mU/m2/min, muscle mitochondrial function using high‐resolution respirometry, H2O2 emission using amplex red, and % myofiber composition. Results SIClamp was greater in CA (p, Present results do not support a role for mitochondrial function or fiber type in determining lower insulin sensitivity in African Americans. The source of lower skeletal‐muscle insulin sensitivity in African Americans remains unclear. Future research could focus on aspects of skeletal muscle composition, such as lipid species, and their association with insulin sensitivity in African Americans.

BACKGROUND: Inflammation is implicated in functional decline and the development of disability in aging. This study aimed to investigate the association of inflammation with physical function and muscle strength in older adults with obesity and increased cardiometabolic risk. DESIGN: In baseline assessments from the CROSSROADS randomized controlled trial, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNFα) and C-reactive protein (hs-CRP) were assayed in 163 older adults (37% males, 24% African American, BMI 34±3, age 70±5yrs) with hypertension, dyslipidemia and/or diabetes. Physical function was assessed by six-minute walk test (6MWT), chair sit-and-reach (CSR), hand-grip and knee-extension strength; specific-strength as muscle strength/mass ratio. Analyses included ANCOVA and multiple linear regression adjusted for thigh skeletal muscle (MRI), arm lean mass (DXA) and moderate-to-vigorous intensity physical activity (MVPA; accelerometry). RESULTS: Higher hs-CRP (p

The Singapore Preconception Study of Long-Term Maternal and Child Outcomes (S-PRESTO) is a preconception, longitudinal cohort study that aims to study the effects of nutrition, lifestyle, and maternal mood prior to and during pregnancy on the epigenome of the offspring and clinically important outcomes including duration of gestation, fetal growth, metabolic and neural phenotypes in the offspring. Between February 2015 and October 2017, the S-PRESTO study recruited 1039 Chinese, Malay or Indian (or any combinations thereof) women aged 18 to 45 years and who intended to get pregnant and deliver in Singapore, resulting in 1032 unique participants and 373 children born in the cohort. The participants were followed up for 3 visits during the preconception phase and censored at 12 months of follow up if pregnancy was not achieved (N=557 censored). Women who successfully conceived (N=475) were characterised at gestational weeks 6-8, 11-13, 18-21, 24-26, 27-28 and 34-36. Follow up of their index offspring (N=373 singletons) is on-going at birth, 1, 3 and 6 weeks, 3, 6, 12, 18, 24 and 36 months and beyond. Women are also being followed up post-delivery. Data is collected via interviewer-administered questionnaires, metabolic imaging (magnetic resonance imaging), standardized anthropometric measurements and collection of diverse specimens, i.e. blood, urine, buccal smear, stool, skin tapes, epithelial swabs at numerous timepoints. S-PRESTO has extensive repeated phenotypic data collected which include genetic and epigenetic sampling from preconception which is unique in mother-offspring epidemiological cohorts This enables prospective assessment of a wide array of potential determinants of future health outcomes in women from preconception to post-delivery and in their offspring across the earliest development from embryonic stages into early childhood. In addition the S-PRESTO study, draws from the three major Asian ethnic groups that represent 50% of the global population, increasing the relevance of its findings to global efforts to address non-communicable diseases.

Very low-carbohydrate (LC) diets are popular for type 2 diabetes (T2DM) management; however, long-term effects on psychological health remain largely unknown. This study reports the effects of a LC diet on mood and cognitive function after 2 years and explores the potential predictors of changes in psychological health.115 adults (57% males; age: 58.5 ± 7.1 years) with obesity and T2DM were randomized to consume an energy reduced (~ 500 to 1000 kcal/day deficit), LC diet [14% energy as carbohydrate, 28% protein, 58% fat ( 10% saturated fat)] or an isocaloric high unrefined carbohydrate, low-fat diet [HC: 53% carbohydrate, 17% protein, 30% fat ( 10% saturated fat)] for 2 years. Both diets were combined with aerobic/resistance exercise (1 h, 3 days/week). Mood/well-being [Beck Depression Inventory (BDI), Spielberger State Anxiety Inventory (SAI), Profile of Mood States (POMS)], diabetes-related quality of life [Diabetes-39 (D-39)] and distress [Problem Areas in Diabetes (PAID) Questionnaire], and cognitive function were assessed during and post-intervention.61 (LC: 33, HC: 28) participants completed the study. Weight loss was 9.1% after 12 months and 6.7% after 2 years with no difference between diet groups. There were no differences between the groups for the changes in any psychological health outcome (smallest p ≥ 0.19 for all time x diet interactions). Overtime, improvements in BDI, POMS [Total Mood Disturbance (TMD); four subscales], PAID, and D-39 (three subscales) scores occurred (p ≤ 0.05, time). Stepwise regression analysis showed improvements in BDI, POMS (TMD; two subscales), D-39, SAI, and PAID scores were significantly (p 0.05) correlated with reductions in body weight and glycated hemoglobin.In adults with obesity and T2DM, energy-restricted LC and HC diets produced comparable long-term improvements on a comprehensive range of psychological health outcomes. The findings suggest both diets can be used as a diabetes management strategy as part of a holistic lifestyle modification program without concern of negative effects on mental well-being or cognition.ACTRN12612000369820, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362168isReview=true . Data described in the manuscript, code book, and analytic code will not be made available because approval has not been granted by participants.

