Pre-diabetes glucose abnormality identified as early risk factor for cardiovascular disease

Findings from worldwide epidemiology study INSPIRE-ME IAA presented at 46th European Association for the Study of Diabetes (EASD) Annual Meeting.

Paris, France –– Sanofi-aventis (Euronext: SAN and NYSE: SNY) announced today the baseline results of a worldwide prospective longitudinal epidemiologic study designed to assess the predictive value of risk factors for developing cardiovascular disease and Type 2 diabetes – INSPIRE-ME IAA (INternational Study of Prediction of Intra-abdominal adiposity and its RElationship with cardioMEtabolic risk/Intra-Abdominal Adiposity).

The key baseline results showed that increasingly poor glucose control is associated with an increased cardiovascular risk profile.1 Four categories of glucose control were studied: people with normal glucose control; those with impaired fasting glucose/impaired glucose tolerance (IFG/IGT); those with well-controlled diabetes; and those with poorly-controlled diabetes.

“Cardiovascular risk factors such as lipid parameters, blood pressure, inflammatory markers, and visceral fat volume were worsened as soon as glucose control began to deteriorate, starting with subjects with IFG/IGT,” noted Jean-Pierre Després, Director of Research, Cardiology, Laval Université, Québec, Canada, and Principal Investigator of the Imaging Study in INSPIRE ME IAA.

“There was clearly a gradient of severity in the cardiovascular risk factors across the four groups of patients, highlighting both the importance of identifying these patients as soon as possible and also the need to offer them pharmacological treatment to control their glucose metabolism and associated cardiovascular risk factors”.

INSPIRE-ME IAA is an international, epidemiological study with a three-year follow up, involving more than 4500 patients, 297 physicians in 29 countries (including Brazil, China, France, Germany, Malaysia, Japan and US) across five continents.

“Aiming to better understand different diabetes patient types and patient profiles and their associated cardiovascular risk, sanofi-aventis is committed to investigating the causes of, and risk factors associated with diabetes, as well as treatments for the disease.” commented Dr Riccardo Perfetti, Vice-President, Medical Affairs, Global Diabetes Division, sanofi-aventis.

One aim of this baseline analysis was to determine the relationship between cardiovascular risk factors and glucose tolerance status. Lipid profile, measures of overweight/obesity, including waist circumference, BMI and visceral adiposity (measured by CT scan) showed a significant relationship with decreasing glucose control, as did inflammatory markers and systolic blood pressure.

Of particular interest is the increase in cardiovascular risk for those with IFG/IGT, as well as those with established diabetes. Addressing cardiovascular risk in those with IFG/IGT is a key aim of the ongoing ORIGIN (Outcome Reduction with an Initial Glargine Intervention) trial.2 The trial is investigating the effectiveness of two treatment options to reduce cardiovascular (CV) outcomes in people aged ?50 years with evidence of CV disease and either IFG, IGT, newly detected or established diabetes: .once-daily injection of the long-acting basal insulin analogue, Lantus (insulin glargine), compared with standard glycemic care. polyunsaturated fatty acids (1g consisting of EPA 465 mg and DHA 375mg), compared with placebo

“From our better understanding of the patient characteristics of those at risk of cardiovascular disease, shown in the INSPIRE-ME IAA study, we can reaffirm the hypothesis of ORIGIN and the benefits of insulin glargine intervention for different patient profiles, including for those with IFG/IGT ” added Dr Perfetti.

The primary outcome for the insulin arm is CV events and for the ?-3 fatty acid arms is CV death. Results from the trial are expected in 2012.

About INSPIRE-ME IAA - INSPIRE ME IAA (INternational Study of Prediction of Intra-abdominal adiposity and its RElationship with cardioMEtabolic risk/Intra-Abdominal Adiposity) is an international observational prospective study with a three-year follow up, involving more than 4500 patients, 297 physicians in 29 countries. All physicians were hospital based and either primary care physicians/ internists; cardiologists; or endocrinologists/diabetologists.

The three-year follow up study will investigate the relationship between the baseline cardiovascular risk characteristics of the subjects, including anthropometric parameters (BW, WC, visceral fat volume measured by CT scan, lipid profile, BP, inflammatory markers, specific metabolic markers) and the new occurrence of an ischemic CV event or onset of Type 2 diabetes.

About diabetes - Diabetes is a long-term disease that occurs either when the pancreas does not produce enough insulin (the hormone that regulates blood glucose concentrations), or when the body cannot effectively use the insulin it produces, or both. This results in raised blood glucose concentrations (hyper glycemia).3 Over time, uncontrolled hyper glycemia leads to the macrovascular and microvascular complications of diabetes. Macrovascular complications, which affect the large blood vessels, include heart attack, stroke and peripheral vascular disease. Microvascular complications affect the small blood vessels of the eyes (retinopathy), kidney (nephropathy) and nerves (neuropathy). Worldwide, in 2010 it is estimated that the number of people with diabetes will reach 285 million people - 6.6% of the population; by 2030 it is estimated that 438 million people will have diabetes - 7.8% of the population.4

About impaired glucose control/impaired fasting glucose - Impaired glucose tolerance (IGT) is used to describe a state of increased risk of progressing to diabetes, although many people with IGT will revert to normal glucose control. IGT is not a clinical condition in itself, but is a risk factor for future diabetes and/or adverse outcomes, including an increased risk of cardiovascular disease.5 Impaired fasting glucose describes the zone between the upper limit of normal fasting glucose and the lower limit of the diabetic fasting glucose. As with IGT, it is not a clinical entity but a risk factor for future diabetes and adverse outcomes.5

About sanofi-aventis - Sanofi-aventis, a leading global pharmaceutical company, discovers, develops and distributes therapeutic solutions to improve the lives of everyone. Sanofi-aventis is listed in Paris (EURONEXT: SAN) and in New York (NYSE: SNY).

References: 1. Despres J-P et al Comparison of Visceral adiposity and liver fat in 4277 individuals from an international cohot of patients cloassified according to their glucose tolerance status: the INSPIRE ME IAA study EASD 2010 Abstract 329

2. The ORIGIN Trial Investigators Rationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: The ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention) Am Heart J 2008;155:26-32.e6.

3. World Health Organisation, Fact sheet No 312, November 2009.

4.International Diabetes Federation, IDF atlas http://www.diabetesatlas.org.

5.Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF Consultation. WHO IDF 2006.