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Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients
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Original Article
Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients Mohamed Larbi Hamlaouia , Ammar Ayachia , Aoulia Dekakenb , Adel Gouric,* a
Laboratoire de microbiologie Immunologie, Institut des Sciences Vétérinaires et Agronomiques, Département Vétérinaire, Université de Batna, Algeria Department of Internal Medicine, Public Hospital El Okbi, Guelma, Algeria c Department of Clinical Biochemistry, College of Medicine, Badji Mokhtar University, Annaba, Algeria b
A R T I C L E I N F O
A B S T R A C T
Article history: Available online xxx
Aims: The aim of this study is to evaluate the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status. Materials and methods: A prospective cross-sectional study was conducted in the internal medicine department at El Okbi Hospital of Guelma (East of Algeria) from January 2014 to September 2015. Eighty six patients attending the specialist consultation for suspected thyroid disorders were included in the study. Gender; blood pressure; body mass index; and serum levels of fasting glucose, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol, and triglyceride were compared between subjects with hypothyroidism, hyperthyroidism and euthyroidism. Results and conclusion: Thyroid dysfunction was found in 59.3% (n = 42) patients, hypothyroidism (45.3%) was the major thyroid dysfunction followed by hyperthyroidism (14.0%). Overall, the prevalence of metabolic syndrome was 48.8% (n = 42). Subjects with hypothyroidism had significantly higher level of BMI, WC, TC, LDL-C, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05). The hyperthyroid group had significantly lower level of TC, LDL-C and HDL-C but a higher level of SBP and UA. Furthermore, abdominal obesity, hypertension and low HDL-C level were the most common metabolic syndrome compounds found in the hyperthyroid group compared to the euthyroid group. We found a positive association between TSH level and the prevalence of the metabolic syndrome. © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Keywords: Metabolic syndrome Cardiovascular risk Thyroid hormone Hypothyroidis Hyperthyroidism
1. Introduction The metabolic syndrome (MetS) is defined as a cluster of interrelated metabolic abnormalities, characterized by central obesity, hyperglycemia, hypertriglyceridemia, decreased high density lipoprotein-cholesterol (HDL), and elevated blood pressure (BP). People with MetS have an increased risk of cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality. MetS requires 3 of the following 5 factors to make a diagnosis: increased waist circumference (WC), elevated triglycerides (TG), reduced HDL, elevated BP, and elevated fasting glucose (FG) [1,2]. Thyroid hormones have pleiotropic effects on lipid and glucose metabolism, blood pressure, and energy expenditure. Thyroid dysfunction is a risk factor of cardiovascular disease [3]. Recently, serum thyroid stimulating hormone (TSH) is also found to be associated with adverse changes of lipid metabolism as well [4,5].
The relationship between mild thyroid dysfunction and MetS traits has become a hot topic of discussion recently; they are the two most common endocrine disorders with a substantial overlap [6]. Both are associated with significant morbidity and mortality and thus impact substantially on health care [7,8]. In Algeria, socioeconomic, nutritional and epidemiological transition had contributes to the increase in different chronic diseases and abnormalities constituting metabolic syndrome [9]. The prevalence of metabolic syndrome in Algerian population was estimated at 20%, higher in women than men [10]. Furthermore, the frequency of thyroid diseases in Algeria continues to rise in recent years; they particularly affect adult female subjects [11,12]. There is no report studying thyroid dysfunction and metabolic syndrome association in Algerian population. The aim of this study is to evaluate the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status.
* Corresponding author . E-mail addresses: [email protected], [email protected] (A. Gouri). http://dx.doi.org/10.1016/j.dsx.2017.08.001 1871-4021/© 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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2. Materials and methods
two-tailed P value of less than 0.05 was considered to be statistically significant.