Background: Growing evidence supports use of very low-carbohydrate (LC) diets for glycaemic control in type 2 diabetes. However, limited data on the micronutrient adequacy of LC diets exist.Objective: This study compared the long-term effects of a very low-carbohydrate, high unsaturated/low saturated fat (LC) diet to a high-carbohydrate, low-fat (HC) diet on micronutrient biomarkers in adults with obesity and type 2 diabetes.Methods: 115 adults with type 2 diabetes (mean[SD]; BMI:34.6[4.3]kg/m2, age:58[7]yrs,HbA1c:7.3[1.1]%, 56[12]mmol/mol) were randomized to one of two planned, nutritionally replete, energy-matched, hypocaloric diets (500–1000 kcal/day deficit): (1) LC:14% energy carbohydrate, 28%protein, 58%fat[

BACKGROUND: Race differences in body composition and fat distribution may in part explain the differences in insulin sensitivity and the disproportionate burden of type 2 diabetes in African Americans. OBJECTIVE: To determine if differences in body composition and fat distribution explain race differences in insulin sensitivity and identify obesity measures that were independently associated with insulin sensitivity. METHODS: Participants were 113 lean, overweight, and obese African-American and Caucasian-American adults without diabetes. Skeletal muscle insulin sensitivity was determined using a hyperinsulinemic-euglycemic clamp (SI(Clamp), insulin rate:120 mU/m(2)/min). Subcutaneous abdominal adipose tissue (SAAT), intra-abdominal adipose tissue (IAAT), and liver fat were measured by MRI; leg fat, total fat, and lean mass were measured by DXA. RESULTS: Race-by-adiposity interactions were significant in cross-sectional analyses utilizing multiple linear regression models for SI(Clamp) (P

