Intensified insulin therapy and the risk of severe hypoglycaemia

Abstract

In the Diabetes Control and Complications Trial (DCCT) intensification of insulin therapy was associated with a threefold increase in the incidence of severe hypoglycaemia when compared to conventional insulin therapy, and there was a strong inverse exponential association between the frequency of severe hypoglycaemia and HbA 1 c levels [1]. This is in accordance with a recent meta-analysis of randomized controlled studies on intensified insulin therapy [2]. However, among the 29 centres participating in the DCCT there was a substantial variation by clinic in the risk of severe hypoglycaemia associated with intensification of insulin therapy (between 0 and 150 episodes per 100 patient-years) despite a narrow range of variation in the median HbA 1 c values (between 6.7 and 7.2 %) [3]. In addition, apart from the DCCT, there are diabetes centres with patients Diabetologia (1997) 40: 926-932 Intensified insulin therapy and the risk of severe hypoglycaemia Summary The objectives of the present analyses were to assess the association between HbA 1 c levels and severe hypoglycaemia (SH, treatment with glucose i. v. or glucagon injection) and to identify predictors of SH in a prospective multicentre trial. The study population consisted of 636 insulin-dependent diabetic patients who had participated in a structured 5-day in-patient group treatment and teaching programme for intensification of insulin therapy (ITTP) in one of 10 hospitals and who were re-examined after 1, 2, 3, and 6 years including assessment of demographic, disease and treatment related parameters, diabetes-related knowledge, behaviour, and emotional coping. At baseline, age (mean ± SD) was 27 ± 7 years, diabetes duration 9 ± 7 years and HbA 1 c 8.3 ± 1.9 %. During the 6-year follow-up, the mean HbA 1 c value improved to 7.6 %, and in patients with a diabetes duration of more than 1 year at entry into the study (n = 538) the incidence of SH decreased from 0.28 cases/patient/year during the year preceding the ITTP to 0.17 cases/patient/year. The patient group was divided into decile groups according to mean follow-up HbA 1 c values. In each group more than 230 patient years could be analysed. Groups with mean HbA 1 c values of 5.7, 7.0, 7.4, 7.7 and 8.9 % had comparable risks of SH (0.15-0.19 cases/ patient/year). In a logistic regression analysis, mean HbA 1 c during follow-up, a history of SH during the year preceding the ITTP, C-peptide level, emotional coping, carrying emergency carbohydrates (as assessed at the 1-year follow-up), and age at onset of diabetes were significant independent predictors of SH. The incidence of SH between centres varied between 0.05 and 0.27 cases/patient/year. In conclusion, in the present analyses no linear or exponential relationship between HbA 1 c and severe hypoglycaemia could be identified by using simple group comparisons. Applying complex regression analyses, various patient-related predictors of severe hypoglycaemia were identified. [Diabetologia (1997) 40: 926-932]

Twice‐ rather than once‐daily basal insulin is associated with better glycaemic control in Type 1 diabetes mellitus 12 months after skills‐based structured education in insulin self‐management

“…These data confirm earlier reports of a major reduction in severe hypoglycaemia 12 months after the ITTP and DAFNE 6, 10, 11, which is largely independent of HbA 1c (above or below 58 mmol/mol, 7.5%), insulin type or injection frequency. We propose the 76% reduced risk of severe hypoglycaemia arises from the total DAFNE education package, not just the basal insulin regimen.…”

Long-term evaluation of a structured outpatient education programme for intensified insulin therapy in patients with Type 1 diabetes: a 12-year follow-up

“…After initial significant improvement, substantial deterioration of metabolic control was observed after 6 years. This pattern is similar to results of a 6-year follow-up investigation of approximately 600 Type 1 diabetic patients [6] whose metabolic control worsened after 3 years. In contrast to the DCCT, where the intensified therapy group attended monthly visits at the centre and had even more telephone contact to review and adjust regimens, patients in our cohort were seen, on average, once to twice a year in our outpatient clinic.…”

“…In patients undergoing a structured teaching and treatment programme for IIT, this unacceptably high risk was not observed. Reduced risk of severe hypoglycaemia and improved metabolic control after intensification of insulin therapy was demonstrated for a period of up to 6 years [5,6]. Moreover, owing to dietary liberalisation, the patients' quality of life was found to be substantially improved in a randomised controlled multicentre trial in the UK using the outpatient teaching programme [7].…”

Prediction of Severe Hypoglycaemia by Angiotensin-Converting Enzyme Activity and Genotype in Type 1 Diabetes

“…These figures are all higher than those of some other studies [38], including the Diabetes Control and Complications Trial [1]. The discrepancy is probably explained by differences in definition and recording of severe hypoglycaemia and in a different selection of patients rather than by a real difference in incidence among comparable subjects.…”