Use of antihypertensive agents and the incidence of Type 2 diabetes: a retrospective analysis
The effect of major antihypertensive medications on blood glucose and newonset diabetes was assessed using medical data from the Central Texas Veterans Health Care System (CTVHCS). Veterans were followed for an average of 3.6 years (total of 51,549 person-years) between 1995 and 2004. The average age of the participants (N=11,187) was 60.7 (SD: 12.7) years; the majority (78.7%) were =50 years of age, White (73.8%) males (95.3%). Commonly used antihypertensive therapies appeared to increase veterans’ blood glucose levels significantly more than what was observed in the control group; i.e., patients who were not treated with medications. The only exception was beta-blocker therapy, which showed similar effect to the control group. Presence of impaired glucose tolerance, higher BMI, “high risk” therapies, and dyslipidemia at baseline significantly increased the risk of developing diabetes. Non-thiazide ‘diuretics’ were associated with the highest risk as indicated by a hazard rate of 1.48 (95% CI: 1.21-1.80). Statistically significant, protective effect was found with ‘alpha-blocker’ therapy: 23 percent reduced risk to develop diabetes (95% CI:0.63-0.93). When ‘dual’ and ‘three or more therapies’ were included into the model, the effect of ‘alpha-blockers’ became non-significant (p=0.196); whereas ‘ACEI’ and ‘CCB’ therapies became significantly associated with an increased risk for diabetes (p-values: 0.003 and 0.008, respectively). The corresponding hazard rates were 1.29 (95% CI: 1.09-1.53) and 1.26 (95% CI: 1.06- 1.50), respectively. The simultaneous use of three or more antihypertensives appeared to be protective against the development of new-onset diabetes (hazard rate: 0.60; 95% CI: 0.43-0.83; p=0.002). This finding conflicts with the majority of previous studies and may have been the result of selection bias (also called “channeling”), in which patients with higher baseline ris k to develop diabetes were “channeled” towards ACEIs and CCBs and away from beta-blockers. Several animal and small clinical trials showed the beneficial effect of ACEIs on carbohydrate metabolism, so our findings might have been the result of confounding by uncontrolled risk factors, such as genetic predisposition for diabetes, lifestlyle habits, and other unmeasured biological differences.