Background: Few well-controlled studies have comprehensively examined the effects of very-low-carbohydrate diets on type 2 diabetes (T2D). Objective: We compared the effects of a very-low-carbohydrate, high-unsaturated fat, low-saturated fat (LC) diet with a high-carbohydrate, low-fat (HC) diet on glycemic control and cardiovascular disease risk factors in T2D after 52 wk. Design: In this randomized controlled trial that was conducted in an outpatient research clinic, 115 obese adults with T2D [mean ± SD age: 58 ± 7 y; body mass index (in kg/m2): 34.6 ± 4.3; glycated hemoglobin (HbA1c): 7.3 ± 1.1%; duration of diabetes: 8 ± 6 y] were randomly assigned to consume either a hypocaloric LC diet [14% of energy as carbohydrate (carbohydrate ,50 g/d), 28% of energy as protein, and 58% of energy as fat (,10% saturated fat)] or an energy matched HC diet [53% of energy as carbohydrate, 17% of energy as protein, and 30% of energy as fat (,10% saturated fat)] combined with supervised aerobic and resistance exercise (60 min; 3 d/wk). Outcomes were glycemic control assessed with use of measurements of HbA1c, fasting blood glucose, glycemic variability assessed with use of 48-h continuous glucose monitoring, diabetes medication, weight, blood pressure, and lipids assessed at baseline, 24, and 52 wk. Results: Both groups achieved similar completion rates (LC diet: 71%; HC diet: 65%) and mean (95% CI) reductions in weight [LC diet: -9.8 kg (-11.7, -7.9 kg); HC diet: -10.1 kg (-12.0, -8.2 kg)], blood pressure [LC diet: -7.1 (-10.6, -3.7)/-6.2 (-8.2, -4.1) mm Hg; HC diet:-5.8 (-9.4,-2.2)/-6.4 (-8.4,-4.3) mm Hg], HbA1c [LC diet: -1.0% (-1.2%, -0.7%); HC diet: -1.0% (-1.3%, -0.8%)], fasting glucose [LC diet: -0.7 mmol/L (-1.3, -0.1 mmol/L); HC diet: -1.5 mmol/L (-2.1, -0.8 mmol/L)], and LDL cholesterol [LC diet: -0.1 mmol/L (-0.3, 0.1 mmol/L); HC diet: -0.2 mmol/L (-0.4, 0.03 mmol/L)] (P-diet effect $ 0.10). Compared with the HC-diet group, the LC-diet group achieved greater mean (95% CI) reductions in the diabetes medication score [LC diet: -0.5 arbitrary units (-0.7, -0.4 arbitrary units); HC diet: -0.2 arbitrary units (-0.4, -0.06 arbitrary units); P = 0.02], glycemic variability assessed by measuring the continuous overall net glycemic action-1 [LC diet: -0.5 mmol/L (-0.6, -0.3 mmol/L); HC diet: -0.05 mmol/L (-0.2, -0.1 mmol/L); P = 0.003], and triglycerides [LC diet: -0.4 mmol/L (-0.5, -0.2 mmol/L); HC diet: -0.01 mmol/L (-0.2, 0.2 mmol/L); P = 0.001] and greater mean (95% CI) increases in HDL cholesterol [LC diet: 0.1 mmol/L (0.1, 0.2 mmol/L); HC diet: 0.06 mmol/L (-0.01, 0.1 mmol/L); P = 0.002]. Conclusions: Both diets achieved substantial weight loss and reduced HbA1c and fasting glucose. The LC diet, which was high in unsaturated fat and low in saturated fat, achieved greater improvements in the lipid profile, blood glucose stability, and reductions in diabetes medication requirements, suggesting an effective strategy for the optimization of T2D management. This trial was registered at www.anzctr.org.au as ACTRN12612000369820. Refereed/Peer-reviewed

The primary therapeutic target for diabetes management is the achievement of good glycemic control, of which glycated hemoglobin (HbA1c) remains the standard clinical marker. However, glycemic variability (GV; the amplitude, frequency, and duration of glycemic fluctuations around mean blood glucose) is an emerging target for blood glucose control. A growing body of evidence supports GV as an independent risk factor for diabetes complications. Several techniques have been developed to assess and quantify intraday and interday GV. Additionally, GV can be influenced by several nutritional factors, including carbohydrate quality, quantity; and distribution; protein intake; and fiber intake. These factors have important implications for clinical nutrition practice and for optimizing blood glucose control for diabetes management. This review discusses the available evidence for GV as a marker of glycemic control and risk factor for diabetes complications. GV quantification techniques and the influence of nutritional considerations for diabetes management are also discussed.

