AUTONOMIC DYSFUNCTION, OBESITY AND PUBERTY IN TYPE 1 DIABETES

Abstract

Autonomic dysfunction can occur after a short diabetes duration, and in adolescents with type 1 diabetes. Whilst autonomic neuropathy is known to be a major risk factor for morbidity and mortality in adults with diabetes, subclinical autonomic neuropathy remains poorly understood and often neglected in the complications assessment of adolescents with type 1 diabetes. This thesis focuses on factors contributing to cardiac autonomic dysfunction in adolescents with type 1 diabetes and their role in the early phase of pathogenesis of the chronic diabetes complications. In particular, the contributions of glycaemia and non-glycaemic factors of adiposity and puberty are explored in the following papers included in this thesis. In Paper 1, skin autofluorescence, a non-invasive measure of accumulated advanced glycation end-products (AGEs) implicated in diabetic vascular pathobiology, was significantly associated with the presence of retinopathy and cardiac autonomic neuropathy, independent of concurrent HbA1c levels. Moreover, skin autofluorescence was associated with long term average HbA1c for up to 10 years in adolescents with type 1 diabetes; potentially providing a clinical measure of metabolic memory of longer term glycaemic control. In Paper 2, cardiac autonomic dysfunction was associated with worse glycaemic control and markers of insulin resistance in adolescent girls with type 1 diabetes. Paper 3 found higher body mass index (BMI) and central adiposity to be independent predictors for cardiac autonomic dysfunction in a four year longitudinal study of adolescents with type 1 diabetes. Paper 4 demonstrated in a multicentre international cohort stratified for their risk of diabetic nephropathy, adolescents with high risk urinary albumin:creatinine phenotype already had evidence of a worse cardiac autonomic profile; independent of age and HbA1c levels. Paper 5 is a review of the factors during puberty which may modify the risk of diabetes complications. Interventions targeting early autonomic dysfunction in type 1 diabetes, particularly during the critical pubertal years, may potentially reduce the risk of future complications in later life.