3 Metabolic Syndrome

Suggested citation:  Endocrine Society. Endocrine Facts and Figures: Obesity. First Edition. 2015.

On the basis of NHANES 2003–2006 data, the age-adjusted prevalence of MetS, a cluster of major cardiovascular risk factors with increased waist circumference and insulin resistance, is 34% (35.1% among men and 32.6% among women).101 MetS components as detailed in the 2001 Adult Treatment Panel (ATP) III report and updated by a joint statement in 2009 are:

  • Elevated waist circumference with population and country-specific definitions (ranging from 85 to 102 cm in men and 80 to 90 cm in women);
  • Elevated fasting triglycerides ≥ 150 mg/dL;
  • Reduced HDL cholesterol < 40 mg/dL in men and < 50 mg/dL in women;
  • Elevated blood pressure ≥ 130/85 mmHg or treatment for hypertension; and
  • Fasting glucose ≥ 100 mg/dL or use of antidiabetic medication.4,102

Three abnormal findings out of these five qualify an adult for MetS. Modified criteria for children and adolescents have been published by a panel of the International Diabetes Federation (IDF).6 These are as follows:

Age 6 to < 10 years

  • Obesity ≥ 90th percentile as assessed by waist circumference
  • MetS cannot be diagnosed, but further measurements should be made if family history of MetS, type 2 diabetes mellitus, dyslipidaemia, cardiovascular disease, hypertension, or obesity

Age 10 to < 16 years

  • Obesity ≥ 90th percentile (or adult cutoff if lower) as assessed by waist circumference
  • Triglycerides ≥ 1.7 mmol/L
  • HDL-cholesterol < 1.03 mmol/L
  • Blood pressure ≥ 130 mmHg systolic or ≥85 mmHg diastolic
  • Glucose ≥ 5.6 mmol/L (oral glucose tolerance test recommended) or known type 2 diabetes mellitus

Age ≥ 16 years

  • Use existing criteria for adults

Jolliffe and Janssen have also proposed age-specific MetS criteria for adolescents (age 12 to 19) that are linked to both the National Cholesterol Education Program Adult Treatment Panel III (ATP) and IDF adult MetS criteria.103

3.1 Metabolic Syndrome: Prevalence and Incidence

Tables 26 and 27 present the estimated prevalence of MetS in a study based on the results of the NHANES 1999-2000 and biannually through 2009-2010.3

Table 26. Age-standardized prevalence of MetS as estimated by the diagnostic criteria.
Years 1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
Total Population 25.54% 27.37% 25.76% 23.18% 24.94% 22.90%
Males 23.35% 27.45% 25.26% 24.57% 26.54% 23.69%
Females 27.50% 26.98% 26.20% 22.10% 23.54% 21.80%

Source: Beltrán-Sánchez H et al. 20133

Table 27. Age-standardized prevalence of MetS as estimated for persons with abdominal obesity.
Years 1999-2000 2001-2002 2003-2004 2005-2006 2007-2008 2009-2010
Total Population 45.35% 48.96% 55.35% 54.24% 53.78% 56.07%
Males 36.48% 39.82% 46.02% 46.41% 45.44% 46.44%
Females 53.53% 57.67% 64.41% 61.70% 61.93% 65.38%

Source: Beltrán-Sánchez H et al. 20133

3.1.1 Trends

The decrease in age-adjusted prevalence of MetS between 1999-2000 and 2009-2010 may be explained by an improved treatment of the underlying risk factors. During that period, prevalence of hypertriglyceridemia decreased (33.5% to 24.3%), as did elevated blood pressure (32.3% to 24.0%). The prevalence of hyperglycemia increased, as did elevated waist circumference (45.4% to 56.1%). These trends varied considerably by gender and race/ethnicity groups. Decreases in elevated blood pressure, suboptimal triglycerides, and HDL-C prevalence have corresponded with increases in antihypertensive and lipid-modifying drugs. The increase in elevated waist circumference parallels the increase in obesity in the US over this time period.3

3.2 Demographic Differences

The recently published cross-sectional cohort, interview-administered Hispanic Community Health Study/Study of Latinos (HCHS/SOL) tested theoretically driven hypotheses concerning psychosocial factors in CVD and was primarily focused on the high prevalence of diabetes among Latinos.104 In general, there was a higher rate of MetS among Latinos than among non-Hispanic whites, but the incidence of MetS differed among different Hispanic/Latino groups. It was highest among Puerto Ricans (37%) and lowest among South Americans (27%). The prevalence of MetS was significantly higher among Puerto Rican women (40.9%) than Puerto Rican men (32.6%) and paralleled the presence of diabetes.105

