A central role for GRB10 in regulation of islet function in man.

Variants in the growth factor receptor-bound protein 10 (GRB10) gene were in a GWAS meta-analysis associated with reduced glucose-stimulated insulin secretion and increased risk of type 2 diabetes (T2D) if inherited from the father, but inexplicably reduced fasting glucose when inherited from the mother. GRB10 is a negative regulator of insulin signaling and imprinted in a parent-of-origin fashion in different tissues. GRB10 knock-down in human pancreatic islets showed reduced insulin and glucagon secretion, which together with changes in insulin sensitivity may explain the paradoxical reduction of glucose despite a decrease in insulin secretion. Together, these findings suggest that tissue-specific methylation and possibly imprinting of GRB10 can influence glucose metabolism and contribute to T2D pathogenesis. The data also emphasize the need in genetic studies to consider whether risk alleles are inherited from the mother or the father.

Perinatal risk factors in young adult-onset type 1 and type 2 diabetes - a population-based case-control study.

OBJECTIVE: To examine the effects of the size of the mother and the newborn, including placental weight and gestational age at delivery, on the risk for young adult-onset type 1 diabetes (T1DM) and type 2 diabetes (T2DM). DESIGN: Case-control study. SETTING: Finland. POPULATION: Subjects with T1DM and T2DM aged 15-39 at diagnosis between the years 1992 and 1996. The number of case-control pairs was 858 for T1DM and 355 for T2DM. METHODS: Diabetic subjects were identified from the Finnish national healthcare registers and reports from diabetes nurses. Control subjects were obtained from the population register. Data on perinatal factors were obtained from the original healthcare records. The odds ratios (ORs) for both types of diabetes were estimated using conditional logistic regression. RESULTS: The risk for early-onset T2DM decreased with increasing birthweight until 4.2 kg (OR 0.49 (95% confidence interval 0.37-0.66) per 1 kg), but with birthweight above 4.2 kg the risk increased (OR 4.8 (1.3-17.6) per 1 kg). The risk for T2DM decreased also with increasing birth length (OR 0.88 (0.81-0.95) per 1 cm), body mass index at birth (OR 0.81 (0.73-0.90) per 1 kg/m2), and placental weight (OR 0.77 (0.61-0.98) per 100 g). The latter was not significant when adjusted for birthweight. The examined perinatal factors did not affect the risk for T1DM in young adults. CONCLUSIONS: Birth size significantly affects the risk for T2DM diagnosed in young adulthood but no evidence was found of an association between late-onset T1DM and perinatal factors.

Early growth and non-alcoholic fatty liver disease in adulthood-the NAFLD liver fat score and equation applied on the Helsinki Birth Cohort Study.

INTRODUCTION: Prenatal and childhood growth influence the risk of developing the metabolic syndrome and type 2 diabetes. Both conditions are associated with non-alcoholic fatty liver disease (NAFLD). Our aim was to explore the associations between early growth and adult NAFLD. METHODS: We studied 1587 individuals from the Helsinki Birth Cohort Study (HBCS) born 1934-44 for whom birth, childhood, and adult clinical data were available. NAFLD was defined using the NAFLD liver fat score and equation. The score was converted into a dichotomous variable, with outcomes defined as either a positive or negative score. The equation predicts liver fat percentage. RESULTS: A positive score was found in 43% of men and 22.5% of women. Several measurements of birth and childhood body size were negatively associated with both NAFLD outcomes after adjustment for adult BMI. Those from the smallest BMI tertile at age 2 who were obese in adulthood had an OR of 18.5 for a positive score compared to those from the same group who were normal weight in adulthood. CONCLUSIONS: A larger childhood body size was negatively associated with NAFLD outcomes. Individuals who are small during early childhood and obese as adults seem to be at the highest risk of developing NAFLD.

Personality and dietary intake - findings in the Helsinki birth cohort study.

