08 August 2009

Biochemistry of Metabolic Syndrome

Connecting the biochemical dots that lead to atherosclerosis is what is best attempted by the term metabolic syndrome (MS) (1). The term, of which is still under controversy, is used as a predictor of cardiovascular disease and type 2 diabetes mellitus (2-4).

MS can begin with abdominal obesity (MS dot 1), a consequence of overeating and a sedentary lifestyle (1;5). The additional adipose tissue can then reduce affinity of insulin receptors and/or create abnormal post-receptor responses resulting in insulin resistance (MS dot 2) (1).

Once insulin resistance overwhelms capacity to produce insulin to overcome it, then type 2 diabetes mellitus (T2DM) ensues (1). T2DM is accompanied by hyperglycemia and often by hyperlipidemia (MS dot 3) (1). The hyperlipidemia results because VLDL and chylomicrons are not cleared by the enzyme lipoprotein lipase of which is dependent on insulin (1). The high levels of free fatty acids then impair insulin action further (1). Plus, new research suggests that reduced secreition of adiponectin along with tumor necrosis factor alpha (TNFa) and a protein called resistin act to impair insulin receptor function (1). Poorly controlled glucose levels is then found along with hyperinsulinemia in cases (1).

Finally, the insulin resistance and hyperinsulinemia can stimulate salt reabsorption in the kidneys causing hypertension (MS dot 4) (5). Hypertension, or elevated blood pressure, and its force on artery walls makes them vulnerable to plaque build-up and narrowing that can ultimately lead to hardening of the arteries or atherosclerosis (6).

Clinically, the knowledge of progressing events in MS is what allows it to serve a valid purpose with patients (5;7). A doctor or nutritionist, for example, can use MS awareness to predict future risk factors and assist in treating obese patients with lower-calorie diet and other methods.

Reference List
1. Devlin TM. Textbook of Biochemistry with Clinical Correlations. Philadelphia: Wiley-Liss, 2002.
2. Lau DC. Metabolic syndrome: perception or reality? Curr Atheroscler Rep 2009;11:264-71.
3. Lien LF, Guyton JR. Metabolic syndrome. Dermatol Ther 2008;21:362-75.
4. Gallagher EJ, LeRoith D, Karnieli E. The metabolic syndrome--from insulin resistance to obesity and diabetes. Endocrinol Metab Clin North Am 2008;37:559-79, vii.
5. Ren J, Kelley RO. Cardiac health in women with metabolic syndrome: clinical aspects and pathophysiology. Obesity (Silver Spring) 2009;17:1114-23.
6. Takeuchi K. [Hypertension and metabolic syndrome/lifestyle diseases]. Rinsho Byori 2007;55:452-6.
7. de ZD, Bakker SJ. Does the metabolic syndrome add to the diagnosis and treatment of cardiovascular disease? Nat Clin Pract Cardiovasc Med 2008;5 Suppl 1:S10-S14.

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