Intensive Insulin Therapy in Type 1 Diabetes Lowers Long-Term Risk for Hypertension 

Hyperglycemia is a risk factor for incident hypertension in type 1 diabetes, and intensive insulin therapy reduces the long-term risk for the development of hypertension.

"Diabetes and hypertension are closely linked, but the long-term blood pressure effects of glucose-lowering therapy and hyperglycemia are not clear," write Ian H. de Boer, MD, MS, and colleagues from the Diabetes Control and Complications Trial (DCCT)/(EDIC) Study Research Group. "We examined the effects of intensive insulin therapy and hyperglycemia on the development of hypertension in the…DCCT and its observational follow-up, the…EDIC study."

Incident hypertension was defined as a systolic blood pressure of at least 140 mm Hg or higher on 2 consecutive study visits with a diastolic blood pressure of at least 90 mm Hg, or use of antihypertensive medications for the treatment of high blood pressure.

Enrollment took place from August 23, 1983, through June 30, 1989, and hypertension developed in 630 of 1441 participants during a 15.8-year median follow-up. Although the incidence of hypertension was similar with intensive therapy vs conventional therapy during the DCCT, the risk for incident hypertension was reduced by 24% during the EDIC study follow-up in the group receiving intensive therapy during the DCCT.

A higher hemoglobin A1c level, either at baseline or during follow-up, was linked to an increased risk for incident hypertension, respectively, for each 1% higher hemoglobin A1c level). Glycemic control appeared to underlie the antihypertensive effects of intensive therapy. Independent predictors of the increased risk for hypertension were older age, male sex, a family history of hypertension, higher body mass index at baseline, weight gain, and higher rate of albumin excretion.

Limitations of this study include analyses assessing blood pressure as a continuous outcome, which may be biased toward the null by not accounting for use of antihypertensive medications; treatment assignment not blinded; and study population consisting of predominantly white clinical trial participants with type 1 diabetes, limiting generalizability.

"Hyperglycemia is a risk factor for incident hypertension in type 1 diabetes, and intensive insulin therapy reduces the long-term risk of developing hypertension," the study authors write.

Diabetes and hypertension are common comorbid conditions, and diabetes may promote elevated blood pressure through multiple mechanisms. Higher serum concentrations of advanced glycated end products, reactive oxygen species, and sorbitol in patients with diabetes promote vasoconstriction and extracellular matrix deposition. The vascular remodeling progress associated with diabetes may take years to promote elevated blood pressure levels. However, hyperinsulinemia can promote acute increases in blood pressure through increased renal sodium reabsorption, sympathetic nervous system activity, and activation of the renin-angiotensin-aldosterone system.

The DCCT compared intensive glycemic control vs standard therapy in patients with type 1 diabetes mellitus, and the EDIC study followed up on these patients after the termination of the randomized treatment period. The current study examines the incidence of hypertension during the DCCT and EDIC study.
Practice Pearls:

• In patients with diabetes, higher serum concentrations of advanced glycated end products and sorbitol, along with effects of hyperinsulinemia on renal sodium reabsorption and sympathetic nervous system activity, can promote hypertension. The vascular remodeling progress associated with diabetes may take years to promote elevated blood pressure levels.
• In the current study, intensive insulin therapy for type 1 diabetes was associated with a reduced risk for incident hypertension vs. standard treatment. However, this effect was only significant after years of treatment.

Arch Intern Med. 2008;168:1867-1873.

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