BACKGROUND: Personality traits are associated with health outcomes including non-communicable diseases. This could be partly explained by lifestyle related factors including diet. The personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness are linked with resilience, meaning adaptability in challenging situations. Resilient people usually comply with favorable health behaviors. OBJECTIVE: Our objective was to explore the associations between food and nutrient intake, personality traits and resilience. DESIGN: A validated semi-quantitative food frequency questionnaire was used to measure diet and the NEO-personality inventory to assess personality in 1681 subjects. Linear regression analysis was used to explore diet-personality associations and cluster analysis to define resilient and non-resilient personality profiles. RESULTS: Adjusting for age, education and energy intake, and applying Bonferroni corrections, openness in men was associated with higher vegetable (14.9 g/d for 1 SD increase in the personality score, PBonf <0.01) and lower confectionery and chocolate (-2.8 g/d, PBonf <0.01) intakes. In women, neuroticism was associated with lower fish (-4.9 g/d, PBonf <0.001) and vegetable (-18.9 g/d, PBonf <0.01) and higher soft drink (19.9 g/d, PBonf <0.001) intakes. Extraversion, in women, associated with higher meat (5.9 g/d, PBonf <0.05) and vegetable (24.8 g/d, PBonf <0.001) intakes, openness with higher vegetable (23.4 g/d, PBonf <0.001) and fruit (29.5 g/d, PBonf <0.01) intakes. Agreeableness was associated with a lower soft drink (-16.2 g/d, PBonf <0.01) and conscientiousness with a higher fruit (32.9 g/d, PBonf<0.01) intake in women. Comparing resilient and non-resilient subjects, we found resilience in women to be associated with higher intakes of vegetables (52.0 g/d, P<0.001), fruits (58.3 g/d, P<0.01), fish (8.6 g/d, P<0.01) and dietary fiber (1.6 g/d, P<0.01). CONCLUSION: Personality traits are associated with dietary intake and especially subjects with resilient personality profiles had healthier dietary intakes. These associations were stronger in women than in men.

Birth-weight and resting metabolic rate in adulthood - sex-specific differences.

INTRODUCTION: Low birth-weight is associated with an increased risk of cardiovascular disease, hypertension, and the metabolic syndrome (MetS) in adulthood. Resting metabolic rate (RMR) has been suggested to be associated with the development of obesity as well as MetS and might be an indirect indicator of sympathetic activity. This study's aim was to examine the association between birth-weight and adult RMR. METHODS: A total of 896 men and women from the Helsinki Birth Cohort Study born 1934-44, for whom a detailed set of birth records were available, underwent measurement of body composition and RMR in adulthood. RESULTS: Among women, birth-weight adjusted for age and fat-free mass (FFM) was inversely associated with RMR (r = -0.12; P < 0.01). For men, a u-shaped relationship was observed, both independently and after adjustment for age, fat mass, and FFM (P = 0.05 for final model). DISCUSSION: The sex-specific differences for the association between birth-weight and adult RMR might partly be explained by differences in the developmental programming of the sympathetic nervous system between men and women. The higher adjusted RMR among those with the lowest birth-weights is consistent with previous evidence of higher sympathetic drive among these individuals.

Prenatal exposure to wartime stress: long-term effect on coronary heart disease in later life.

Background. Increased rates of coronary heart disease (CHD) and cerebrovascular disease in later life have been repeatedly observed in subjects with low birth-weight. One possible reason for low birth-weight is prenatal stress. Little is known about the influence of prenatal stress on lifelong health outcomes. Aims. In this study we investigate the influence of prenatal stress on CHD and cerebrovascular disease incidence in adult life. Methods. We analysed data originating from the Helsinki Birth Cohort Study including hospital data from all men and women born between 1934 and 1944 (n = 13,039) in two hospitals of Helsinki. We estimated the hazard function based on Weibull distribution. We compared those exposed and unexposed to bombings while in utero in terms of lifelong CHD and cerebrovascular disease hazard. Results. In women exposed to bombings while in utero, we observed higher survival rates of both CHD and cerebrovascular disease than in those unexposed. In men, the results were ambiguous. Conclusions. Our findings suggest that prenatal exposure to severe stress may be associated with protective effects on the development of CHD in later life.