Differential Effects of Type 2 Diabetes Treatment Regimens on Diabetes Distress and Depressive Symptoms in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. RESEARCH DESIGN AND METHODS: The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years' duration, HbA1c 6.8-8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined differences at 1 year and over the 3-year follow-up. RESULTS: Across treatments, diabetes distress (-0.24, P < 0.0001) and depressive symptoms (-0.67, P < 0.0001) decreased over 1 year. Diabetes distress was lower at 1 year for the glargine group than for the other groups combined (-0.10, P = 0.002). Diabetes distress was also lower for liraglutide than for glimepiride or sitagliptin (-0.10, P = 0.008). Over the 3-year follow-up, there were no significant group differences in total diabetes distress; interpersonal diabetes distress remained lower for those assigned to liraglutide. No significant differences were observed for depressive symptoms. CONCLUSIONS: Contrary to expectations, this randomized trial found no evidence for a deleterious effect of basal insulin on emotional distress. Glargine lowered diabetes distress modestly at 1 year rather than increasing it. Liraglutide also reduced diabetes distress at 1 year. Results can inform treatment decisions for adults with early T2DM.

Time-restricted eating did not alter insulin sensitivity or ß-cell function in adults with obesity: A randomized pilot study.

OBJECTIVE: Decreased insulin sensitivity and impairment of ß-cell function predate and predict development of type 2 diabetes mellitus. Time-restricted eating (TRE) might have a benefit for these parameters. The objective of this pilot study was to investigate this possibility. METHODS: Secondary analysis of a randomized controlled trial comparing 12 weeks of TRE (8-hour eating window) to unrestricted eating (non-TRE) was performed. Participants were adults with overweight or obesity and without diabetes. Two-hour oral glucose tolerance testing was performed at baseline and end-intervention. Glucose tolerance test-derived measures of insulin sensitivity, insulin secretion, and ß-cell function were compared between groups. RESULTS: Participants (17 women/3 men with mean [SD] age 45.5 [12.1] years and BMI 34.1 [7.5] kg/m2 ) with a prolonged eating window (15.4 [0.9] hours) were randomized to TRE (n = 11) or non-TRE (n = 9). The quantitative insulin sensitivity check index (QUICKI), Stumvoll index, Avignon index, insulinogenic index, insulin area under the curve/glucose area under the curve, and oral disposition index did not differ between the TRE and non-TRE groups at end-intervention. CONCLUSIONS: In adults with overweight or obesity and without diabetes, TRE did not significantly alter insulin sensitivity, insulin secretion, or ß-cell function over a 12-week intervention. Whether TRE is beneficial in adults with prediabetes or type 2 diabetes mellitus warrants further investigation.

Racial residential segregation, racial discrimination, and diabetes: The Coronary Artery Risk Development in Young Adults study.

Although racial residential segregation and interpersonal racial discrimination are associated with cardiovascular disease, few studies have examined their link with diabetes risk or management. We used longitudinal data from 2,175 black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine associations of racial residential segregation (Gi* statistic) and experiences of racial discrimination with diabetes incidence and management. Multivariable Cox models estimated associations for incident diabetes and GEE logistic regression estimated associations with diabetes management (meeting targets for HbA1c, systolic blood pressure, and LDL cholesterol). Neither segregation nor discrimination were associated with diabetes incidence or management.

High-Protein Diets for Treatment of Type 2 Diabetes Mellitus: A Systematic Review.

Diet has the potential to be a powerful and cost-effective tool for treatment of type 2 diabetes mellitus (T2D). High-protein diets have shown promise for this purpose. The objective of this systematic review was to evaluate whether high-protein diets improve glycemic outcomes in people with T2D. We conducted a systematic search of literature published prior to 1 February 2018 to find clinical studies of high-protein diet patterns for treatment of T2D in human participants. A high-protein diet was defined as a diet with protein content greater than that of a typical diet in the United States (>16% of total energy as protein). Studies were excluded if weight loss >5% occurred or if no glycemic outcomes were measured. A total of 21 independent articles met our criteria and were included. Most tested diets had a protein content of around 30% of total energy. Many studies supported the use of high-protein diets for patients with T2D, but were limited by small size (n = 8-32) and short duration (1-24 wk). Randomized controlled trials tended to be larger (n = 12-419) and longer (6 wk-2 y), and had mixed results, with many trials showing no difference between a high-protein diet and control. Many randomized controlled trials were limited by low compliance and high dropout rates >15%. There were no consistent beneficial or detrimental effects of high-protein diets on renal or cardiovascular outcomes. Evidence was insufficient to recommend 1 type of protein (plant or animal) over the other. Our review suggests that interventions to improve compliance with diet change over the long term may be equally important as specific macronutrient recommendations for treatment of T2D.

