Better glycaemic control and risk reduction of diabetic complications in Type 2 diabetes: comparison with the DCCT

Abstract

Objective: To construct dose response curves relating the development of diabetic complications (retinopathy and microalbuminuria) to mean glycaemic exposure in a cohort of Type 2 patients followed over a period of several years. This allows a comparison with similar data on Type 1 subjects reported by the Diabetes Control and Complications Trial (DCCT) and provides a rational basis for deciding what levels of glycaemic control should be aimed for in advising individual patients and in setting guidelines for conducting health services. Research design and methods: This was an analysis of data prospectively collected in our computerized data base for Type 2 patients who attended and were followed up at the Complications Assessment Service of our Diabetes Center. The initial development of retinopathy and microalbuminuria was analyzed with respect to the mean HbA_1c during the follow up period. Statistical procedures identical to those employed in the DCCT were used to construct the dose response curve. Results: A smooth relationship between the development of retinopathy with increasing hyperglycaemia was found. For every 10% decrease in HbA_1c, there was a 24% (confidence interval (CI): 16–32) reduction in relative risk, about 2/3 of that reported for insulin-dependent diabetes mellitus (IDDM) patients. The relationship between microalbuminuria and HbA_1c was more linear and less steep with a relative risk reduction of 9% (CI: −2–19%) for any 10% fall in HbA_1c, about 1/3 of that reported for IDDM subjects. No threshold of HbA_1c can be found for the relative risk of developing complications. However, more cases of complications are prevented by the same degree of improvement in glycaemic control at higher levels of HbA_1c. Conclusions: The development of diabetic retinopathy in Type 2 subjects is also related to the magnitude of hyperglycaemia although the degree of dependence is less than that in Type 1. Glycaemic control has less influence on microalbuminuria in Type 2. In terms of relative risk, no threshold of `safe HbA_1c' can be found but in absolute terms more cases of diabetic complications can be prevented by improving the glycaemic control of the very hyperglycaemic patients.

Introduction

The benefits of achieving near-normoglycaemia for Type 1 subjects have been established unequivocally by the findings of the Diabetes Control and Complications Trial (DCCT) 1, 2. What has been debated in the literature is whether there is a threshold below which further improvement in glycaemic control does not result in a substantial reduction in diabetic complications 3, 4. This is an important question because near-normoglycaemia in Type 1 diabetes can only be achieved at a cost of increased hypoglycaemia. Therefore, taking into consideration the risk/benefit ratio, it is important not only in advising an individual patient whether he/she should undergo intensive insulin treatment, but also in deciding how much of the health care resources should be spent on supporting this philosophy of treatment. In this context, information about the shape and the slope of the dose-response curve relating development of diabetic complications to glycaemic control is crucial. Whilst the DCCT has provided excellent data in this regard, a similar approach to analysis for Type 2 diabetes is far more scanty, although we acknowledge that there is also overwhelming evidence that hyperglycaemia is associated with more complications 5, 6, 7, 8, 9. Therefore we have studied data from our computerized database to examine the relationship between initial development of diabetic complications and glycaemic control over time for Type 2 patients who have attended our Complications Assessment Service on more than one occasion. By employing identical statistical procedures as those used by the DCCT 1, 2, 3, our aim was to compare our data with that of the DCCT to evaluate if improvement in glycaemic control in Type 2 patients will result in the same degree of risk reduction in diabetic complications [10].