Higher frequency of hospitalization but lower relative mortality for pandemic influenza in people with type 2 diabetes.

BACKGROUND: There is limited evidence linking type 2 diabetes (T2D) to influenza-related complications. OBJECTIVES: To test a set of research questions relating to pandemic influenza vaccination, hospitalization and mortality in people with and without T2D. METHODS: In this population-based cohort study, we linked individual-level data from several national registers for all Norwegian residents aged 30 years or more as of January 2009. People with or without T2D at baseline (n = 2 992 228) were followed until December 2013. We used Cox regression to estimate adjusted hazard ratios (aHRs). RESULTS: Pandemic influenza hospitalization was more common in individuals with T2D (aHR = 2.46, 95% CI 2.04-2.98). The mortality hazard ratio associated with hospitalization for pandemic influenza was lower in people with T2D (aHR = 1.82, 95% CI 1.21-2.74) than in those without T2D (aHR = 3.89, 95% CI 3.27-4.62). The same pattern was observed when restricting to 90-day mortality (aHR = 3.89, 95% CI 1.25-12.06 amongst those with T2D and aHR = 10.79, 95% CI 7.23-16.10 amongst those without T2D). The rate of hospitalization for pandemic influenza was 78% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.22, 95% CI 0.11-0.39), whilst the corresponding estimate for those without T2D was 59% lower (aHR = 0.41, 95% CI 0.33-0.52). Mortality was 25% lower in those vaccinated compared to nonvaccinated amongst people with T2D (aHR = 0.75, 95% CI 0.73-0.77), whilst the corresponding estimate for those without T2D was 9% (aHR = 0.91, 95% CI 0.90-0.92). CONCLUSIONS: There may have been a lower threshold for pandemic influenza hospitalization for people with T2D, rather than more severe influenza infection. Our combined results support the importance of influenza vaccination amongst people with T2D, especially during pandemics.

Causes of death in childhood-onset Type 1 diabetes: long-term follow-up.

AIMS: To assess the causes of death and cause-specific standardized mortality ratios in two nationwide, population-based cohorts diagnosed with Type 1 diabetes during the periods 1973-1982 and 1989-2012, and to evaluate changes in causes of death during the follow-up period. METHODS: People with Type 1 diabetes who were aged < 15 years at diagnosis were identified in the Norwegian Childhood Diabetes Registry and followed from diagnosis until death, emigration or September 2013 (n = 7871). We assessed causes of death by linking data to the nationwide Cause of Death Registry and through a review committee that evaluated medical records, autopsy reports and death certificates. RESULTS: During a mean (range) follow-up of 16.8 (0-40.7) years, 241 individuals (3.1%) died, representing 132 143 person-years. The leading cause of death before the age of 30 years was acute complications (41/119, 34.5%). After the age of 30 years cardiovascular disease was predominant (41/122, 33.6%), although death attributable to acute complications was still important in this age group (22/122, 18.0%). A total of 5% of deaths were caused by 'dead-in-bed' syndrome. The standardized mortality ratio was elevated for cardiovascular disease [11.9 (95% CI 8.6-16.4)] and violent death [1.7 (95% CI 1.3-2.1)] in both sexes combined, but was elevated for suicide only in women [2.5 (95% CI 1.2-5.3)]. The risk of death from acute complications was approximately half in women compared with men [hazard ratio 0.43 (95% CI 0.25-0.76)], and did not change with more recent year of diagnosis [hazard ratio 1.02 (0.98-1.05)]. CONCLUSIONS: There was no change in mortality attributable to acute complications during the study period. To reduce premature mortality in people with childhood-onset diabetes focus should be on prevention of acute complications. Male gender implied increased risk.

25-Hydroxyvitamin D in pregnancy and genome wide cord blood DNA methylation in two pregnancy cohorts (MoBa and ALSPAC).

