Effects of genetic risk on incident type 2 diabetes and glycemia: the T2D-GENE lifestyle intervention trial.

CONTEXT: Lifestyle intervention prevents or delays type 2 diabetes (T2D) in subjects at a high risk of T2D. However, it is not known whether genetic variants modify the effect on incident T2D during lifestyle intervention. OBJECTIVE: To investigate whether a low or high genetic risk has effects on incident T2D in a group-based lifestyle intervention study. METHODS: The T2D-GENE trial involved 973 men from the Metabolic Syndrome in Men (METSIM) cohort, aged 50-75 years, body mass index ≥25 kg/m2, fasting plasma glucose 5.6-6.9 mmol/l, and HbA1c <48 mmol/mol and either a low or high genetic risk score for T2D. There were two intervention groups, a low (n=315) and high genetic risk for T2D (n=313). They were provided with a 3-year group-based intervention with access to a web portal focused on healthy diet and physical activity. There were also corresponding population-based control groups at low (n=196), and high genetic risk for T2D (n=149) who had two laboratory visits (0 and 3 years) and general health advice as a part of their METSIM cohort protocol. The primary outcome was incident T2D, and a secondary outcome glycemia. RESULTS: The intervention significantly lowered the risk of T2D among the participants with a high genetic risk for T2D (HR 0.30, 95% CI 0.16-0.56, p<0.001) whereas in the low genetic risk group the effect was not significant (HR 0.69, 95% CI 0.36-1.32, p=0.262). The intervention effect was not significantly different between the high and low genetic risk groups (p=0.135). The intervention significantly ameliorated the worsening of glycemia and decreased weight both in the low and high genetic risk groups. CONCLUSIONS: Our results showed that individuals with a high genetic risk for T2D benefited from a low-cost group-based intervention focusing on healthy diet and physical activity. Therefore, all individuals at risk of T2D should be encouraged to make lifestyle changes regardless of genetic risk.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Metabolite Signature of Physical Activity and the Risk of Type 2 Diabetes in 7271 Men.

Large population-based studies investigating the association of physical activity (PA) with the metabolite signature contribute significantly to the understanding of the effects of PA on metabolic pathways associated with the risk of type2 diabetes. Our study included 8749 Finnish men without diabetes at baseline recruited from the Metabolic Syndrome in Men (METSIM) cohort. We used a questionnaire to measure leisure-time PA. Metabolites were measured in 7271 men as a part of Metabolon's untargeted Discovery HD4 platform using ultrahigh-performance liquid chromatography-tandem mass spectrometry. We found 198 metabolites significantly associated with PA. Several of these metabolites were novel including especially steroids, amino acids, imidazoles, carboxylic acids, and hydroxy acids. Increased PA was significantly associated with high levels of choline plasmalogens, lysophosphatidylcholines, polyunsaturated fatty acids, carotenoids, long chain acylcarnitines, imidazoles, bilirubins, aryl sulfates, hydroxy acids, indolepropionate, and indolelactate. Several of these metabolites have been previously associated with a decreased risk of type 2 diabetes and with a healthy diet. Our population-based study shows that the metabolite signature of increased PA includes multiple metabolic pathways and is associated with better adherence to a healthy lifestyle.