Metabolic Syndrome: The Tip of the Diabetic Iceberg

Salcido, Richard MD, EdD

Advances in Skin & Wound Care:
doi: 10.1097/01.ASW.0000436696.111171.f3
Departments: Editorial
Author Information

Richard “Sal” Salcido, MD, EdD, is the Editor-in-Chief of Advances in Skin & Wound Care and the Course Director for the Annual Clinical Symposium on Advances in Skin & Wound Care. He is the William Erdman Professor, Department of Rehabilitation Medicine; Senior Fellow, Institute on Aging; and Associate, Institute of Medicine and Bioengineering, at the University of Pennsylvania Health System, Philadelphia.

Article Outline

Type 2 diabetes is a common preventable public health affliction. Unfortunately, type 2 diabetes or diabetes associated with obesity is now a disorder found in children and is now reaching epidemic proportions.1,2 Recently, attempts have been made to classify signs and symptoms that indicate clues to the early and late ravages of type 2 diabetes on the body’s systems and organs, including the skin, which has been variably defined as a constellation of systemic manifestations pointing to metabolic perturbations.3–5

Figure. No caption a...

Metabolic syndrome is variously termed, including insulin-resistance syndrome, syndrome X, deadly quartet, dysmetabolic syndrome, cardiometabolic syndrome, and plurimetabolic syndrome. Cumulatively, metabolic syndrome has been variously defined by several entities, including the World Health Organization (WHO, 1999), the National Cholesterol Education Program Adult Treatment Panel III (2001), the American College of Endocrinology (2003), and the International Diabetes Federation (2005).3–6

A syndrome is “an aggregate, constellation, or triad of signs and symptoms” associated with disease process. Together, they form a construct of the disease—exemplified in the case of metabolic syndrome.3–6 The WHO definition encompasses diabetes, impaired fasting glucose, impaired glucose tolerance, or insulin resistance, plus 2 or more of the following risk factors: a body mass index greater than 30 kg/m2, a waist-to-hip ratio greater than 0.85 (female) or greater than 0.90 (male), abnormal serum lipids, triglycerides greater than 150 mg/dL, HDL cholesterol less than 39 mg/dL (female) or less than 35 mg/dL (male), a blood pressure greater than 140/90 mm Hg, the existence of microalbuminuria greater than 20 or greater than 30 mg/g, and a high albumin-creatinine ratio, indicating renal impairment.3–6

The key skin manifestations of metabolic syndrome include Acanthuses nigricans, skin tags (acrochordon) in the nuchal area or the interiginous skin folds, eczema, folliculitis, foot ulcers, venous stasis disease, and folliculitis nuchae at the nape of the neck. Clinical and subclinical inflammatory processes of the mouth, gums, and dentition are usually involved.7–9

Metabolic syndrome should be considered a biologically defined syndrome with a common underlying etiology, probably insulin resistance. To date, no evidence exists to attribute the symptoms of metabolic syndrome to a common cause. Treating risk factors separately may be a better approach.10

Depression is also nonspecifically linked to obesity, diabetes, and sleep apnea. All of these comorbidities are associated with metabolic syndrome and are thought to increase insulin resistance. In addition, antidepressant use increases the risk of evolving from “prediabetes” to type 2 diabetes. Bariatric surgery has also been shown to normalize glucose tolerance and in some case reverse insulin resistance. In the emerging field of “personalized medicine,” genetic markers may provide early identification of those at risk as well.

There are new classes of drugs, such as incretin mimetics, which regulate gut hormones (amylin) that slow the flow of sugar from the stomach to the blood, and new drugs that have the potential to treat intra-abdominal adiposity (an established marker for cardiometabolic risk factors). Many patients with metabolic syndrome or its components take medications to specifically temporize or to treat the underlying causes.

A radical but not too far-fetched concept is a daily cocktail to treat type 2 diabetes. The “polypill” would include a lipid-lowering agent, angiotensin-converting enzyme inhibitors for hypertension and potentially cardioprotection, and aspirin as a platelet inhibitor to reduce new thrombus formation. Such a drug agent could potentially save lives, prevent myocardial infarctions, reduce renal failure, and result in fewer cases of blindness associated with diabetes. However, the potential economic impact could be huge, potentially reducing pharmacy and medical cost. As attractive as the concept is, more work needs to be done to prove the efficacy of such a strategy.11,12

Nonetheless, the simplest and most cost-effective prevention and treatment therapies for metabolic syndrome are daily exercise (exercise reduces insulin resistance), appropriate caloric intake, and expenditure management.13

Richard “Sal” Salcido, MD, EdD

Figure. No caption a...
Back to Top | Article Outline


1. Wilson V. Type 2 diabetes: an epidemic in children. Nurs Child Young People 2013; 25 (2): 14–7.
2. Hardin DS. Screening for type 2 diabetes in children with acanthosis nigricans. Diabetes Educ 2006; 32: 547–52.
3. Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, 2001. JAMA 2003; 289 76–9.
4. Sarafidis PA, Nilsson PM. The metabolic syndrome: a glance at its history. J Hypertens 2006; 24: 621–6.
5. Huang Paul L. A comprehensive definition for metabolic syndrome. Dis Model Mech 2009; 2: 231–7.
6. Alberti KG, Zimmet P, Shaw JIDF Epidemiology Task Force Consensus Group. The metabolic syndrome—a new worldwide definition. Lancet 2005; 366: 1059–62.
7. Lopez-Alvarenga JC, Garcia-Hidalgo L, Landa-Anell MV, et al. Influence of skin color on the diagnostic utility of clinical acanthosis nigricans to predict insulin resistance in obese patients. Arch Med Res 2006; 37: 744–8.
8. Zadak Z. Internist’s view on skin manifestations of hyperlipidemia in diabetic patients [in Czech]. Vnitr Lek 2006; 52: 465–9.
9. Cahill J, Sinclair R. Cutaneous manifestations of systemic disease. Aust Fam Physician 2005; 34: 335–40.
10. Peck PAHA and ADA declare truce in metabolic syndrome squabble. Last accessed September 24, 2013.
11. Dabhadkar KC, Kulshreshtha A, Ali MK, Narayan KM. Prospects for a cardiovascular disease prevention polypill. Annu Rev Public Health 2011; 32: 23–38.
12. Reddy KS. The preventive polypill–much promise, insufficient evidence. N Engl J Med 2007; 356: 212.
13. Pimlott N. Getting bums out of seats. Can Fam Physician 2013; 59: 911.
© 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins. All world rights reserved.