- Diagnosis and Classification of Diabetes
- Initial Assessment and Criteria for Specialist Referral
- Glycaemic Control in Type 2 Diabetes - Oral Hypoglycaemic Agents
- Indications for Insulin in Type 2 Diabetes
- Hypertension
- Dyslipidaemia
- Aspirin Therapy in Diabetes
- Retinopathy
- Nephropathy
- Neuropathy and Foot Ulcers
- Sexual Dysfunction in Men
- Diabetes in Pregnancy and Pre-conception Guidance
5. Hypertension
- Please also refer to NICE Guideline H: Management of Type 2 Diabetes - management of blood pressure and blood lipids
Hypertension is a common problem in diabetic patients. Among those with type 1 diabetes, the incidence of hypertension rises from 5 percent at 10 years, to 33 percent at 20 years, and 70 percent at 40 years. There is a close relationship between hypertension and diabetic renal disease in these patients; the former is relatively rare in the absence of the latter. The blood pressure typically begins to rise within the normal range about three years after the onset of microalbuminuria. Ultimately, the incidence of hypertension is approximately 15 to 25 percent in all patients with microalbuminuria and 75 to 85 percent in those with overt diabetic nephropathy. The risk of hypertension is highest in blacks, who are also at much greater risk for renal failure due to diabetic nephropathy.
The findings are somewhat different in type 2 diabetic patients. In UKPDS, 39% of newly diagnosed patients were already hypertensive. In approximately 50% of these patients, the elevation in blood pressure (BP) occurred before the onset of microalbuminuria. Hypertension was strongly associated with obesity and, not surprisingly, the hypertensive patients were at increased risk for cardiovascular morbidity and mortality. It is also clearly associated with an increased risk of microvascular complications.
Treatment – Early treatment of hypertension is particularly important in diabetic patients both to prevent cardiovascular disease and to minimise progression of renal disease and diabetic retinopathy. Among type 2 diabetics, the benefits of tight blood pressure control may be as great or greater than the benefit of strict glycaemic control.
Initial therapy should include non-pharmacological methods, such as weight reduction, exercise, sodium restriction, and avoidance of smoking and excess alcohol ingestion. However, all diabetics with blood pressures above 140/80 mmHg are considered to be at such high risk of cardiovascular complications that they should also be immediately begun on antihypertensive drug therapy.
Prior observations concerning adverse effects of various antihypertensive drugs are now understood to be due in part to the administration of inappropriately high doses of diuretics and non-cardioselective beta-blockers.
Intensive drug therapy is unequivocally protective. All diabetics should therefore have their blood pressure lowered to below 140/80 mmHg.
Angiotensin converting enzyme inhibitors – When antihypertensive drugs are used, angiotensin converting enzyme (ACE) inhibitors offer a number of advantages:
• they lower the blood pressure, although they may not be sufficient as monotherapy.
• they have no specific toxicity, except for cough and raising the plasma potassium concentration in patients with underlying hyperkalemia or renal insufficiency.
• they have no adverse effects on lipid metabolism.
• they may lower the plasma glucose concentration by increasing responsiveness to insulin.
• They protect against the development of progressive nephropathy due to type 1 diabetes, at least in part by lowering intraglomerular pressure. Although blood pressure control is also important in type 2 diabetes, there is at present only limited evidence that ACE inhibitors have the same preferential renoprotective effect in this disorder.
• ACE inhibitors may slow the progression of retinopathy and neuropathy.
• they appear to lower the incidence of adverse cardiovascular outcomes among diabetics at increased risk for cardiovascular disease (the Heart Outcomes Prevention Evaluation (HOPE) trial). Ramipril therapy significantly lowered the incidence of myocardial infarction, stroke, and total mortality by 22, 33, and 24%, respectively. This benefit remained after adjustments for the small decrease in blood pressure (2mmHg) observed with active therapy and it was felt that the large improvement in outcomes was most likely attributable to favourable vascular effects of ACE inhibition. It is not known if this benefit from ACE inhibition is seen in diabetics who are not at high risk for adverse cardiovascular outcomes. Data from the UKPDS found that Atenolol was as effective as Captopril in terms of both blood pressure lowering and protection against microvascular disease among patients with type 2 diabetes who were not selected for being at increased risk for cardiovascular disease. However, the mean fall in blood pressure was 10/5 mmHg in the UKPDS. It is therefore possible that a unique benefit of ACE inhibition might be lost when there is also a substantial fall in blood pressure. Another possible explanation is that beta-blockers as well as ACE inhibitors have a benefit in diabetics beyond that due to blood pressure reduction.
Angiotensin II-receptor blockers – The impressive benefits of ACE inhibitors in slowing progression of diabetic nephropathy is most clearly shown in patients with type 1 diabetes. There has been much less information on the effect of antihypertensive therapy with ACE inhibitors with type 2 diabetes. More data are currently available on the efficacy of angiotensin receptor blockers (ARBs) in this setting. As examples, two major trials, the Irbesartan Diabetic Nephropathy trial and the RENAAL trial, demonstrated a clear benefit in terms of renoprotection with ARBs in patients with nephropathy due to type 2 disease.
