Patients with type 2 diabetes frequently also have elevated blood pressure and are therefore at even greater risk of cardiovascular complications. Epidemiological studies indicate an increased risk for the development of type 2 diabetes in patients with hypertension. However, this correlation has not been fully confirmed. Now, a meta-analysis including evaluation of the patients' individual raw data should shed more light on this question.
For most people affected, type 2 diabetes is not the only health problem as obesity, hypertension, physical inactivity and lipometabolic disorders often coexist. Combined data obtained from cohort studies have shown that for every 20 mmHg increase in systolic blood pressure, the risk of type 2 diabetes increases by 77%. Yet, the causality of this correlation is unclear due to the many possible influential variables and the lack of randomized controlled trials. The same holds true for a possible preventive effect of individual antihypertensive drugs.
Given that these types of randomized trials are unlikely in the future simply for ethical reasons, Milad Nazarzadeh of the University of Oxford and the team of the Blood Pressure Lowering Treatment Trialists' Collaboration (BPLTTC) opted for a meta-analysis based on the raw patient data and subsequent Mendelian randomization.
The meta-analysis included 19 studies dating from 1973 to 2008 with a total of 145,939 participants examining the effect of blood pressure reduction on the incidence of type 2 diabetes. During the observation period of 4.5 years, a total of 9,883 new cases of type 2 diabetes were diagnosed. Successful blood pressure lowering had a clear positive effect: Lowering systolic blood pressure by 5 mmHg significantly reduced the risk of new onset type 2 diabetes by 11% (HR 0.89) across all studies.
The type of antihypertensive drugs used appeared to be important. Inhibitors of the renin-angiotensin-aldosterone system (RAAS) such as ACE inhibitors and angiotensin II receptor blockers (sartans) reduced the risk by 16% (HR 0.84). In contrast, beta blockers and thiazide diuretics tended to increase the risk of diabetes (HR 1.48 and 1.20, respectively). The effect of calcium antagonists on the risk of diabetes was neutral (HR 1.02).
Using Mendelian randomization, the risk of diabetes was compared among people with varying genetic risk for hypertension. Again, it was found that people with a genetic predisposition to hypertension were less likely to develop type 2 diabetes if they showed lower levels of blood pressure. In this case, a 5 mmHg lower blood pressure was associated with a 12% lower risk of type 2 diabetes (HR 0.88). What this suggests is that it is not only the specific effect of certain antihypertensive drugs that reduces the risk of diabetes, but also that inherently lower blood pressure levels also reduce the risk.
Lowering elevated blood pressure levels is evidently an important strategy in the prevention of type 2 diabetes. It remains unclear through which mechanisms ACE inhibitors and sartans reduce the risk of diabetes while lowering blood pressure by comparable rates. However, these drugs should be used preferentially to lower blood pressure especially in high-risk groups. This might include people on statin therapy, since statins have been shown to increase the risk of diabetes.
Sources: Milad Nazarzadeh et al; Blood pressure lowering and risk of new-onset type 2 diabetes: an individual participant data meta-analysis; Lancet (2021); 398 (10313): 1803-1810; DOI:https://doi.org/10.1016/S0140-6736(21)01920-6