Effect of zinc supplementation on insulin secretion: interaction between zinc and SLC30A8 genotype in Old Order Amish.

AIMS/HYPOTHESIS: SLC30A8 encodes a zinc transporter in the beta cell; individuals with a common missense variant (rs13266634; R325W) in SLC30A8 demonstrate a lower early insulin response to glucose and an increased risk of type 2 diabetes. We hypothesised that zinc supplementation may improve insulin secretion in a genotype-dependent manner. METHODS: We evaluated the early insulin response to glucose (using frequently sampled intravenous glucose tolerance testing) by R325W genotype before and after 14 days of supplementation with oral zinc acetate (50 mg elemental zinc) twice daily in healthy non-diabetic Amish individuals (N = 55). RESULTS: Individuals with RW/WW genotypes (n = 32) had the lowest insulin response to glucose at 5 and 10 min at baseline (vs RR homozygotes [n = 23]). After zinc supplementation, the RW/WW group experienced 15% and 14% increases in the insulin response to glucose at 5 and 10 min, respectively (p ≤ 0.04), and, compared with RR homozygotes, experienced a 26% (p = 0.04) increase in insulin at 5 min. We observed reciprocal decreases in proinsulin:insulin in the RW/WW (p = 0.002) vs RR group (p = 0.048), suggesting a genotype-specific improvement in insulin processing. CONCLUSIONS/INTERPRETATION: Zinc supplementation appears to affect the early insulin response to glucose differentially by rs13266634 genotype and could be beneficial for diabetes prevention and/or treatment for some individuals based on SLC30A8 variation. TRIAL REGISTRATION: ClinicalTrials.gov NCT00981448.

The pharmacogenetics of type 2 diabetes: a systematic review.

OBJECTIVE: We performed a systematic review to identify which genetic variants predict response to diabetes medications. RESEARCH DESIGN AND METHODS: We performed a search of electronic databases (PubMed, EMBASE, and Cochrane Database) and a manual search to identify original, longitudinal studies of the effect of diabetes medications on incident diabetes, HbA1c, fasting glucose, and postprandial glucose in prediabetes or type 2 diabetes by genetic variation. Two investigators reviewed titles, abstracts, and articles independently. Two investigators abstracted data sequentially and evaluated study quality independently. Quality evaluations were based on the Strengthening the Reporting of Genetic Association Studies guidelines and Human Genome Epidemiology Network guidance. RESULTS: Of 7,279 citations, we included 34 articles (N = 10,407) evaluating metformin (n = 14), sulfonylureas (n = 4), repaglinide (n = 8), pioglitazone (n = 3), rosiglitazone (n = 4), and acarbose (n = 4). Studies were not standalone randomized controlled trials, and most evaluated patients with diabetes. Significant medication-gene interactions for glycemic outcomes included 1) metformin and the SLC22A1, SLC22A2, SLC47A1, PRKAB2, PRKAA2, PRKAA1, and STK11 loci; 2) sulfonylureas and the CYP2C9 and TCF7L2 loci; 3) repaglinide and the KCNJ11, SLC30A8, NEUROD1/BETA2, UCP2, and PAX4 loci; 4) pioglitazone and the PPARG2 and PTPRD loci; 5) rosiglitazone and the KCNQ1 and RBP4 loci; and 5) acarbose and the PPARA, HNF4A, LIPC, and PPARGC1A loci. Data were insufficient for meta-analysis. CONCLUSIONS: We found evidence of pharmacogenetic interactions for metformin, sulfonylureas, repaglinide, thiazolidinediones, and acarbose consistent with their pharmacokinetics and pharmacodynamics. While high-quality controlled studies with prespecified analyses are still lacking, our results bring the promise of personalized medicine in diabetes one step closer to fruition.

Insights from the POWER practice-based weight loss trial: a focus group study on the PCP's role in weight management.

BACKGROUND: Despite U.S. Preventive Services Task Force recommendations, few primary care providers (PCPs) counsel obese patients about weight loss. The POWER practice-based weight loss trial used health coaches to provide weight loss counseling, but PCPs referred their patients and reviewed their patients' progress reports. This trial provided a unique opportunity to understand PCPs' actual and desired roles in a multi-component weight loss intervention. OBJECTIVE: 1) To explore the PCP role, inclusive of and beyond the trial's intended role, in a practice-based weight loss trial; and 2) to elicit recommendations by PCPs for wider dissemination of the successful multi-component program. DESIGN: Qualitative focus group study of PCPs with ≥ 4 patients enrolled in trial. PARTICIPANTS: Twenty-six out of 30 PCPs from six community practices participated between June and August 2010. MAIN MEASURES: We used a semi-structured moderator guide. Focus groups were audio-recorded and transcribed verbatim. Two investigators independently coded transcripts for thematic content, identified meaningful segments within the responses and assigned codes using an editing style analysis. Atlas.ti software was used for organization/analysis. MAIN RESULTS: We identified five major themes related to the PCP's role in patients' weight management: (1) refer patients into program, provide endorsement; (2) provide accountability for patients; (3) "cheerlead" for patients during visits; (4) have limited role in weight management; and (5) maintain the long-term trusting relationship through the ups and downs. PCPs provided several recommendations for wider dissemination of the program into primary care practices, highlighting the need for specific feedback from coaches as well as efficient, integrated processes. CONCLUSIONS: Weight loss programs have the potential to partner with PCPs to build upon the patient-provider relationship to improve patient accountability and sustain behavior change. However, rather than directing the weight loss, PCPs preferred a peripheral role by utilizing health coaches.

The long-term effectiveness of a lifestyle intervention in severely obese individuals.

OBJECTIVE: Severe obesity (body mass index [BMI] ≥40 kg/m(2)) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus, nonsurgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared with overweight (25 ≤BMI <30), class I (30 ≤BMI <35), and class II obese (35 ≤BMI <40) participants. METHODS: There were 5145 individuals with type 2 diabetes (45-76 years, BMI ≥25 kg/m(2)) randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention group received a behavioral weight loss program that included group and individual meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. Four-year changes in body weight and cardiovascular disease risk factors were assessed. RESULTS: Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared with diabetes support and education (Ps <.05). At year 4, severely obese lifestyle participants lost 4.9%±8.5%, which was similar to class I (4.8%±7.2%) and class II obese participants (4.4%±7.6%), and significantly greater than overweight participants (3.4%±7.0%; P <.05). Four-year changes in low-density-lipoprotein cholesterol, triglycerides, diastolic blood pressure, HbA(1c), and blood glucose were similar across BMI categories in lifestyle participants; however, the severely obese had less favorable improvements in high-density-lipoprotein cholesterol (3.1±0.4 mg/dL) and systolic blood pressure (-1.4±0.7 mm Hg) compared with the less obese (Ps <.05). CONCLUSION: Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals.