Research Article| Volume 90, ISSUE 4, P450-459, April 1991

Download started.


Epidemiology of severe hypoglycemia in the diabetes control and complications trial

  • The DCCT Research Group
      This paper is only available as a PDF. To read, Please Download here.


      The present study describes the epidemiology of severe hypoglycemia and identifies patient characteristics or behaviors associated with severe hypoglycemia in patients with insulin-dependent diabetes mellitus (IDDM) participating in the Diabetes Control and Complications Trial (DCCT).

      Patients and Methods

      The DCCT is a multicenter randomized clinical trial designed to compare the benefits and risks of intensive therapy with those of conventional management of IDDM. The DCCT's feasibility phase demonstrated that intensive therapy, with the aim of achieving glucose levels as close to the non-diabetic range as possible, was accompanied by a threefold increase in severe hypoglycemia compared with conventional therapy. This report is based on the first 817 subjects who entered the DCCT, with a mean follow-up of 21 months.


      Two hundred sixteen subjects reported 714 episodes of severe hypoglycemia; 549 (77%) occurred in intensively treated subjects. The incidence of severe hypoglycemia in the intensive treatment group ranged from two to six times that observed with conventional treatment. Severe hypoglycemia occurred more often during sleep (55%); 43% of all episodes occurred between midnight and 8 AM. Of episodes that occurred while subjects were awake, 36% were not accompanied by warning symptoms. In intensively treated subjects, predictors of severe hypoglycemia included history of severe hypoglycemia, longer duration of IDDM, higher baseline glycosylated hemoglobin (HbA1c) levels, and a lower recent HbA1c. Multivariate analyses failed to yield predictive models with high sensitivity.


      In the DCCT, intensive treatment of IDDM increased the frequency of severe hypoglycemia relative to conventional therapy. Intensive treatment may cause even more frequent severe hypoglycemia when applied to less selected and less motivated populations in the clinical practice setting. These findings underscore the importance of determining the benefit-risk ratio of intensive and standard therapy of IDDM.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Muhlhausser I
        • Berger M
        • Sonnenberg G
        • et al.
        Incidence and management of severe hypoglycemia in 434 adults with insulin-dependent diabetes mellitus.
        Diabetes Care. 1985; 8: 274-278
        • Goldstein DE
        • England JD
        • Hess R
        • Rawlings SS
        • Walker B
        A prospective study of symptomatic hypoglycemia in young diabetic patients.
        Diabetes Care. 1981; 4: 601-604
        • Mecklenburg RS
        • Benson EA
        • Benson JW
        Acute complications associated with insulin infusion pump therapy: report of experience with 161 patients.
        JAMA. 1984; 252: 3265-3269
        • Goldgewicht C
        • Slama G
        • Papoz L
        • Tchobroutsky G
        Hypoglycaemic reactions in 172 type 1 (insulin-dependent) diabetic patients.
        Diabetologia. 1983; 24: 95-99
        • Wilson DE
        Excessive insulin therapy: biochemical effects and clinical repercussions: current concepts of counter-regulation in type I diabetics.
        Ann Intern Med. 1983; 98: 219-227
        • Cryer PE
        • Gerich JE
        Glucose counterregulation, hypoglycemia and intensive insulin therapy in diabetes mellitus.
        N Engl J Med. 1985; 313: 232-241
        • The DCCT Research Group
        The Diabetes Control and Complications Trial: results of the feasibility study.
        Diabetes Care. 1987; 10: 1-9
        • The Kroc Collaborative Study Group
        Blood glucose and the evolution of diabetic retinopathy and albuminuria.
        N Engl J Med. 1984; 311: 365-372
        • Feldt-Rasmussen BF
        • Mathiesen ER
        • Deckert T
        Effect of two years of strict metabolic control on progression of incipient nephropathy in insulin-dependent diabetes.
        Lancet. 1986; 2: 1300-1304
        • Dahl Jorgensen K
        • Brinchmann-Hansen O
        • Hanssen KF
        • et al.
        Rapid tightening of blood glucose control leads to transient deterioration of retinopathy in insulin dependent diabetes mellitus: the Oslo study.
        BMJ. 1985; 290: 811-815
        • Amiel SA
        • Tamborlane WV
        • Simonson DC
        • Sherwin RS
        Defective glucose counterregulation after strict glycemic control of insulin dependent diabetes mellitus.
        N Engl J Med. 1987; 316: 1376-1383
        • Simonson DC
        • Tamborlane WV
        • DeFronzo RA
        • Sherwin RS
        Intensive insulin therapy reduces counter-regulatory response to hypoglycemia in patients with type I diabetes.
        Ann Intern Med. 1985; 103: 184-190
        • The DCCT Research Group
        The Diabetes Control and Complications Trial (DCCT): design and methodological considerations for the feasibility phase.
        Diabetes. 1986; 35: 530-545
      1. The DCCT Research Group. Protocol for Diabetes Control and Complicacions Trial (DCCT). NIH publication no. 88-2951.

        • Early Treatment Diabetic Retinopathy Study Research Group
        Manual of operations, accession no. PB85 223006/AS. US Dept. of Commerce, National Technical Information Service, Springfield, Virginia1985
        • Wilcoxon I
        Individual comparisons by ranking methods.
        Biometrics. 1945; 1: 80-83
        • Kalbfleisch JD
        • Prentice RL
        The statistical analysis of failure time data.
        John Wiley and Sons, ew York1980
        • Ramlau-Hansen H
        Smoothing counting process intensities by means of Kernel functions.
        Annals of Statistics. 1983; 11: 453-466
        • Andersen PK
        • Borgan O
        • Gill RD
        • Keiding N
        Linear non-parametric tests for comparison of counting processes, with applications of censored survival data.
        International Statistical Review. 1982; 50: 219-258
        • Cox DR
        Analysis of binary data.
        Methuen, London1970
        • McNemar Q
        Notes on the sample error of the difference between correlated proportions or percentages.
        Psychometrics. 1947; 12: 153-157
        • Berger M
        Human insulin: much ado about hypoglycemia (un)awareness.
        Diabetologia. 1987; 30: 829-833
        • Gale EAM
        Hypoglycaemia and human insulin.
        Lancet. 1989; 2: 1264-1266
        • Gorden P
        Human insulin and hypoglycemia [Letter].
        N Engl J Med. 1990; 322: 1007-1008
        • White NH
        • Skor D
        • Cryer PE
        • Bier DM
        • Levandoski L
        • Santiago JV
        Identification of type I diabetic patients at increased risk for hypoglycemia during intensive therapy.
        N Engl J Med. 1983; 308: 485-491
        • Lawrence RD
        Insulin hypoglycemia. Changes in nervous manifestations.
        Lancet. 1941; 2: 602-603
        • Balodimos C
        • Root HF
        Hypoglycemic insulin reactions without warning symptoms.
        JAMA. 1959; 171: 261-266
        • Sussman KE
        • Crout JR
        • Marbel A
        Failure in warning in insulin-induced hypoglycemic reactions.
        Diabetes. 1963; 12: 38-45
        • Hoeldtke RD
        • Boden G
        • Shuman CR
        • Owen OE
        Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy.
        Ann Intern Med. 1982; 96: 459-462
        • Heller SR
        • Herbert M
        • MacDonald I
        • Tattersall RB
        Influence of sympathetic nervous system on hypoglycemic warning symptoms.
        Lancet. 1987; 2: 359-363
        • Bolli G
        • DeFeo P
        • Compagnucci P
        • et al.
        Abnormal counterregulation in insulin-dependent diabetes mellitus.
        Diabetes. 1983; 32: 134-141