Aim: To examine whether a low-carbohydrate, high-unsaturated/low-saturated fat diet (LC) improves glycaemic control and cardiovascular disease (CVD) risk factors in overweight and obese patients with type 2 diabetes (T2D). Methods: A total of 115 adults with T2D (mean [SD]; BMI, 34.6 [4.3] kg/m 2 ; age, 58 [7] years; HbA1c, 7.3 [1.1] %) were randomized to 1 of 2 planned energy-matched, hypocaloric diets combined with aerobic/resistance exercise (1 hour, 3 days/week) for 2 years: LC: 14% energy as carbohydrate, 28% as protein, 58% as fat ( < 10% saturated fat); or low-fat, high-carbohydrate, low-glycaemic index diet (HC): 53% as CHO, 17% as protein, 30% as fat ( < 10% saturated fat). HbA1c, glycaemic variability (GV), anti-glycaemic medication effect score (MES, calculated based on the potency and dosage of diabetes medication), weight, body composition, CVD and renal risk markers were assessed before and after intervention.A total of 61 (LC = 33, HC = 28) participants completed the study (trial registration: http://www.anzctr.org.au/, ANZCTR No. ACTRN12612000369820). Reductions in weight (estimated marginal mean [95% CI]; LC, −6.8 [−8.8,−4.7], HC, −6.6 [−8.8, −4.5] kg), body fat (LC, −4.3 [−6.2, −2.4], HC, −4.6 [−6.6, −2.7] kg), blood pressure (LC, −2.0 [−5.9, 1.8]/ −1.2 [−3.6, 1.2], HC, −3.2 [−7.3, 0.9]/ −2.0 [−4.5, 0.5] mmHg), HbA1c (LC, −0.6 [−0.9, −0.3], HC, −0.9 [−1.2, −0.5] %) and fasting glucose (LC, 0.3 [−0.4, 1.0], HC, −0.4 [−1.1, 0.4] mmol/L) were similar between groups (P ≥ 0.09). Compared to HC, the LC achieved greater reductions in diabetes medication use (MES; LC, −0.5 [−0.6, −0.3], HC, −0.2 [−0.4, −0.02] units; P = 0.03), GV (Continuous Overall Net Glycemic Action calculated every 1 hour (LC, −0.4 [−0.6, −0.3], HC, −0.1 [−0.1, 0.2] mmol/L; P = 0.001), and 4 hours (LC, −0.9 [−1.3, −0.6], HC, −0.2 [−0.6, 0.1] mmol/L; P = 0.02)); triglycerides (LC, −0.1 [−0.3, 0.2], HC, 0.1 [−0.2, 0.3] mmol/L; P = 0.001), and maintained HDL‐C levels (LC, 0.02 [−0.05, 0.1], HC, −0.1 [−0.1, 0.01] mmol/L; P = 0.004), but had similar changes in LDL‐C (LC, 0.2 [−0.1, 0.5], HC, 0.1 [−0.2, 0.4] mmol/L; P = 0.85), brachial artery flow mediated dilatation (LC, −0.5 [−1.5, 0.5], HC, −0.4 [−1.4, 0.7] %; P = 0.73), eGFR and albuminuria. Conclusions: Both diets achieved comparable weight loss and HbA1c reductions. The LC sustained greater reductions in diabetes medication requirements, and in improvements in diurnal blood glucose stability and blood lipid profile, with no adverse renal effects, suggesting greater optimization of T2D management. Refereed/Peer-reviewed

This study compared the longer-term effects of a very low-carbohydrate, high-fat diet with a high-carbohydrate, low-fat diet on cognitive performance in individuals with type 2 diabetes (T2D). In total, 115 obese adults with T2D (sixty-six males, BMI: 34·6 (sd 4·3) kg/m2, age: 58 (sd 7) years, HbA1c: 7·3 (sd 1·1) %, diabetes duration: 8 (sd 6) years) were randomised to consume either an energy-restricted, very low-carbohydrate, low-saturated-fat (LC) diet or an energy-matched high unrefined carbohydrate, low-fat (HC) diet with supervised aerobic/resistance exercise (60 min, 3 d/week) for 52 weeks. Body weight, HbA1c and cognitive performance assessing perceptual speed, reasoning speed, reasoning ability, working memory, verbal fluency, processing speed, short-term memory, inhibition and memory scanning speed were assessed before and after intervention. No differences in the changes in cognitive test performance scores between the diet groups were observed for any of the cognitive function outcomes assessed (P≥0·24 time×diet). Percentage reduction in body weight correlated with improvements with perceptual speed performance. In obese adults with T2D, both LC and HC weight-loss diets combined with exercise training had similar effects on cognitive performance. This suggests that an LC diet integrated within a lifestyle modification programme can be used as a strategy for weight and diabetes management without the concern of negatively affecting cognitive function.