The aim of the study was to investigate whether maternal mid-pregnancy 25-hydroxyvitamin D concentrations are associated with cord blood DNA methylation. DNA methylation was assessed using the Illumina HumanMethylation450 BeadChip, and maternal plasma 25-hydroxyvitamin D was measured in 819 mothers/newborn pairs participating in the Norwegian Mother and Child Cohort (MoBa) and 597 mothers/newborn pairs participating in the Avon Longitudinal Study of Parents and Children (ALSPAC). Across 473,731CpG DNA methylation sites in cord blood DNA, none were strongly associated with maternal 25-hydroxyvitamin D after adjusting for multiple tests (false discovery rate (FDR)>0.5; 473,731 tests). A meta-analysis of the results from both cohorts, using the Fisher method for combining p-values, also did not strengthen findings (FDR>0.2). Further exploration of a set of CpG sites in the proximity of four a priori defined candidate genes (CYP24A1, CYP27B1, CYP27A1 and CYP2R1) did not result in any associations with FDR<0.05 (56 tests). In this large genome wide assessment of the potential influence of maternal vitamin D status on DNA methylation, we did not find any convincing associations in 1416 newborns. If true associations do exist, their identification might require much larger consortium studies, expanded genomic coverage, investigation of alternative cell types or measurements of 25-hydroxyvitamin D at different gestational time points.

The prenatal environment and type 1 diabetes.

There is ample evidence that environmental factors are involved in the aetiology of type 1 diabetes, but the nature and timing of the interactions are poorly understood. The intrauterine environment is known to play a role in the later development of type 2 diabetes, and this review considers a possible role in type 1 diabetes. Autoimmune type 1 diabetes is rare in those diagnosed before 6 months of age, but endogenous autoantibodies predictive of future type 1 diabetes may be detectable by 6-12 months of age, suggesting that environmental factors may operate before this age in some cases. Indirect evidence of a protective effect for the intrauterine environment comes from the observation that mothers with type 1 diabetes are less likely than affected fathers to transmit diabetes to their offspring, although the precise role (if any) is unclear. The risk of childhood-onset type 1 diabetes increases with maternal age at delivery, and with high birthweight, but these associations are weak and heterogeneous, and these factors are unlikely to be directly causally related to type 1 diabetes. No firm conclusion can be drawn from studies of maternal enteroviral infection or from various nutritional exposures. The birth process itself may play a role, as suggested by the slightly increased risk in children born by Caesarean section; lack of contact with maternal bacteria is one suggested mechanism. In sum, there is circumstantial evidence, but no proof of principle, that maternal or intrauterine conditions may modulate genetic risk of type 1 diabetes. The disease process culminating in type 1 diabetes typically begins in early life, but it is not clear whether the trail begins before or after birth.

Serum long chain n-3 fatty acids (EPA and DHA) in the pregnant mother are independent of risk of type 1 diabetes in the offspring.

BACKGROUND: This article aims to study whether higher proportions of the long chain n-3 fatty acids eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) in the phospholipid fraction of serum samples in pregnancy were associated with a lower risk of childhood onset type 1 diabetes in the offspring. METHODS: In a prospective cohort of nearly 30 000 pregnant women who gave birth in Norway during 1992-1994, we analysed serum samples from 89 women whose child developed type 1 diabetes and was included in the nationwide Norwegian Childhood Diabetes Registry and 125 randomly selected women whose child did not develop type 1 diabetes before 15 years of age. Specific fatty acids were expressed as the proportion of total fatty acids (g/100 g) in the phospholipid fraction in serum analysed using solid phase extraction and gas chromatography with flame ionization detection. RESULTS: There was no significant association between EPA or DHA in maternal serum and risk of type 1 diabetes in the offspring. Odds ratio (OR) for upper versus lower quartile of EPA was 0.75 [95% confidence interval (CI) 0.34-1.65], test for trend p = 0.4, and for DHA OR = 0.71 (95% CI 0.33-1.53), test for trend p = 0.6. No significant association was found for the sum of n-3 fatty acids, or for n-6/n-3 ratio in the mother with risk of type 1 diabetes in the offspring. CONCLUSIONS: Our data did not support the hypothesis that higher proportions of maternal EPA or DHA during pregnancy are associated with a lower risk of type 1 diabetes in the offspring.

Immunology in the clinic review series; focus on type 1 diabetes and viruses: the enterovirus link to type 1 diabetes: critical review of human studies.

