Metabolic syndrome (MetS) is a combination of risk factors such as hypertension, atherogenic dyslipidemia, hyperglycemia, truncal (central) obesity, and prothrombotic and proinflammatory conditions, which could increase the risk of cardiovascular illness, diabetes, and death. According to an estimate by the International Diabetes Foundation, nearly one-fourth of the world’s population has MetS [
Thyroid diseases are among the most prevalent endocrine disorders worldwide. Based on the estimation from various studies, it has been projected that about 42 million people in India suffer from thyroid diseases [
Several studies have shown a correlation between thyroid function and the indices of MetS [
In this multicenter cross-sectional study, adult patients with an established diagnosis of MetS were enrolled across ten sites in India between October 2016 and January 2017. The study protocol was approved by local independent ethics committees. The study was conducted in accordance with the principles of the Declaration of Helsinki, International Council on Harmonization Good Clinical Practice (ICH GCP) guidelines, and Indian regulatory guidelines (Indian Council of Medical Research and Indian GCP guidelines). The study was registered on a publicly accessible database of clinical trials in India with registration number CTRI/2016/09/007270.
Patients aged 18 to 65 years, with an established diagnosis of MetS based on the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III criteria (with modified waist), with or without known TD, were invited to participate in the study during their routine clinical visit to the endocrinologists, gastroenterologists, and/or hepatologists. Pregnant patients or patients with a history of jejunoileal bypass, biliopancreatic diversion, extensive small bowel resection, total parenteral nutrition, any forms of chronic liver disease, hepatocellular carcinoma, patients on weight loss therapies or steatogenic drugs, and known HIV-positive cases were excluded from the study. At the screening visit, the following data were collected in the case report forms: demographics, anthropometric measurements, significant medical (including FPG, serum TG, and HDL-C values from patients’ medical records) and surgical history, family history, lifestyle parameters, history of consumption of any obesogenic medicines, vital signs, and details of physical examination.
After obtaining an informed signed consent to participate in the study, the eligible patients from the screening visit were requested to visit the clinic after an overnight fast within 3-10 days of consenting. At this visit (visit 1), abdominal ultrasound examination (USG) was performed in patients who did not consume alcohol or consumed less than 20 g of alcohol per day and had not received corticosteroids, amiodarone, or tamoxifen. Blood samples were collected for assessment of hemogram, coagulogram (activated partial thromboplastin time, thrombin time, and prothrombin time), plasma insulin, plasma glucose, lipid profile (TG, total cholesterol (TC), HDL-C, and low-density lipoprotein cholesterol (LDL-C)), and thyroid function (free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH)). The fasting plasma glucose and plasma insulin were used for the calculation of homeostatic model assessment-established IR (HOMA-IR). The patients were followed up for a mean of one year to check for new diagnoses of TD.
The primary endpoint was the prevalence of TD among patients with MetS. Other endpoints included the percentage of patients with hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, and subclinical hypothyroidism and percentage of patients with TD with respect to individual components of MetS (waist circumference, TG, HDL-C, SBP, DBP, and fasting glucose) and IR (
The BMI cutoff limits for overweight and obesity were as follows: overweight (
Insulin resistance was assessed using the HOMA score. The cutoff for IR was HOMA-IR
The MetS was diagnosed based on the NCEP-ATP III criteria. The MetS was present, if ≥3 risk factors of the following five criteria were met: abdominal obesity (waist circumference: men: >102 cm (>40 in), women: >88 cm (>35 in)); TG (≥150 mg/dL); HDL-C (men: <40 mg/dL, women: <50 mg/dL); blood pressure (≥130/≥85 mmHg); and fasting glucose (≥110 mg/dL) [
TD was graded as described in Table
Definitions for different grades of thyroid dysfunction.
Parameters | Hyperthyroidism | Hypothyroidism | ||
---|---|---|---|---|
Overt | Subclinical | Overt | Subclinical | |
TSH ( |
<0.45 | <0.45 | >4.50 | >4.50 |
FT4 (ng/dL) | >1.8 | 0.8-1.8 | <0.8 | 0.8-1.8 |
FT3 (pg/mL) | >4.4 | 1.4-4.4 | <1.4 | 1.4-4.4 |
TSH: thyroid-stimulating hormone; FT4: free thyroxine; FT3: free triiodothyronine.
Assuming that the prevalence rate of hypothyroidism in patients with MetS was approximately 26% [
All statistical analyses were performed using SAS® version 9.2 (SAS Institute Inc., USA). The prevalence of TD in MetS patients was calculated as a number and percentage with 95% CI.
In this study, we had enrolled 432 patients with MetS. The baseline demographic characteristics of these patients are shown in Table
Demographics and baseline characteristics of 432 patients with metabolic syndrome.
