Sulfonylureas, a commonly used class of medication used to treat type 2 diabetes, have been associated with an increased risk of cardiovascular disease. Their effects on QT interval duration and ...related electrocardiographic phenotypes are potential mechanisms for this adverse effect. In 11 ethnically diverse cohorts that included 71 857 European, African-American and Hispanic/Latino ancestry individuals with repeated measures of medication use and electrocardiogram (ECG) measurements, we conducted a pharmacogenomic genome-wide association study of sulfonylurea use and three ECG phenotypes: QT, JT and QRS intervals. In ancestry-specific meta-analyses, eight novel pharmacogenomic loci met the threshold for genome-wide significance (P<5 × 10
), and a pharmacokinetic variant in CYP2C9 (rs1057910) that has been associated with sulfonylurea-related treatment effects and other adverse drug reactions in previous studies was replicated. Additional research is needed to replicate the novel findings and to understand their biological basis.
Aims/hypothesis
We aimed to describe the prevalence of retinopathy in an aged cohort of Icelanders with and without diabetes mellitus.
Methods
The study population consisted of 4,994 persons aged ...≥67 years, who participated in the Age, Gene/Environment Susceptibility—Reykjavik Study (AGES-R). Type 2 diabetes mellitus was defined as HbA
1c
≥6.5% (>48 mmol/mol). Retinopathy was assessed by grading fundus photographs using the modified Airlie House adaptation of the Early Treatment Diabetic Retinopathy Study protocol. Associations between retinopathy and risk factors were estimated using odds ratios obtained from multivariate analyses.
Results
The overall prevalence of retinopathy in AGES-R was 12.4%. Diabetes mellitus was present in 516 persons (10.3%), for 512 of whom gradable fundus photos were available, including 138 persons (27.0%, 95% CI 23.2, 31.0) with any retinopathy. Five persons (1.0%, 95% CI 0.3, 2.3) had proliferative retinopathy. Clinically significant macular oedema was present in five persons (1.0%, 95% CI 0.3, 2.3). Independent risk factors for retinopathy in diabetic patients in a multivariate model included HbA
1c
, insulin use and use of oral hypoglycaemic agents, the last two being indicators of longer disease duration. In 4478 participants without diabetes mellitus, gradable fundus photos were available for 4,453 participants, with retinopathy present in 476 (10.7%, 95% CI 9.8, 11.6) and clinically significant macular oedema in three persons. Independent risk factors included increasing age and microalbuminuria.
Conclusions/interpretation
Over three-quarters (78%) of retinopathy cases were found in persons without diabetes and a strong association between microalbuminuria and non-diabetic retinopathy was found. These results may have implications for patient management of the aged.
Equations for estimating GFR with serum creatinine overestimate measured GFR in Blacks. The authors report new equations, without race as an inflation factor, using cystatin C and creatinine that ...reduced errors in estimation between Black participants and non-Black participants.
Summary A variety of reference curves are used to derive predicted values for adult lung function, even within ethnically similar populations. Alternatives to percentage predicted value are sometimes ...used to allow for height in research. Strength of association with total mortality can be used to choose the optimal expression, between forced expiratory volume in 1 s (FEV1 ) divided by height2 , FEV1 /height3 , FEV1 % predicted and difference from predicted. Data from the Reykjavik Study cohort, 1976–2002, included 5544 men and 8062 women randomly selected from the population. Total mortality was analysed by Cox proportional hazards regression in relation to each height-adjusted measure, allowing for age group, period of recruitment and body mass index, and smoking before or at baseline. FEV1 /height2 and FEV1 /height3 had stronger associations with mortality than FEV1 % predicted and difference from predicted in men and in women. There were similar findings for forced vital capacity (FVC) in non-smokers and in women. FEV1 /height2 was slightly better predictive than FEV1 /height3 in men, but distributions of FEV1 /height3 in men and women were closer than those of FEV1 /height2. Clinical practise and epidemiological research would benefit from agreement on how to adjust lung function for height. Replication of these analyses in other cohort studies would inform the choice between FEV1 /height2 and FEV1 /height3.
Background
Deficits in n-3 fatty acids may be associated with depression. However, data are scarce from older adults who are at greater risk of poor dietary intake and of developing depression.
...Objective
To investigate proportion of plasma phospholipid fatty acids with respect to depressive symptoms and major depressive disorder in community dwelling older adults.
Methods
Cross-sectional analyses of 1571 participants in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study aged 67-93 years. Depressive symptoms were measured using the 15-item Geriatric Depression Scale (GDS-15). Major depressive disorder was assessed according to Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria using the Mini-International Neuropsychiatric Interview (MINI).
Results
Depressive symptoms were observed in 195 (12.4%) subjects and there were 27 (1.7%) cases of major depressive disorder. Participants with depressive symptoms were less educated, more likely to be smokers, less physically active and consumed cod liver oil less frequently. Difference in GDS-15 scores by tertiles of n-3 fatty acid proportion was not significant. Proportion of long chain n-3 fatty acids (Eicosapentaenoic- + Docosahexaenoic acid) were inversely related to major depressive disorder, (tertile 2 vs. tertile 1) OR: 0.31 (95% CI: 0.11, 0.86); tertile 3 vs. tertile 1, OR: 0.45 (95% CI: 0.17, 1.21).
Conclusion
In our cross sectional analyses low proportions of long chain n-3 fatty acids in plasma phospholipids appear to be associated with increased risk of major depressive disorder. However, the results from this study warrant further investigation in prospective setting with sufficiently long follow-up.
Summary
Association between bone mineral density and bone mineral content in old age and milk consumption in adolescence, midlife, and old age was assessed. The association was strongest for milk ...consumption in midlife: those drinking milk daily or more often had higher bone mineral density and content in old age than those drinking milk seldom or never.
Introduction
The role of lifelong milk consumption for bone mineral density (BMD) and bone mineral content (BMC) in old age is not clear. Here we assess the association between hip BMD and BMC in old age and milk consumption in adolescence, midlife, and current old age.
Methods
Participants of the Age, Gene/Environment Susceptibility-Reykjavik Study, aged 66–96 years (
N
= 4,797), reported retrospective milk intake during adolescence and midlife as well as in current old age, using a validated food frequency questionnaire. BMC of femoral neck and trochanteric area was measured by volumetric quantitative computed tomography and BMD obtained. Association was assessed using linear regression models. Differences in BMC, bone volume, and BMD in relation to milk intake were portrayed as gender-specific Z-scores.
Results
Men consuming milk ≥ once/day during midlife had 0.21 higher Z-scores for BMD and 0.18 for BMC in femoral neck (95 % confidence interval 0.05–0.39 and 0.01–0.35, respectively) compared with < once/week. Results were comparable for trochanter. For women the results were similar, with slightly lower differences according to midlife milk consumption. For current and adolescent milk consumption, differences in Z-scores were smaller and only reached statistical significance in the case of BMD for current consumption in men, while this association was less pronounced for BMC.
Conclusions
Our data suggest that regular milk consumption throughout life, from adolescence to old age, is associated with higher BMC and BMD in old age, with no differences seen in bone volume. The strongest associations are seen for midlife milk consumption in both genders.
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