Letters

Effect of intensive treatment in insulin dependent diabetes mellitus with microalbuminuria

EDITOR,--The Microalbuminuria Collaborative Study Group concludes that intensive glycaemic control has no effect on the progression of albuminuria in people with insulin dependent diabetes mellitus who already have microalbuminuria.¹ These conclusions have important implications for the care of diabetic patients and should not go unchallenged.

The main problem with this study, as the authors admit, is the sample size. If we assume that 21% of patients with microalbuminuria will progress to overt albuminuria, as shown in this and other studies, and we wish to show a reduction in progression by 50% in the intensively treated group (that is, a rate of progression of 10.5%) with 80% power and a significance level of 5%, we would need 412 participants (206 in each group). A more modest reduction in risk would require a larger sample. Thus the inclusion of just 70 patients is not enough, even if the risk of progression in the intensively treated group was close to zero.

The authors quote earlier studies showing significant reductions in risk associated with intensive treatment, which had similar sample sizes to theirs. But these results could partly have been due to a type I error. The authors also quote findings from the diabetes control and complications trial in support of their conclusions. In this trial the difference in the rate of change in albumin excretion rate in the group given intensive treatment compared with the group given conventional treatment was similar in patients with normal albumin excretion to that in patients with microalbuminuria at baseline.² But this difference was significant only in those with normal albumin excretion rates as the number of participants with microalbuminuria was too small to provide adequate power.

The authors' study had two main outcome measures--progression to clinical albuminuria and rate of change in the albumin excretion rate. Only detailed results for the former are presented, and we are not shown how the rate of change in the albumin excretion rate differed between the two groups. Simply stating that these differences were not significant is inadequate: rates of change for each group, with confidence intervals, should be presented.

Little mention is made of retinopathy in this paper, but the EURODIAB insulin dependent diabetes mellitus complications study has shown that about half the patients with microalbuminuria have some degree of retinopathy,³ the progression of which is slowed by improved glycaemic control.⁴

We believe that this study has important methodological limitations and that the target of improving glycaemic control in patients with insulin dependent diabetes mellitus with microalbuminuria should not be abandoned.

Research fellow Reader in epidemiology EURODIAB, Department of Epidemiology and Public Health, University College, London WC1E 6BT

Nish Chaturvedi, John H Fuller 

1. Microalbuminuria Collaborative Study Group, United Kingdom. Intensive therapy and progression to clinical albuminuria in patients with insulin dependent diabetes mellitus and microalbuminuria. BMJ 1995;311:973-7. (14 October.) [Abstract/Free Full Text]
2. 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;47:1703-20. [Medline]
3. Stephenson JM, Fuller JH, Viberti GC, Sjolie AK, Navalesi R, EURODIAB IDDM Complications Study Group. Blood pressure, retinopathy and urinary albumin excretion in IDDM: the EURODIAB IDDM complications study. Diabetologia 1995;38:599-603. [Medline]
4. 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;329:977-86. [Abstract/Free Full Text]