Identifying risk of type 2 diabetes : epidemiologic perspectives from biomarkers to lifestyle

Sammanfattning: Type 2 diabetes is a significant health problem because of its high prevalence and strong association with cardiovascular morbidity and mortality. An increase of type 2 diabetes is predicted due to increasing obesity and sedentary lifestyle habits. The development from latent to diagnostic disease spans many years and during this time it is possible to prevent or postpone type 2 diabetes using lifestyle and pharmacological interventions. The objective of this thesis is to investigate and describe early patterns and risk indicators of type 2 diabetes. The focus is on type 2 diabetes as one component in metabolic syndrome, i.e. the clustering of several cardiovascular risk markers. Two studies based on the Västerbotten Intervention Programme (VIP) provided the data; one case-referent study nested within VIP which includes 237 diabetes cases that were clinically diagnosed 5.4 years after the health survey, each with two referents; and one panel study with 5 consecutive annual cohorts including subjects that participated in VIP between1990 and 1994 and returned to a follow-up after 10 years, a total of 16 492 individuals. Associations between risk markers and type 2 diabetes or metabolic syndrome are evaluated by several statistical techniques. A model of metabolic syndrome is hypothesized. A prediction model for developing type 2 diabetes among middle-aged individuals is proposed, where high risk is defined as having at least two out of three risk criteria (fasting plasma glucose ≥6.1 mmol/L, HbA1c ≥4.7% (Swedish Mono-S standard) and BMI ≥27 in men and BMI ≥30 in women). With positive predictive values of 32% in men and 46% in women, this model performs at least as well as other published prediction models. Information on family history of diabetes does not improve the result and the cumbersome oral glucose tolerance test is not needed. Therefore this model should be feasible for use in routine care. A model of metabolic syndrome with five composite factors, based on 14 variables including markers produced by adipose tissue and b-cells, suggest that obesity with insulin resistance and b-cell decompensation are the core perturbations in the early stages of type 2 diabetes, while inflammation and dyslipidemia could not be shown to be independent early risk indicators. The composite factors do not improve the prediction as compared to the single markers of fasting glucose, BMI and proinsulin and, possibly blood pressure values. Stress (measured as passive or tense working conditions) and weak social support (measured as emotional support), are suggested to be strong risk indicators along with high BMI for type 2 diabetes in women. In men BMI is predictive, but the stress variables are not shown to be associated with future type 2 diabetes. A social gap is indicated by double risk of metabolic syndrome among subjects with low (≤ 9 years at school) compared to high education (≥ 13 years). High consumption of Swedish smokeless tobacco, snuff (>4 cans/week), is independently associated with metabolic syndrome, obesity and hypertriglyceridemia, but not with dysregulation of glucose. To conclude, single markers, that are commonly used in daily practice, are useful and sufficient for identification of subjects that are in the early stages of type 2 diabetes. Obesity with insulin resistance and b-cell decompensation are the core perturbations in early development to T2DM. Lifestyle, socioeconomic and psychosocial markers, in addition to biomarkers, are important determinants of future type 2 diabetes and metabolic syndrome, albeit not similarly among men and women.