2.1. Population and study design 2.5. Ethics This cross-sectional study was conducted in the internal medicine department at El Okbi Hospital of Guelma (East of Algeria) from January 2014 to September 2015. Eighty six patients attending the specialist consultation for suspected thyroid disorders were included in the study. A structured questionnaire was filled out by each patient, which details: age, sex, height, weight, blood pressure, personnel and family medical history, clinical findings and laboratory results. Written informed consent was obtained from each patient after full explanation of the purpose and nature of all procedures used. 2.2. Clinical and biological measurements Fasting blood samples (venous blood samples taken after overnight fast of a minimum of 8 h) were collected; Serum glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), albumin, total serum proteins, urea, creatinine, uric acid, calcium, phosphorus, iron, magnesium, liver transaminases, creatine phosphokinase (CPK), lactate deshydrogenase (LDH), alkaline phosphatase (ALP) were measured using an clinical chemistry autoanalyzer (XL 200 Erba diagnostics Mannheim), complete blood count, including hemoglobin (Hb), haematocrite (Hct), red blood cells, white blood cells and platelets, using an hematology coulter (Diatron Abacus). Ferritin (Ferr), serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibody (ATPO Ab) and anti-thyroglobulin antibody (ATG Ab) were measured by using fluorescent immunoassay (VIDAS, biomeriux SA, France). Reference range for TSH was 0.25–5 mIU/L, FT3 (4.0– 8.3 pmol/L), FT4 (9.0–20.0 pmol/L) anti-TPO (0–8 UI/ml) and antiTG (0–18 UI/ml). All blood samples were analyzed in the laboratory of Medical Biochemistry, Ibn Zohr Public Hospital, Guelma, Algeria. 2.3. Definitions Metabolic syndrome (MetS) was diagnosed by the modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATPIII) criteria [13], which requires 3 or more of the following parameters: Elevated waist circumference (WC) >102 cm for men and >88 cm for women, hypertriglyceridemia (TG 1.7 mmol/L); low HDL cholesterol (HDL-C <1.03 mmol/L for men and <1.30 mmol/L for women); elevated blood pressure (systolic blood pressure 130 mmHg and/or diastolic blood pressure 85 mmHg or current use of antihypertensive drugs); impaired fasting glucose (fasting plasma glucose 5.6 mmol/L). Thyroid function subgroups were determined as following; patients were said to be euthyroid if all thyroid hormone levels fell within reference range. Hypothyroidism was defined as TSH >5. Hyperthyroidism was defined as TSH <0.25 mIU/L. 2.4. Data analysis Continuous variables are expressed as means standard deviation (SD); and categorical variables as frequencies and percentages. Using the euthyroid group as reference, the differences in baseline characteristics were tested using the Student’s ttest for continuous data and Chi-square test for categorical data at 95% confidence interval. Pearson correlation coefficients were calculated to find relationship between the components of metabolic syndrome and thyroid profile parameters at 95% confidence interval. All statistical analyses were performed with the SPSS 20.0 (SPSS, Chicago, IL) statistical package for Windows. A
