Intervention of insulin resistance at two stages in the evolution of type 2 diabetes

ABSTRACT

The purpose of this study was to compare the impact of treating insulin resistance with a thiazolidinedione drug before versus at the onset of diabetes on as per diagnosed by glucose levels and funduscopy. The study was conducted in Medical OPD, BVH, BWP from January 2001 to January 2007. One hundred twenty six non-diabetic young women who were 18-30 year old, with a history of GDM in the prior 4 year and a total glucose level on a 75-g oral glucose tolerance test [oGTT] above the median for women with gestational diabetes mellitus [GDM]were randomized to troglitazone [early intervention], 400 mg/d, or placebo [later intervention]. Women who developed diabetes were placed on open-label troglitazone. Glucose tolerance, insulin resistance, and funduscopy were measured at randomization, at the diagnosis of diabetes, and 8 months post trial to determine the long-term impact of the two treatments strategies on glucose levels and eye. During a mean follow-up of 4.3 year between baseline and post-trial tests, glucose tolerance [oral glucose tolerance test, P<0.04] and insulin resistance [P< 0.02] worsened more in women randomized to late intervention [n= 69] than to early intervention [n = 57]. Among women in the late intervention group who developed diabetes, retinopathy and cataract deteriorated significantly during development of diabetes on placebo and then did not change significantly [P >0.50] during treatment with troglitazone and post-treatment washout. In high-risk women, amelioration of insulin resistance can stabilize glycemia at the time diabetes develops. These findings highlight the role of insulin resistance in the genesis of progressive evolution of type 2 diabetes and successful treatment of insulin resistance in young, nondiabetic women with recent GDM lowered endogenous insulin requirements and stabilized pancreatic-cell function, thereby preventing type 2 diabetes in later life