The hypothesis that under some circumstances enteroviral infections can lead to type 1 diabetes (T1D) was proposed several decades ago, based initially on evidence from animal studies and sero-epidemiology. Subsequently, enterovirus RNA has been detected more frequently in serum of patients than in control subjects, but such studies are susceptible to selection bias and reverse causality. Here, we review critically recent evidence from human studies, focusing on longitudinal studies with potential to demonstrate temporal association. Among seven longitudinal birth cohort studies, the evidence that enterovirus infections predict islet autoimmunity is quite inconsistent in our interpretation, due partially, perhaps, to heterogeneity in study design and a limited number of subjects studied. An association between enterovirus and rapid progression from autoimmunity to T1D was reported by one longitudinal study, but although consistent with evidence from animal models, this novel observation awaits replication. It is possible that a potential association with initiation and/or progression of islet autoimmunity can be ascribed to a subgroup of the many enterovirus serotypes, but this has still not been investigated properly. There is a need for larger studies with frequent sample intervals and collection of specimens of sufficient quality and quantity for detailed characterization of enterovirus. More research into the molecular epidemiology of enteroviruses and enterovirus immunity in human populations is also warranted. Ultimately, this knowledge may be used to devise strategies to reduce the risk of T1D in humans.

Perinatal and infant mortality in term and preterm births among women with type 1 diabetes.

AIMS/HYPOTHESIS: The aim of this study was to estimate the risks of adverse birth outcomes such as stillbirth, infant death, preterm birth and pre-eclampsia in women with type 1 diabetes, compared with the background population. We further aimed to explore the risks of adverse birth outcomes in preterm and term deliveries separately. METHODS: By linkage of two nationwide registries, the Medical Birth Registry of Norway and the Norwegian Childhood Diabetes Registry, we identified 1,307 births among women with pregestational type 1 diabetes registered in the Diabetes Registry, and 1,161,092 births in the background population during the period 1985-2004. The ORs with 95% CIs for adverse outcome among women with type 1 diabetes vs the background population were estimated using logistic regression. RESULTS: The OR for stillbirth (≥22 weeks of gestation) was 3.6 (95% CI 2.5, 5.3), and for perinatal death (stillbirth or death in the first week of life) it was 2.9 (95% CI 2.0, 4.1). The OR for infant death (first year of life) was 1.9 (95% CI 1.1, 3.2). For preterm birth (< 37 weeks of gestation) and pre-eclampsia the ORs were 4.9 (95% CI 4.3, 5.5) and 6.3 (95% CI 5.5, 7.2), respectively. When preterm and term deliveries were analysed separately, the excess risk of stillbirth and infant death in women with diabetes was confined to term deliveries. CONCLUSIONS/INTERPRETATION: Pregestational type 1 diabetes was associated with a considerably higher risk of adverse pregnancy outcomes, including infant death, compared with the background population. A novel finding of the study was that the increased risk was confined to term births.

Fecundability among women with type 1 and type 2 diabetes in the Norwegian Mother and Child Cohort Study.

AIMS/HYPOTHESIS: We assessed the effects of type 1 diabetes and type 2 diabetes on fecundability (as manifest by increased time-to-pregnancy [TTP]) in a large cohort of pregnant women. METHODS: This study is based on the Norwegian Mother and Child Cohort Study. Members of this large cohort were enrolled early in pregnancy and asked about TTP and other factors. Among the 58,004 women included in the analysis, we identified 221 cases of type 1 diabetes and 88 cases of type 2 diabetes using the Medical Birth Registry of Norway. A logistic analogue of the proportional probability model, a Cox-like discrete-time model, was used to compute fecundability odds ratios (FORs) and 95% CI for type 1 diabetes and type 2 diabetes, adjusted for maternal age and prepregnancy BMI. RESULTS: Compared with non-diabetic women, the adjusted FOR for women with type 1 diabetes was 0.76 (95% CI 0.64-0.89) and the adjusted FOR for women with type 2 diabetes was 0.64 (95% CI 0.48-0.84). These FORs did not change substantively and remained statistically significant after excluding women with irregular menstrual cycles and accounting for cycle length. CONCLUSIONS/INTERPRETATION: The results from the present study provide evidence of substantially decreased fecundability for women with type 1 and type 2 diabetes, even among those with a normal menstrual cycle.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Caesarean section is associated with an increased risk of childhood-onset type 1 diabetes mellitus: a meta-analysis of observational studies.