The study was carried out in accordance with the ethical principles for medical research involving human subjects. The participants gave their free informed consent (verbally when it was not possible otherwise, e.g. in the case of illiteracy). Data was analyzed anonymously. 3. Results The baseline characteristics of the population have been displayed in Table 1. Among the eighty six patients enrolled in this study, 18.6% (n = 16) were males and 81.4% (n = 70) were females. The mean age was 52.3 15.3 years, ranging between 17 and 81 years. Height, weight, body mass index (BMI), waist circumference, systolic BP and diastolic BP were 161.1 7.4 cm, 73.3 8 kg, 28.7 4.3 kg/m2, 94.5 9.2 cm, 135.5 30.2 mmHg and 81.5 13 mmHg respectively. Levels of thyroid function test; FT3, FT4 and TSH were, 5.8 1.0 pmol/L, 14.6 2.9 pmol/L and 12.69 3.4 mIU/L respectively. Thyroid dysfunction was found in 59.3% (n = 42) patients, hypothyroidism (45.3%) was the major thyroid dysfunction followed by hyperthyroidism (14.0%). Prevalence of thyroid
Table 1 Baseline characteristics of the study population. Characteristic (n = 86)
Mean SD or%
Gender (male/female) Age (years) BMI, kg/m2 WC, cm SBP, mmHg DBP, mmHg DM (%) HTN (%) TD (%) MetS (%) FHTD (%) TSH FT3 FT4 ATPO Ab ATG Ab FBS (mmol/L) Cr (mmol/L) UA (mmol/L) Urea (mmol/L) Alb (g/L) Hct (%) AST (UI/L) ALT (UI/L) ALP (UI/L) LDH (UI/L) CPK (UI/L) Ferritine (ng/ml) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L)
16/70 52.3 15.3 28.7 4.3 94.5 9.2 135.5 30.2 81.5 13 31.4 39.5 59.3 48.8 19.88 12.69 3.4 5.8 1.0 14.6 2.9 167.9 56.1 240.1 93.2 6.4 1.8 77.4 17.1 267.1 101.9 4.8 1.5 43.1 5.1 38.4 4.8 27.4 18.1 20.5 12.3 101.6 70.2 515.6 156.9 153.1 48.2 73.4 32.2 4.6 1.6 1.7 0.9 3.1 1.5 1.1 0.3
Alb = albumin, ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, ATG Ab = anti-thyroglobulin antibody, ATPO Ab = antithyroperoxidase antibody, BMI = body mass index, CPK = creatine phosphokinase, Cr = creatinine, DM = diabetes mellitus; DBP = diastolic blood pressure, FBS = fasting blood sugar, FHTD = Family history of thyroid disease, FT3 = free triiodothyronine, FT4 = free thyroxine, Hct = hematocrit, HDL-C = high-density lipoprotein cholesterol, HTN = hypertension, LDH = lactate deshydrogenase, LDL-C = low-density lipoprotein cholesterol, MetS = metabolic syndrome, SBP = systolic blood pressure, TC = total cholesterol, TD = Thyroid dysfunction, TG = triglycerides, TSH = thyroid stimulation hormone, UA = uric acid, WC = waist circumference.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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Table 2 Baseline characteristics according to thyroid function status. Characteristic
Euthyroid (n = 35)
Hypothyroid (n = 39)
Hyperthyroid (n = 12)
Male gender (n, %) Age (years) BMI (kg/m2) WC (cm) SBP (mmHg) DBP (mmHg) FBG (mmol/L) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L) UA (mmol/L) MetS (n, (%)) AO (n, (%)) HTN (n, (%)) Low HDL-C (n, (%)) IFG (n, (%)) HTG (n, (%))
5 (14.3) 50.38 14.6 28.0 3.9 91.9 9.1 128.5 29.0 80.8 11.7 6.3 1.4 4.1 1.1 1.8 1.0 3.0 1.0 1.2 0.3 244.4 88.2 12 (34.2) 22 (62.8) 10 (28.5) 24 (68.5) 12 (34.2) 15 (42.8)
2 (5.1)** 52.9 15.8 30.1 3.9* 97.2 8.6* 138.1 24.2 82.2 13.7 6.4 1.8 4.9 0.5* 1.6 0.9 3.9 0.5* 1.1 0.4 265.8 113.5 25 (64.1)* 33 (84.6)** 20 (51.2)* 27 (69.2) 10 (25.6) 14 (35.8)
9 (75.0)** 55.8 16.0 25.8 4.7 93.5 9.4 146.2 45.3* 81.2 15.5 7.1 3.0 3.5 0.5** 1.6 0.7 2.2 0.5* 0.9 0.3* 328.5 82.6** 7 (58.3) 4 (33.3)** 6 (50.0)* 10 (83.3)* 5 (41.6) 4 (33.3)
Data are expressed as mean SD or percentage. * p < 0.05, ** p < 0.01. AO = abdominal obesity, BMI = body mass index, DBP = diastolic blood pressure, FBS = fasting blood sugar, HDL-C = high-density lipoprotein cholesterol, HTG = hypertriglyceridemia, HTN = hypertension, IFG = impaired fasting glucose, LDL-C = low-density lipoprotein cholesterol, MetS = metabolic syndrome, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid, WC = waist circumference.
