Lifestyle and glycaemic control before and after the onset of type 2 diabetes
Type 2 diabetes (T2D) is a complex disease with widespread physiological insults to the regulation of metabolic homeostasis, above all glycaemic regulation. The pathogenesis of T2D and its progression is broadly understood to be through a gradual decrease in peripheral insulin sensitivity, a compens...
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| Format: | Doctoral or Postdoctoral Thesis |
| Language: | English |
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Lund University: Faculty of Medicine
2016
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| Online Access: | https://lup.lub.lu.se/record/016d0ab4-a8e4-44bf-a573-d5b4078e568d https://portal.research.lu.se/files/16394567/Robert_Koivula_PhD_Thesis_kappa_only.pdf |
| Summary: | Type 2 diabetes (T2D) is a complex disease with widespread physiological insults to the regulation of metabolic homeostasis, above all glycaemic regulation. The pathogenesis of T2D and its progression is broadly understood to be through a gradual decrease in peripheral insulin sensitivity, a compensatory rise in insulin secretion, and a gradual decline in beta-cell function, resulting in glycaemic dysregulation and eventual T2D. Unhealthful lifestyle factors such as low physical activity (PA), energy dense diets with poor nutritional value, and chronic positive calorie balance are associated with an accelerated decline in glycaemic control and obesity. Single nucleotide polymorphisms (SNPs) discovered in genome wide association studies (GWAS) have demonstrated a genetic susceptibility to T2D (65 SNPs), fasting glucose (36 SNPs), 2-hr glucose (9 SNPs), and obesity (97 SNPs). In Paper 1, in 3,444 adults in northern Sweden, we compared the predictive ability of lifestyle factors and the aforementioned SNPs with T2D and obesity for incidence of T2D, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and obesity over ~10 years. We found that lifestyle and genetic factors had broadly the same predictive ability (by ROC AUC) for incidence in T2D (75% vs. 74%), IFG (63% vs. 66%), IGT (64% vs. 61%) and obesity (68% vs. 73%). With exception of IGT, adding genetic factors to lifestyle models improved predictive ability with resulting continuous net reclassification improvements of 58%, 36% and, 64% for T2D, IFG and obesity, respectively. In paper 2 and 3, we overview the rationale, design and baseline results from two new prospective cohort studies within the DIRECT (Diabetes Research into Patient Stratification) Consortium. These cohort studies aim to improve prevention and treatment of T2D by discovering new biomarkers for glycaemic deterioration before (Cohort 1, N =2,335) and after the onset of T2D (Cohort 2, N =830). The cohorts are comprehensively assessed at follow-up visits at 18, 36 (Cohort 2) and 48 ... |
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