In a 2011 study of 300 Filipino-Americans, representative of the second largest Asian subgroup in the United States, a modified definition of MetS was used to take account of the ethnic-specific body structure: elevated waist circumference was defined as ≥90 cm in men and ≥88 cm in women. In participants 35 to 75 years of age, 18.3% of the participants (21.1% of males and 15.7% of females) met the threshold for MetS. The prevalence of MetS was considerably lower than the NHANES values for 2009-2010.106

Another study examining NHANES 2003-2006 found that non-Hispanic black males were about one-half as likely as non-Hispanic white males to meet the criteria for MetS, whereas non-Hispanic black and Mexican-American females were about 1.5 times as likely as non-Hispanic white females to meet the criteria. Further, MetS increased with age but even more dramatically as BMI increased.107

A more recent study taking account of both the WHO and Adult Treatment Panel III criteria for MetS found that rates for racial/ethnic minority groups are higher than those for adults overall. The modest decrease in MetS from 1999-2000 to 2009-2010 among US adults noted previously was not shared by racial/ethnic minorities: there was little change in prevalence among blacks (22.0% vs 22.71%) or Hispanics (32.9% vs 31.9%).108

The pediatric and adolescent prevalence of MetS, on the basis of NHANES 1999-2002 data, is summarized in Table 28. The prevalence of MetS in adolescents 12 to 19 years of age was 9.4%, which represents about 2.9 million people.

Table 28. Prevalence of MetS in US adolescents 12 years of age.
Adolescent Demographic MetS Prevalence (%)
Boys 13.2
Girls 5.3
White 10.7
Black 5.2
Mexican American 11.1
Overall 9.4

Source: Beltrán-Sánchez H et al, 20133; Falkner B et al, 2014108

 In 1999 to 2004, about 4.5% of US adolescents 12 to 17 years of age had MetS, according to the definition developed by the International Diabetes Federation. In 2006, this prevalence would have represented about 1.1 million adolescents aged 12 to 17. Prevalence increased from 1.2% among those 12 to 13 years of age to 7.1% among those 14 to 15 years of age, and was higher among boys (6.7%) than girls (2.1%). Furthermore, 4.5% of white adolescents, 3.0% of black adolescents, and 7.1% of Mexican American adolescents had MetS. The prevalence of MetS remained relatively stable during successive 2-year periods: 4.5% for 1999 to 2000, 4.4% to 4.5% for 2001 -2002, and 3.7% to 3.9% for 2003 -2004. Between 1999 and 2002, 44% of overweight adolescents or adolescents with obesity had MetS. From 1988 to 1994, two-thirds of all adolescents had at least 1 metabolic abnormality.73

3.3 Health Outcomes

Presence of MetS has health consequences beyond cardiovascular risk. A recent study using the ATPIII definition of MetS found a borderline-significant (P=0.06) relationship between MetS and glaucoma. In a sample of 3026 adult men and women from the 2005-2008 NHANES (weighted mean age: 57.0 years), the prevalence of glaucoma in patients with and without MetS was 5.3% and 3.6%, respectively.102 In a retrospective cohort study of 4216 women enrolled in an integrated health plan who were diagnosed with incident early-stage breast cancer between 1990 and 2008, 26% had at least 3 MetS components. Compared with women with no MetS components, presence of at least 3 MetS components was associated with an increased risk of second breast cancer events (hazard ratio, 1.50) and breast-cancer specific mortality (hazard ratio, 1.65).109 In a study of a large cohort (40,977 men; 21,277 women) in France using the NCEP-ATP criteria to define MetS, the following clinical and biological parameters were significantly associated with MetS in men and women, after adjustment for age: lower physical activity, lower vital capacity ratio, higher pulse pressure and heart rate, higher gamma-glutamyl transpeptidase, ASA and ALA transaminase and alkaline phosphatase levels, higher uricemia, leukocyte and globulin levels, dental and gingival inflammation, and higher stress and depression scores. After adjustment for age, the excess risk of all-cause mortality in subjects with MetS compared to subjects without MetS was 1.82 in men and 1.80 in women. After adjustment for age and gender, the risk of death associated with each MetS component was 2.36 for high waist circumference, 2.08 for elevated triglyceride levels, 1.71 for low HDL-cholesterol levels, 1.75 for elevated arterial pressure, and 2.93 for elevated glucose levels.109

