Hypertension in patients with diabetes mellitus: goal and treatment

Hypertension is a common diabetes comorbidity that affects the majority of patients, with the prevalence depending on type of diabetes, age, obesity, and ethnicity.
Hypertension is a major risk factor for both cardiovascular disease and microvascular complications.
In type 1 diabetes, hypertension is often the result of underlying nephropathy, while in type 2 diabetes it usually coexists with other cardiometabolic risk factors.

People with diabetes mellitus and hypertension should be treated to a systolic blood pressure ( SBP ) goal of less than 140 mmHg [ A ].
Lower systolic targets, such as less than 130 mmHg, may be appropriate for certain individuals, such as younger patients, if they can be achieved without undue treatment burden [ C ].

Individuals with diabetes should be treated to a diastolic blood pressure ( DBP ) less than 90 mmHg [ A ].
Lower diastolic targets, such as less than 80 mmHg, may be appropriate for certain individuals, such as younger patients, if they can be achieved without undue treatment burden [ B ].


Patients with blood pressure more than 120/80 mmHg should be advised on lifestyle changes to reduce blood pressure [ B ].
Patients with confirmed office-based blood pressure higher than 140/90 mmHg should, in addition to lifestyle therapy, have prompt initiation and timely subsequent titration of pharmacological therapy to achieve blood pressure goals [ A ].

Lifestyle therapy for elevated blood pressure consists of weight loss, if overweight or obese; a Dietary Approaches to Stop Hypertension (DASH)-style dietary pattern including reducing sodium and increasing potassium intake; moderation of alcohol intake; and increased physical activity [ B ].

Pharmacological therapy for patients with diabetes mellitus and hypertension should comprise a regimen that includes either an ACE inhibitor or an angiotensin receptor blocker ( ARB ) [ B ]. If one class is not tolerated, the other should be substituted [ C ].
Multiple-drug therapy ( including a thiazide diuretic and ACE inhibitor / ARB, at maximal doses ) is generally required to achieve blood pressure targets [ B ].
If ACE inhibitors, ARBs, or diuretics are used, serum creatinine / estimated glomerular filtration rate ( eGFR ) and serum potassium levels should be monitored [ E ].

In pregnant patients with diabetes mellitus and chronic hypertension, blood pressure targets of 110–129 / 65–79 mmHg are suggested in the interest of optimizing long-term maternal health and minimizing impaired fetal growth. ACE inhibitors and ARBs are contraindicated during pregnancy [ E ].

Pharmacological interventions

Lowering of blood pressure with regimens based on a variety of antihypertensive agents, including ACE inhibitors, ARBs ( or sartans ), beta-blockers, diuretics, and calcium channel blockers, has been shown to be effective in reducing cardiovascular events.

Several studies have suggested that ACE inhibitors may be superior to dihydropyridine calcium channel blockers in reducing cardiovascular events.
However, several studies have also shown no specific advantage to ACE inhibitors as initial treatment of hypertension in the general hypertensive population, while showing an advantage of initial therapy with low-dose thiazide diuretics on cardiovascular outcomes.

In people with diabetes, inhibitors of the renin-angiotensin system ( RAS ) may have unique advantages for initial or early treatment of hypertension.

In a trial of individuals at high risk for cardiovascular disease, including a large subset with diabetes, an ACE inhibitor reduced cardiovascular outcomes.

In patients with congestive heart failure ( CHF ), including subgroups with diabetes, ARBs have been shown to reduce major cardiovascular outcomes.
In type 2 diabetic patients with significant diabetic kidney disease, ARBs were superior to calcium channel blockers for reducing heart failure.

Although evidence for distinct advantages of RAS inhibitors on cardiovascular outcomes in diabetes remains conflicting, the high cardiovascular risks associated with diabetes mellitus, and the high prevalence of undiagnosed cardiovascular disease, may still favor recommendations for their use as first-line hypertension therapy in people with diabetes mellitus.

The blood pressure arm of the ADVANCE trial demonstrated that routine administration of a fixed combination of the ACE inhibitor Perindopril and the diuretic Indapamide significantly reduced combined microvascular and macrovascular outcomes, as well as death from cardiovascular causes and total mortality.
The improved outcomes could also have been due to lower achieved blood pressure in the Perindopril-Indapamide arm.

Another trial showed a decrease in morbidity and mortality in those receiving Benazepril and Amlodipine versus Benazepril and Hydrochlorothiazide ( HCTZ ).

The compelling benefits of RAS inhibitors in diabetic patients with albuminuria or renal insufficiency provide additional rationale for these agents.
If needed to achieve blood pressure targets, Amlodipine, Hydrochlorothiazide, or Chlorthalidone can be added.
If eGFR is less than 30 mL/min/m2, a loop diuretic, rather than Hydrochlorothiazide or Chlorthalidone, should be prescribed.
Titration of and/or addition of further blood pressure medications should be made in timely fashion to overcome clinical inertia in achieving blood pressure targets.

Growing evidence suggests that there is an association between increase in sleep-time blood pressure and incidence of cardiovascular events.
A randomized controlled trial of 448 participants with type 2 diabetes and hypertension demonstrated reduced cardiovascular events and mortality with median follow-up of 5.4 years if at least one antihypertensive medication was given at bedtime. Consider administering one or more antihypertensive medications at bedtime.

An important caveat is that most patients with hypertension require multiple-drug therapy to reach treatment goals. Identifying and addressing barriers to medication adherence ( such as cost and side effects ) should routinely be done.
If blood pressure remains uncontrolled despite confirmed adherence to optimal doses of at least three antihypertensive agents of different classifications, one of which should be a diuretic, clinicians should consider an evaluation for secondary forms of hypertension.

Pregnancy and antihypertensive medications

In a pregnancy complicated by diabetes mellitus and chronic hypertension, target blood pressure goals of SBP 110–129 mmHg and DBP 65–79 mmHg are reasonable, as they contribute to improved long-term maternal health.
Lower blood pressure levels may be associated with impaired fetal growth.
During pregnancy, treatment with ACE inhibitors and ARBs is contraindicated, since they may cause fetal damage.
Antihypertensive drugs known to be effective and safe in pregnancy include Methyldopa, Labetalol, Diltiazem, Clonidine, and Prazosin.
Chronic diuretic use during pregnancy has been associated with restricted maternal plasma volume, which may reduce uteroplacental perfusion. ( Xagena )

Source: American Diabetes Association ( ADA ) – Diabetes Care, 2015



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