10/07/2009 — Glucose, Insulin, and Incident Hypertension in the Multi-Ethnic Study of Atherosclerosis

Greg Levin

Diabetes mellitus and hypertension commonly coexist, but the nature of this link is not well understood. We examined whether diabetes and higher concentrations of fasting serum glucose and insulin were associated with increased risk of developing incident hypertension in the community-based Multi-Ethnic Study of Atherosclerosis. In addition, we explored whether these associations may be mediated by kidney disease and diminished arterial elasticity. Of 3,513 participants free of hypertension at baseline, 965 (27%) developed incident hypertension over 4.7 years median follow-up. Compared to participants with baseline fasting glucose < 100 mg/dL, relative risk of hypertension was 1.16 [95% CI: 0.96, 1.40] among participants with glucose 100-125 mg/dL and 1.41 [1.17, 1.71] among participants with diabetes, adjusting for age, gender, race/ethnicity, education, physical activity, smoking, alcohol use, body mass index, and waist circumference (p=0.0015). Higher concentrations of fasting glucose and insulin within their normal ranges were also associated with increased risk of incident hypertension.  Further adjustment for serum cystatin C, urine albumin-creatinine ratio, and arterial elasticity measured by tonometry attenuated the magnitudes of these associations by approximately 50%. In conclusion, diabetes and higher concentrations of glucose and insulin were associated with increased risks of developing hypertension. The results also suggest that these associations may be mediated by damage to the kidney and arterial wall, but this hypothesis should be studied further.

In the process of carrying out this study, we encountered several challenging statistical and epidemiological questions. These included discussions about the merits of baseline adjustment in analyses of change (in the presence of measurement error), the choice of regression model in the setting of longitudinal measurements and a dichotomous outcome, and the difficulty in attempting to identify mechanisms in a causal pathway (diagnosing mediation).