title: Interrupting the natural history of diabetes mellitus: lifestyle, pharmacological and surgical strategies targeting disease progression.
abstract: 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.
authors.forename: Kaivan
authors.initials: K
authors.lastname: Khavandi
authors.forename: Jack
authors.initials: J
authors.lastname: Brownrigg
authors.forename: Mohammed
authors.initials: M
authors.lastname: Hankir
authors.forename: Harpreet
authors.initials: H
authors.lastname: Sood
authors.forename: Naveed
authors.initials: N
authors.lastname: Younis
authors.forename: Joy
authors.initials: J
authors.lastname: Worth
authors.forename: Adam
authors.initials: A
authors.lastname: Greenstein
authors.forename: Handrean
authors.initials: H
authors.lastname: Soran
authors.forename: Anthony
authors.initials: A
authors.lastname: Wierzbicki
authors.affiliation: King's College London BHF Centre, The Rayne Institute, St. Thomas Hospital, Westminster Bridge Road, London SE1 7EH, UK. Kaivan@doctors.org.uk.
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldsmith
mesh_terms: D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D050110:Bariatric Surgery; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004038:Diet, Reducing; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D008019:Life Style; D024821:Metabolic Syndrome / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D009765:Obesity / Q000150:complications* / Q000188:drug therapy / Q000601:surgery; D016896:Treatment Outcome
chemical_list: D019440:Anti-Obesity Agents; D007004:Hypoglycemic Agents