UKPDS in Harrisons Medical Text Book

  Clinical Trial Related to Chapter 334: Diabetes Mellitus Intensive Treatment of Type 2 Diabetes Mellitus:Results of the United Kingdom Prospective Diabetes Study.
By J.Larry Jameson

DCCT -UKPDS
   The Diabetes Control and Complications Trial (DCCT) showed conclusively that intensive efforts to lower blood glucose reduced microvascular complications (retinopathy, neuropathy, nephropathy) in patients with type 1 diabetes mellitus (DM). The results of the United Kingdom Prospective Diabetes Study (UKPDS) used a similar design to address the relationship between glycemic control and diabetic complications in patients with type 2 DM.

   The findings of this study underscore the importance of intensive glycemic control in both type 1 and type 2 diabetes.
   In the UKPDS, which was performed between 1977 and 1991, more than 5000 patients with newly diagnosed diabetes were randomized to receive either intensive glycemic control using various combinations of insulin, metformin,and sulfonylureas or conventional therapy using dietary modification as well as pharmacotherapy, but without specific efforts to achieve intensive blood sugar control.Analysis was also performed for intensive versus conventional blood pressure control. Patients were followed for an average of 10 years. Patients in this study began with a mean HbA1c of 9.1 percent. The mean HbA1c in the intensive group was 7.0 percent compared to 7.9 percent in the conventional group.
(I Sverige mono-s HbA1c-metod;HbA1c 7.0 motsvarar 7.0-1.14=5.9%, reds anm).

Risk reduction
   There was a 25 percent reduction in the overall microvascular complication rate in the intensively treated group. Additional analysis revealed a 35 percent reduction in the risk of complications for each percentage point decrease in HbA1c. Although there was no statistically significant difference in cardiovascular complications (16 percent reduction,p =.052), epidemiologic analysis revealed a continuous association between lowering the HbA1c and cardiovascular complications; for each percentage point reduction in HbA1c (e.g.,98 percent) there was a 25 percent decrease in diabetes- related deaths, a 7 percent reduction in all-cause mortality, and an 18 percent reduction in combined fatal and nonfatal myocardial infarction.

   Hypoglycemic events were uncommon, consistent with the presence of insulin resistance and intact counterregulatory hormone responses in patients with type 2 DM.

   The study also showed that lowering the blood pressure to 144/82 mmHg significantly reduced strokes, heart failure, and microvascular complications.

Conclusion
   The UKPDS study strongly supports the idea that hyperglycemia plays a causative role in the pathogenesis of diabetic microvascular complications. Although the effect of intensive management on macrovascular complications remains uncertain, the results suggest that efforts to normalize blood glucose may also be associated with fewer cardiovascular complications.
   This issue is being investigated further. The findings of the UKPDS study emphasize the importance of diagnosing type 2 DM as early as possible, using aggressive treatment to lower the blood glucose to close to normal, and assuring that blood pressure is kept below 130/85 mmHg.

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