DXA-Determined Regional Adiposity Relates to Insulin Resistance in a Young Adult Population with Overweight andObesity.

Obesity is a well-established risk factor for insulin resistance and type 2 diabetes mellitus, and body fat distribution has important implications for this metabolic risk. In this cross-sectional study, we used dual X-ray absorptiometry body composition data from 123 young adult participants with overweight or obesity, and correlatedwith 2 indices of insulin resistance calculated from oral glucose tolerance tests. Participants were 70% women, with mean (standard error) age 30.1 (0.6) yr, body mass index (BMI) 34.0 (0.6) kg/m2, homeostatic model assessment of insulin resistance (HOMA-IR) of 2.1 (0.2), and Matsuda insulin sensitivity index (Matsuda ISI) of 5.8 (0.4). In women, the strongest correlations were observed with the android-to-gynoid ratio (r = 0.52, p < 0.001 for HOMA-IR; r = -0.46, p < 0.001 for Matsuda ISI), and these correlations remained significant after adjustment for BMI. For men, the strongest correlations were with android fat mass (r = 0.40, p = 0.01 for HOMA-IR; r = -0.37, p = 0.02 for Matsuda ISI). Visceral adipose tissue was correlated with HOMA-IR and Matsuda ISI in women, and only with Matsuda ISI in men. BMI correlated with HOMA-IR and with Matsuda ISI in both women and men. Regional adiposity determined by dual X-ray absorptiometry correlates with indices of insulin resistance in sedentary young adults with overweight and obesity.

VE/VCO2 slope in lean and overweight women and its relationship to lean leg mass.

Ventilation/carbon dioxide production (VE/VCO2slope) is used clinically to determine cardiorespiratory fitness and morbidity in heart failure (HF). Previously, we demonstrated that lower lean leg mass is associated with high VE/VCO2slope during exercise in HF. In healthy individuals, we evaluated 1) whether VE/VCO2slope differed between lean and overweight women and 2) the relationship between lean leg mass and VE/VCO2slope in overweight sedentary (OWS), overweight trained (OWTR) and lean, trained (LTR) women. METHODS: Gas exchange and ventilation were collected during a treadmill peak oxygen uptake test (VO2peak) in 40 women [26 OWS (29 ±â€¯7 yrs., mean ±â€¯SD), 7 OWTR (33 ±â€¯5 yrs) and 7 LTR (26 ±â€¯6 yrs)]. Body composition was measured by dual X-ray absorptiometry. RESULTS: VO2peak was highest in LTR (46.6 ±â€¯8 ml/kg/min) compared with OWTR (38.1 ±â€¯4.9 ml/kg/min) and OWS women (25.3 ±â€¯4.8 ml/kg/min, p < 0.05). Lean leg mass was highest in OWTR and lowest in LTR women (p < 0.05). VE/VCO2slope was similar between groups (p > 0.05). Higher lean leg mass was associated with lower VE/VCO2slope in overweight women (OWS + OWTR: r = -0.55, p < 0.001), contrasting with higher VE/VCO2slope in LTR women (r = 0.86, p < 0.001). CONCLUSIONS: These findings suggest VE/VCO2slope may not differentiate between low and high cardiorespiratory fitness in healthy individuals and muscle mass may play a role in determining the VE/VCO2slope, independent of disease.

High Body Mass Index Masks Body Composition Differences in Physically Active Versus Sedentary Participants.

BACKGROUND: Despite the benefits of aerobic exercise on body composition, runners with high body mass index (BMI) remain understudied. We examined body composition differences between sedentary insulin-resistant [obese insulin-resistant sedentary (OS-IR)], sedentary insulin-sensitive [obese insulin-sensitive sedentary (OS-IS)], and trained [obese trained (OT)] individuals with high BMI (≥25 kg/m2). We hypothesized that after matching for high BMI, OT individuals would have less fat mass (absolute and relative) and greater lean mass than OS-IR or OS-IS individuals. METHODS: This is a retrospective analysis of OS-IR, OS-IS, and OT participants selected for similar age, sex, and BMI. Activity was self-reported. OT participants exercised at least 30 min/day (predominantly running) for 3-5 days/week. OS-IS and OS-IR participants actively exercised <0.5 hr/week. Body composition was measured by dual X-ray absorptiometry. RESULTS: Thirty-three participants were recruited [n = 11/group, mean age 31.7 years (standard error): (0.9)], 7 females/group, overall BMI [31.6 kg/m2 (0.7)]. Insulin resistance, quantified by the homeostatic model assessment for insulin resistance, was higher in the OS-IR [3.3 (0.2)] than the OS-IS [0.9 (0.2): P < 0.0001] or OT [1.6 (0.2): P < 0.0001] groups. We found the following: (i) Compared to the OS-IR group, the OT group had lower region-specific fat mass as measured by percent fat (trunk) or absolute fat mass (trunk, android region, and abdominal visceral region). (ii) OT and OS-IS groups had similar body composition. (iii) Total fat mass and percent body fat correlated with BMI, (iv) Visceral fat correlated with BMI (r = 0.80, P = 0.003) only in the OS-IR (P = 0.03 for BMI × group interaction). CONCLUSIONS: Using BMI to classify obesity masks body composition differences in high BMI individuals discrepant for insulin resistance and physical activity status.

