When to Suspect Metabolic Syndrome

Given the widespread and increasing prevalence of metabolic dysfunction,1 identifying it in our patients is increasingly important. For many, obesity may be the first indicator of metabolic issues, but research suggests that not all obese patients are metabolically unhealthy.2 The converse is also true;

approximately 20% of normal-weight individuals are estimated to have metabolic disturbances.3

Moreover, certain conditions may predispose a patient to metabolic dysfunction, as can prescribed medications. How can clinicians move beyond BMI and use advanced physical exam skills and comprehensive testing to identify insulin resistance in individuals of all body types?

For a patient who isn’t a textbook example of insulin resistance, there are some clues that point to such dysfunction as a possibility. Even for normal weight individuals, a brief physical exam offers numerous ways to highlight nutritional and metabolic concerns—and IFM’s Cardiometabolic Advanced Practice Module (APM) teaches you how to see these signs.

One study suggests that manifestations of insulin resistance on the skin may be more reliable than other forms of diagnosis.10 Skin manifestations may also indicate severity of metabolic syndrome.11 Even in children and adolescents, acanthosis nigricans offers a reliable physical exam clue for metabolic syndrome.12 Other physical signs of metabolic syndrome can be hirsutism,13 peripheral neuropathy,14 and xanthelasma palpebrarum.15 Inflammation also appears to play a key role in the development of insulin resistance and future atherogenesis in patients with metabolic syndrome.16

Once you suspect there may be a metabolic issue, you may want to consider testing fasting and two-hour insulin levels, as IFM educator Kristi Hughes, ND, discusses in the following video, as a way to gain deeper insight into patients’ unique metabolic states:

IFM educator Kristi Hughes, ND, manages an integrated team of healthcare providers: naturopathic physicians, nurses, acupuncturists, massage therapists, and lifestyle coaches.

Beyond BMI

The first head-to-head comparison of a large number of cardiometabolic risk phenotypes revealed that normal-weight people (as defined by a BMI of <25 kg/m2) may experience insulin secretion failure, insulin resistance, and increased carotid intima-media thickness (cIMT).3 According to this study, insulin secretion failure may be of major relevance for cardiometabolic risk in normal-weight patients, as it promotes hyperglycemia. Furthermore, compared to people who are of normal weight and metabolically healthy, subjects who are of normal weight but metabolically unhealthy (?20% of the normal-weight adult population) have a greater than three-fold higher risk of all-cause mortality and/or cardiovascular events.3

A variety of factors may increase the likelihood of metabolic syndrome, including:

  • Celiac disease: A 2015 study of patients with celiac disease showed a high risk of metabolic syndrome one year after starting a gluten-free diet; the authors suggested potential causes such as an improvement in intestinal absorption and the subjects eating foods that were higher in sugar, fat, and calories after going gluten-free.4 A 2018 study found that in celiac disease patients, following a gluten-free diet may contribute to the development of metabolic syndrome.5
  • Polycystic ovary syndrome (PCOS): In women with polycystic ovary syndrome, the risk of developing gestational diabetes is approximately three times greater than in non-PCOS women;6 insulin resistance occurs in 30% of lean women with PCOS.7
  • Schizophrenia: A genetic study in 2014 found that a large percentage (45%) of patients with schizophrenia using clozapine as the primary treatment modality suffered adverse metabolic effects.8
  • Stress: A five-year longitudinal study in a rapid response police unit supports the hypothesis that work-related stress induces metabolic syndrome, particularly through its effects on blood lipids.9

Researchers suggest that when a patient with normal weight has two or more parameters of the metabolic syndrome, it is important to determine whether impaired glucose tolerance, fatty liver, or early atherosclerosis is present.3 The physical exam offers numerous ways to zero in on nutritional and metabolic concerns to help the clinician precisely understand the pathophysiology of cardiometabolic disease and develop targeted lifestyle and pharmacological interventions.3 With early diagnosis and intervention, the disease course of metabolic syndrome may be controlled or even reversed.

