Evidence-Based Reviews

Metabolic syndrome: 5 risk factors guide therapy

Current Psychiatry. 2005 April;4(4):73-88

References

1. Haffner SM, Valdez RA, Hazuda HP, et al. Prospective analysis of the insulin-resistance syndrome (syndrome X). Diabetes 1992;41:715-22.

2. Isomma B, Almgren P, Tuomi T, et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9.

3. Trevisan M, Liu J, Bahsas FB, Menotti A. Syndrome X and mortality: a population-based study. Am J Epidemiol 1998;148:958-66.

4. Lakka HM, Laaksonen DE, Lakka TA, et al. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.

5. National Institutes of Health: Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Cholesterol in Adults (Adult Treatment Panel III). Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA 2001;285:2486-97.

6. Consensus Development Conference on Antipsychotic Drugs and Obesity and Diabetes. Diabetes Care 2004;27:596-601.

7. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults—the evidence report. National Institutes of Health. Obes Res 1998;6(suppl 2):51S-209S.

8. Darwin D. Metabolic syndrome: time for action. Am Fam Physician 2004;69:2875-82.

9. Maki KC. Fibrates for treatment of the metabolic syndrome. Curr Atheroscler Rep 2004;6:45-51.

10. Boden WE. Therapeutic implications of recent ATP III guidelines and the important role of combination therapy in total dyslipidemia management. Curr Opin Cardiol 2003;18:278-85.

11. Showers JR. Effects of statins on the vasculature: implications for aggressive lipid management in the cardiovascular metabolic syndrome. Am J Cardiol 2003;91(suppl):14B-22B.

12. Yusuf S, Gerstein H, Hoogwerf B, et al. for the HOPE Study Investigators. Ramipril and the development of diabetes. JAMA 2001;286:1882-5.

13. American Diabetes Association. Treatment of hypertension in adults with diabetes. Diabetes Care 2003;26(suppl 1):S80-S82.

14. Derosa G, Cicero AF, Bertone G, et al. Comparison of the effects of telmisartan and nifedipine gastrointestinal therapeutic system on blood pressure control, glucose metabolism, and the lipid profile in patients with type 2 diabetes mellitus and mild hypertension: a 12-month, randomized double-blind study. Clin Ther 2004;26:1228-36.

15. Diabetes prevention program research group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403.

16. Buchanan T, Xiang A, Peters R, et al. Prevention of type 2 diabetes by treatment of insulin resistance: comparison of early vs. late in the TRIPOD study [abstract]. Diabetes 2002;51(suppl 2):A35.-

17. Leon AS, Sanchez O. Meta-analysis of the effects of aerobic exercise training on blood lipids. Circulation 2001;104(suppl II):414-15 (abstract).

18. Fagard RH. Exercise characteristics and blood pressure response to dynamic physical training. Med Sci Sports Exerc 2001;33(6 suppl):S484-S492.

19. Thompson PD, Crouse SF, Goodpaster B, et al. The acute versus the chronic response to exercise. Med Sci Sports Exerc 2001;33(6 suppl):S438-S445.

20. Katzmarzyk PT, Leon AS, Wilmore JH, et al. Targeting the metabolic syndrome with exercise: evidence from the HERITAGE Family Study. Med Sci Sports Exerc 2003;35:1703-9.

21. Littrell KH, Hilligoss NM, Kirshner CD, et al. The effects of an educational intervention on antipsychotic-induced weight gain. J Nurs Scholarsh 2003;35:237-41.

22. Menza M, Vreeland B, Minsky S, et al. Managing atypical antipsychotic-associated weight gain: 12-month data on a multimodal weight control program. J Clin Psychiatry 2004;65:471-7.

23. Cohen SA, Fitzgerald BJ, Khan SR, Khan A. The effect of a switch to ziprasidone in an adult population with autistic disorder: chart review and naturalistic, open-label treatment. J Clin Psychiatry 2004;65:110-13.

24. Casey DE, Carson WH, Saha AR, et al. Switching patients to aripiprazole from other antipsychotic agents: a multicenter randomized study. Psychopharmacology 2003;166:391-9.

25. Wong ND, Pio J, Franklin SS, et al. Preventing coronary events by optimal control of blood pressure and lipids in patients with the metabolic syndrome. Am J Cardiol 2003;91:1421-6.

Table 2

Suggested monitoring intervals for patients taking atypical antipsychotics*

	Baseline	4 weeks	8 weeks	12 weeks	Quarterly	Annually	Every 5 years
Personal/family history	X					X
Weight (BMI)	X	X	X	X	X
Waist circumference	X					X
Blood pressure	X			X		X
Fasting plasma glucose	X			X		X
Fasting lipid profile	X			X			X
*Clinical status may warrant more-frequent assessments
BMI: Body mass index
Source: Reference 6.

MANAGING METABOLIC PROBLEMS

Managing metabolic abnormalities or metabolic syndrome is aimed at preventing type 2 diabetes and CVD. Levels of intervention include:

weight management, weight control education, and promoting regular exercise and a healthy diet
switching to a psychotropic that is less likely to cause weight gain, if clinically appropriate
working with the patient’s primary care physician to manage dyslipidemia, hypertension, obesity, or hyperglycemia.