dysfunction was significantly higher among males 68.7% (n = 11) than females 57.1% (n = 40) (p < 0.001). Among males, 2 had hypothyroidism and 9 had hyperthyroidism. Similarly among females, 37 had hypothyroidism and 3 had subclinical hyperthyroidism. Overall, the prevalence of metabolic syndrome was 48.8% (n = 42) with the gender-wise prevalence of 37.5% (n = 6) in men, and 51.4% (n = 36) in women but not statistically significant (p = 0.409). Comparison of baseline characteristics and components of metabolic syndrome according to thyroid dysfunction type is shown in Table 2. Subjects with hypothyroidism had significantly higher level of BMI, WC, TC, LDL-C, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05). The hyperthyroid group had significantly lower level of TC, LDL-C and HDL-C but a higher level of SBP and UA. Furthermore, abdominal obesity, hypertension and low HDL-C level were the most common metabolic syndrome compounds found in the hyperthyroid group compared to the euthyroid group. Impaired fasting glucose and hypertriglyceridemia were similar in all participants with no significant difference. The relationship of TSH, FT3 and FT4 levels with the presence of MetS components and other cardiometabolic markers was evaluated using Pearson correlation coefficients analysis and is shown in Table 3. LDL-C (r = 0.329, p = 0.002) and TC (r = 0.312, p = 0.003) showed significant positive correlation with TSH level. BMI had negative correlation with free T3 (r = 0.272, p = 0.011) and free T4 (r = 0.351, p = 0.001) and positive correlation with TSH (r = 0.391, p = 0.001). 4. Discussion Thyroid endocrine disorders may be associated with metabolic syndrome. The facts of thyroid function on lipid metabolism, glucose and blood pressure in subjects with thyroid disorder are well known but clinically the changes are not obvious and the relationship between thyroid dysfunction and the components of the metabolic syndrome is ambiguous and remains debatable. This study assesses the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status. The most common endocrine thyroid disease was hypothyroidism (45.3%), followed by hyperthyroidism (14.0%). Contrary to recent studies [14–16], thyroid dysfunction was more prevalent in men (68.7%) than in women (57.1%), which may be justified by the
difference in race and age of participants as well as the sample size. The prevalence of the MetS in the euthyroid population was estimated at 34.2%, this considerable increase in the rate of metabolic syndrome was reported also by other studies [9–12], may be explicated by the diet and the sedentary lifestyle of Algerian population. According to previous studies [17–19] the prevalence of MetS was significantly more important in hypothyroid patients (64.1%) compared to euthyroid and hyperthyroid (58.3%) population. Furthermore, higher level of BMI, WC, TC, LDLC, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05) were significantly reported in the hypothyroid group. These findings are consistent with previous studies and indicate that high TSH levels may be a predictive factor of MetS [20–24]. Previous studies demonstrated that thyroid hormones affect lipid metabolism and thus the components of metabolic syndrome, and there is positive relation between TSH and LDL-C, whereas negative relation between TSH and HDL cholesterol [15]. In the present study, no significant relationship between components of metabolic syndrome and thyroid dysfunction parameters were found except for BMI and LDLC. There are contrasting reports about the correlation of thyroid function parameters and cardiometabolic markers.
Table 3 Correlation of thyroid function parameters and cardiometabolic markers. TSH
Age (years) BMI (kg/m2) WC (cm) SBP (mmHg) DBP (mmHg) FBG (mmol/L) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L) UA (mmol/L)
FT3
FT4
R
P value
R
P value
R
P value
0.041 0.396** 0.149 0.030 0.008 0.024 0.312** 0.088 0.329** 0.068 0.126
0.632 0.001 0.170 0.832 0.955 0.828 0.003 0.420 0.002 0.531 0.281
0.006 0.272* 0.116 0.087 0.013 0.010 0.108 0.025 0.113 0.000 0.284*
0.896 0.011 0.289 0.544 0.929 0.930 0.322 0.821 0.302 1.0 0.013
0.123 0.351** 0.154 0.010 0.005 0.005 0.166 0.067 0.158 0.116 0.268*
0.291 0.001 0.156 0.943 0.973 0.965 0.127 0.540 0.145 0.287 0.020
Data are expressed as mean SD or percentage. * p < 0.05, ** p < 0.01. BM I = body mass index, DBP = diastolic blood pressure, FBS = fasting blood sugar, FH = fasting hyperglycemia, HDL-C = high-density lipoprotein cholesterol, LDLC = low-density lipoprotein cholesterol, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid, WC = waist circumference.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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A few studies showed a positive relation between TSH levels within the reference range and prevalent MetS [24–26]. Recently, Bojin Xu et al. have found no linear association between SBP or DBP and TSH level and no difference in the prevalence of hypertension between the high- and low-TSH groups [15]. The inconsistent results between TSH levels and MetS may be due to differences in study populations, in the categorization of thyroid function, in the factors included for adjustments in the analyses and in crosssectional or longitudinal approaches. Furthermore, inverse associations between FT4 levels within reference range and metabolic parameters have been reported in several studies [27–30]. Mehran et al. [31] found that lower normal fT4 levels were significantly related to a higher risk of insulin resistance and MetS. In contrast, high normal total T3 or FT3 levels have been positively