Physician's Weekly Article - Conference Highlights: The ADA 2008 Annual Meeting

       The American Diabetes Association held its 68th Scientific Sessions from June 6 to June 10 in San Francisco. The features below highlight just some of the news emerging from the meeting. For more information on these items and other research that was presented, go to http://professional.diabetes.org/.

      Three Studies Yield Insights on Intensifying Glucose Control

      Study #1: ACCORD

      The Particulars: The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was conducted to determine if a strategy of intensive glucose control in patients with type 2 diabetes could reduce the risk of cardiovascular disease (CVD). All ACCORD patients had long-standing type 2 diabetes and were at high risk for CVD; 35% had a CVD event prior to entering the trial. The remaining participants had subclinical CVD or major cardiovascular risk factors. The goal for the intensive treatment group was to reach an A1C level of less than 6%, while the standard group A1C goal was between 7% and 7.9%.

      Data Breakdown: Patients with type 2 diabetes who received intensive therapy to control glucose levels had a 22% higher relative risk of death when compared with the standard therapy group. Intensive group patients only had a non-significant 10% lower risk of a first occurrence of a major fatal or non-fatal CVD event during follow-up. However, these patients had a 24% lower risk of non-fatal heart attacks. A safety review terminated the intensive treatment arm early due to an increased death rate in the intensive treatment group.

      Take Home Pearls: There appears to be some risk associated with intensifying glycemic control by the treatment algorithms used in ACCORD in high-risk CVD patients with type 2 diabetes. All ACCORD patients will continue to be followed for at least another 18 months, and results will be reanalyzed at that time.

      Study #2: ADVANCE

      The Particulars: The Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation (ADVANCE) trial, an international study involving 11,140 high-risk patients with type 2 diabetes, was designed to address whether important clinical benefits would result from reducing A1C to 6.5% or lower and from intensive blood pressure lowering. Patients received hypertension treatment with a fixed-dose combination of perindopril (an ACE inhibitor) and indapamide (a diuretic) or a placebo, and diabetes treatment with gliclazide MR plus other anti-diabetic drugs as needed.

      Data Breakdown: At baseline, the average A1C of all participants was 7.5%. At 5 years follow-up, the average A1C in the intensive group was 6.5% compared with 7.3% for the standard group. Intensively controlling blood glucose reduced risk for the development or progression of kidney disease by 21%. ADVANCE showed no evidence of any increased risk of death when blood glucose was intensively controlled. The intensive control strategy reduced the combined risk of macrovascular and microvascular complications by 10%, but these findings were driven largely by microvascular results. ADVANCE did not show a statistically significant effect of intensive glucose control on CVD.

      Take Home Pearls: Intensive control of blood glucose appears to have an important role in the prevention of kidney complications associated with type 2 diabetes. A multifactorial approach addressing all major risk factors (eg, blood pressure and lipids) is recommended to prevent macrovascular disease.

      Study #3: VADT

      The Particulars: The VA Diabetes Trial (VADT) involved patients with long-standing type 2 diabetes who had multiple health problems, including 40% with prior CVD events. The primary goal of VADT was to reduce all other CVD risk factors to compare outcomes between standard and intensive blood glucose treatment groups.

      Data Breakdown: The VADT specifically included only patients who had unacceptable A1C levels on maximal doses of at least one oral anti-diabetes drug and/or insulin. Among the study group, 80% had hypertension, more than 50% had lipid abnormalities, and the vast majority were obese. On average, participants in both the standard and intensive blood glucose treatment groups were at or below targets for lipid levels and blood pressure within the first 2 years, and maintained these targets for 6 years during participation. Although intensive treatment of patients with type 2 diabetes suggested some benefits from glucose control, it did not reach significance for a reduction in a composite of specified CVD events. Significantly fewer CVD events occurred in both groups than predicted; researchers believe this was largely due to excellent blood pressure control, lipid control, improved diet and exercise, and treatment with aspirin. Sub-analyses of the data and a sub-study of the relationship between coronary artery calcification and the effect of intensive glycemic control on CVD events suggested that intensive glycemic control might have a benefit in reducing CVD events in type 2 diabetic patients with more recent onset of diagnosed diabetes (less than 6 years) and with low coronary artery calcium scores.