Weight management. Start by controlling weight and promoting regular exercise and healthy eating. Switching medications—often the first response—may not be the best option, particularly if the offending agent is relieving the patient’s psychiatric symptoms.

Losing weight, increasing exercise, and reducing fat and carbohydrate intake can reverse metabolic syndrome and delay onset of type 2 diabetes and CVD.⁷ Even a small weight loss, such as 10% of baseline body weight in persons who are overweight (BMI >25) or obese (BMI >30) can significantly reduce the risk of hypertension, hyperlipidemia, hyperglycemia, and death.⁷

Rather than promoting a single diet, tailor dietary advice to each patient’s metabolic abnormalities (Table 3). Although researchers disagree over whether a low-fat or low-carbohydrate diet produces better results, either diet will work as long as the patient consumes fewer calories than he or she expends. This is because weight loss alone reverses metabolic syndrome.

Likewise, exercise can reverse metabolic syndrome independent of diet change. Regular exercise at modest levels improves HDL,² triglycerides,¹⁷ blood pressure,¹⁸ and hyperglycemia.¹⁹

In one prospective study,²⁰ 621 subjects without chronic disease or injury underwent supervised aerobic training three times weekly for 20 weeks. Participants were told not to otherwise change their health and lifestyle habits.

Of the 105 persons in the cohort who had metabolic syndrome at baseline, 32 (30%) no longer had it after the aerobics program. Among these participants:

43% had lower triglycerides than at baseline
16% had higher HDL cholesterol
38% had lower blood pressure
9% had improved fasting glucose
28% reduced their waist circumference.

Table 3

Interventions for specific metabolic complications

Metabolic complication	Nondrug interventions⁸	Medications
Abdominal obesity	Encourage weight loss	Sibutramine^*†
	Increase physical activity	Appetite suppressant
		Orlistat^*†
		Lipase inhibitor
Hypertriglyceridemia	Encourage weight loss	Fibrates^9*
	Increase physical activity	Reduce fasting and postprandial triglycerides 20% to 50%
	Increase low-glycemic-index food intake	Shift small dense LDL to large buoyant particles
	Reduce total carbohydrate intake	Increase HDL particles 10% to 35%
	Increase consumption of omega-3 fatty acids	Nicotinic acid¹⁰
	Limit alcohol consumption	Reduces triglycerides 20% to 50%
		Statins¹¹
		Reduce fasting and postprandial triglycerides 7% to 30%
		Reduce LDL particles
		Increase HDL particles
		Reduce major coronary vascular events
Low HDL	Encourage weight loss	Nicotinic acid^*
	Increase physical activity	Increases HDL particles 15% to 35%
	Stop smoking	Fibrates⁹
	Increase monounsaturated fat intake	See above
		Statins¹¹
		See above
Hypertension	Encourage weight loss	ACE inhibitors^*
	Increase physical activity	May slow progression to diabetes¹²
	Reduce saturated fat intake	Decrease CVD events¹³
	Reduce sodium intake	Delay progression of microalbuminuria¹³
	Limit alcohol consumption	Angiotensin receptor blockers
		May improve dyslipidemia associated with metabolic syndrome¹⁴
		Delay progression of microalbuminuria¹³
Hyperglycemia	Encourage weight loss	*Metformin,^ thiazolidinediones**
	Increase physical activity	Slow progression to diabetes in persons with insulin resistance^15,16 (metformin less effective than lifestyle changes)¹⁵
	Reduce total carbohydrates
^* Suggested first-line therapy.
^† For patients with BMI 30 kg/m2
ACE: Angiotensin-converting enzyme
CVD: Cardiovascular disease
HDL: High-density lipoprotein cholesterol
LDL: Low-density lipoprotein cholesterol

Selling the benefits of exercise and weight loss to a mentally ill patient can be difficult. Attention, memory, and motivation deficits as well as smoking and substance abuse often get in the way.

By teaming up with clinicians with expertise in dieting such as nurses, dietitians, and recreational therapists, psychiatrists can more effectively promote long-term diet, exercise, and lifestyle changes.²¹

In a prospective 12-month trial,²² 20 patients who were taking atypical antipsychotics for schizophrenia or schizoaffective disorder completed a 52-week program that incorporated nutrition, exercise, and behavioral interventions. Twenty similar patients received treatment as usual. Patients in the program saw significant improvements in weight, blood pressure, exercise habits, nutrition, and hemoglobin A1c compared with the treatment-as-usual group.²²

Psychiatrists who treat privately insured patients should collaborate with the patient’s primary care physician. Many insurance plans will pay for 1 or 2 personal or group sessions with a dietitian, especially if the patient is diagnosed as being obese (BMI >30). Some large plans, such as Kaiser Permanente, will cover intensive multimodal treatment, especially for patients with a BMI >35. Calculating the patient’s BMI can help you document the need for antiobesity treatment (see Related resources).

Medication. If weight control and exercise do not reduce metabolic risk factors after 3 to 6 months, consider switching to an atypical antipsychotic with a lower propensity for causing metabolic effects.

Which agents most decrease metabolic risk has been debated. Preliminary evidence indicates that switching from other antipsychotics to aripiprazole or ziprasidone may reduce weight and improve cholesterol ratios.^23,24 These findings are consistent with the ADA/APA consensus guidelines, which indicate that metabolic risk varies among atypical antipsychotics (Table 4).⁶