A gene variant near ATM is significantly associated with metformin treatment response In type 2 diabetes: A replication and meta-analysis of five cohorts

_Aims/hypothesis:_ In this study we aimed to replicate the previously reported association between the glycaemic response to metformin and the SNP rs11212617 at a locus that includes the ataxia telangiectasia mutated (ATM) gene in multiple additional populations. _Methods:_ Incident users of metformin selected from the Diabetes Care System West-Friesland (DCS, n=929) and the Rotterdam Study (n=182) from the Netherlands, and the CARDS Trial (n=254) from the UK were genotyped for rs11212617 and tested for an association with both HbA1c reduction and treatment success, defined as the ability to reach the treatment target of an HbA1c ≤7 % (53 mmol/mol). Finally, a meta-analysis including data from literature was performed. _Results:_ In the DCS cohort, we observed an association between rs11212617 genotype and treatment success on metformin (OR 1.27, 95% CI 1.03, 1.58, p=0.028); in the smaller Rotterdam Study cohort, a numerically similar but non-significant trend was observed (OR 1.45, 95% CI 0.87, 2.39, p=0.15); while in the CARDS cohort there was no significant association. In meta-analyses of these three cohorts separately or combined with the previously published cohorts, rs11212617 genotype is associated with metformin treatment success (OR 1.24, 95% CI 1.04, 1.49, p=0.016 and OR 1.25, 95% CI 1.33, 1.38, p=7.8×10-6, respectively). _ Conclusions/inte

Triglycerides and small dense low density lipoprotein in the discrimination of coronary heart disease risk in South Asian populations

<b>Introduction</b>: Coronary heart disease (CHD) is exceptionally prevalent amongst globally dispersed migrant groups originating from the Indian subcontinent, but the contribution of dyslipidaemia to their increased risk remains poorly defined. <b>Methods</b>: Fasting lipids and lipoproteins, apolipoproteins (Apo), low density lipoprotein (LDL) diameter and oxidised LDL were measured amongst rural Indians in India (n = 294) and their migrant contemporaries in the UK (n = 242). The performance of qualitative and quantitative measures of lipid metabolism were compared in the discrimination of WHO defined metabolic risk and raised Framingham CHD risk scores (>15%) using Receiver Operating Characteristic (ROC) curves. <b>Results</b>: LDL diameter was correlated with triglycerides (R2 = 0.12, P < 0.001) and with high density lipoprotein (HDL) cholesterol levels (R2 = 0.15, P < 0.001) in both groups. Migrants had less small dense LDL (95% CI: 12.5–14.2%) vs. rural Indians (15.7–17.2, P < 0.05). On ROC analysis, triglycerides were the only consistent discriminators of metabolic and CHD risk scores (all P ≤ 0.001). Apo B was also a strong indicator of raised CHD risk scores. Irrespective of site, individuals with raised triglycerides also had higher total cholesterol and Apo B, denser LDL, lower HDL and more oxidised LDL (all P ≤ 0.01). <b>Discussion</b>: Fasting triglycerides reflect both qualitative and quantitative aspects of lipid metabolism, and are a comprehensive discriminator of CHD risk in this South Asian population

Omega-3 fatty acids for prevention and treatment of cardiovascular disease

Background It has been suggested that omega 3 (W3, n-3 or omega-3) fats from oily fish and plants are beneficial to health. Objectives To assess whether dietary or supplemental omega 3 fatty acids alter total mortality, cardiovascular events or cancers using both RCT and cohort studies. Search strategy Five databases including CENTRAL, MEDLINE and EMBASE were searched to February 2002. No language restrictions were applied. Bibliographies were checked and authors contacted. Selection criteria RCTs were included where omega 3 intake or advice was randomly allocated and unconfounded, and study duration was at least six months. Cohorts were included where a cohort was followed up for at least six months and omega 3 intake estimated. Data collection and analysis Studies were assessed for inclusion, data extracted and quality assessed independently in duplicate. Random effects meta-analysis was performed separately for RCT and cohort data. Main results Forty eight randomised controlled trials (36,913 participants) and 41 cohort analyses were included. Pooled trial results did not show a reduction in the risk of total mortality or combined cardiovascular events in those taking additional omega 3 fats (with significant statistical heterogeneity). Sensitivity analysis, retaining only studies at low risk of bias, reduced heterogeneity and again suggested no significant effect of omega 3 fats. Restricting analysis to trials increasing fish-based omega 3 fats, or those increasing short chain omega 3s, did not suggest significant effects on mortality or cardiovascular events in either group. Subgroup analysis by dietary advice or supplementation, baseline risk of CVD or omega 3 dose suggested no clear effects of these factors on primary outcomes. Neither RCTs nor cohorts suggested increased relative risk of cancers with higher omega 3 intake but estimates were imprecise so a clinically important effect could not be excluded. Authors' conclusions It is not clear that dietary or supplemental omega 3 fats alter total mortality, combined cardiovascular events or cancers in people with, or at high risk of, cardiovascular disease or in the general population. There is no evidence we should advise people to stop taking rich sources of omega 3 fats, but further high quality trials are needed to confirm suggestions of a protective effect of omega 3 fats on cardiovascular health. There is no clear evidence that omega 3 fats differ in effectiveness according to fish or plant sources, dietary or supplemental sources, dose or presence of placebo