Parameter | Total ( | ||
---|---|---|---|
Age in years | |||
Mean (SD) | 36.7 (6.08) | 55.6 (5.52) | 47.9 (10.96) |
Range | 21.0-45.0 | 46.0-65.0 | 21.0-65.0 |
Gender | |||
Women, |
104 (58.76%) | 149 (58.43%) | 253 (58.56%) |
Men, |
73 (41.24%) | 106 (41.57%) | 179 (41.44%) |
Height in cm, mean (SD) | 163.0 (9.02) | 160.8 (8.44) | 161.7 (8.74) |
Weight in kg, mean (SD) | 79.4 (13.13) | 75.8 (12.29) | 77.3 (12.75) |
Waist circumference in cm, mean (SD) | 98.5 (9.41) | 98.7 (9.92) | 98.6 (9.70) |
Hip circumference in cm, mean (SD) | 106.3 (11.07) | 104.7 (11.14) | 105.4 (11.13) |
SD: standard deviation.
Of the 432 MetS patients, overt hypothyroidism was reported in 76 (17.59%) patients and overt hyperthyroidism in 7 (1.62%) patients (Table
Percentage prevalence of different grades of thyroid dysfunction.
Classification of TD | MetS patients ( |
---|---|
Hypothyroidism |
69 (16.00) |
New overt hypothyroidism | 7 (1.60) |
New subclinical hypothyroidism | 35 (8.10) |
Hyperthyroidism |
7 (1.60) |
New overt hyperthyroidism | 0 |
New subclinical hyperthyroidism | 3 (0.70) |
Total number of TD patients | 121 (28.00) |
TD: thyroid dysfunction; MetS: metabolic syndrome.
The most common MetS components associated with TD were high waist circumference (121 (99.17%); women (>80 cm): 75.21%; men (>90 cm): 23.97%), reduced HDL-C (87.60%), systolic blood pressure (94 (77.69%)), diastolic blood pressure (94 (59.50%)), fasting glucose (71 (58.68%)), TG (40 (33.06%)), and elevated HOMA-IR (>1.64) (105 (86.78%)). All the MetS components except TG were more prevalent in patients with >45 years age group (Figure
Percentage of TD patients in different age groups with MetS components and insulin resistance.
Thyroid hormones play an essential role in regulating energy balance and metabolism of glucose and lipids, thereby affecting the MetS parameters, including HDL-C, TG, blood pressure, and plasma glucose. Hypothyroidism is found to be associated with obesity, dyslipidemia, and increased risk of atherogenic CVD [
Oxidative stress, chronic inflammation, and angiogenesis are believed to enhance the pathogenesis of MetS [
In our study, 28% of the patients with MetS were diagnosed with TD. This is in agreement with the results of other studies from India [
In our study, women with MetS had a higher incidence of TD in comparison to men (21.06% vs. 6.94%). This corroborates reports from other studies where women outnumbered men in terms of prevalence of TD in MetS [
In this study, the MetS components observed in patients diagnosed with TD were high waist circumference, reduced HDL-C, raised HOMA-IR, systolic blood pressure, diastolic blood pressure, fasting glucose, and TG. A higher proportion of females had waist circumference above the cutoff (>80 cm) as compared to men (>90 cm; 75.21% vs. 23.97%). Though the other studies have also reported an association between TD and components of MetS, but it is still debatable. A Nigerian study reported MetS to be significantly associated with higher FT4 [
It should be noted that while exploring the relationship between TD and components of MetS, most studies have focused on the subclinical hypothyroidism. Further, it should be noted that the pattern of TD in MetS and its relationship with components may vary upon geographic locale, age, gender, diet, and genetics, and environmental factors [
There are a few limitations of the present study. First, as this was a cross-sectional study, a cause and effect relationship could not be determined. Second, the grades of hypothyroidism in the subjects who were already on levothyroxine supplement could not be assessed due to lack of adequate previous data. Moreover, a cohort study is needed to evaluate the deleterious effect of TD on metabolic functions. Third, the iodine nutrition status or thyroid autoimmunity was not assessed in the study. Fourth, the impact of age, gender, and body weight on thyroid functions was not assessed in the study.
To conclude, the prevalence of TD in patients with MetS was high, indicating a possible interplay between thyroid status and MetS. Hypothyroidism was the most common TD in Indian patients with MetS. The data generated from the present study will aid in establishing a correlation between TD and MetS in Indian patients. This data will have prognostic importance for practitioners in their routine clinical practice to develop strategies for better management of their patients of TD with associated MetS. This early diagnosis of TD in MetS would help in modifying the disease course by early interventions with appropriate lifestyle modification regimens, as applicable. However, future large sample-sized prospective studies are warranted which could evaluate the impact of TD management in terms of reduction in MetS and its related components.
The data used to support the findings of this study are included within the article.
This data was presented at the 87th Annual Meeting of the American Thyroid Association, held on October 18-22, 2017, in Canada.
Dr. Deshmukh and Dr. Farishta received research funding from Abbott India Ltd as investigators. Dr. Bhole is an employee of Abbott India Ltd.
The authors thank the study participants without whom this study would not have been accomplished, as well as the investigators for their participation in this study. The authors also thank Dr. Natasha Das (freelance medical writer, Delhi) and Dr. Shalini Nair (Abbott) for providing writing and editing assistance in developing this manuscript. This study was funded by Abbott India Ltd.