For the patient with diabetes mellitus (DM), blood pressure control is of paramount importance because the patient is at increased risk for cardiovascular disease and renal disease. Patients with existing comorbid conditions should be taken into account before beginning therapy. Usually a trial of diet and exercise is attempted, especially in Type 2 DM, but if the diabetes and blood pressure are still uncontrolled, pharmacologic options are available.
Angiotensin Converting Enzyme (ACE) Inhibitors
Angiotensin converting enzymes are usually first-line agents for patients with DM. These are antihypertensives that offer additional nephroprotective benefits. In addition to lowering blood pressure, they decrease the intraglomerular pressure and the membrane permeability to albumin. This is significant, as the decrease in blood pressure and the decrease in urine protein are shown to be independent of each other and show the ability to prevent progression to nephropathy. Creatinine levels must be monitored; a significant or continual increase in levels can point to problems such as volume depletion or renal artery stenosis that must be addressed.
Angiotensin Receptor Blockers (ARB)
Angiotensin receptor blockers blocks the angiotensin II receptor and offer comparable antihypertensive efficacy to ACE Inhibitors, albeit with fewer side effects such as angioedema and dry cough. Their nephroprotective effects are also similar to ACE Inhibitors. In a recent Candesartan and Lisinopril Microalbuminuria study, it was concluded that doses of ACE Inhibitors and ARB given at half maximal doses were superior in reducing proteinurea than any single agent alone.
Thiazide Diuretics
Thiazide diuretics are used as adjuncts to ACE Inhibitor/ARB therapy. Though they aren't the mainstays of diabetic therapy, they offer their own benefits. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study in 2002 concluded that thiazides reduced coronary artery disease (fatal and nonfatal) compared to both calcium channel blockers and ACE inhibitors, and that they provide very effective prevention of congestive heart failure. On the flip side, they tend to cause electrolyte abnormalities and unfavorable effects on carbohydrate and lipid metabolism--but these effects seem minimized with low-dose therapy.
Calcium Channel Blockers (CCB)
Calcium channel blockers block the calcium channels in the vasculature, causing dilation and subsequent lowering of blood pressure. These are also adjuncts to ACE inhibitor/ARB therapy as more often than not, a second drug is needed to control blood pressure in diabetics. Because thiazides and beta blockers tend to create unfavorable metabolic profiles and thus increase the incidence of Type 2 DM, many physicians tend to go with CCBs as their second line of defense.
Beta Blockers
Though it's been suggested that these drugs can increase new-onset DM incidence due to adverse effects on lipid and glucose profiles--along with worsening peripheral vascular disease symptoms--their effectiveness has been proven in respect to cardiac disease. Carvedilol (which has alpha blocking properties in addition to beta blocking) in particular has been shown to reduce microalbuminuria and cardiovascular disease without the lipid/glucose profile alterations of its predecessors. It also slows nephropathy progression and improves sensitivity to insulin, which make it useful to diabetics--especially those with cardiac comorbidities.
Alpha Antagonists
Although alpha antagonists are the only class of antihypertensives that lower LDL, raise HDL and improve insulin sensitivity all at once; the ALLHAT trial showed that they had the highest incidence of side effects. As such, they are not considered first-line therapy. They also have side effects (dizziness, weakness) that can decrease compliance, causing them to fall out of favor with many physicians.
Other Agents
Hydralazine has been noted to help those with heart failure and/or HTN who can't tolerate or have contraindications to the above agents. Clonidine has also been suggested for those with comorbid orthostatic hypotension, but the side effects can be considerably limiting (sexual dysfunction, CNS effects).
References
- Hypertension, 1st ed. Black 2006
- JAMA. "ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group: Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic" 2002; 288:2981-2997.
- New England Journal of Medicine. "Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients: The Heart Outcomes Prevention Evaluation Study Investigators" Yusuf S, Sleight P, Pogue J2000, 342; 145-153.