Although both studies found that patients administered ARB had significant reductions in the development of and subsequent hospitalisation for heart failure, neither study showed any significant cardiovascular mortality reduction with these agents. This is in contrast to Ramipril in the HOPE trial.
A separate issue is whether an ARB can be given with an ACE inhibitor and there is some evidence to suggest that this combination may be effective.
Diuretics – Dietary salt restriction and diuretics are likely to be effective in hypertensive diabetic patients. Furthermore, mild fluid contraction increases the antihypertensive effect of an ACE inhibitor, since the hypovolaemia-induced rise in renin and angiotensin II production that normally limits the diuretic response is diminished. ACE inhibitors also may minimise or prevent some of the metabolic complications associated with diuretic therapy, such as hypokalemia (by lowering angiotensin II-induced aldosterone release), hyperlipidaemia (via an unknown mechanism), and hyperuricaemia (perhaps by decreasing proximal sodium and urate reabsorption).
Metabolic complications have been a concern with high doses of diuretics in diabetic patients, however, it is likely that these problems are avoided with low-dose therapy, such as 2.5mg Bendroflurazide or 1.5mg Indapamide MR daily.
Calcium channel blockers – Somewhat similar considerations (efficacy and lack of adverse effects of lipid or carbohydrate metabolism) apply to the nondihydropyridine calcium channel blockers (Diltiazem and Verapamil), although their long-term effect on diabetic nephropathy remains to be determined. Amlodipine (5-10mg daily) and Nifedipine LA (30-60mg daily) are also suitable alternatives.
Alpha-adrenergic antagonists – Although not widely used as primary therapy in diabetes because of side effects such as orthostatic hypotension, peripheral alpha-adrenergic antagonists (such as doxazosin) are as effective in lowering blood pressure as ACE inhibitors and calcium channel blockers and have a more favourable metabolic profile.
Beta-blockers – Although there are concerns about masking of hypoglycaemic symptoms and possible exacerbation of peripheral vascular disease, beta-blockers are effective therapy for hypertension in diabetics. In the UKPDS study of patients with type 2 diabetes, Atenolol was as effective as Captopril in terms of both blood pressure lowering and protection against microvascular disease. It is unclear whether beta-blocker therapy has an adverse effect on glucose metabolism in diabetic hypertensives but it is probably advisable to not combine with a thiazide diuretic.
Goal of blood pressure reduction – A separate issue is the blood pressure goal, since a lower than usual pressure may be required to protect maximally against cardiovascular disease and progressive diabetic nephropathy. The results of the HOT trial described above suggest that a lower target diastolic pressure has a cardioprotective effect in diabetics and that 80 rather than 85 mmHg might be the preferred goal in these patients. The attainment of a blood pressure of below 130/85 mmHg appears to be even more cost-effective. A later report from the UKPDS evaluated the risk of complications according to the systolic blood pressure. Each 10mmHg reduction in systolic pressure was associated with a 12% risk reduction (P<0.001); the lowest risk occurred at a systolic pressure below 120mmHg. Similar benefits were noted for individual complications such as death related to diabetes, myocardial infarction, and microvascular complications. The goal blood pressure to protect against cardiovascular disease in patients with diabetes should be below 130/85mmHg. Blood pressure reduction should be gradual and, if attainable, systolic pressures of 120mmHg may provide the greatest protection
Recommendations – The optimal initial antihypertensive agent for hypertensive diabetic patients among type 1 diabetes is usually an ACE inhibitor because of its lack of metabolic complications, its renal-sparing effect, and, at least in Caucasians, the net mortality benefit demonstrated in the HOPE trial. The best choice for the treatment of hypertension in those with type 2 diabetes is less certain.
For patients without nephropathy, an ACE inhibitor is the perhaps the optimal first choice. However, in terms of renoprotection among those with renal disease, the benefit of an ARB is clear as shown in the Irbesartan Diabetic Nephropathy and RENAAL trials; by comparison, only small studies have evaluated an ACE inhibitor. However, an ARB is not necessarily the best choice among hypertensive patients with diabetic nephropathy due to type 2 disease.
When an ACE inhibitor or ARB does not produce the desired level of blood pressure control, addition of a low-dose of a long-acting diuretic or perhaps combination therapy with an ACE inhibitor and an ARB. If the patient does not tolerate an ACE inhibitor (usually due to cough), an ARB should be substituted. One of the first-line anti-hypertensive drugs that were not used can be added if the blood pressure goal is still not achieved.
These drugs, usually in combination, normalise the blood pressure in over 80 percent of patients with diabetes and hypertension. A higher thiazide dose or a loop diuretic is likely to be necessary in patients with renal or cardiac disease. Prevention of volume expansion can be an important component of blood pressure control in these patients.
An alternative (and cheaper) strategy, supported by UKPDS, is treating hypertension with alternative first-line agents such as thiazide diuretics, beta-blockers and calcium channel blockers. In any event, multiple agents will probably be required to achieve targets.