Authors' replyBMJ 1996; 312 doi: https://doi.org/10.1136/bmj.312.7025.254a (Published 27 January 1996) Cite this as: BMJ 1996;312:254
- Giancarlo Viberti,
- R John Jarrett
- For the Microalbuminuria Collaborative Study Group Professor of diabetes and metabolic medicine Retired professor of clinical epidemiology Department of Metabolic Medicine and Endocrinology, Division of Medicine, UMDS, Guy's Hospital, London SE1 9RT
EDITOR,—Nish Chaturvedi and John H Fuller point to a limitation of our study—the sample size—which we acknowledged in our paper. A larger sample size was planned, but screening yielded fewer suitable patients than expected. Nevertheless, this is the largest study of the kind published to date, and its size in combination with that of the subgroup with microalbuminuria in the diabetes control and complications trial1 could detect a reduction in the risk of progression to clinical albuminuria of 33% or more. Neither study showed any effect of intensive treatment on the categorical change from microalbuminuria to clinical albuminuria.
In the 73 patients with insulin dependent diabetes mellitus and baseline microalbuminuria in the diabetes control and complications trial the difference in the rate of change in albumin excretion rate between the two treatment groups was far from significant (P=0.09). Chaturvedi and Fuller assume that a larger sample would have shown a significant difference between the two groups. The direction of change in a “next lot” of similar patients, however, is unpredictable. Indeed, in the next lot in our study the difference in the rate of change in albumin excretion rate was less than 1% (P=0.31). Moreover, whether the non-significant difference in the mean slope of the albumin excretion rate in the diabetes control and complications trial can be ascribed to glycaemic differences is unknown as the data for the subset of patients with microalbuminuria are unpublished.
The only study comparable to ours that showed a significant reduction in the risk of development of persistent albuminuria in the intensive treatment group was half the size of ours2; we agree with Chaturvedi and Fuller that this result is most likely to have been due to a type I error.
We accept that results, particularly if controversial and contrary to expectation, should be challenged, but such challenges should preferably be based on factual data, which Chaturvedi and Fuller do not provide. Whether strict glycaemic control delays the progression of microalbuminuria remains to be proved.
Our study was not designed to test the effect of intensive treatment on retinopathy, and 67% of subjects already had moderate to severe retinopathy, confirming previous reports3 and making them unsuitable for this type of study.
Like R Davison and colleagues, we found blood pressure to be a more significant predictor of progression of microalbuminuria. We do not, however, advocate replacing optimised diabetes care with antihypertensive treatment in these subjects. Rather, we believe that these two approaches should go together, though we would advise doctors of their relative importance and impact in different phases of the evolution of diabetic renal complications.
Ralf Bender and Peter T Sawicki have misread our paper. Our conclusions were based mainly on the categorical change from microalbuminuria to clinical albuminuria; no differences between the two groups were found. Detailed analysis of the rate of change in the slopes of albumin excretion rate (which we did not present because of space restrictions) again showed no differences between the two groups. The direction of change was the same in the two groups. The question of the duration of glycaemic separation is discussed in our paper.
We disagree with Bender and Sawicki that analysis on an intention to treat basis was inappropriate. However, even when we analysed the data on the basis of attained glycaemia and compared the groups with better and worse blood glucose control (haemoglobin A1c concentrations below and above the median, respectively) no differences were found in albumin excretion rate as either a categorical or a continuous variable.