Background & Aims Many companies provide genetic tests for obesity-related polymorphisms (nutrigenetics) and make dietary recommendations for weight loss based on the results. We performed a randomized controlled trial to determine whether more participants who followed a nutrigenetic-guided diet lost ≥5% of their body weight than participants on a standard balanced diet, for 8 and 24 weeks. Methods We performed a prospective study of 51 obese or overweight US veterans on an established weight management program at the Veterans Administration San Diego Healthcare System (the MOVE! Program). Participants were randomly assigned to groups placed on a nutrigenetic-guided diet (balanced, low-carbohydrate, low-fat, or Mediterranean; n=30) or a standard balanced diet (n=21). Nutrigenetic diets were selected based on results from the Pathway FIT test (Pathway Genomics; San Diego, CA). Results There was no significant difference in the percentage of participants on the balanced diet vs the nutrigenetic-guided diet who lost 5% of their body weight at 8 weeks (35.0%±20.9% vs 26.9%±17.1%, respectively; P=.28) or at 24 weeks. Both groups had difficulty adhering to the diets. However, adherence to the nutrigenetic-guided diet correlated with weight loss (r=0.74; P= 4.0 × 10−5), but not adherence to standard therapy (r=0.34; P=.23). Participants who had low-risk polymorphisms for obesity lost more weight than all other participants at 8 weeks (5.0% vs 2.9%, respectively; P=.02), and had significantly greater reductions in body mass index (6.4% vs 3.6% respectively; P=.03) and waist circumference (6.5% vs 2.6% respectively; P=.02) at 24 weeks. Conclusions In a prospective study, a nutrigenetic-based diet did not increase weight loss compared with a standard balanced diet. However, genetic features can identify individuals most likely to benefit from a balanced diet weight loss strategy; these findings require further investigation. ClincialTrials.gov number: NCT01859403

BackgroundObesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs), for 6 months in rodent models restores insulin receptor function and insulin sensitivity.MethodsThis 12-week double-blind, randomized, placebo (PL)-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI), doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2). The study included non-DM2 controls (n = 15), and DM2 subjects randomized to PL (n = 13) or doxycycline 100 mg twice daily (MMPI; n = 11). All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment.ResultsThere was a significant decrease in inflammatory markers C-reactive protein (P < 0.05) and myeloperoxidase (P = 0.01) in the MMPI but not PL group. The MMPI also significantly increased skeletal muscle activated/total insulin signaling mediators: 3’phosphoinositide kinase-1 (PDK1) (p < 0.03), protein kinase B (PKB/Akt) (p < 0.004), and glycogen synthase kinase 3ß (GSK3ß) (p < 0.03).ConclusionsThis study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes.Trial RegistrationClinicaltrials.gov NCT01375491

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