UK Prospective Diabetes Study

UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998 352 837-853. 

UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascu-lar complications in type 2 diabetes UKPDS 38. BMJ 1998 317(7160) 703-13. 

The effect of adding acarbose (maximum 100 mg tds) or placebo to insulin (20) or metformin (21) has been investigated in 1946 patients with type 2 diabetes. The results were comparable with the results of the UK Prospective Diabetes Study (22). After 3 years, 39% were still using acarbose compared with 58% using placebo. The main reasons for stopping were flatulence (30 versus 12%) or diarrhea (16 versus 8%). After 3 years the HbAic concentration was 0.5% lower (median 8.1 versus 8.6%). Acarbose was equally effective when added to diet, sulfonylurea, metformin, or insulin. 

Contraindications to the use of metformin have been debated (34), in relation to the reduced number of cardiovascular events seen in the obese patients treated with metformin in the UK prospective diabetes study (UKPDS) (35). The authors stated inter alia that lactic acidosis is rare (1-5 cases per 100 000) and that in the absence of renal insufficiency accumulation of metformin is rare. Moreover, the authors of a Cochrane systematic review concluded that treatment with metformin was not associated with an increased risk of lactic acidosis (36). Tissue hypoxia is often the trigger for metformin accumulation. Many physicians do not comply with the official British contraindications. The author suggested the following necessary precautionary measures ... 

The most frequent complication of insulin therapy is inadvertent hypoglycemia (21-23). Over 5% of deaths in diabetes can be attributed to hypoglycemia. The frequency increases with rigorous maintenance of normogly-cemia (24,25). In the Diabetes Control and Complications Trial (DCCT) (26) the frequency of serious hypoglycemia was more than three times increased in the intensively treated group, and the frequency of the attacks was related to the concentration of HbAlc (27). The UK Prospective Diabetes Study in patients with type 2 diabetes also showed an increased risk of hypoglycemia with more intensive treatment (28). 

The use of insulin lispro instead of regular insulin reduced the frequency of nocturnal attacks of hypoglycemia but did not change HbAic (17). This was confirmed by the UK Prospective Diabetes Study (18), which also found a fall in postprandial glucose with an increase in fasting and preprandial glucose. 

The UK Prospective Diabetes Study (3) has shown that timely treatment, by reducing blood glucose concentrations before subjective complaints develop, reduces secondary complications in type 2 diabetes mellitus. 

Turner RC, Holman RR, Cull CA, Stratton IM, Matthews DR, Frighi V, Manley E, Neil A, McElroy H, Wright D, Kohner E, Fox C, Hadden D. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998 352(9131) 837-53. 

Varadi, A., Lebel, L., Hashim, Y., Mehta, Z., Ashcroft, S. J., and Turner, R., 1999, Sequence variants of the sarco(endo)plasmic reticulum Ca(2+)-transport ATPase 3 gene (SERCA3) in Caucasian type II diabetic patients (UK Prospective Diabetes Study 48). Diabetologia, 42 1240—3. 

Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes UKPDS 40. UK Prospective Diabetes Study Group. BMJ 1998 317 720-726. 

Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC UKPDS 26 sulphonylurea failure in non-insulin diabetic patients over six years UK Prospective Diabetes Study (UKPDS) Group. Diahet Med 15 297-303, 1998. 

According to the DCCT and the UK Prospective Diabetes study, insuiin and/or insuiin anaiogues are the standard treatment for type 1, gestationai, and some type 2 diabetes. ... 

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