correlated with components of MetS [28,30,32]. Our findings, showed a significant inverse relationship between BMI level and the thyroid hormones levels, whereas, serum uric acid level (UA) was positively correlated with FT3 (r = 0.284, p = 0.013) and FT4 (r = 0.268, p = 0.020) levels. The main limitation of our study is the small sample size that may influence the correlation of metabolic syndrome components with different statuses thyroid, the short duration of follow-up of thyroid patients with the metabolic syndrome does not allow a proper assessment. In conclusion, this study gives, for the first time, an idea on the prevalence of MetS among Algerian patients with thyroid endocrine dysfunction, and its relationship with thyroid parameters. Conflicts of interest All the authors declare no conflict of interest with regard to this study. Acknowledgments The authors acknowledge the laboratory technical staff; Bouchareb Mohamed, Chiakha Aziz and al for their cooperation and assistance. References [1] Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006;47:1093–100. [2] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications: part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Med 1998;15:539–53. [3] Walsh JP, Bremner AP, Bulsara MK, et al. Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol 2005;63:670–5. [4] Wang F, Tan Y, Wang C, et al. Thyroid-stimulating hormone levels within the reference range are associated with serum lipid profiles independent of thyroid hormones. J Clin Endocrinol Metab 2012;97:2724–31. [5] Xu C, Yang X, Liu W, et al. Thyroid stimulating hormone, independent of thyroid hormone, can elevate the serum total cholesterol level in patients with coronary heart disease: a crosssectional design. Nutr Metab 2012;9:44. [6] Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body composition study. Clin Endocrinol (Oxf) 2012;76:911–8. [7] Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210–4. [8] Cameron AJ, Magliano DJ, Zimmet PZ, Welborn TA, Colagiuri S, Tonkin AM, et al. The metabolic syndrome as a tool for predicting future diabetes: the AUSDIAB study. J Intern Med 2008;264:177–86. [9] Yahia-Berrouiguet A, Benyoucef M, Meguenni K, Brouri M. Enquête sur la prévalence des facteurs de risque de maladies cardiovasculaires à Tlemcen (Algérie) Médecine des maladies. Médecine des maladies Métaboliques 2009;3(mai–juin(3)):313–9.
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Diabetes & Metabolic Syndrome: Clinical Research & Reviews xxx (2017) xxx–xxx
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Original Article
Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients Mohamed Larbi Hamlaouia , Ammar Ayachia , Aoulia Dekakenb , Adel Gouric,* a
Laboratoire de microbiologie Immunologie, Institut des Sciences Vétérinaires et Agronomiques, Département Vétérinaire, Université de Batna, Algeria Department of Internal Medicine, Public Hospital El Okbi, Guelma, Algeria c Department of Clinical Biochemistry, College of Medicine, Badji Mokhtar University, Annaba, Algeria b
A R T I C L E I N F O
A B S T R A C T
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Aims: The aim of this study is to evaluate the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status. Materials and methods: A prospective cross-sectional study was conducted in the internal medicine department at El Okbi Hospital of Guelma (East of Algeria) from January 2014 to September 2015. Eighty six patients attending the specialist consultation for suspected thyroid disorders were included in the study. Gender; blood pressure; body mass index; and serum levels of fasting glucose, total cholesterol (TC), high-density-lipoprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol, and triglyceride were compared between subjects with hypothyroidism, hyperthyroidism and euthyroidism. Results and conclusion: Thyroid dysfunction was found in 59.3% (n = 42) patients, hypothyroidism (45.3%) was the major thyroid dysfunction followed by hyperthyroidism (14.0%). Overall, the prevalence of metabolic syndrome was 48.8% (n = 42). Subjects with hypothyroidism had significantly higher level of BMI, WC, TC, LDL-C, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05). The hyperthyroid group had significantly lower level of TC, LDL-C and HDL-C but a higher level of SBP and UA. Furthermore, abdominal obesity, hypertension and low HDL-C level were the most common metabolic syndrome compounds found in the hyperthyroid group compared to the euthyroid group. We found a positive association between TSH level and the prevalence of the metabolic syndrome. © 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Keywords: Metabolic syndrome Cardiovascular risk Thyroid hormone Hypothyroidis Hyperthyroidism
1. Introduction The metabolic syndrome (MetS) is defined as a cluster of interrelated metabolic abnormalities, characterized by central obesity, hyperglycemia, hypertriglyceridemia, decreased high density lipoprotein-cholesterol (HDL), and elevated blood pressure (BP). People with MetS have an increased risk of cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality. MetS requires 3 of the following 5 factors to make a diagnosis: increased waist circumference (WC), elevated triglycerides (TG), reduced HDL, elevated BP, and elevated fasting glucose (FG) [1,2]. Thyroid hormones have pleiotropic effects on lipid and glucose metabolism, blood pressure, and energy expenditure. Thyroid dysfunction is a risk factor of cardiovascular disease [3]. Recently, serum thyroid stimulating hormone (TSH) is also found to be associated with adverse changes of lipid metabolism as well [4,5].