AIMS/HYPOTHESIS: The aim of this study was to investigate the evidence of an increased risk of childhood-onset type 1 diabetes in children born by Caesarean section by systematically reviewing the published literature and performing a meta-analysis with adjustment for recognised confounders. METHODS: After MEDLINE, Web of Science and EMBASE searches, crude ORs and 95% CIs for type 1 diabetes in children born by Caesarean section were calculated from the data reported in each study. Authors were contacted to facilitate adjustments for potential confounders, either by supplying raw data or calculating adjusted estimates. Meta-analysis techniques were then used to derive combined ORs and to investigate heterogeneity between studies. RESULTS: Twenty studies were identified. Overall, there was a significant increase in the risk of type 1 diabetes in children born by Caesarean section (OR 1.23, 95% CI 1.15-1.32, p < 0.001). There was little evidence of heterogeneity between studies (p = 0.54). Seventeen authors provided raw data or adjusted estimates to facilitate adjustments for potential confounders. In these studies, there was evidence of an increase in diabetes risk with greater birthweight, shorter gestation and greater maternal age. The increased risk of type 1 diabetes after Caesarean section was little altered after adjustment for gestational age, birth weight, maternal age, birth order, breast-feeding and maternal diabetes (adjusted OR 1.19, 95% CI 1.04-1.36, p = 0.01). CONCLUSIONS/INTERPRETATION: This analysis demonstrates a 20% increase in the risk of childhood-onset type 1 diabetes after Caesarean section delivery that cannot be explained by known confounders.

Joint effects of HLA, INS, PTPN22 and CTLA4 genes on the risk of type 1 diabetes.

BACKGROUND/HYPOTHESIS: HLA, INS, PTPN22 and CTLA4 are considered to be confirmed type 1 diabetes susceptibility genes. HLA, PTPN22 and CTLA4 are known to be involved in immune regulation. Few studies have systematically investigated the joint effect of multiple genetic variants. We evaluated joint effects of the four established genes on the risk of childhood-onset type 1 diabetes. METHODS: We genotyped 421 nuclear families, 1,331 patients and 1,625 controls for polymorphisms of HLA-DRB1, -DQA1 and -DQB1, the insulin gene (INS, -23 HphI), CTLA4 (JO27_1) and PTPN22 (Arg620Trp). RESULTS: The joint effect of HLA and PTPN22 on type 1 diabetes risk was significantly less than multiplicative in the case-control data, but a multiplicative model could not be rejected in the trio data. All other two-way gene-gene interactions fitted multiplicative models. The high-risk HLA genotype conferred a very high risk of type 1 diabetes (OR 20.6, using the neutral-risk HLA genotype as reference). When including also intermediate-risk HLA genotypes together with risk genotypes at the three non-HLA loci, the joint odds ratio was 61 (using non-risk genotypes at all loci as reference). CONCLUSION: Most established susceptibility genes seem to act approximately multiplicatively with other loci on the risk of disease except for the joint effect of HLA and PTPN22. The joint effect of multiple susceptibility loci conferred a very high risk of type 1 diabetes, but applies to a very small proportion of the general population. Using multiple susceptibility genotypes compared with HLA genotype alone seemed to influence the prediction of disease only marginally.

Low cumulative incidence of proliferative retinopathy in childhood-onset type 1 diabetes: a 24-year follow-up study.

AIMS/HYPOTHESIS: We estimated cumulative incidence of proliferative diabetic retinopathy (PDR) and risk factors for developing diabetic retinopathy (DR) in childhood-onset type 1 diabetes. MATERIALS AND METHODS: A sample of 294 patients with childhood-onset type 1 diabetes (<15 years) diagnosed in Norway between 1973 and 1982 was examined for retinopathy at baseline between 1989 and 1990 and at follow-up from 2002 to 2003. At follow-up, mean age was 33 years (range: 21-44), mean diabetes duration 24 years (19-30) and total person-time contributed 7,152 person-years. Retinal photographs were taken at baseline and follow-up. Associations between baseline factors and PDR were estimated using Cox regression models. RESULTS: Overall, 262 of 294 (89.1%) developed DR from diabetes onset, of whom 31 developed PDR. The 25-year cumulative incidence of PDR was 10.9% (95% CI 7.3-14.5). Among 194 without retinopathy at baseline, 163 (84%) developed DR and nine (5%) progressed to PDR. Among 97 patients with non-proliferative DR at baseline, 19 (20%) progressed to PDR. Significant predictors for developing PDR were retinopathy at baseline (relative risk [RR]=3.71, 95% CI 1.59-8.68), HbA(1c) (RR=2.05, 1.44-2.93), and triglycerides (RR=1.55, 1.06-1.95). CONCLUSIONS/INTERPRETATION: Nine out of every ten patients diagnosed with type 1 diabetes developed DR, but only one out of ten developed PDR within their first 25 years of diabetes duration. The cumulative incidence of PDR is lower than previously reported from other countries. Potentially modifiable risk factors predict the development of DR and PDR.

