Glycaemic control and diabetic neuropathy

The Diabetes Control and Complications Trial Research Group undertook a single-blind randomised trial of standard IDDM treatment versus intensive treatment in young patients with no, or mild, diabetic complications at outset. The study assessed the incidence or progression of the microvascular complications of IDDM, namely retinopathy, nephropathy and neuropathy.

A total of 1441 patients were randomised to either:

• standard treatment:
  • 1-2 insulin injections per day
  • daily monitoring of urine or blood glucose
  • three-monthly reviews in clinic
  • aimed to keep patients asymptomatic and without ketones in the urine
    
    
• intensive treatment:
  • 3+ insulin injections per day
  • blood glucose monitoring 4+ times per day
  • weekly 3 am blood glucose measurement
  • frequent telephone counselling and monthly clinics
  • goals of treatment included:
    • post-meal blood glucose <10 mmol/l)
    • pre-meal blood glucose 3.9-6.7 mmol/l)
    • 3 am blood glucose >3.6 mmol/l)
    • HbA1c <6.05%

Patients were aged 13-39 years. 726 had no retinopathy on entry; 715 had mild retinopathy on entry. Mean duration of follow-up was 6.5 years.

Results:

The main results of the DCCT were:

• retinopathy:
  • in patients without baseline retinopathy the incidence of retinopathy was reduced by 76%
  • in the intensive treatment group in patients with mild baseline retinopathy the rate of progression was slowed by 54%
  • severe retinopathy was reduced by 47%
• nephropathy:
  • incidence of microalbuminuria was reduced by 39%in the intensive treatment group
  • incidence of albuminuria was reduced by 54%
• neuropathy:
  • the incidence of clinical neuropathy was reduced by 60% in the intensive treatment group

There was a 2-3 fold increase in the incidence of severe hypoglycaemic attacks in the intensive treatment group.

Notes:

• there is evidence that sudden improved glycaemic control in diabetic patients may cause a type of 'painful neuritis' (2)
• a follow-up study for the DCCT population has provided evidence that intensive diabetes therapy has long-term beneficial effects on the risk of cardiovascular disease in patients with type 1 diabetes (3)
  • intensive treatment reduced the risk of any cardiovascular disease event by 42 percent (95 percent confidence interval, 9 to 63 percent; P=0.02) and the risk of nonfatal myocardial infarction, stroke, or death from cardiovascular disease by 57 percent (95 percent confidence interval, 12 to 79 percent; P=0.02)
  • the decrease in glycosylated hemoglobin values during the DCCT was significantly associated with most of the positive effects of intensive treatment on the risk of cardiovascular disease

Reference:

1. The 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. New Engl. J. Med. 1993; 32(14): 977-86
2. Kihara M, Zollman PJ, Smithson IL, Lagerlund TD, Low PA. Hypoxic effect of exogenous insulin on normal and diabetic peripheral nerve. Am J Physiol 1994; 226: E980-985.
3. Nathan DM et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005 Dec 22;353(25):2643-53.