Early-onset type 2 diabetes in obese white subjects is characterised by a marked defect in beta cell insulin secretion, severe insulin resistance and a lack of response to aerobic exercise training

Abstract

Aims/hypothesis Early-onset type 2 diabetes is associated with marked visceral obesity and extreme insulin resistance, but its pathogenesis and response to treatment are not completely understood. We studied physical fitness, wholebody and hepatic glucose turnover, and insulin secretion in young obese Irish subjects before and after 3 months of aerobic exercise training. We hypothesised that exercise alone, with stable diet, should improve insulin sensitivity. Materials and methods Anthropometric parameters and maximum volume of oxygen utilisation (VO 2max ) were measured in 13 subjects with type 2 diabetes and 18 nondiabetic control subjects, matched for age and BMI. Insulin sensitivity and hepatic glucose turnover were measured using the hyperinsulinaemic-euglycaemic clamp. Insulin secretion was assessed from an OGTT and a modified intravenous glucose tolerance test. Some subjects (seven type 2 diabetic, 14 non-diabetic control subjects) then completed a 12-week supervised aerobic exercise programme. All measurements were repeated on completion of the exercise programme. Results Type 2 diabetic subjects had higher WHR, systolic blood pressure and triacylglycerols than non-diabetic control subjects. They were significantly more insulinresistant as measured both by the clamp and oral glucose insulin sensitivity. They also displayed marked defects in insulin secretion in response to oral and intravenous glucose challenges. Exercise intervention had no significant effect on whole-body or hepatic insulin sensitivity or insulin secretion. VO 2max increased significantly in the non-diabetic control subjects, but not in the type 2 diabetic subjects after exercise training. Conclusions/interpretation Young obese subjects with type 2 diabetes are severely insulin-resistant with marked loss of beta cell function compared with control subjects matched for age and obesity. Neither group responded metabolically to aerobic exercise intervention.

Ageing brain abnormalities in young obese patients with type 2 diabetes: a cause for concern

“…These patients have a phenotype very similar to those reported above in previous studies [1][2][3][4][5]. All participants underwent a series of neuropsychological tests and brain magnetic resonance imaging studies.…”

“…Young patients with type 2 diabetes have been shown to have higher rates of hypertension and microalbuminuria than age-matched peers who have type 1 diabetes, despite better metabolic control and a shorter duration of diabetes [3]. We and others have shown that young obese patients with this phenotype are severely insulin resistant (even when compared with equally obese non-diabetic peers of similar age) and have a characteristic dyslipidaemia, with low HDL-cholesterol and elevated fasting triacylglycerol [2,4]. It has recently been shown that young type 2 diabetic patients also have blunted or absent metabolic and fitness responses to aerobic exercise training, associated with abnormalities in key muscle mitochondrial regulatory responses to exercise [4,5].…”

“…We and others have shown that young obese patients with this phenotype are severely insulin resistant (even when compared with equally obese non-diabetic peers of similar age) and have a characteristic dyslipidaemia, with low HDL-cholesterol and elevated fasting triacylglycerol [2,4]. It has recently been shown that young type 2 diabetic patients also have blunted or absent metabolic and fitness responses to aerobic exercise training, associated with abnormalities in key muscle mitochondrial regulatory responses to exercise [4,5]. Given the early onset of diabetes in these young individuals, the marked distinctions between their phenotype and that of typical type 1 diabetes and the potentially long subsequent duration of disease, the most important clinical question, unanswered up to now, has been whether this early onset form of type 2 diabetes will lead to more serious end-organ complications.…”

Non-pharmacological interventions to reduce the risk of diabetes in people with impaired glucose regulation: a systematic review and economic evaluation.

“…These findings were based on post hoc analyses from the intervention arm. Burns et al (2007) 363 examined the effects of a 3-month aerobic exercise training programme in young obese insulin-resistant subjects with and without T2DM. They recruited 13 subjects with T2DM and 18 non-diabetic control subjects for the baseline study.…”

Hypermethylation of hepatic Gck promoter in ageing rats contributes to diabetogenic potential

“…Insulin resistance is a major contributor to development of the disease and to its complications [6][7][8].…”