The relation between size at birth and risk of type 1 diabetes is not influenced by adjustment for the insulin gene (-23HphI) polymorphism or HLA-DQ genotype.

AIMS/HYPOTHESIS: Associations have been described between higher birthweight and increased risk of type 1 diabetes, and of insulin (INS) and human leucocyte antigen (HLA) genotypes that protect against diabetes with larger size at birth. We studied simultaneously the effects of size at birth, INS and HLA genotypes on the risk of type 1 diabetes to test whether the relation between size at birth and risk of type 1 diabetes would be strengthened after adjustment for INS and HLA genotypes. SUBJECTS AND METHODS: We designed a population-based case-control study in Norway with 471 cases of childhood-onset type 1 diabetes and 1,369 control subjects who were genotyped for the INS -23HphI polymorphism (surrogate for INS variable number of tandem repeats) and HLA-DQ alleles associated with type 1 diabetes. Data on birthweight and other perinatal factors were obtained from the Medical Birth Registry of Norway by record linkage. RESULTS: The data fitted a multiplicative model for the protective INS class III allele both within the INS locus and for the model with INS- and HLA-DQ-conferred risk of type 1 diabetes. We found no overall significant association between weight or head circumference at birth and the risk of type 1 diabetes, and adjustment for INS and HLA genotype did not influence this result. There was also no evidence for association of INS or HLA with size at birth among control subjects. CONCLUSIONS/INTERPRETATION: In contrast to suggestions from previous indirect studies, direct adjustment for INS and HLA genotypes did not lead to a stronger relation between birthweight and the risk of type 1 diabetes.

Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway.

AIMS/HYPOTHESIS: We examined long-term total and cause-specific mortality in a nationwide, population-based Norwegian cohort of patients with childhood-onset type 1 diabetes. MATERIALS AND METHODS: All Norwegian type 1 diabetic patients who were diagnosed between 1973 and 1982 and were under 15 years of age at diagnosis were included (n=1,906). Mortality was recorded from diabetes onset until 31 December 2002 and represented 46,147 person-years. The greatest age attained among deceased subjects was 40 years and the maximum diabetes duration was 30 years. Cause of death was ascertained by reviews of death certificates, autopsy protocols and medical records. The standardised mortality ratio (SMR) was based on national background statistics. RESULTS: During follow-up 103 individuals died. The mortality rate was 2.2/1000 person-years. The overall SMR was 4.0 (95% CI 3.2-4.8) and was similar for males and females. For ischaemic heart disease the SMR was 20.2 (7.3-39.8) for men and 20.6 (1.8-54.1) for women. Acute metabolic complications of diabetes were the most common cause of death under 30 years of age (32%). Cardiovascular disease was responsible for the largest proportion of deaths from the age of 30 years onwards (30%). Violent death accounted for 28% of the deaths in the total cohort (35% among men and 11% among women). CONCLUSIONS/INTERPRETATION: Childhood-onset type 1 diabetes still carries an increased mortality risk when compared with the general population, particularly for cardiovascular disease. To reduce these deaths, attention should be directed to the prevention of acute metabolic complications, the identification of psychiatric vulnerability and the early detection and treatment of cardiovascular disease and associated risk factors.

Atopic disorders and risk of childhood-onset type 1 diabetes in individuals.

BACKGROUND: Data on the relationship between Th2-biased atopic disorders and Th1-biased autoimmune diseases such as type 1 diabetes are conflicting. Many studies have not defined the time sequence of disease appearance, and few have investigated the role of candidate risk factors. OBJECTIVE: The objective was to investigate whether the presence of parents' report of physician-diagnosed atopic disorders is lower among cases of type 1 diabetes before diagnosis, as compared with population-based control subjects, and whether this may be explained by candidate risk factors such as day-care attendance, breastfeeding habits, and perinatal factors. METHODS: We designed a population-based case-control study in Norway with 545 cases of childhood-onset type 1 diabetes and 1668 control subjects. Families were contacted by mail, and they completed a questionnaire on physician-diagnosed atopic eczema, allergic rhino-conjunctivitis and asthma, and other relevant factors. Data on birth order, maternal age at delivery, birth weight, gestational age, pre-eclampsia, and caesarean section were obtained from the Medical Birth Registry of Norway by record linkage. RESULTS: Atopic eczema was inversely associated with risk of type 1 diabetes, odds ratio=0.55 (95% confidence interval 0.35-0.87) after adjustment for age, sex, maternal education, day-care attendance, duration of exclusive breastfeeding, and perinatal factors. Allergic rhino-conjunctivitis and asthma were not significantly associated with type 1 diabetes. CONCLUSIONS: Atopic eczema was associated with a lower risk of type 1 diabetes, independent of a number of candidate risk factors, suggesting that it may confer partial protection against type 1 diabetes.