Background: Despite the popularity of the VLCHF diet, no studies have compared the chronic effects of weight loss and metabolic change to a conventional HCLF diet under isocaloric conditions. Conclusions Under isocaloric conditions, VLCHF and HCLF diets result in similar weight loss. Overall, although both diets had similar improvements for a number of metabolic risk markers, an HCLF diet had more favorable effects on the blood lipid profile. This suggests that the potential long-term effects of the VLCHF diet for CVD risk remain a concern and that blood lipid levels should be monitored. (Long-term health effects of high and low carbohydrate, weight loss diets in obese subjects with the metabolic syndrome; http://www.anzctr.org.au; ACTR No. 12606000203550 Methods: A total of 88 abdominally obese adults were randomly assigned to either an energy-restricted (∼6 to 7 MJ, 30% deficit), planned isocaloric VLCHF or HCLF diet for 24 weeks in an outpatient clinical trial. Body weight, blood pressure, fasting glucose, lipids, insulin, apolipoprotein B (apoB), and C-reactive protein (CRP) were measured at weeks 0 and 24. Objectives: This study was designed to compare the effects of an energy-reduced, isocaloric very-low-carbohydrate, high-fat (VLCHF) diet and a high-carbohydrate, low-fat (HCLF) diet on weight loss and cardiovascular disease (CVD) risk outcomes. Results: Weight loss was similar in both groups (VLCHF −11.9 ± 6.3 kg, HCLF −10.1 ± 5.7 kg; p = 0.17). Blood pressure, CRP, fasting glucose, and insulin reduced similarly with weight loss in both diets. The VLCHF diet produced greater decreases in triacylglycerols (VLCHF −0.64 ± 0.62 mmol/l, HCLF −0.35 ± 0.49 mmol/l; p = 0.01) and increases in high-density lipoprotein cholesterol (HDL-C) (VLCHF 0.25 ± 0.28 mmol/l, HCLF 0.08 ± 0.17 mmol/l; p = 0.002). Low-density lipoprotein cholesterol (LDL-C) decreased in the HCLF diet but remained unchanged in the VLCHF diet (VLCHF 0.06 ± 0.58 mmol/l, HCLF −0.46 ± 0.71 mmol/l; p < 0.001). However, a high degree of individual variability for the LDL response in the VLCHF diet was observed, with 24% of individuals reporting an increase of at least 10%. The apoB levels remained unchanged in both diet groups.

Maiorino et al. (1) correctly identify that HbA1c was the primary outcome of our previously reported study (2) but may have misunderstood the statistical approach used to evaluate the diet effects on outcomes, including HbA1c, when they suggest a subgroup analysis was used as opposed to the whole-population analysis that was performed. The primary objective of our study was to compare the effects of a very low-carbohydrate (LC) diet to a high–unrefined carbohydrate (HC) diet on glycemic control and cardiovascular disease risk factors in obese adults with type 2 diabetes. The study used a randomized groups, pretest-posttest design and the planned analysis of the …

OBJECTIVE To comprehensively compare the effects of a very low-carbohydrate, high–unsaturated/low–saturated fat diet (LC) with those of a high–unrefined carbohydrate, low-fat diet (HC) on glycemic control and cardiovascular disease (CVD) risk factors in type 2 diabetes (T2DM). RESEARCH DESIGN AND METHODS Obese adults (n = 115, BMI 34.4 ± 4.2 kg/m2, age 58 ± 7 years) with T2DM were randomized to a hypocaloric LC diet (14% carbohydrate [ RESULTS A total of 93 participants completed 24 weeks. Both groups achieved similar completion rates (LC 79%, HC 82%) and weight loss (LC −12.0 ± 6.3 kg, HC −11.5 ± 5.5 kg); P ≥ 0.50. Blood pressure (−9.8/−7.3 ± 11.6/6.8 mmHg), fasting blood glucose (−1.4 ± 2.3 mmol/L), and LDL cholesterol (−0.3 ± 0.6 mmol/L) decreased, with no diet effect (P ≥ 0.10). LC achieved greater reductions in triglycerides (−0.5 ± 0.5 vs. −0.1 ± 0.5 mmol/L), MES (−0.5 ± 0.5 vs. −0.2 ± 0.5), and GV indices; P ≤ 0.03. LC induced greater HbA1c reductions (−2.6 ± 1.0% [−28.4 ± 10.9 mmol/mol] vs. −1.9 ± 1.2% [−20.8 ± 13.1 mmol/mol]; P = 0.002) and HDL cholesterol (HDL-C) increases (0.2 ± 0.3 vs. 0.05 ± 0.2 mmol/L; P = 0.007) in participants with the respective baseline values HbA1c >7.8% (62 mmol/mol) and HDL-C CONCLUSIONS Both diets achieved substantial improvements for several clinical glycemic control and CVD risk markers. These improvements and reductions in GV and antiglycemic medication requirements were greatest with the LC compared with HC. This suggests an LC diet with low saturated fat may be an effective dietary approach for T2DM management if effects are sustained beyond 24 weeks.