OBJECTIVETo examine whether diabetes genetic risk testing and counseling can improve diabetes prevention behaviors.RESEARCH DESIGN AND METHODSWe conducted a randomized trial of diabetes genetic risk counseling among overweight patients at increased phenotypic risk for type 2 diabetes. Participants were randomly allocated to genetic testing versus no testing. Genetic risk was calculated by summing 36 single nucleotide polymorphisms associated with type 2 diabetes. Participants in the top and bottom score quartiles received individual genetic counseling before being enrolled with untested control participants in a 12-week, validated, diabetes prevention program. Middle-risk quartile participants were not studied further. We examined the effect of this genetic counseling intervention on patient self-reported attitudes, program attendance, and weight loss, separately comparing higher-risk and lower-risk result recipients with control participants.RESULTSThe 108 participants enrolled in the diabetes prevention program included 42 participants at higher diabetes genetic risk, 32 at lower diabetes genetic risk, and 34 untested control subjects. Mean age was 57.9 ± 10.6 years, 61% were men, and average BMI was 34.8 kg/m2, with no differences among randomization groups. Participants attended 6.8 ± 4.3 group sessions and lost 8.5 ± 10.1 pounds, with 33 of 108 (30.6%) losing ≥5% body weight. There were few statistically significant differences in self-reported motivation, program attendance, or mean weight loss when higher-risk recipients and lower-risk recipients were compared with control subjects (P > 0.05 for all but one comparison).CONCLUSIONSDiabetes genetic risk counseling with currently available variants does not significantly alter self-reported motivation or prevention program adherence for overweight individuals at risk for diabetes.

Lower estimated insulin sensitivity was associated with risk for hyperfiltration over time, whereas increased albumin excretion was associated with hyperglycemia in youth-onset T2DM.

BACKGROUND: Intensive lifestyle interventions (LI) improve outcomes in obesity and type 2 diabetes but are not currently available in usual care. OBJECTIVE: To compare the effectiveness and costs of two group LI programs, in-person LI and telephone conference call (telephone LI), to medical nutrition therapy (MNT) on weight loss in primary care patients with type 2 diabetes. DESIGN: A randomized, assessor-blinded, practicebased clinical trial in three community health centers and one hospital-based practice affiliated with a single health system. PARTICIPANTS: A total of 208 primary care patients with type 2 diabetes, HbA1c 6.5 to < 11.5, and BMI > 25 kg/m 2 (> 23 kg/m 2 in Asians). INTERVENTIONS: Dietitian-delivered in-person or telephone group LI programs with medication management or MNT referral. MAIN MEASURES: Primary outcome: mean percent weight change. Secondary outcomes: 5% and 10% weight loss, change in HbA1c, and cost per kilogram lost. KEY RESULTS: Participants' mean age was 62 (SD 10) years, 45% were male, and 77% were White, with BMI 35 (SD 5) kg/m 2 and HbA1c 7.7 (SD 1.2). Seventy were assigned to in-person LI, 72 to telephone LI, and 69 to MNT. The mean percent weight loss (95% CI) at 6 and 12 months was 5.6% (4.4-6.8%) and 4.6% (3.1-6.1%) for in-person LI, 4.6% (3.3-6.0%) and 4.8% (3.3-6.2%) for telephone LI, and 1.1% (0.2-2.0%) and 2.0% (0.9-3.0%) for MNT, with statistically significant differences between each LI arm and MNT (P < 0.001) but not between LI arms (P = 0.63). HbA1c improved in all participants. Compared with MNT, the incremental cost per kilogram lost was $789 for in-person LI and $1223 for telephone LI. CONCLUSIONS: In-person LI or telephone group LI can achieve good weight loss outcomes in primary care type 2 diabetes patients at a reasonable cost. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02320253

Weight-loss interventions generally improve lipid profiles and reduce cardiovascular disease risk, but effects are variable and may depend on genetic factors. We performed a genetic association analysis of data from 2,993 participants in the Diabetes Prevention Program to test the hypotheses that a genetic risk score (GRS) based on deleterious alleles at 32 lipid-associated single-nucleotide polymorphisms modifies the effects of lifestyle and/or metformin interventions on lipid levels and nuclear magnetic resonance (NMR) lipoprotein subfraction size and number. Twenty-three loci previously associated with fasting LDL-C, HDL-C, or triglycerides replicated (P = 0.04–1×10−17). Except for total HDL particles (r = −0.03, P = 0.26), all components of the lipid profile correlated with the GRS (partial |r| = 0.07–0.17, P = 5×10−5–1×10−19). The GRS was associated with higher baseline-adjusted 1-year LDL cholesterol levels (β = +0.87, SEE±0.22 mg/dl/allele, P = 8×10−5, P interaction = 0.02) in the lifestyle intervention group, but not in the placebo (β = +0.20, SEE±0.22 mg/dl/allele, P = 0.35) or metformin (β = −0.03, SEE±0.22 mg/dl/allele, P = 0.90; P interaction = 0.64) groups. Similarly, a higher GRS predicted a greater number of baseline-adjusted small LDL particles at 1 year in the lifestyle intervention arm (β = +0.30, SEE±0.012 ln nmol/L/allele, P = 0.01, P interaction = 0.01) but not in the placebo (β = −0.002, SEE±0.008 ln nmol/L/allele, P = 0.74) or metformin (β = +0.013, SEE±0.008 nmol/L/allele, P = 0.12; P interaction = 0.24) groups. Our findings suggest that a high genetic burden confers an adverse lipid profile and predicts attenuated response in LDL-C levels and small LDL particle number to dietary and physical activity interventions aimed at weight loss.

