Sept. 11, 1998 *** Note: The following is my own interpretation of the findings and all are encouraged to read the full studies in the current issues of The Lancet and the British Medical Journal. *** UKPDS ISSUES LONG-AWAITED REPORT For nearly twenty years, researchers conducting the United Kingdom Prospective Diabetes Study (UKPDS) have been working to establish whether there is any type of treatment for Type 2 diabetes that can reduce the complications of Type 2 diabetes. While they have issued interim reports with valuable observations along the way, it was widely hoped that the report released yesterday (9/10/98) would yield helpful answers to questions about Type 2 diabetes such as: - Does keeping BGs lower delay the onset of complications? - Does reducing BGs reduce cardiovascular death rates? - Do some types of medications increase the rate of heart attacks or cardiovascular death? - Is there one type of treatment that is most effective for most Type 2 diabetics? The researchers recruited over 4,000 newly diagnosed Type 2 diabetics from across the United Kingdom. The majority were white and the median age was approx. 53 yrs old. The study participants were all without evidence of complications at the time of enrollment. While a large number of Type 2 diabetics show evidence of complications at the time they are diagnosed, it was important to recruit only diabetics without evidence of complications in order to look at how to prevent and delay complications. Study participants were initially assigned to either intensive treatment with medication or to diet treatment, with medication added as needed. The goals of treatment were to maintain fasting plasma glucose levels of 108 mg/dl [6 mmol/L) or below. * Intensive Treatment Did Not Reduce Death Risks After a median followup of 11 years, the diabetics using intensive treatment had average A1c levels that were 11% lower than the diabetics on conventional therapy. (It should be remembered that 11% reduction in A1c might be less than 1 point -- the difference between an 8.0 A1c and a 7.1 A1c is 11%). The diabetics using intensive therapy also showed a 12% reduction in the the risk of developing common complications, such as heart attack, stroke, and retinopathy (eye disease). Intensive treatment did not significantly reduce the risk of death from diabetes-related causes nor the overall risk of death from all causes. * Blood Pressure Treatment Is MORE Important Than Blood Glucose Control for Type 2 Diabetics for Long Life A subgroup of 1148 diabetics with hypertension or high blood pressure were assigned to either conventional or intensive blood pressure treatment. 54% were male and median age was 56.4 yrs old. The goals for conventional care were to keep BP below 154/97 and the goal for intensive care were to keep BP below 144/82. After a median followup of 8.4 years, the diabetics in the intensive BP care group showed remarkable average reductions in risks: - 32% reduction in risk for death from diabetes-related causes - 44% reduction in risk of stroke - 27% reduction in risk of microvascular complications After 9 years, the intensive treatment group also had greatly reduced risks (34% and 47%) of deterioration of their retinopathy and vision loss. To achieve the tight control of blood pressure, however, more than 1/4th (29%) of the participants had to use 3 or more types of medications to control their blood pressure. Comparison of beta-blockers vs ACE Inhibitors in study participants did not reveal that one was significantly more beneficial than the other in reducing high blood pressure to the goals of the intensive therapy group. Diabetics using beta-blockers had a slightly higher rate A1c and gained slightly more weight than those using ACE inhibitors, but the difference did not significantly affect rate of complications or death. It should be noted that the intensive treatment goals were much higher than the blood pressure goals recommended by the American Diabetes Assn. and the 6th JNC report, which advise that all diabetics should maintain BP below 130/85 and that diabetics with kidney damage should maintain BP below 125/75. * Metformin Used Alone Found Helpful For Obese Diabetics Looking at the subgroup of 1,704 obese diabetics in the study, researchers found that those using intensive treatment with sulfonlyurea and metformin combination treatment had nearly double the risk of diabetes-related death and a 60% increase in the risk of death from all-causes. However, it appeared that obese diabetics using metformin without having first used sulfonylurea medication had a significantly reduced rate of complications, as well as reduced rates of diabetes-related death and death from all-causes. Obese metformin users had a 39% reduction in heart attacks, a 42% reduction in risk of death from diabetes-related causes and a 36% reduction in risk of death from all-causes. This result did not apply to those who first used a sulfonlyurea drug first and then added metformin. The analytical methodology used in this aspect of the study has already been called into question and will likely remain a subject of controversy for some time to come. * The Bottom Line The UKPDS has been an important source of information about the treatment and progression of Type 2 diabetes for many years. Its findings can only be suggestive, not definitive, for U.S. diabetics due to many factors, including the different health care delivery system and different types of ethnic heritages of diabetics in the U.S. The recent reports have not settled the question about whether sulfonylurea medications (e.g., Glyburide, Micronase, Diabeta, Glucatrol) increase the risk of heart attacks and cardiovascular events, as found in the UGDP study in 1970, and as listed in the Warnings section on every patient information insert for these drugs. The reports have not shown that any specific type of treatment is clearly preferable for initial treatment of Type 2 diabetes, with the possible exception of metformin alone for obese diabetics -- and the findings regarding metformin will remain controversial for the time being. The reports indicate that intensive therapy for newly diagnosed Type 2 diabetics without evidence of complications at the time of diagnosis does not appear to result in greater life expectancy. Intensive diabetes therapy may reduce some complications, including heart attacks, by 12%. The reports suggest that intensive control of hypertension, or high blood pressure (which is found in 40% of 40 yr old Type 2 diabetics and 60% by age 75) is associated with very large reductions in the rate of strokes and eye damage, as well as a 32% reduction in the risk of death from diabetes-related causes. There are 40 reports now from the UKPDS researchers and each has yielded some interesting information. However, there are now still nearly as many important questions whose answers we must still await. - Paula