Therapeutics
Present and future challenges in Type 2 diabetes
According to the International Diabetes Federation, more than 285 million people (6.4% of the world population) are currently estimated to suffer from diabetes, a figure which is expected to rise to 438 million (7.8%) by 2030. Moreover, the World Health Organisation calculates that nearly three million deaths worldwide are attributable to diabetes each year; by 2030, this figure is expected to double. Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of the cases of diabetes. These astonishing statistics help to illustrate the epidemic prevalence of T2DM, and the major need for effective diagnostic, intervention and disease management strategies.
P
rediabetes is presently defined as moderately elevated fasting blood glucose (FBG), and is estimated to affect 79 million adult Americans, or 35% of the adult population. This altered glucose metabolism state is associated with an increased risk of developing T2DM (Figure 1), although other parameters including excess adi- posity, inflammation and dyslipidemia are risk fac- tors associated with the development of insulin resistance, loss of pancreatic function, worsening of hyperglycemia and progression to diabetes1. Type 2 diabetics, but also prediabetics, are at increased risk for a wide range of debilitating dis- eases and diabetes is the leading cause of new cases of kidney failure and blindness and of non- traumatic lower limb amputation. Moreover, car- diovascular disease (CVD) is 2-4 times higher in diabetics2. An emerging lesser known, but poten- tially fatal complication of T2DM is the accumu- lation of fat in hepatocytes (steatosis), that leads
Drug Discovery World Summer 2011
to the chronic liver disorder Non-Alcoholic Fatty Liver Disease (NAFLD) and its more advanced form, Non-Alcoholic Steato-Hepatitis (NASH). NAFLD/NASH can progress to hepatitis, cirrho- sis, and even liver cancer, thus illustrating the importance of addressing these serious complica- tions of T2DM.
Despite beneficial effects of current glucose-low- ering treatments, disease-related morbidity and mortality remain considerable in T2DM patients, galvanising the search for innovative medications that target the multiple metabolic abnormalities as well as inflammatory processes and other path- ways predisposing to diabetes-associated disorders. One of the greatest challenges in T2DM disease management is the prevention of its long-term complications and the treatment of associated dis- orders, including NAFLD/NASH and CVD. Prospective studies in T2DM have shown an association between the degree of hyperglycemia
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By Dr Lesley J Millatt, Dr Rémy Hanf and Dr Dean W Hum
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