Metabolic markers associated with insulin resistance predict type 2 diabetes in Koreans with normal blood pressure or prehypertension

Background: Questions remain as to the association between essential hypertension and increased incidence of type 2 diabetes (T2DM). The premise of this analysis is that insulin resistance/compensatory hyperinsulinemia is a major predictor of T2DM, and the greater the prevalence of insulin resistance within any population, normotensive or hypertensive, the more likely T2DM will develop. The hypothesis to be tested is that surrogate estimates of insulin resistance will predict incident T2DM to a significant degree in persons with normal blood pressure or prehypertension. Methods: Analysis of data from a population-based survey of 10, 038 inhabitants of rural and urban areas of Korea, >= 40 years-old, initiated in 2001, with measures of demographic and metabolic characteristics at baseline and 8-years later. Participants were classified as having normal blood pressure or prehypertension, and three simple manifestations of insulin resistance related to the pathophysiology of T2DM used to predict incident T2DM: (1) glycemia (plasma glucose concentration 2-hour after 75 g oral glucose challenge = 2-hour PG); (2) hyperinsulinemia (plasma insulin concentration 2-hour after 75 g oral glucose challenge = 2-hour PI); and (3) dyslipidemia (ratio of fasting plasma triglyceride/high/density lipoprotein cholesterol concentration = TG/HDL-C ratio). Results: Fully adjusted hazard ratios (HR, 95 % CI) for incident T2DM were highest (P < 0.001) in the quartile of individuals with the highest 2-hour PG concentrations, ranging from 5.84 (3.37-10.1) in women with prehypertension to 12.2 (7.12-21.00) in men with normal blood pressure. T2DM also developed to a significantly greater degree in subjects within the highest quartile of TG/HDL-C ratios, with HRs varying from 2.91 (1.63-2.58) in women with prehypertension (P < 0.001) to 1.77 (1.12-2.81, P < 0.05) in men with prehypertension. The least predictive index of insulin resistance was the 2-hour PI concentration. Subjects with normal blood pressure in the highest quartile of 2-hour PI concentrations were significantly associated with incident T2DM, with HRs of 1.5 (1.02-2.20, P = 0.25) and 2.02 (1.35-3.02, P < 0.001), in men and women, respectively. Finally, incidence of T2DM in the highest quartile was somewhat greater in patients with prehypertension, irrespective of predictor. Conclusions: Metabolic variables associated with insulin resistance (glycemia, insulinemia, and dyslipidemia) predict the development of T2DM in patients with either normal blood pressure or prehypertension.