The impact of high BMI on acute changes in body composition following 90 minutes of running.

OBJECTIVES: Although physical activity ameliorates the metabolic impact of high body mass index (BMI), runners with BMI≥25 kg/m2 are relatively understudied.This study had two goals: 1) Identify differences in body composition, as measured by dual X-ray absorptiometry (DXA), between overweight (BMI≥25 kg/m2) runners (OWR) and normal weight (BMI<25 kg/m2) runners (NWR) and 2) Examine whether an 90 minute run alters total or regional fat mass, as measured by DXA, in OWR and NWR. We hypothesized that OWR would have higher total body fat than NWR and OWR with greater changes in visceral fat after a prolonged run. DESIGN: Body composition analysis before and after a supervised run. METHODS: We recruited NWR (n=16,F:n=7,28.1±1.4 years, BMI 22.0±0.4 kg/m2, results as mean±SE) and OWR (n=11,F:n=7,32.0±1.6 years, BMI 30.5±1.4kg/m2) participants. DXA based body composition was measured before and after a supervised, 90 minute run at 60% heart rate reserve. RESULTS: OWR had higher body fat than NWR in all measured regions.. Both groups did not significantly reduce fat mass at any measured fat depots after the running exposure. CONCLUSIONS: OWR had higher body fat in all measured regions than NWR. DXA could not demonstrate any acute fat mass changes after a prolonged run.

Association of Mediterranean diet and cardiorespiratory fitness with the development of pre-diabetes and diabetes: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

OBJECTIVE: To better understand the association between a modified Mediterranean diet pattern in young adulthood, cardiorespiratory fitness in young adulthood, and the odds of developing pre-diabetes or diabetes by middle age. RESEARCH DESIGN AND METHODS: Participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study who did not have pre-diabetes or diabetes at baseline (year 0 (Y0), ages 18-30) and who had data available at the Y0 and year 25 (Y25) visits were included in this analysis (n=3358). Polytomous logistic regression models were used to assess the association between baseline dietary intake and fitness data and odds of pre-diabetes or diabetes by middle age (Y25, ages 43-55). RESULTS: At the Y25 visit, 1319 participants (39%) had pre-diabetes and 393 (12%) had diabetes. Higher baseline fitness was associated with lower odds of pre-diabetes and of diabetes at Y25. After adjustment for covariates, each SD increment in treadmill duration (181 s) was associated with lower odds for pre-diabetes (OR 0.85, 95% CI 0.75 to 0.95, p=0.005) and for diabetes (OR 0.71, 95% CI 0.60 to 0.85, p=0.0002) when compared to normal glycemia. A modified Mediterranean diet pattern was not associated with either pre-diabetes or diabetes. No interaction between cardiorespiratory fitness and dietary intake was observed, but baseline fitness remained independently associated with incident pre-diabetes and diabetes following adjustment for diet. CONCLUSIONS: Higher cardiorespiratory fitness in young adulthood, but not a modified Mediterranean diet pattern, is associated with lower odds of pre-diabetes and of diabetes in middle age. TRIAL REGISTRATION NUMBER: NCT00005130.

Twenty year fitness trends in young adults and incidence of prediabetes and diabetes: the CARDIA study.

AIMS/HYPOTHESIS: The prospective association between cardiorespiratory fitness (CRF) measured in young adulthood and middle age on development of prediabetes, defined as impaired fasting glucose and/or impaired glucose tolerance, or diabetes by middle age remains unknown. We hypothesised that higher fitness levels would be associated with reduced risk for developing incident prediabetes/diabetes by middle age. METHODS: Participants were from the Coronary Artery Risk Development in Young Adults (CARDIA) study who were free from prediabetes/diabetes at baseline (year 0 [Y0]: 1985-1986). CRF was quantified by treadmill duration (converted to metabolic equivalents [METs]) at Y0, Y7 and Y20 and prediabetes/diabetes status was assessed at Y0, Y7, Y10, Y15, Y20 and Y25. We use an extended Cox model with CRF as the primary time-varying exposure. BMI was included as a time-varying covariate. The outcome was development of either prediabetes or diabetes after Y0. Model 1 included age, race, sex, field centre, CRF and BMI. Model 2 additionally included baseline (Y0) smoking, energy intake, alcohol intake, education, systolic BP, BP medication use and lipid profile. RESULTS: Higher fitness was associated with lower risk for developing incident prediabetes/diabetes (difference of 1 MET: HR 0.99898 [95% CI 0.99861, 0.99940], p < 0.01), which persisted (difference of 1 MET: HR 0.99872 [95% CI 0.99840, 0.99904], p < 0.01] when adjusting for covariates. CONCLUSIONS/INTERPRETATION: Examining participants who had fitness measured from young adulthood to middle age, we found that fitness was associated with lower risk for developing prediabetes/diabetes, even when adjusting for BMI over this time period. These findings emphasise the importance of fitness in reducing the health burden of prediabetes and diabetes.

