Insulin Therapy, Hyperglycemia, and Hypertension in Type 1 Diabetes Mellitus | Hypertension | JAMA Internal Medicine | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.205.38.159. Please contact the publisher to request reinstatement.
1.
 The Seventh Report of the Joint National Committee in Prevention: Detection, Evaluation, and Treatment of High Blood Pressure.  Bethesda, MD National Heart, Lung, and Blood Institute, National Institutes of Health, US Dept of Health and Human Services2004;
2.
Sowers  JREpstein  M Diabetes mellitus and associated hypertension, vascular disease, and nephropathy: an update.  Hypertension 1995;26 (6, pt 1) 869- 879PubMedGoogle ScholarCrossref
3.
Anderson  EAHoffman  RPBalon  TWSinkey  CAMark  AL Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans.  J Clin Invest 1991;87 (6) 2246- 2252PubMedGoogle ScholarCrossref
4.
Perlstein  TSGerhard-Herman  MHollenberg  NKWilliams  GHThomas  A Insulin induces renal vasodilation, increases plasma renin activity, and sensitizes the renal vasculature to angiotensin receptor blockade in healthy subjects.  J Am Soc Nephrol 2007;18 (3) 944- 951PubMedGoogle ScholarCrossref
5.
Purnell  JQHokanson  JEMarcovina  SMSteffes  MWCleary  PABrunzell  JD Effect of excessive weight gain with intensive therapy of type 1 diabetes on lipid levels and blood pressure: results from the DCCT.  JAMA 1998;280 (2) 140- 146PubMedGoogle ScholarCrossref
6.
Brownlee  M The pathobiology of diabetic complications: a unifying mechanism.  Diabetes 2005;54 (6) 1615- 1625PubMedGoogle ScholarCrossref
7.
Ceriello  A Controlling oxidative stress as a novel molecular approach to protecting the vascular wall in diabetes.  Curr Opin Lipidol 2006;17 (5) 510- 518PubMedGoogle ScholarCrossref
8.
Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.  N Engl J Med 1993;329 (14) 977- 986PubMedGoogle ScholarCrossref
9.
DCCT Research Group, Weight gain associated with intensive therapy in the diabetes control and complications trial.  Diabetes Care 1988;11 (7) 567- 573PubMedGoogle ScholarCrossref
10.
Parving  HHAndersen  ARSmidt  UMSvendsen  PA Early aggressive antihypertensive treatment reduces rate of decline in kidney function in diabetic nephropathy.  Lancet 1983;1 (8335) 1175- 1179PubMedGoogle ScholarCrossref
11.
Orchard  TJOlson  JCErbey  JR  et al.  Insulin resistance-related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications Study.  Diabetes Care 2003;26 (5) 1374- 1379PubMedGoogle ScholarCrossref
12.
Diabetes Control and Complications (DCCT) Research Group, Effect of intensive therapy on the development and progression of diabetic nephropathy in the Diabetes Control and Complications Trial.  Kidney Int 1995;47 (6) 1703- 1720PubMedGoogle ScholarCrossref
13.
 Sustained effect of intensive treatment of type 1 diabetes mellitus on development and progression of diabetic nephropathy: the Epidemiology of Diabetes Interventions and Complications (EDIC) study.  JAMA 2003;290 (16) 2159- 2167PubMedGoogle ScholarCrossref
14.
Steffes  MCleary  PGoldstein  D  et al.  Hemoglobin A1c measurements over nearly two decades: sustaining comparable values throughout the Diabetes Control and Complications Trial and the Epidemiology of Diabetes Interventions and Complications study.  Clin Chem 2005;51 (4) 753- 758PubMedGoogle ScholarCrossref
15.
Haffner  SMValdez  RMorales  PAMitchell  BDHazuda  HPStern  MP Greater effect of glycemia on incidence of hypertension in women than in men.  Diabetes Care 1992;15 (10) 1277- 1284PubMedGoogle ScholarCrossref
16.
Suematsu  CHayashi  TFujii  S  et al.  Impaired fasting glucose and the risk of hypertension in Japanese men between the 1980s and the 1990s: the Osaka Health Survey.  Diabetes Care 1999;22 (2) 228- 232PubMedGoogle ScholarCrossref
17.
Bjørnholt  JVErikssen  GKjeldsen  SEBodegard  JThaulow  EErikssen  J Fasting blood glucose is independently associated with resting and exercise blood pressures and development of elevated blood pressure.  J Hypertens 2003;21 (7) 1383- 1389PubMedGoogle ScholarCrossref
18.
de Simone  GDevereux  RBChinali  M  et al.  Risk factors for arterial hypertension in adults with initial optimal blood pressure: the Strong Heart Study.  Hypertension 2006;47 (2) 162- 167PubMedGoogle ScholarCrossref
19.
Chiasson  JLJosse  RGGomis  RHanefeld  MKarasik  ALaakso  M Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial.  JAMA 2003;290 (4) 486- 494PubMedGoogle ScholarCrossref
20.
UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33).  Lancet 1998;352 (9131) 837- 853PubMedGoogle ScholarCrossref
21.
Dyer  ARLiu  KWalsh  MKiefe  CJacobs  DR  JrBild  DE Ten-year incidence of elevated blood pressure and its predictors: the CARDIA study.  J Hum Hypertens 1999;13 (1) 13- 21PubMedGoogle ScholarCrossref
22.
Wilson  PWD’Agostino  RBSullivan  LParise  HKannel  WB Overweight and obesity as determinants of cardiovascular risk: the Framingham experience.  Arch Intern Med 2002;162 (16) 1867- 1872PubMedGoogle ScholarCrossref
23.
Lauer  RMBurns  TLClarke  WRMahoney  LT Childhood predictors of future blood pressure.  Hypertension 1991;18 (3) ((suppl)) I74- I81PubMedGoogle ScholarCrossref
24.
Sonne-Holm  SSorensen  TIJensen  GSchnohr  P Independent effects of weight change and attained body weight on prevalence of arterial hypertension in obese and non-obese men.  BMJ 1989;299 (6702) 767- 770PubMedGoogle ScholarCrossref
25.
de Boer  IHSibley  SDKestenbaum  B  et al.  Central obesity, incident microalbuminuria, and change in creatinine clearance in the Epidemiology of Diabetes Interventions and Complications Study.  J Am Soc Nephrol 2007;18 (1) 235- 243PubMedGoogle ScholarCrossref
26.
de Boer  IHSteffes  MW Glomerular filtration rate and albuminuria: twin manifestations of nephropathy in diabetes.  J Am Soc Nephrol 2007;18 (4) 1036- 1037PubMedGoogle ScholarCrossref
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
Abstract

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.

×