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Original Investigation
September 22, 2008

Insulin Therapy, Hyperglycemia, and Hypertension in Type 1 Diabetes Mellitus

Ian H. de Boer, MD, MS; Bryan Kestenbaum, MD, MS; Tessa C. Rue, MS; et al Michael W. Steffes, MD, PhD; Patricia A. Cleary, MS; Mark E. Molitch, MD; John M. Lachin, ScD; Noel S. Weiss, MD, DrPH; John D. Brunzell, MD; Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Study Research Group
Author Affiliations

Author Affiliations: Divisions of Nephrology (Drs de Boer and Kestenbaum) and Metabolism, Endocrinology, and Nutrition (Dr Brunzell), Department of Medicine, and Departments of Biostatistics (Ms Rue) and Epidemiology (Dr Weiss), University of Washington, Seattle; Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis (Dr Steffes); The Biostatistics Center (Ms Cleary and Dr Lachin), George Washington University, Washington, DC; and Division of Endocrinology, Department of Medicine, Northwestern University, Chicago, Illinois (Dr Molitch).Group Information: A list of the DCCT/EDIC Study Research Group was published in JAMA. 2003;290(16):2166.

Arch Intern Med. 2008;168(17):1867-1873. doi:10.1001/archinternmed.2008.2

Background  Diabetes mellitus and hypertension are closely linked, but the long-term blood pressure effects of glucose-lowering therapy and hyperglycemia are not clear.

Methods  We examined the effects of intensive insulin therapy and hyperglycemia on the development of hypertension in the Diabetes Control and Complications Trial (DCCT) and its observational follow-up, the Epidemiology of Diabetes Intervention and Complications (EDIC) study. Incident hypertension was defined as 2 consecutive study visits with a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or use of antihypertensive medications to treat high blood pressure.

Results  Participants were enrolled from August 23, 1983, through June 30, 1989. During a 15.8-year median follow-up, 630 of 1441 participants developed hypertension. During the DCCT, the incidence of hypertension was similar comparing participants assigned to intensive vs conventional therapy. However, intensive therapy during the DCCT reduced the risk of incident hypertension by 24% during EDIC study follow-up (hazard ratio, 0.76; 95% confidence interval [CI], 0.64-0.92). A higher hemoglobin A1c level, measured at baseline or throughout follow-up, was associated with increased risk for incident hypertension (adjusted hazard ratios, 1.11 [95% CI, 1.06-1.17] and 1.25 [95% CI, 1.14-1.37], respectively, for each 1% higher hemoglobin A1c level), and glycemic control appeared to mediate the antihypertensive benefit of intensive therapy. Older age, male sex, family history of hypertension, greater baseline body mass index, weight gain, and greater albumin excretion rate were independently associated with increased risk of hypertension.

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