The American Journal of Medicine
Volume 120, Issue 9, Supplement 1 , Pages S1-S2, September 2007

Introduction

  • Scott M. Grundy, MD, PhD

      Affiliations

    • Corresponding Author InformationRequests for reprints should be addressed to Scott M. Grundy, MD, PhD, Center for Human Nutrition, Department of Clinical Nutrition, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas, 75390-9052.

Center for Human Nutrition, Department of Clinical Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas, Veterans Affairs Medical Center, Dallas, Texas

Article Outline

 

The rates of obesity and type 2 diabetes mellitus in the United States are approaching epidemic proportions. Currently, the majority of US adults (>56%) are overweight, and, according to a Centers for Disease Control and Prevention (CDC) surveillance study, in 2000 the prevalence of obesity (body mass index [BMI] ≥30) was 19.8%, and the prevalence of diabetes was 7.3%.1 These statistics, which are based on self-reported information, probably underestimate the true prevalence. A community-based sample of middle-aged adults reported that the incidence of diabetes doubled over the past 30 years.2 According to the Third National Health and Nutrition Examination Survey (NHANES III) 86% of patients aged >50 years with type 2 diabetes also have the metabolic syndrome, which is a clustering of atherogenic risk factors including dyslipidemia, elevated blood pressure, elevated blood glucose, a prothrombotic state, and a proinflammatory state, and is a precursor to cardiovascular disease (CVD).3, 4 Despite widely disseminated management guidelines,5, 6, 7, 8 the obesity and diabetes epidemics continue unabated and if the current trends continue, obesity and its associated complications (metabolic syndrome, type 2 diabetes, coronary heart disease [CHD], cancer, and other diseases)3, 9, 10, 11 threaten to undermine gains in life expectancy in this century.

Early intervention strategies can prevent overweight and obesity (specifically abdominal obesity) from progressing to the cascade of cardiometabolic complications that begins with insulin resistance and borderline CVD risk factors and culminates in type 2 diabetes and CVD events.12 The National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)5 and subsequent guidelines6 use metabolic syndrome criteria to facilitate the clinical simplification of cardiometabolic risk factor assessment in office practice.4 The term metabolic syndrome describes a constellation of metabolic risk factors that includes atherogenic dyslipidemia, elevated blood pressure, elevated plasma glucose, a prothrombotic state, and a proinflammatory state.6 Individuals with the metabolic syndrome typically are overweight or obese with an “apple-shaped” body type characterized by a large waist circumference.13

The primary treatment for the metabolic syndrome is lifestyle therapy—weight loss, increased physical activity, and an antiatherogenic diet—with the objective of preventing progression to diabetes and CVD.12 Risk factor assessment algorithms should be used to guide the intensity of therapy, particularly regarding use of drugs, for patients with the metabolic syndrome, as detailed in my article in this supplement to The American Journal of Medicine. Unfortunately, despite its proven potential to reduce the severity of cardiometabolic risk at every stage of progression,8, 14 lifestyle intervention (alone or in combination with drug therapy) is often overlooked in routine clinical practice.12

Currently, the drugs approved for the treatment of metabolic syndrome are those that target individual risk factors: lipid-lowering drugs, antihypertensive agents, hypoglycemic drugs, antiplatelet drugs, and weight-loss agents. However, the concept of reducing multiple risk factors with a single drug or a combination of drugs (thereby avoiding the risks associated with polypharmacy) has become increasingly attractive, particularly as the population prevalence of obesity and cardiometabolic risk continue to climb.12

Sibutramine and orlistat, weight-loss agents approved for long-term use, improve cardiometabolic risk factors and produce moderate weight loss.12, 15, 16 The endocannabinoid (EC) system, a newly identified physiologic system involved in lipid and glucose metabolism, may be linked to the development of various cardiometabolic risk factors. Cannabinoid (CB) receptors, specifically CB1 receptors, found in the brain and in various peripheral organs, appear to play a pivotal role in regulating energy balance and body weight. Rimonabant,⁎ the first CB1 receptor antagonist, offers a new approach to reducing weight and abdominal adiposity and to improving various cardiometabolic risk factors. In the Rimonabant in Obesity (RIO) clinical trials program,17, 18, 19, 20 rimonabant in combination with a hypocaloric diet caused sustained weight loss over 1- and 2-year periods17, 19 and reduced cardiometabolic risk factors seemingly through both weight loss–dependent and weight loss–independent mechanisms, even in patients with preexisting diabetes and dyslipidemia.18, 20

