The metabolic and vascular effects of intentional weight loss in type 2 diabetes.
MD thesis, University of Glasgow.
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Obesity is increasing in prevalence, in both the developed and the developing worlds This is due to an increase in the availability of energy dense food and globally reduced levels of physical activity. Obesity would appear to be the driving force for increased prevalence of type 2 diabetes.
The processes that lead to the development of insulin resistance and ultimately type 2 diabetes may also play a significant role in the development of endothelial function. Biological changes leading to insulin resistance may also cause impairment of endothelium-mediated vasodilatation. This is thought to be one of the first manifestations of atherosclerotic cardiovascular disease (CVD), also a major burden on individuals and health services. Endothelial dysfunction has been shown to be a surrogate marker of underlying risk for atherosclerotic cardiovascular disease.
The effects of intentional weight loss on reducing the burden of cardiovascular disease remain unclear. Although it is recognised that intentional weight reduction can ameliorate insulin resistance, hypertension and abnormalities of lipoprotein metabolism, there is little evidence to suggest that weight loss reduces CVD-related morbidity. A number of studies have attempted to address this issue by assessing the effects of weight loss on endothelial function. However, few of these studies have included subjects with type 2 diabetes, and a number of them have included exercise interventions, which have been shown to have effects on vasculature over and above the effects of weight reduction.
Given the increased risk of cardiovascular morbidity and mortality associated with type 2 diabetes, and the need for further strategies addressing this issue, this study aimed to assess the effects of intentional weight loss using solely dietary manipulation in a cohort of subjects with type 2 diabetes.
Fifteen male and female subjects with type 2 diabetes were recruited from local diabetes clinics and advertisements in local press. A six-week period of dietary intervention in the form of a 1200kal/day liquid diet was prescribed, with subjects being closely monitored by a dietician during this period. Vascular and metabolic assessments were performed at baseline and following a one-week dietary washout period at the end of the intervention.
This dietary intervention led to significant reductions in body weight, waist and hip circumferences and body fat percentage, measured by three distinct methods. Change in body weight correlated with change in waist circumference, but there were no correlations between change in body composition or any of the other anthropometric measurements. The probable reason for this was the small numbers involved.
Weight reduction was associated with improvements in metabolic parameters. Significant reductions in fasting plasma glucose, glycated haemoglobin and whole body insulin sensitivity as measured by the isoglycaemic hyperinsulinaemic clamp technique were noted after the intervention. In addition, there were significant reductions in liver enzymes (surrogate markers of hepatic steatosis), and in serum total cholesterol concentrations. Changes in glycaemic control were closely correlated with changes in liver enzymes.
With the exception of serum intercellular adhesion molecule-1 (ICAM-1), there were no improvements in any of the measured concentrations of adipocytokines or inflammatory markers following weight reduction. Serum concentrations of ICAM-1 were significantly reduced as a result of the intervention, with no changes in C-reactive protein, interleukin-6 or adiponectin being observed. The possible reasons for these results are multifactorial.
Weight loss was associated with variable effects on vascular function. Three modalities were employed for the assessment of the vasculature; wire myography, laser Doppler inontophoresis and pulse wave analysis / velocity measurements. Significant reductions in endothelium-dependent vasodilatation as measured by both wire myography and laser Doppler iontophoresis were observed after weight reduction. In contrast, however, there was a significant improvement in pulse wave velocity measurements.
In summary, weight reduction in a cohort of subjects with type 2 diabetes led to significant improvements in metabolic parameters, little change in markers of inflammation and a deterioration in endothelium-dependent vasodilatation.
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