3.4 Life Expectancy and Mortality

3.4.1 Death from Cardiovascular Disease

A prospective cohort study used data from 6255 adult participants in the NHANES II (30 to 74 years of age, 54% female) weighted to 63.9, representative of 64 million adults in the US. All subjects had mortality information, and were followed for a mean of 13.3 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior cardiovascular disease (CVD), age-, gender-, and risk factor-adjusted hazard ratios (HRs) for congestive heart disease (CHD) mortality were 2.02 for those with MetS and 4.19 for those with pre-existing CVD. For CVD mortality, HRs were 1.82 and 3.14, respectively; for overall mortality, HRs were 1.40 and 1.87, respectively. In persons with MetS but without diabetes, risks of CVD and CHD mortality remained elevated. Diabetes predicted all mortality end points. Those with even 1 to 2 MetS risk factors were at increased risk for mortality from CHD and CVD. Furthermore, MetS more strongly predicted CHD, CVD, and total mortality than did its individual components.110

In a 2014 study, the age-adjusted prevalence of MetS was 26.7% in the US Of the five MetS components, obesity significantly predicted CVD mortality in the US In that study, after a median follow-up of 13.8 years in the US, based on NHANES III for patients 30 year of age and older, 1,683 patients died from CVD (11.75 per 1,000 person-years).111

3.5 Diagnosis, Treatment and Prescription Trends

3.5.1 Treatment

The primary approaches for management of the individual components of MetS range from bariatric surgery to pharmaceutical intervention to behavioral modification. These treatments target the individual risk factors of MetS or obesity/insulin resistance. Because it results in weight loss, bariatric surgery significantly reduces prevalence. For instance, increased weight among breast cancer patients with MetS was the major factor in increased risk for a second breast cancer occurrence.109

Bariatric Surgery

A population-based, retrospective study of patients who had MetS as defined by the American Heart Association/National Heart, Lung, and Blood Institute were evaluated for bariatric surgery between January 1, 1990, and December 31, 2003. 180 underwent Roux-en-Y gastric bypass, and 157 were assessed in a weight-reduction program but did not undergo surgery. In the surgical group, all MetS components improved and medication use decreased. Nonsurgical patients showed improvements in high-density lipoprotein cholesterol levels. After bariatric surgery, the number of patients with MetS decreased from 156 (87%) of 180 patients to 53 (29%); of the 157 nonsurgical patients, MetS prevalence decreased from 133 patients (85%) to 117 (75%). A relative risk reduction of 0.59 was observed in patients who underwent bariatric surgery and had MetS at follow-up. Results were similar after excluding patients with diabetes or cardiovascular disease or after using diagnostic criteria other than body mass index for MetS. Significant predictors of MetS resolution included a 5% loss in excess weight; the reversibility of MetS depended more on the amount of excess weight loss than on other parameters.112

Bariatric surgery brings serious risks along with possibility of improvement. Among 186,576 bariatric surgery patients drawn from the Bariatric Outcomes Longitudinal Database between 2007 and 2010, 23,106 met the criteria for MetS. Among those patients, 62% underwent gastric bypass, 32% gastric banding, and 4.5% sleeve gastrectomy. MetS patients had an increase in serious complications compared with those without MetS (2.4% vs 1.0%), readmissions (6.2% vs 4.7%) and mortality (0.3% vs 0.1%) within 90 days of surgery. In 12,144 (53%) of the MetS patients, remission of hypertension, diabetes, and dyslipidemia occurred in 6%, 50%, and 35% of patients, respectively; 76% of MetS patients with sleep apnea went off all forms of treatment 12 months after the bariatric operation. Among procedures, adjustable gastric banding had a lower 12-month rate of remission of MetS compared with Roux-en-Y gastric bypass, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch.113

Pharmaceutical Intervention

A direct pharmaceutical intervention has been the subject of investigation since the discovery in 2003 that it was possible to lower MetS through a combination of drugs— statin, aspirin, and folic acid—termed the “polypill” or ”polycap.” In 2009, a group in India had some success in a clinical trial using 3 different statins with aspirin and folic acid to reduce cardiovascular risk factors.114