Learn more 

Learn more about lifestyle modifications to modify cardiometabolic disease risk.

Gain some clinical pearls on cardiometabolic treatment.

Read about the effects of the microbiome on cardiovascular health.


  1. Kelli HM, Kassas I, Lattouf OM. Cardio metabolic syndrome: a global epidemic. J Diabetes Metab. 2015;6(3):513. doi:4172/2155-6156.1000513
  2. Jung CH, Lee WJ, Song KH. Metabolically healthy obesity: a friend or foe? Korean J Intern Med. 2017;32(4):611-621. doi:3904/kjim.2016.259
  3. Stefan N, Schick F, Häring HU. Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab. 2017;26(2):292-300. doi:1016/j.cmet.2017.07.008
  4. González-Saldivar G, Rodríguez-Gutiérrez R, Ocampo-Candiani J, González-González JG, Gómez-Flores M. Skin manifestations of insulin resistance: from a biochemical stance to a clinical diagnosis and management. Dermatol Ther. 2017;7(1):37-51. doi:1007/s13555-016-0160-3
  5. Huang Y, Chen J, Wang X, Li Y, Yang S, Qu S. The clinical characteristics of obese patients with acanthosis nigricans and its independent risk factors. Exp Clin Endocrinol Diabetes. 2017;125(3):191-195. doi:1055/s-0042-123035
  6. Velazquez-Bautista M, López-Sandoval JJ, González-Hita M, Vázquez-Valls E, Cabrera-Valencia IZ, Torres-Mendoza BM. Association of metabolic syndrome with low birth weight, intake of high-calorie diets and acanthosis nigricans in children and adolescents with overweight and obesity. Endocrinol Diabetes Nutr. 2017;64(1):11-17. doi:1016/j.endinu.2016.09.004
  7. Talaei A, Adgi Z, Mohamadi Kelishadi M. Idiopathic hirsutism and insulin resistance. Int J Endocrinol. 2013;2013:593197. doi:1155/2013/593197
  8. Stino AM, Smith AG. Peripheral neuropathy in prediabetes and the metabolic syndrome. J Diabetes Investig. 2017;8(5):646-655. doi:1111/jdi.12650
  9. Nair PA, Singhal R. Xanthelasma palpebrarum – a brief review. Clin Cosmet Investig Dermatol. 2017;11:1-5. doi:2147/CCID.S130116
  10. Devaraj S, Jialal I. The skinny on metabolic syndrome in adolescents. Transl Pediatr. 2016;5(2):97-99. doi:21037/tp.2016.03.06
  11. Tortora R, Capone P, De Stefano G, et al. Metabolic syndrome in patients with coeliac disease on a gluten-free diet. Aliment Pharmacol Ther. 2015;41(4):352-359. doi:1111/apt.13062
  12. Ciccone A, Gabrieli D, Cardinale R, et al. Metabolic alterations in celiac disease occurring after following a gluten-free diet. Digestion. 2018;14:1-7. doi:1159/000495749
  13. Yao K, Bian C, Zhao X. Association of polycystic ovary syndrome with metabolic syndrome and gestational diabetes: aggravated complication of pregnancy. Exp Ther Med. 2017;14(2):1271-1276. doi:3892/etm.2017.4642
  14. Baldani DP, Skrgatic L, Ougouag R. Polycystic ovary syndrome: important underrecognised cardiometabolic risk factor in reproductive-age women. Int J Endocrinol. 2015;2015:786362. doi:1155/2015/786362
  15. Faasen N, Niehaus DJH, Koen L, Jordaan E. Undiagnosed metabolic syndrome and other adverse effects among clozapine users of Xhosa descent. S Afr J Psychiatr. 2014;20(2):a528. doi:4102/sajpsychiatry.v20i2.528
  16. Garbarino S, Magnavita N. Work stress and metabolic syndrome in police officers. A prospective study. PLoS One. 2015;10(12):e0144318. doi:1371/journal.pone.0144318


Related Insights