The articles presented in this supplement are based on an educational program held during the 66th Scientific Session of the American Diabetes Association (ADA) Congress in Washington, DC, in June 2006, and address the issues of obesity and cardiometabolic risk, exploring new approaches to their management.

An estimated 47 million individuals in the United States have the metabolic syndrome,21 making its management a top clinical priority. In the first article, I discuss the importance of early identification of high-risk patients to implement risk-reduction strategies targeted toward each patient’s cardiometabolic risk factor profile. Next, Dr. Steven M. Haffner focuses on overweight and obesity, particularly abdominal adiposity, and other cardiometabolic risk factors that increase the risk of developing diabetes and CVD, emphasizing lifestyle intervention as an effective first-line management strategy. He also describes the association of obesity, the metabolic syndrome, insulin resistance, and type 2 diabetes with nonalcoholic fatty liver disease. Dr. George Kunos reports on both his research and that of other investigators regarding the role of the EC system in energy and fat metabolism, both through central and peripheral actions, with central sites within the hypothalamus and peripheral sites, including adipose tissue, skeletal muscle, and the liver. He concludes that preclinical studies demonstrate that CB1 blockade reduces weight and adiposity, decreases hepatic lipogenesis, increases fatty acid oxidation, and improves glucose homeostasis. Finally, the clinical efficacy of CB1 blockade with rimonabant in promoting weight loss and improvements in cardiometabolic parameters is covered by Dr. Michael D. Jensen in his review of data from the phase 3 RIO clinical trials.

The authors believe that the information presented in this supplement will help physicians improve outcomes for patients at high cardiometabolic risk. It is our hope that widespread early intervention with risk-targeted management approaches will reduce the prevalence of overweight and obesity and its associated cardiometabolic risks.

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References 

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  2. Fox CS, Pencina MJ, Meigs JB, Vasan RS, Levitzky YS, D’Agostino RB. Trends in the incidence of type 2 diabetes mellitus from the 1970s to the 1990s: the Framingham Heart Study. Circulation. 2006;113:2914–2918
  3. Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes. 2003;52:1210–1214
  4. Grundy SM. Diabetes and coronary risk equivalency: what does it mean?. Diabetes Care. 2006;29:457–460
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  6. Grundy SM, Brewer B, Cleeman JI, Smith SC, Lenfant C Conference Participants. NHLBI/AHA Conference Proceedings: definition of metabolic syndrome (Report of the National Heart, Lung, and Blood Institute/American Heart Association Conference on Scientific Issues Related to Definition). Circulation. 2004;109:433–438
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  12. Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol. 2006;47:1093–1100
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  17. Van Gaal LF, Rissanen AM, Scheen AJ, Ziegler O, Rossner S RIO-Europe Study Group. Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience for the RIO-Europe study. Lancet. 2005;365:1389–1397
  18. Despres JP, Golay A, Sjostrom L Rimonabant In Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005;353:2121–2134
  19. Pi-Sunyer FX, Aronne LJ, Heshmati HM, Devin J, Rosenstock J RIO-North American Study Group. Effect of rimonabant, a cannabinoid-1 receptor blocker, on weight and cardiometabolic risk factors in overweight or obese patients: RIO-North America (A randomized controlled trial). JAMA. 2006;295:761–775
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  • ⁎ Recently, an FDA Advisory Committee recommended a delay in the approval of rimonabant because of safety issues that need to be addressed in further studies.

PII: S0002-9343(07)00542-6

doi:10.1016/j.amjmed.2007.06.004

The American Journal of Medicine
Volume 120, Issue 9, Supplement 1 , Pages S1-S2, September 2007

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