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- Kilpeläinen, Tuomas O, et al.
(author)
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Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
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| 2. |
- Kivimäki, Mika, et al.
(author)
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Influence of retirement on nonadherence to medication for hypertension and diabetes
- 2013
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In: CMJA. Canadian Medical Association Journal. Onlineutg. Med tittel. - : CMA Joule Inc.. - 0820-3946 .- 1488-2329. ; 85:17, s. E784-E790
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Journal article (peer-reviewed)abstract
- BACKGROUND: The extent to which common life transitions influence medication adherence among patients remains unknown. We examined whether retirement is associated with a change in adherence to medication in patients with hypertension or type 2 diabetes. METHODS: Participants in the Finnish Public Sector study were linked to national registers. We included data for the years 1994-2011. We identified and followed 3468 adult patients with hypertension and 412 adult patients with type 2 diabetes for medication adherence for the 3 years before their retirement and the 4 years after their retirement (mean follow-up 6.8 yr). Our primary outcome was proportion of patients with poor adherence to medication, which we defined as less than 40% of days covered by treatment. We determined these proportions before and after retirement using data from filled prescriptions. RESULTS: The preretirement prevalence of poor adherence to medication was 6% in men and women with hypertension, 2% in men with diabetes and 4% in women with diabetes. Among men, retirement was associated with an increased risk of poor adherence to both antihypertensive agents (odds ratio [OR] 1.32, 95% confidence interval [CI] 1.03-1.68) and antidiabetic drugs (OR 2.40, 95% CI 1.37-4.20). Among women, an increased risk of poor adherence was seen only for antihypertensive agents (OR 1.25, 95% CI 1.07-1.46). Similar results were apparent for alternative definitions of poor adherence. Our results did not differ across strata of age, socioeconomic status or comorbidity. INTERPRETATION: We found a decline in adherence to medication after retirement among men and women with hypertension and men with type 2 diabetes. If these findings can be confirmed, we need randomized controlled trials to determine whether interventions to reduce poor adherence after retirement could improve clinical outcomes of treatments for hypertension and diabetes.
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