We examined the effects of metformin on diabetes prevention and the subgroups that benefited most over 15 years in the Diabetes Prevention Program (DPP) and its follow-up, the Diabetes Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS During the DPP (1996-2001), adults at high risk of developing diabetes were randomly assigned to masked placebo (n = 1,082) or metformin 850 mg twice daily (n = 1,073). Participants originally assigned to metformin continued to receive metformin, unmasked, in the DPPOS (2002-present). Ascertainment of diabetes development was based on fasting or 2-h glucose levels after an oral glucose tolerance test or on HbA 1c. Reduction in diabetes incidence with metformin was compared with placebo in subgroups by hazard ratio (HR) and rate differences (RDs). RESULTS During 15 years of postrandomization follow-up, metformin reduced the incidence (by HR) of diabetes compared to placebo by 17% or 36% based on glucose or HbA 1c levels, respectively. Metformin's effect on the development of glucose-defined diabetes was greater for women with a history of prior gestational diabetes mellitus (GDM) (HR 0.59, RD 24.57 cases/100 person-years) compared with parous women without GDM (HR 0.94, RD 20.38 cases/100 person-years [interaction P = 0.03 for HR, P = 0.01 for RD]). Metformin also had greater effects, by HR and RD, at higher baseline fasting glucose levels. With diabetes development based on HbA 1c , metformin was more effective in subjects with higher baseline HbA 1c by RD, with metformin RD 21.03 cases/100 person-years with baseline HbA 1c <6.0% (42 mmol/mol) and 23.88 cases/100 person-years with 6.0-6.4% (P = 0.0001). CONCLUSIONS Metformin reduces the development of diabetes over 15 years. The subsets that benefitted the most include subjects with higher baseline fasting glucose or HbA 1c and women with a history of GDM.

A culturally sensitive 3-month intervention was provided to 18 Caribbean Latino men and women with non-insulin-dependent (type 2) diabetes mellitus. Compared to the randomly assigned control group, the intervention group showed statistically significant decreases in total calories, fat calories, percent of calories from fat, saturated fat calories, and percent of calories from saturated fat The intervention group showed increases in calories from carbohydrates and in the percent of calories from fiber.

NCT02320253.

Across the Diabetes Prevention Program (DPP) follow-up, cumulative diabetes incidence remained lower in the lifestyle compared with the placebo and metformin randomized groups and could not be explained by weight. Collection of self-reported physical activity (PA) (yearly) with cross-sectional objective PA (in follow-up) allowed for examination of PA and its long-term impact on diabetes prevention. RESEARCH DESIGN AND METHODS Yearly self-reported PA and diabetes assessment and oral glucose tolerance test results (fasting glucose semiannually) were collected for 3,232 participants with one accelerometry assessment 11-13 years after randomization (n 5 1,793). Mixed models determined PA differences across treatment groups. The association between PA and diabetes incidence was examined using Cox proportional hazards models. RESULTS There was a 6% decrease (Cox proportional hazard ratio 0.94 [95% CI 0.92, 0.96]; P < 0.001) in diabetes incidence per 6 MET-h/week increase in time-dependent PA for the entire cohort over an average of 12 years (controlled for age, sex, baseline PA, and weight). The effect of PA was greater (12% decrease) among participants less active at baseline (<7.5 MET-h/week) (n 5 1,338) (0.88 [0.83, 0.93]; P < 0.0001), with stronger findings for lifestyle participants. Lifestyle had higher cumulative PA compared with metformin or placebo (P < 0.0001) and higher accelerometry total minutes per day measured during follow-up (P 5 0.001 and 0.047). All associations remained significant with the addition of weight in the models. CONCLUSIONS PA was inversely related to incident diabetes in the entire cohort across the study, with cross-sectional accelerometry results supporting these findings. This highlights the importance of PA within lifestyle intervention efforts designed to prevent diabetes and urges health care providers to consider both PA and weight when counseling high-risk patients.