In recent decades we have seen a surge in the incidence of diabetes in industrialized nations; a threat which has
now extended to the developing world. Type 2 diabetes is associated with significant microvascular and macrovascular
disease, with considerable impact on morbidity and mortality. Recent evidence has cast uncertainty on the benefits of very
tight glycaemic goals in these individuals. The natural history of disease follows an insidious course from disordered glucose
metabolism in a pre-diabetic state, often with metabolic syndrome and obesity, before proceeding to diabetes mellitus.
In the research setting, lifestyle, pharmacological and surgical intervention targeted against obesity and glycaemia has
shown that metabolic disturbances can be halted and indeed regressed if introduced at an early stage of disease. In addition
to traditional anti-diabetic medications such as the glinides, sulphonylureas and the glitazones, novel therapies manipulating
the endocannabinoid system, neurotransmitters, intestinal absorption and gut hormones have shown dual benefit
in weight loss and glycaemic control normalisation. Whilst these treatments will not and should not replace lifestyle
change, they will act as invaluable adjuncts for weight loss and aid in normalising the metabolic profile of individuals at
risk of diabetes. Utilizing novel therapies to prevent diabetes should be the focus of future research, with the aim of preventing
the challenging microvascular and macrovascular complications, and ultimately cardiovascular death.
Keywords: Diabetes, obesity, cardiometabolic, cardiovascular disease, metabolic syndrome, weight loss, renin-angiotensinaldosterone
system, preventive medicine, vascular disease.
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