Diabetes News
DALLAS, Nov. 16, 2005 (PRNewswire) -- Data from more than 43,000 people screened for the landmark NAVIGATOR trial involving the anti-hypertension drug Diovan(R) (valsartan) have shown a high prevalence of multiple risk factors for cardiovascular and metabolic disease, often with an association of these diseases in individual patients.
A new analysis of the screening data presented at the American Heart Association's Scientific Sessions 2005 showed that patients with higher cardiovascular or metabolic risks had increasing levels of a marker called alanine aminotransferase, or ALT, for non-alcoholic fatty liver disease (NAFLD). An earlier analysis also showed that a high percentage of people with cardiovascular risk who were screened for the trial also had previously unrecognized type 2 diabetes or impaired glucose tolerance (IGT), which is also known as "pre-diabetes."
Of the people who completed the NAVIGATOR screening process, a total of 22 percent (n=9,092) had undiagnosed type 2 diabetes, while a further 28 percent (n=11,853) had unrecognized IGT, which can progress to type 2 diabetes. Type 2 diabetes and IGT are both risk factors for the development of cardiovascular disease.
"NAVIGATOR is one of the largest trials to examine interventions to simultaneously prevent diabetes and cardiovascular disease. The screening data provide an opportunity to understand the multiple intercorrelated risk factors present in people at high risk for both conditions," said Dr. M. Angelyn Bethel, Assistant Professor of Medicine at Duke University Medical Center. "Type 2 diabetes is associated with an increased risk of cardiovascular disease and mortality related to cardiovascular events. As the incidence of type 2 diabetes continues to grow to epidemic proportions, it becomes more important that healthcare providers focus their efforts on interventions proven not only to improve diabetes control, but also to prevent the morbidity and mortality associated with cardiovascular disease."
Results of NAVIGATOR, the first and largest study designed to understand the progression and prevention of diabetes and cardiovascular disease, are expected to be reported in 2008 and will further clarify treatment strategies for patients with IGT.
The new analysis found that risk factors comprising the metabolic syndrome, including high blood pressure, increasing body mass index (BMI), increasing waist circumference, and worsening glucose tolerance were independently associated with increasing levels of ALT. The term NAFLD defines a spectrum of liver abnormalities ranging from benign fatty liver (steatosis) to the more advanced condition known as non-alcoholic steatohepatitis. Recent studies have demonstrated the link between insulin resistance in the liver and the subsequent development of NAFLD, which can progress to cirrhosis and end-stage liver disease.
More about NAVIGATOR and recent screening data
The ongoing NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) trial examines whether Diovan and/or Starlix(R) (nateglinide) delays or prevents the progression to type 2 diabetes and/or cardiovascular events. Diovan, a high blood pressure agent, is the most prescribed medication in the ARB (angiotensin receptor blocker) class in the US and worldwide. Starlix is indicated for the treatment of diabetes.
NAVIGATOR, which is unique in its size and design, is a prospective, multinational, randomized, double-blind, placebo controlled, two-by-two factorial design trial being conducted in 39 countries at nearly 800 sites. The 9,306 patients enrolled in the trial have IGT and are either older than age 50 with diagnosed cardiovascular disease or older than age 55 with at least one risk factor for cardiovascular disease, such as high blood pressure, family history of heart disease, high cholesterol or smoking.
More than 43,000 patients were screened for enrollment in the NAVIGATOR trial using a glucose tolerance test to assess their insulin sensitivity. Of the patients screened, 69 percent (n=28,556) were found to have hypertension, 42 percent (n=17,382) to have high levels of cholesterol, 28 percent (n=11,853) to have IGT and 22 percent (n=9,092) to have diabetes. Researchers found that 3.8 percent (n=1,546) had more than 1.5 times the normal upper limit of the liver enzyme ALT, a marker for NAFLD. A multivariate analysis showed risk factors for cardiovascular disease and metabolic syndrome were also associated with rising ALT levels. The associated risk factors included the following: increasing baseline systolic and diastolic blood pressure levels (p=0.03 and p=0.0001, respectively), increasing BMI (p<0.0001), waist circumference (p<0.0001), worsening glucose tolerance (both fasting and two hours post-challenge, p<0.0001) and metabolic syndrome (p<0.0001).
NAVIGATOR is one of the studies in the Diovan clinical trials program, which represents a large-scale research commitment across the cardiovascular continuum. Completed Diovan trials include VALUE in high blood pressure patients at high risk for cardiovascular events, VALIANT in post-heart attack patients and Val-HeFT in heart failure patients.