Obesity in a rural and an urban Palestinian West Bank population.

OBJECTIVE: To compare the prevalence of obesity, household food consumption patterns, physical activity patterns and smoking between a rural and an urban community in the Palestinian West Bank and to describe the associations of the latter factors with body mass index (BMI). DESIGN: A population-based cross-sectional survey in a rural and an urban Palestinian West Bank community. SUBJECTS: A total of 549 women and 387 men aged 30-65 y, excluding pregnant women. MEASUREMENTS: Obesity was defined as BMI >/=30 kg/m(2). RESULTS: The prevalence of obesity was 36.8 and 18.1% in rural women and men, respectively, compared with 49.1 and 30.6% in urban women and men, respectively. The mean difference (s.e) in BMI levels was 1.6 (0.52) kg/m(2) between urban and rural women and 0.9 (0.46) kg/m(2) in men. At the household level, the mean energy consumption from 25 selected food items was 13.8 MJ (3310 kcal)/consumption unit/day in the rural community compared to 14.5 MJ (3474 kcal)/consumption unit/day in the urban community (P=0.021). BMI was positively associated with age in both men and women and with urban residence in women. BMI was negatively associated with smoking and physical activity in men and with educational level in women. CONCLUSION: BMI was associated with urban residence in women after adjusting for age, smoking, education, physical activity and nutrition-related variables, suggesting that the differences in the conventional determinants of obesity could not fully explain the difference in the prevalence of obesity between the two communities. Among men, the measured determinants explained the rural-urban differences in BMI.

Diabetes-associated HLA-DQ genes and birth weight.

An association has recently been described between increased birth weight and increased risk of childhood-onset type 1 diabetes. Whether this relationship is explained by genes associated with both increased birth weight and increased risk of type 1 diabetes is unknown. In the present study, we tested the association between birth weight and HLA-DQ genotypes known to confer risk for type 1 diabetes among 969 nondiabetic children randomly selected from the Norwegian population. We found that HLA genotypes previously shown to confer risk for type 1 diabetes were associated with reduced birth weight (the mean difference in birth weight between the DQB1*0602/DQB1*0602 and DQ8/DQ2 genotypes was 354 g [95% CI 105-604]), which was opposite of that expected if HLA genes explained the birth weight-type 1 diabetes association.

Relation between occurrence of type 1 diabetes and asthma.

A negative association has been observed between type 1 diabetes and atopic diseases in individuals, a finding that supports the Th1/Th2 paradigm. By using published data on disease occurrence in different countries, we show a strong positive association between the occurrence of type 1 diabetes and symptoms of asthma at the population level in Europe and elsewhere. Our finding suggests that there may be common factors influencing susceptibility to the two disorders at the country level. Our observation must be accommodated in explanations of the epidemiology of type 1 diabetes or atopic diseases.

Obesity and associated factors in a Palestinian West Bank village population.

OBJECTIVE: To describe body mass index (BMI), waist circumference and waist-hip ratio in a Palestinian West Bank village population, and to assess the associations of these variables to blood pressure and serum lipids. DESIGN: Cross-sectional study. SETTING: Community-based study in a prototypic semi-rural Palestinian village in the central West Bank. SUBJECTS: All individuals aged 30-65 y in the study village were invited for the study and 500 (85%) participated. MAIN OUTCOME MEASURES: BMI > or = 30 was used as the measure of obesity. RESULTS: The prevalence of obesity was 37.5% among women and 18.8% among men. The prevalence of abdominal obesity was 62.5% among women and 14.8% among men. BMI seemed to be the more important correlate of blood pressure whereas waist-hip ratio seemed to be the more important correlate of serum triglycerides, compared to the other obesity measures. CONCLUSIONS: The prevalence of obesity in the study population was very high compared to most other countries in the world, particularly among women. SPONSORSHIP: The study was funded by the Norwegian Universities' Committee for Development Research (NUFU). LCM Stene was supported by a grant from the Throne Holst Foundation.