      Take Home Pearls: Intense control of blood glucose in type 2 diabetes appears to reduce the risk of CVD by reducing cardiovascular events, but data from the entire VADT cohort were not considered statistically significant. If all the other CVD risk factors are reduced, A1C levels appear to be a stronger marker for microvascular complications (eg, retinopathy, nephropathy, and neuropathy) than for macrovascular complications (eg, heart attacks and strokes).

      The Impact of Periodontal Disease on Type 2 Diabetes

      The Particulars: Periodontal disease may make it more difficult to control glucose levels, and could have a significant impact on diabetes and its complications.

      Data Breakdown: Several studies were analyzed. An analysis of data from 1988-1994 found that people with periodontal disease were twice as likely to have insulin resistance as those without such disease, even after controlling for other insulin-resistance characteristics and diabetes status. Other research found that patients with type 2 diabetes with periodontitis were more than four times as likely to develop worsening glycemic control after 2 years of follow-up. Higher risks of death due to diabetic nephropathy or ischemic heart disease were observed in patients with periodontal disease. An NIH-funded trial of people with type 2 diabetes found a statistically significant reduction of 0.67% in A1C levels when patients with periodontitis were reevaluated at 15 months after routine periodontal treatment.

      Take Home Pearl: When glucose levels are difficult to control, physicians should consider asking patients about their last visit to the dentist, whether periodontitis has been diagnosed, and what treatment, if any, has been completed.

      Translating the A1C to Facilitate Patient Education

      The Particulars: A1C has been understood to represent an estimated average glucose (eAG) in the blood over time, and some small studies have shown a correlation between A1C and eAG. The A1C-Derived Average Glucose (ADAG) study was conducted to confirm and define the relationship between A1C and eAG.

      Data Breakdown: The ADAG study was successful in defining the relationship between eAG and A1C levels. A1C was measured in a central laboratory at the end of 3 months, and patients’ glucose levels were measured using a combination of continuous glucose monitoring and frequent self-monitoring. A mathematical equation was developed that defines a linear relationship between A1C and eAG. With the results of the study in hand, the ADA and other organizations are encouraging labs to report both A1C and eAG values in their reports to give physicians and other health professionals a new measurement, in mg/dL or mmol/L, that may facilitate patient education about diabetes control.

      Take Home Pearls: A strategy of using the mathematical relationship between glucose levels over the preceding 3 months and A1C measurements allows A1C to be reported as eAG. When treatment goals are set based on eAG units, patients can know how close they are to reaching their goals every day when they use self-monitoring tests.

      Silent Ischemia: Assessing Asymptomatic Patients

      The Particulars: The incidence of silent myocardial ischemia in people with diabetes has been reported to be as high as 60%, but such estimates have been debated because of patient selection criteria for studies. The Detection of Ischemia in Asymptomatic Diabetics (DIAD) study was conducted to assess the prevalence of such ischemia and discern whether expensive coronary artery disease (CAD) screening should be offered to all people with type 2 diabetes.

      Data Breakdown: Patients in the DIAD study were randomly assigned to either a screening or control (no screening) group. All DIAD participants were called every 6 months to check if they had developed any symptoms of cardiac problems. After nearly 5 years, there was essentially no difference in CVD outcomes between the groups; the overall cumulative rate of cardiac events was 2.8%. Of patients screened at the outset of DIAD, 22% had silent myocardial ischemia, of which only 6% of cases were considered severe. The physicians of 30% of the unscreened control group independently found reasons to recommend various diagnostic and treatment procedures to their patients. Because these control patients likely had an equal prevalence of ischemia as those who were screened, standard clinical care and attentive follow-up appear to be sufficient to detect at-risk patients and those in need of intensive cardiologic care.

      Take Home Pearls: DIAD found favorable 5-year outcomes for asymptomatic patients with type 2 diabetes without evidence of CAD. Investigators reported that expensive screenings are not needed when standard clinical care and careful follow-up are attentive.

      Harold E. Lebovitz, MD has indicated to Physician’s Weekly that he has worked as a consultant for LifeScan, Novartis Pharmaceuticals Corporation, and Sanofi-aventis. He is also on the advisory board of Amylin Pharmaceuticals, Inc. and is in the speaker’s bureau of GlaxoSmithKline International and Lilly International. He is also a stockholder of Amylin Pharmaceuticals, Inc, and Merck Pharmaceuticals.