Quality of life and metabolic status in mildly depressed patients with type 2 diabetes treated with paroxetine: A double-blind randomised placebo controlled 6-month trial

<p>Abstract</p> <p>Background</p> <p>Depression is prevalent in people with type 2 diabetes and affects both glycaemic control and overall quality of life. The aim of this investigator-initiated trial was to evaluate the effect of the antidepressant paroxetine on quality of life, metabolic control, and mental well-being in mildly depressed diabetics aged 50–70 years.</p> <p>Methods</p> <p>We randomised 49 mildly depressed primary care outpatients with non-optimally controlled diabetes to a 6-month double-blind treatment with either paroxetine 20 mg per day or matching placebo. Primary efficacy measurements were quality of life and glycaemic control. The primary global outcome of the study was defined as a 10 points improvement in the SF-36 quality of life score. The primary metabolic outcome of the study was defined as a 0.8%-units decrease in glycosylated haemoglobin A_1c(GHbA_1c). Psychiatric symptoms were assessed with the Hospital Anxiety and Depression Scale.</p> <p>Results</p> <p>Six patients withdrew their consent before starting medication and six dropped out later in the study. We performed analysis of covariance with the baseline value as a covariate. Quality of life and glycaemic control as well as symptoms of depression and anxiety improved in both groups over the 6-month study period. After three months of treatment we found a statistically significant difference between the two treatment groups in GHbA_1c(mean difference = 0.59%-units, p = 0.018) and in SF-36 score (mean difference = 11.0 points, p = 0.039). However, at the end of the study, no statistically significant differences between the treatment groups were observed. No severe adverse events occurred.</p> <p>Conclusion</p> <p>This pragmatic study of primary care patients did not confirm earlier preliminary findings indicating a beneficial effect of paroxetine on glycaemic control. The study indicates that in pragmatic circumstances any possible benefit from administration of paroxetine in diabetic patients with sub-threshold depression is likely to be modest and of short duration. Routine antidepressant prescription for patients with diabetes and sub-threshold depressive symptoms is not indicated.</p> <p>Trial registration</p> <p>Current controlled trials ISRCTN55819922</p

Developmental Origins of Physical Fitness: The Helsinki Birth Cohort Study

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A comprehensive pharmacogenomic study indicates roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics

AimsThe aim was to comprehensively investigate the effects of genetic variability on the pharmacokinetics of rosuvastatin.MethodsWe conducted a genome-wide association study and candidate gene analyses of single dose rosuvastatin pharmacokinetics in a prospective study (n = 159) and a cohort of previously published studies (n = 88).ResultsIn a genome-wide association meta-analysis of the prospective study and the cohort of previously published studies, the SLCO1B1 c.521 T > C (rs4149056) single nucleotide variation (SNV) associated with increased area under the plasma concentration–time curve (AUC) and peak plasma concentration of rosuvastatin (P = 1.8 × 10−12 and P = 3.2 × 10−15). The candidate gene analysis suggested that the ABCG2 c.421C > A (rs2231142) SNV associates with increased rosuvastatin AUC (P = .0079), while the SLCO1B1 c.388A > G (rs2306283) and SLCO2B1 c.1457C > T (rs2306168) SNVs associate with decreased rosuvastatin AUC (P = .0041 and P = .0076). Based on SLCO1B1 genotypes, we stratified the participants into poor, decreased, normal, increased and highly increased organic anion transporting polypeptide (OATP) 1B1 function groups. The OATP1B1 poor function phenotype associated with 2.1-fold (90% confidence interval 1.6–2.8, P = 4.69 × 10−5) increased AUC of rosuvastatin, whereas the OATP1B1 highly increased function phenotype associated with a 44% (16–62%; P = .019) decreased rosuvastatin AUC. The ABCG2 c.421A/A genotype associated with 2.2-fold (1.5–3.0; P = 2.6 × 10−4) increased AUC of rosuvastatin. The SLCO2B1 c.1457C/T genotype associated with 28% decreased rosuvastatin AUC (11–42%; P = .01).ConclusionThese data suggest roles for SLCO1B1, ABCG2 and SLCO2B1 in rosuvastatin pharmacokinetics. Poor SLCO1B1 or ABCG2 function genotypes may increase the risk of rosuvastatin-induced myotoxicity. Reduced doses of rosuvastatin are advisable for patients with these genotypes.</p

Role of socioeconomic indicators on development of obesity from a lifecourse perspective

Aims: Development of obesity is modified by several factors, including socioeconomic ones. We studied the importance of socioeconomic indicators on the development of obesity from a life course perspective. Methods. 2003 people born 1934–1944 in Helsinki, Finland, participated in clinical examinations in 2001–2004. Obesity was defined as body mass index (BMI) &gt;30?kg/m2. Results. Prevalence of obesity was 22.3% in men and 27.2% in women. Lower educational attainment and lower adult social class were associated with higher BMI in both men (P=.03 and P&lt;.01) and women (P&lt;.001 and P=.01). Childhood social class was inversely associated with BMI only in men (P&lt;.001); lower household income was associated with higher BMI in women only (P&lt;.001). Those men belonging to the lowest childhood social class had higher risk of being obese than those of the highest childhood social class (OR 1.8 (95% CI: 1.0–3.1)). Household income was the strongest predictor of obesity among women. Conclusion. Overweight and obesity are inversely associated with socioeconomic status. Men seem to be more susceptible to adverse childhood socioeconomic circumstances than women, while adult socioeconomic indicators were more strongly associated with obesity in women.<br/

Childhood socio-economic status modifies the association between intellectual abilities at age 20 and mortality in later life

Background: People who score poorly in intellectual ability tests have shorter life expectancy. We studied whether this association is different in people from different socio-economic backgrounds. Methods: We studied the mortality of 2786 men born in Helsinki, Finland, during 1934-44, who as military conscripts underwent a standardised intellectual ability test comprising verbal, visuospatial and arithmetic reasoning subtests. Mortality data came from the Finnish Death Register. Results: Comparing men in the lowest and highest test score fourths, hazard ratios for all-cause mortality were 1.9 (95% confidence interval 1.4-2.5) for verbal, 2.2 (1.6-3.0) for visuospatial and 1.9 (1.4-2.5) for arithmetic reasoning, corresponding to 2.6, 3.4 and 2.6 excess years of life lost, respectively. Associations were similar for cardiovascular and non-cardiovascular mortality. Intellectual ability scores were stronger predictors in men who grew up in middle class families. Compared with middle class men in the highest fourth of visuospatial reasoning score, middle class men in the lowest fourth lost 6.5 years of life, while men from manual workers- families in the highest fourth lost 2.8 years and men in the lowest fourth lost 5.6 years. Conclusions: High intellectual ability in men aged 20 protects from mortality in later life. This effect is stronger in men who grew up in middle class as compared with manual workers- families. We suggest that early life conditions that are unfavourable to development of cognitive abilities negate the life expectancy benefits of being born into a more affluent family.<br/