Insulin resistance and cardiovascular risk factors in obese children and adolescents

Abstract

Obesity in children and adolescents is an increasingly prevalent health problem. This heralds the potential risks of impaired glucose homeostasis, features of the insulin resistance syndrome and premature-onset cardiovascular disease. Valid and simple methods to measure insulin sensitivity are hence important. An imperative consideration is whether evidence of adverse cardiovascular effects such as increased arterial stiffness is already present in this at-risk group. Obesity-related comorbidities may be linked to adverse cardiovascular effects by common mechanisms such as oxidative stress. Interventions that are effective, feasible and sustainable for individuals, families and communities are critical. Outcomes measures of such interventions should include parameters such as insulin sensitivity and other cardiovascular risk markers, in addition to adiposity. A detailed review of the literature relating to these issues is described in Chapter 1.Hence the aims of this thesis were:- 1. To describe the glycaemic status and associated co-morbidities of a cohort of obese children and adolescents referred to a paediatric endocrinology clinic in a tertiary referral hospital. 2. To assess the validity of indices of insulin sensitivity and secretion derived from fasting glucose and insulin using the Modified (insulin) Minimal Model as a criterion measure in a cohort of obese children and adolescents (prepubertal and pubertal). 3. To assess A. in obese adolescents compared with normal weight control subjects, i. Insulin sensitivity ii. Blood pressure iii. Lipids iv. Free fatty acidsv. Inflammatory cytokines (C-reactive protein interleukin-6, tumour necrosis factor-a) vi. Adipocytokines (leptin, adiponectin)nvii. Fibrinolytic parameters (Plasminogen activator inhibitor antigen and activity, tissue-type plasminogen activator antigen and activity, fibrinogen, D-dimer) viii. Ghrelin ix. Liver function tests x. Oxidative stress and antioxidant systems xi. Arterial stiffness assessed by pulse wave analysis and pulse wave velocity B. the relationship between insulin resistance and other cardiovascular risk factors. C urinary albumin and protein excretion in obese adolescents. 4. To assess the feasibility of a 10-week, home-based, moderateintensity physical activity program and the effect on insulin sensitivity and other components of the insulin resistance syndrome, including blood pressure, lipids and fibrinolytic parameters. The materials and methods relevant to the studies in this thesis are outlined in Chapter 2. n n n