The relationship between mild thyroid dysfunction and MetS traits has become a hot topic of discussion recently; they are the two most common endocrine disorders with a substantial overlap [6]. Both are associated with significant morbidity and mortality and thus impact substantially on health care [7,8]. In Algeria, socioeconomic, nutritional and epidemiological transition had contributes to the increase in different chronic diseases and abnormalities constituting metabolic syndrome [9]. The prevalence of metabolic syndrome in Algerian population was estimated at 20%, higher in women than men [10]. Furthermore, the frequency of thyroid diseases in Algeria continues to rise in recent years; they particularly affect adult female subjects [11,12]. There is no report studying thyroid dysfunction and metabolic syndrome association in Algerian population. The aim of this study is to evaluate the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status.
* Corresponding author . E-mail addresses: [email protected], [email protected] (A. Gouri). http://dx.doi.org/10.1016/j.dsx.2017.08.001 1871-4021/© 2017 Diabetes India. Published by Elsevier Ltd. All rights reserved.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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2. Materials and methods
two-tailed P value of less than 0.05 was considered to be statistically significant.
2.1. Population and study design 2.5. Ethics This cross-sectional study was conducted in the internal medicine department at El Okbi Hospital of Guelma (East of Algeria) from January 2014 to September 2015. Eighty six patients attending the specialist consultation for suspected thyroid disorders were included in the study. A structured questionnaire was filled out by each patient, which details: age, sex, height, weight, blood pressure, personnel and family medical history, clinical findings and laboratory results. Written informed consent was obtained from each patient after full explanation of the purpose and nature of all procedures used. 2.2. Clinical and biological measurements Fasting blood samples (venous blood samples taken after overnight fast of a minimum of 8 h) were collected; Serum glucose, total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), albumin, total serum proteins, urea, creatinine, uric acid, calcium, phosphorus, iron, magnesium, liver transaminases, creatine phosphokinase (CPK), lactate deshydrogenase (LDH), alkaline phosphatase (ALP) were measured using an clinical chemistry autoanalyzer (XL 200 Erba diagnostics Mannheim), complete blood count, including hemoglobin (Hb), haematocrite (Hct), red blood cells, white blood cells and platelets, using an hematology coulter (Diatron Abacus). Ferritin (Ferr), serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid stimulating hormone (TSH), anti-thyroid peroxidase antibody (ATPO Ab) and anti-thyroglobulin antibody (ATG Ab) were measured by using fluorescent immunoassay (VIDAS, biomeriux SA, France). Reference range for TSH was 0.25–5 mIU/L, FT3 (4.0– 8.3 pmol/L), FT4 (9.0–20.0 pmol/L) anti-TPO (0–8 UI/ml) and antiTG (0–18 UI/ml). All blood samples were analyzed in the laboratory of Medical Biochemistry, Ibn Zohr Public Hospital, Guelma, Algeria. 2.3. Definitions Metabolic syndrome (MetS) was diagnosed by the modified National Cholesterol Education Program-Adult Treatment Panel-III (NCEP-ATPIII) criteria [13], which requires 3 or more of the following parameters: Elevated waist circumference (WC) >102 cm for men and >88 cm for women, hypertriglyceridemia (TG 1.7 mmol/L); low HDL cholesterol (HDL-C <1.03 mmol/L for men and <1.30 mmol/L for women); elevated blood pressure (systolic blood pressure 130 mmHg and/or diastolic blood pressure 85 mmHg or current use of antihypertensive drugs); impaired fasting glucose (fasting plasma glucose 5.6 mmol/L). Thyroid function subgroups were determined as following; patients were said to be euthyroid if all thyroid hormone