In a study based on 10-year longitudinal observations in an Australian population, in 1,991 cases classified as MetS in individuals free of existing diabetes mellitus or CVD, treatment with the polypill (or its components) was shown by mathematical analysis to be effective at reducing cardiovascular events. In 1,000 individuals, statin use alone could reduce MetS in 171 patients; aspirin (acetylsalicylic acid), in 201; and an antihypertensive in 186. The more drug therapies employed, the greater the reduction, with the polypill reducing up to 351 cardiovascular events per 10,000 individuals. Although not cost-effective compared with aspirin alone in the general population, in a high-risk population, among whom combination therapy is often prescribed, the polypill is likely to be more cost-effective than antihypertensive therapy alone or dual therapy with a statin and antihypertensive combination.115

Recently, interest in possible intervention has focused on the presence of reactive oxygen species as initiators of a vicious cycle activating an inflammatory response, ultimately contributing to diabetes, cardiovascular diseases, and steatosis. It is known that MetS is associated with oxidative stress and mitochondrial dysfunction.116 Recent evidence suggests that because Co-enzyme Q10 (Co-Q10), is an essential component of mitochondrial electron transport, Co-Q10 supplementation may be useful in MetS therapy. The anti-inflammatory response and lipid metabolizing effect of Co-Q10 is probably mediated by transcriptional regulation of inflammation and lipid metabolism.117 A study of obesogenic mice indicated that the mitochondria-targeted antioxidant MitoQ, a ubiquinone compound with the same antioxidant component as Coenzyme Q, had potential as a helpful therapy for MetS components.118 However, a recent study that investigated levels of Co-Q10, vitamin E, and antioxidant status in subjects with MetS concluded that only a higher level of antioxidant enzyme activities was significantly associated with a reduction in the risk of MetS independent of the levels of Co-Q10 and vitamin E.119

Behavioral modification

Behavioral modification as a way to reduce obesity and MetS seems to have a higher success rate in studies of pediatric populations, perhaps because adults were able to enforce changes in behavior among the children. 457 Singaporean children and adolescents (age 2-18 years) with obesity were guided through a 24-week lifestyle modification trial with components of exercise, diet education, and behavior modification. Among the 98% of the children who completed the trial, prevalence of MetS decreased from 20.8% to 1.8%.120

In a family-based approach, Swedish tutors guided 26 children with obesity aged 8 to 12 years and their parents through a study of eating habits, physical and sedentary activity, meeting every 3 months for a period of 2 years. For most of the participants, the favorable changes were in the increased amount of physical activity; eating habits according to the children’s self-reports improved after the intervention, whereas parental reports showed only a decrease in binge eating.121 A similar program among families of 423 children ages 2 to 5 years in preschool centers showed significant improvements in the rate of obesity and favorable trends in the BMI z-score.

Another approach used a combination of pharmaceuticals and behavioral modification. In a Diabetes Prevention Program randomized trial involving community volunteers having 3 or more MetS characteristics (waist circumference; blood pressure; and levels of high-density lipoprotein cholesterol, triglycerides, and fasting plasma glucose) that met criteria from the National Cholesterol Education Program Adult Treatment Panel II, 3 groups were compared. One group received metformin, 850 mg, twice daily; a second group received a placebo in place of metformin, and a third group underwent intensive lifestyle intervention designed to achieve and maintain a 7% weight loss and 150 minutes of exercise per week. Incidence of the MetS  was reduced by 41% in the lifestyle group and by 17% in the metformin group compared with placebo.122

Finally, dietary changes have been shown to reduce MetS. In 2008, a one-year trial showed that in a cohort where 61.4% of the participants met criteria for MetS, a Mediterranean diet supplemented with nuts reduced the prevalence of MetS in 13.7% of the participants originally presenting with MetS.123

Further corroboration of the Mediterranean diet’s effectiveness came in a secondary analysis of the multicenter, randomized PREDIMED trial conducted between 2003 and 2010. In a group of participants at high risk for CVD, MetS developed in 50.0%; reversion occurred in 28.2% of the participants who followed either the Mediterranean diet supplemented with nuts (HR, 1.10) or olive oil (HR, 1.35) as opposed to a control group who had received only advice to follow a low-fat diet. There was a significant reduction in both central obesity and high fasting glucose in the group supplemented with olive oil, and a significant decrease in central obesity in the group supplemented with nuts.124

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