Gender differences and temporal variation in the incidence of type 1 diabetes: results of 8012 cases in the nationwide Diabetes Incidence Study in Sweden 1983-2002.

OBJECTIVES: To establish the gender difference amongst newly diagnosed type 1 diabetic patients aged 15-34 years, considering age at diagnosis, temporal trend and seasonal variation at time of diagnosis. STUDY DESIGN: A population-based prospective study with a mean annual population at risk of 2.3 million. SETTING: All departments of medicine, endocrinology and paediatrics and primary health care units in Sweden. SUBJECTS: Incident cases of diabetes aged 15-34 years at diagnosis 1983-2002. MEASURE INSTRUMENT: Basic characteristics of patients at diagnosis were reported by the diagnosing doctor on a standardized form. Level of ascertainment was estimated at 80-90%. RESULTS: Amongst all incident cases (n = 8012), 74% was diagnosed with type 1 diabetes. The mean annual incidence rate of type 1 diabetes was 12.7/100,000, in men 16.4/100,000 and in women 8.9/100,000. The incidence of type 1 diabetes decreased slowly by increasing age but was in all age groups higher in men, yielding an overall male/female ratio of 1.8. In both genders the incidence of type 1 diabetes decreased in average of 1.0% per year. A seasonal pattern with significantly higher incidence during January-March and lower during May-July was seen in both genders. CONCLUSIONS: A clear male predominance of type 1 diabetes was seen in all ages. The temporal trend and the seasonal pattern was similar in men and women. Hence, internal factors related to the gender rather than differences in the exposure to environmental factors seem to explain the consistent male-female bias in the postpubertal risk of developing type 1 diabetes.

Lower levels of plasma 25-hydroxyvitamin D among young adults at diagnosis of autoimmune type 1 diabetes compared with control subjects: results from the nationwide Diabetes Incidence Study in Sweden (DISS).

AIMS/HYPOTHESIS: Low plasma vitamin D concentrations may promote the development of type 1 diabetes. To test this hypothesis, we measured plasma 25-hydroxyvitamin D (25OHD) in young adults with type 1 diabetes. METHODS: The nationwide Diabetes Incidence Study in Sweden (DISS) covers 15- to 34-year-old people with newly diagnosed diabetes. Blood samples at diagnosis were collected during the 2-year period 1987/1988. Patients with islet antibodies (islet cell antibodies, GAD antibodies or tyrosine phosphatase-like protein antibodies) were defined as having autoimmune type 1 diabetes. Plasma 25OHD was measured in samples taken from 459 patients at the time of diagnosis, and in 138 of these subjects 8 years later. The results were compared with age- and sex-matched control subjects (n=208). RESULTS: At diagnosis, plasma 25OHD levels were significantly lower in patients with type 1 diabetes than in control subjects (82.5+/-1.3 vs 96.7+/-2.0 nmol/l; p<0.0001). Eight years later, plasma 25OHD had decreased in patients (81.5+/-2.6 nmol/l; p=0.04). Plasma 25OHD levels were significantly lower in diabetic men than in diabetic women at diagnosis (77.9+/-1.4 vs 90.1+/-2.4 nmol/l; p<0.0001) and at follow-up (77.1+/-2.8 nmol/l vs 87.2+/-4.5 nmol/l; p=0.048). CONCLUSIONS/INTERPRETATION: The plasma 25OHD level was lower at diagnosis of autoimmune type 1 diabetes than in control subjects, and may have a role in the development of type 1 diabetes. Plasma 25OHD levels were lower in men than in women with type 1 diabetes. This difference may be relevant to the high incidence of type 1 diabetes among young adult men.

HLA-DQB1 genotypes, islet antibodies and beta cell function in the classification of recent-onset diabetes among young adults in the nationwide Diabetes Incidence Study in Sweden.

AIMS/HYPOTHESIS: The World Health Organization considers an aetiological classification of diabetes to be essential. The aim of this study was to evaluate whether HLA-DQB1 genotypes facilitate the classification of diabetes as compared with assessment of islet antibodies by investigating young adult diabetic patients. SUBJECTS AND METHODS: Blood samples were available at diagnosis for 1,872 (90%) of the 2,077 young adult patients (aged 15-34 years old) over a 5-year period in the nationwide Diabetes Incidence Study in Sweden. Islet antibodies were measured at diagnosis in 1,869 patients, fasting plasma C-peptide (fpC-peptide) after diagnosis in 1,522, while HLA-DQB1 genotypes were determined in 1,743. RESULTS: Islet antibodies were found in 83% of patients clinically considered to have type 1 diabetes, 23% with type 2 diabetes and 45% with unclassifiable diabetes. After diagnosis, median fpC-peptide concentrations were markedly lower in patients with islet antibodies than in those without (0.24 vs 0.69 nmol/l, p<0.0001). Irrespective of clinical classification, patients with islet antibodies showed increased frequencies of at least one of the risk-associated HLA-DQB1 genotypes compared with patients without. Antibody-negative patients with risk-associated HLA-DQB1 genotypes had significantly lower median fpC-peptide concentrations than those without risk-associated genotypes (0.51 vs 0.74 nmol/l, p=0.0003). CONCLUSIONS/INTERPRETATION: Assessment of islet antibodies is necessary for the aetiological classification of diabetic patients. HLA-DQB1 genotyping does not improve the classification in patients with islet antibodies. However, in patients without islet antibodies, HLA-DQB1 genotyping together with C-peptide measurement may be of value in differentiating between idiopathic type 1 diabetes and type 2 diabetes.

Cigarette smoking and the risk of goitre and thyroid nodules amongst parous women.

OBJECTIVES: To clarify the mechanisms by which smoking is associated to toxic and nontoxic goitre and thyroid nodules. DESIGN: Cohort study. SETTING: Sweden. SUBJECTS: A cohort of 874,507 parous women identified through the Medical Birth Registry, with smoking behaviour assessed through self-reported information at the first pre-natal visit, and follow-up between 1983 and 1997. MAIN OUTCOME MEASURES: Hospital diagnoses of toxic and nontoxic goitre and thyroid nodules, identified by record-linkage with the national Inpatient Registry. Cox regression was employed to estimate the hazard ratio (HR) of smokers compared with nonsmokers and the corresponding 95% confidence limits (CL). RESULTS: There was a significantly increased risk of goitre and nodules amongst smokers. The positive association was stronger for toxic (age adjusted HR = 1.94, CL = 1.74-2.16) than for nontoxic goitre and nodules (age-adjusted HR = 1.26; CL = 1.14-1.38). There was generally no clear risk trend with regard to amount smoked (below and above 10 cigarettes per day). Elevated body mass attenuated these associations, whilst being born in Swedish areas of endemic goitre enhanced the association with nontoxic goitre and nodules. CONCLUSIONS: Smoking enhances the risk of thyroid goitre and nodules requiring hospital admission. Iodine deficiency and body weight are likely to be important modifiers of the risk of thyroid hyperplastic diseases amongst smokers.