Treatment of diabetic complications: how can we learn by seeking and blundering?

Abstract

Some of the clinical features of diabetes mellitus (DM) were first described in Egypt 3500 years ago. However, understanding the relevant pathophysiology and introduction of the first therapeutic principles were late in following, with slow progress between 1500 and 1990. In the latter part of the 20th century, it was realized that the prevalence of type 2 DM (T2DM) was rising, calling for improved management of DM and its complications. New insulin analogs, glucagon-like peptide 1 agonists, and valuable oral hypoglycemic agents have been introduced during the last 30 years. In 1993, the results of the Diabetes Control and Complications Trial (DCCT) were released, followed by the publication of the United Kingdom Prospective Diabetes Study (UKPDS) in 1998. These landmark trials concluded that tight glycemic control contributed to reduced incidence of some of diabetic complications in type 1 DM (T1DM) and T2DM, respectively. The next step was to explore the effect of rapidly attaining tight glycemic control in patients with T2DM and high cardiovascular risk. This was the aim of 3 trials, the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Veterans Administration Diabetes Trial (VADT), and the Action in Diabetes and Vascular Disease (ADVANCE), which showed that tight glycemic control conferred virtually no benefit in this setting. However, trials do not reflect everyday situations, and so a recent publication in the New England Journal of Medicine assessed the incidence of diabetic complications in the United States between 1990 and 2010. Data were obtained from the National Health Interview Survey, the National Hospital Discharge Survey, the US Renal Data System, and the US National Vital Statistics System. The rates of 5 major diabetic complications, namely acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), amputations, and death from hyperglycemic crisis, were significantly reduced. Among these, ESRD exhibited the smallest relative decline, while the most marked decrease was seen for AMI. The reduction in the latter, accompanied by the increased absolute number of strokes, led to comparable rates between AMI and stroke. Furthermore, the greatest absolute decline was seen for AMI and the smallest for deaths from hyperglycemic crisis. Interestingly, the greatest reductions were observed in patients older than 75 years of age, with the exception of ESRD: as a result, amputation rates were comparable in younger and older patients, while deaths from hyperglycemic crisis were more frequent among younger patients. Importantly, rates of stroke, AMI, ESRD, and amputations showed a smaller reduction in the population without DM, suggesting that greater progress had been accomplished in the treatment of diabetic patients. The authors attributed their findings to improved (1) preventative health care, (2) treatment of acute complications, (3) availability of drugs and therapeutic procedures (eg, revascularization), and (4) earlier detection and management of diabetic complications. Even neuropathy, which remains a frequently overlooked complication, can now be diagnosed more reliably by new tests. Moreover, there appears to have been some improvement in lifestyle factors such as smoking and dietary habits as well as in self-monitoring of blood glucose. These achievements notwithstanding, the overall burden of diabetic complications has not been reduced, at least not to the extent that was set as a goal by the St Vincent declaration. This is primarily attributable to the growing diabetes epidemic, which is, in turn, due to urbanization, Westernized dietary habits, obesity, and prolonged life expectancy. Arguably, obesity and industrialization apply more to patients with T2DM, while prolonged survival after diagnosis, resulting in increased lifetime DM duration, applies more not only to patients with T1DM but also to patients with T2DM. The New England Journal of Medicine analysis has its limitations. These include the lack of data on microvascular diabetic complications and hypoglycemia, the failure to compare complication rates between the 2 DM types as well as the absence of more detailed ascertainment of the progress hitherto achieved in DM management and adherence to guidelines. Accordingly, further data are now desirable in an endeavor to increase our knowledge in these areas. In this context, some improvements are now highly welcome. First, it would be useful to obtain more data on less