The benefit of strict glycaemic control in diminishing the risks of the development of long-term complications of diabetes is beyond doubt, but the negative aspects of such therapies need to be considered, and their risks identified, understood and minimised. Modern intensified insulin management need not necessarily increase the risk of iatrogenic problems and can deliver better glycaemic control more safely than in the past, although substantial scope remains for improvement. New drugs for type 2 diabetes may offer greater opportunities to achieve near-normoglycaemia but may also bring new risks. These risks need to be explained carefully to every patient, who can then make an individual, informed choice about the management of their diabetes.
The risks of intensified insulin therapy, the focus of this chapter, are those of insulin itself - intensified. Thus the major side-effects are weight gain (The Diabetes Control and Complications Trial Research Group, 1988) and hypoglycaemia (The Diabetes Control and Complications Trial Research Group, 1993; 1995a; 1997). Both of these problems may appear to be minimised with modern strategies for patient self-management, at least in published studies (Jorgens et al., 1993; DAFNE Study Group, 2002; Plank 2004 et al.; Samann et al. 2005), yet they remain serious issues for large numbers of people. Weight gain, attributed primarily to the resolution of caloric loss in glycosuria (Carlson and Campbell, 2003), is theoretically responsive to dietary strategies, but insulin and peripheral insulin sensitizers do cause lipogenesis and fluid retention, both of which contribute to a rise in weight that may be unacceptable to patients. Evidence is accumulating about the potential effects of insulin and other anti-diabetic agents on appetite control and satiety that may make the control of weight more difficult. Although the long-term diminution of risk of vascular complications is now established beyond doubt, the sudden institution of strict glycaemic control after a prolonged period of hyperglycaemia, can transiently, but sometimes seriously, destabilise microvascular disease (Agardh et al., 1992; The Diabetes Control and Complications Trial Research Group, 1998). In type 1 diabetes, the long-term follow up of the DCCT cohorts unequivocally has extended the evidence to include slowed progression of macrovascular, as well as microvascular, disease (Nathan et al., 2003; Writing team for the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications Research Group, 2002), and so the risks of intensified therapy need to be balanced against the potentially large gains. A new risk, of unknown magnitude, is the increasing use of novel insulins, which have different properties from endogenous human insulin and thus, at least in theory, may have different side-effects.
Hypoglycaemia in Clinical Diabetes, 2nd Edition. Edited by B.M. Frier and M. Fisher © 2007 John Wiley & Sons, Ltd
When cohorts of patients are studied rather than individuals, other potential risks of the demands of intensified insulin therapies, and in particular the inherent psychosocial strains, do not emerge as a problem. Concerns have been expressed that greater use of home blood glucose monitoring may increase anxiety, particularly in type 2 patients who are not taking insulin, and who have limited means at their disposal of responding to high blood glucose values (Franciosi et al., 2001). In contrast, in type 1 diabetes, research suggests that patients may prefer intensified treatment regimens. In the Diabetes Control and Complications Trial, patients in the intensive treatment arm of the study had an overall improvement in their subjective feelings of control and well-being, although it was offset by a greater fear of hypoglycaemia (The Diabetes Control and Complications Trial Research Group, 1996a). However, this balance may be particularly positive in people who actively choose to use intensified therapies. In the DAFNE Trial, all participants had selected the intensive programme of treatment, and significant and apparently lasting benefits in quality of life measures were demonstrated using the intensified management strategy (DAFNE Research Group, 2002). However, it must be acknowledged that when individual patients are exhorted to achieve perfection in glycaemic control, they may experience difficulties and frustration with the impossible task of trying to eliminate blood glucose readings that lie outside the normal range, especially if they are not equipped to act upon such readings.
In general, the main risk of intensified diabetes therapy remains hypoglycaemia. This chapter examines the problem of hypoglycaemia that is specifically associated with strict glycaemic control, an area that has aroused much concern and controversy. Most comments relate to patients with type 1 diabetes. The risks of severe hypoglycaemia associated with strict control in insulin-treated type 2 diabetes are likely to be similar, but occur much later in the natural history of the disease, when insulin deficiency is profound (see Chapter 11).
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