Paul A. Blomstedt

Association between type 2 diabetes and exposure to persistent organic pollutants.

OBJECTIVE The prevalence of type 2 diabetes is increasing alarmingly in both developed and developing countries. Recently, exposure to persistent organic pollutants (POPs) has been associated with the prevalence of type 2 diabetes. The purpose of this cross-sectional study is to examine the association between type 2 diabetes and POP exposure in the Helsinki Birth Cohort Study. RESEARCH DESIGN AND METHODS The cohort consists of 8,760 people born in Helsinki during 1934–1944, before the global POP emission peak. In 2003, a clinical examination was performed, including blood sampling for laboratory analyses of serum lipids and POPs. Complete data from the examination were available for 1,988 participants. The concentrations of each POP were categorized into four groups on the basis of percentile intervals, and logistic regression was performed to examine diabetes prevalence across the POP categories, adjusting for sex, age, waist circumference, and mean arterial pressure and using the lowest category as the reference group. RESULTS Among the participants with the highest exposure to oxychlordane, trans-nonachlor, 1,1-dichloro-2,2-bis-(p-chlorophenyl)-ethylene (p,p’-DDE, and polychlorinated biphenyl 153, the risk of type 2 diabetes was 1.64–2.24 times higher than that among individuals with the lowest exposure (Plin = 0.003–0.050, where Plin is the P value for linear trend across POP categories). In the stratified analysis, the associations between type 2 diabetes and oxychlordane and trans-nonachlor remained significant and were strongest among the overweight participants. Exposure to 2,2′,4,4′-tetrabromodiphenyl ether (BDE 47) and 2,2′,4,4′,5,5′-hexabromodiphenyl ether (BDE 153) was not associated with type 2 diabetes. CONCLUSIONS This study confirms the association between type 2 diabetes and adult-only exposure to organochlorine pesticides in a general urban population.

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.

Marked temporal increase in the incidence of type 1 and type 2 diabetes among young adults in Finland.

To the Editor: Previously we reported data on trends in the incidence of type 1 and type 2 diabetes in Finnish young adults aged 15–39 years during 1992–1996 [1] and found a 7.9% average annual increase in the incidence of type 2 diabetes. This rising trend needed to be confirmed during a longer period of follow-up, and therefore we extended the study until the year 2001. The collection of data and the classification of patients with diabetes ascertained during 1992 to 1996 have been described in detail previously [1]. The information on new diagnoses of diabetes in the age group of 15–39 years between 1997 and 2001 were obtained from three nationwide registers in Finland. The first register was the Drug Prescription Register of the Social Insurance Institute, which comprises ATC-DDD codes [2] on all prescriptions since 1994, and for this study all the class A10 drugs (drugs used in diabetes) were reviewed. The second register was the Drug Reimbursement Register of the Social Insurance Institute, which comprises information on persons entitled to free-of-charge medication for diabetes. The entitlement is given in response to an application that includes a detailed medical statement prepared by the treating physician. The third register was the Hospital Discharge Register, maintained by the National Research and Development Centre for Welfare and Health, which includes the treating physician’s diagnoses in ICD-10 codes [3]. Data from these registers were linked using the unique personal identification number assigned to every Finnish resident. The date of the first entry in any of these registers was set as the date of the diagnosis of diabetes. The patient had to be recorded in at least two of these registers to be included. A patient was classified as having type 1 diabetes if two of the following three criteria were fulfilled: (1) an ICD-10 diagnosis referring only to type 1 diabetes; (2) permanent entitlement to free-of-charge medication; (3) only insulin was administered immediately at diagnosis and continued until the end of the year 2004. A patient was classified as having type 2 diabetes if two of the following three criteria were fulfilled: (1) an ICD-10 diagnosis referring only to type 2 diabetes; (2) permanent or temporary entitlement to free-of-charge medication; (3) only oral glucose-lowering agents had been prescribed. For patients who could not be reliably classified with this method, the application records for free-of-charge medication were acquired from the Social Insurance Institute and reviewed in order to assign the type of diabetes (n=791). Information on patients with no entitlement to free-of-charge medication (n=563) was reviewed, and most were classified as having gestational diabetes, as expected (persons with gestational diabetes are not entitled to free-of-charge medication). Patients who were impossible to classify as having type 1 or type 2 diabetes were classified as having an undefined type of diabetes. Diabetologia (2008) 51:897–899 DOI 10.1007/s00125-008-0952-9

Leukocyte telomere length and its relation to food and nutrient intake in an elderly population

Background/objectives:Shorter leukocyte telomere length (LTL) is associated with several chronic diseases, but only a few studies have assessed the association between dietary factors and LTL. Our objective was to study the association between fats, fruits, vegetables and LTL in a cross-sectional study design. We hypothesized that intakes of fruits and vegetables would be positively associated with LTL and that intakes of fats, and especially saturated fatty acids (SFAs), would be negatively associated with LTL.Subjects/methods:LTL was measured by quantitative real-time polymerase chain reaction in 1942 men and women aged 57–70 years from the Helsinki Birth Cohort Study. We assessed the whole diet by a validated semiquantitative 128-item food-frequency questionnaire.Results:In general, there were only a few significant results. However, total fat and SFA intake (P=0.04 and 0.01, respectively) were inversely associated with LTL in men adjusting for age and energy intake. In women, vegetable intake was positively associated with LTL (P=0.05). Men consuming the most butter and least fruits had significantly shorter telomeres than those consuming the lowest amounts of butter and highest amounts of fruits (P=0.05). We found no association between LTL and body mass index, waist–hip ratio, smoking, physical activity or educational attainment.Conclusions:In this cross-sectional study of elderly men and women, there were only a few statistically significant effects of diet, but in general they support the hypothesis that fat and vegetable intakes were associated with LTL.

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.

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

Abstract 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.

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.

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

Abstract 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 studys 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

Abstract 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.

Statistical modelling of measurement errors in gas chromatographic analyses of blood alcohol content

Headspace gas chromatographic measurements of ethanol content in blood specimens from suspect drunk drivers are routinely carried out in forensic laboratories. In the widely established standard statistical framework, measurement errors in such data are represented by Gaussian distributions for the population of blood specimens at any given level of ethanol content. It is known that the variance of measurement errors increases as a function of the level of ethanol content and the standard statistical approach addresses this issue by replacing the unknown population variances by estimates derived from large sample using a linear regression model. Appropriate statistical analysis of the systematic and random components in the measurement errors is necessary in order to guarantee legally sound security corrections reported to the police authority. Here we address this issue by developing a novel statistical approach that takes into account any potential non-linearity in the relationship between the level of ethanol content and the variability of measurement errors. Our method is based on standard non-parametric kernel techniques for density estimation using a large database of laboratory measurements for blood specimens. Furthermore, we address also the issue of systematic errors in the measurement process by a statistical model that incorporates the sign of the error term in the security correction calculations. Analysis of a set of certified reference materials (CRMs) blood samples demonstrates the importance of explicitly handling the direction of the systematic errors in establishing the statistical uncertainty about the true level of ethanol content. Use of our statistical framework to aid quality control in the laboratory is also discussed.