Post-Gastric Bypass Hyperinsulinemic Hypoglycemia: Fructose is a Carbohydrate Which Can Be Safely Consumed.

CONTEXT: Postprandial hypoglycemia after gastric bypass surgery is a serious problem. Available treatments are often ineffective. OBJECTIVE: The objective was to test the hypotheses that injection of rapid-acting insulin before a high-carbohydrate meal or replacement of other carbohydrates with fructose in the meal would prevent hypoglycemia. DESIGN: This was a randomized, crossover trial comparing a high-carbohydrate meal with premeal saline injection (control), a high-carbohydrate meal with premeal insulin injection, and a high-fructose meal with total carbohydrate content similar to the control meal. SETTING: The setting was an academic medical center. PATIENTS: Ten patients with post-gastric bypass hyperinsulinemic hypoglycemia participated. INTERVENTIONS: Interventions included lispro insulin injected before test meals and replacement of other carbohydrates with fructose in test meals. MAIN OUTCOME MEASURE: The main outcome measure was plasma glucose < 60 mg/dL after test meals. RESULTS: After the control meal, mean peak glucose and insulin were 173 ± 47 mg/dL and 134 ± 55 mU/L, respectively; mean glucose nadir was 44 ± 15 mg/dL; and eight of 10 subjects demonstrated glucose < 60 mg/dL. Five subjects demonstrated a glucose nadir < 40 mg/dL. There were no significant differences in the corresponding values after premeal insulin treatment, except that the mean glucose nadir of 34 ± 10 mg/dL was lower (P < .05). After the fructose meal, mean peak postprandial glucose and insulin were 117 ± 20 mg/dL and 45 ± 31 mU/L, respectively (both P < .001 for comparison with control), mean glucose nadir was 67 ± 10 mg/dL (P < .001), and two of 10 subjects demonstrated glucose < 60 mg/dL (P < .05). CONCLUSIONS: People with post-gastric bypass hypoglycemia can consume a meal sweetened with fructose with little risk of hypoglycemia. Treatment with rapid-acting insulin before a carbohydrate-containing meal did not prevent hypoglycemia.

Metabolic effects of alcohol in the form of wine in persons with type 2 diabetes mellitus.

Moderate alcohol consumption is associated with reduced cardiovascular disease rates in nondiabetic populations. However, the effects of alcohol in people with diabetes are not well defined. Accordingly, we tested the hypothesis that alcohol would raise plasma high-density lipoprotein (HDL) cholesterol or have other beneficial metabolic effects in persons with type 2 diabetes mellitus. To assess the acute effects of alcohol on plasma glucose and serum insulin, subjects were inpatients for 2 days during which they received, in random order, 240 mL wine or grape juice with their evening meal. To assess the chronic effects of alcohol on fasting plasma lipids, subjects consumed, in random order, 120 to 240 mL wine daily for 30 days and abstained from alcohol for 30 days. Participants were 18 non-insulin-treated volunteers with type 2 diabetes mellitus. Acutely, 240 mL wine containing 24 g alcohol had no effect on plasma glucose or serum insulin. Chronically, wine consumption for 30 days (mean consumption, 18 g alcohol per day) compared with abstinence for 30 days resulted, respectively, in mean +/- SEM fasting plasma cholesterol of 160 +/- 6 and 160 +/- 8 mg/dL (P = .98), HDL cholesterol of 47 +/- 3 and 46 +/- 3 mg/dL (P = .87), low-density lipoprotein cholesterol of 82 +/- 5 and 82 +/- 6 mg/dL (P = .98), triglycerides of 157 +/- 19 and 159 +/- 19 mg/dL (P = .88), glucose of 128 +/- 6 and 128 +/- 7 mg/dL (P = .84), and serum insulin of 14 +/- 2 and 17 +/- 3 microU/mL (P = .03). Moderate consumption of alcohol in the form of wine did not raise plasma HDL cholesterol. However, alcohol did not have any harmful metabolic effect; and chronic consumption lowered fasting serum insulin. People with type 2 diabetes mellitus should not be discouraged from using alcohol in moderation.