Oral Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Early Management of insulin resistance in Type 2 Diabetes (#85)

Donald J Chisholm 1
  1. Garvan Institute, Sydney, NSW, Australia

Insulin resistance [IR] occurs long before onset of hyperglycaemia in type 2 diabetes [T2D] and remains relatively stable through its course, whereas decline in B cell function occurs later and is progressive.

Early treatment of IR, perhaps even in prediabetes, is supported for a number of reasons. First, because of reduced disease progression [eg metformin in DPP and rosiglitazone in DREAM] probably in part by “taking the heat off” the B cell and slowing its decline. Second, IR is associated with adverse cardiovascular [CV] risk markers and outcomes so treatment of IR could improve CV outcomes. However, supportive evidence for this is limited, eg CV benefit of metformin in UKPDS, and it remains unclear to what extent adverse outcomes associated with IR are related to IR itself or to its causative factors, particularly central adiposity. We are learning more about molecular/metabolic  consequences of IR and its pathway “selectivity” ; ie while glucoregulatory responses are “resistant” other pathways including lipogenesis and MAP Kinase activation appear unimpaired and therefore hyperstimulated by prevailing hyperinsulinaemia. Further study of the consequences of these responses may strengthen the case for aggressive treatment of IR.

If one accepts the need for early treatment, how is this best achieved? Reduced energy intake in the overweight/obese is paramount, if necessary using bariatric surgery in “resistant obese”. Frequent physical activity is beneficial [the effects of exercise  on IR are immediate but short-lasting]. After that metformin is first line therapy and possibly should be used in prediabetes. TZDs are highly effective over the long term , in part by raising adiponectin levels, but fluid retention, weight gain and bone loss mitigate against early use. Evidence for the role of inflammation in IR has led to trials of anti-inflammatory agents, particularly high-dose salicylate, with  clear glycaemic benefit but elevation of insulin levels has been more impressive than improved IR.