levels fell within reference range. Hypothyroidism was defined as TSH >5. Hyperthyroidism was defined as TSH <0.25 mIU/L. 2.4. Data analysis Continuous variables are expressed as means standard deviation (SD); and categorical variables as frequencies and percentages. Using the euthyroid group as reference, the differences in baseline characteristics were tested using the Student’s ttest for continuous data and Chi-square test for categorical data at 95% confidence interval. Pearson correlation coefficients were calculated to find relationship between the components of metabolic syndrome and thyroid profile parameters at 95% confidence interval. All statistical analyses were performed with the SPSS 20.0 (SPSS, Chicago, IL) statistical package for Windows. A
The study was carried out in accordance with the ethical principles for medical research involving human subjects. The participants gave their free informed consent (verbally when it was not possible otherwise, e.g. in the case of illiteracy). Data was analyzed anonymously. 3. Results The baseline characteristics of the population have been displayed in Table 1. Among the eighty six patients enrolled in this study, 18.6% (n = 16) were males and 81.4% (n = 70) were females. The mean age was 52.3 15.3 years, ranging between 17 and 81 years. Height, weight, body mass index (BMI), waist circumference, systolic BP and diastolic BP were 161.1 7.4 cm, 73.3 8 kg, 28.7 4.3 kg/m2, 94.5 9.2 cm, 135.5 30.2 mmHg and 81.5 13 mmHg respectively. Levels of thyroid function test; FT3, FT4 and TSH were, 5.8 1.0 pmol/L, 14.6 2.9 pmol/L and 12.69 3.4 mIU/L respectively. Thyroid dysfunction was found in 59.3% (n = 42) patients, hypothyroidism (45.3%) was the major thyroid dysfunction followed by hyperthyroidism (14.0%). Prevalence of thyroid
Table 1 Baseline characteristics of the study population. Characteristic (n = 86)
Mean SD or%
Gender (male/female) Age (years) BMI, kg/m2 WC, cm SBP, mmHg DBP, mmHg DM (%) HTN (%) TD (%) MetS (%) FHTD (%) TSH FT3 FT4 ATPO Ab ATG Ab FBS (mmol/L) Cr (mmol/L) UA (mmol/L) Urea (mmol/L) Alb (g/L) Hct (%) AST (UI/L) ALT (UI/L) ALP (UI/L) LDH (UI/L) CPK (UI/L) Ferritine (ng/ml) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L)
16/70 52.3 15.3 28.7 4.3 94.5 9.2 135.5 30.2 81.5 13 31.4 39.5 59.3 48.8 19.88 12.69 3.4 5.8 1.0 14.6 2.9 167.9 56.1 240.1 93.2 6.4 1.8 77.4 17.1 267.1 101.9 4.8 1.5 43.1 5.1 38.4 4.8 27.4 18.1 20.5 12.3 101.6 70.2 515.6 156.9 153.1 48.2 73.4 32.2 4.6 1.6 1.7 0.9 3.1 1.5 1.1 0.3
Alb = albumin, ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, ATG Ab = anti-thyroglobulin antibody, ATPO Ab = antithyroperoxidase antibody, BMI = body mass index, CPK = creatine phosphokinase, Cr = creatinine, DM = diabetes mellitus; DBP = diastolic blood pressure, FBS = fasting blood sugar, FHTD = Family history of thyroid disease, FT3 = free triiodothyronine, FT4 = free thyroxine, Hct = hematocrit, HDL-C = high-density lipoprotein cholesterol, HTN = hypertension, LDH = lactate deshydrogenase, LDL-C = low-density lipoprotein cholesterol, MetS = metabolic syndrome, SBP = systolic blood pressure, TC = total cholesterol, TD = Thyroid dysfunction, TG = triglycerides, TSH = thyroid stimulation hormone, UA = uric acid, WC = waist circumference.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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Table 2 Baseline characteristics according to thyroid function status. Characteristic
Euthyroid (n = 35)
Hypothyroid (n = 39)
Hyperthyroid (n = 12)
Male gender (n, %) Age (years) BMI (kg/m2) WC (cm) SBP (mmHg) DBP (mmHg) FBG (mmol/L) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L) UA (mmol/L) MetS (n, (%)) AO (n, (%)) HTN (n, (%)) Low HDL-C (n, (%)) IFG (n, (%)) HTG (n, (%))
5 (14.3) 50.38 14.6 28.0 3.9 91.9 9.1 128.5 29.0 80.8 11.7 6.3 1.4 4.1 1.1 1.8 1.0 3.0 1.0 1.2 0.3 244.4 88.2 12 (34.2) 22 (62.8) 10 (28.5) 24 (68.5) 12 (34.2) 15 (42.8)
2 (5.1)** 52.9 15.8 30.1 3.9* 97.2 8.6* 138.1 24.2 82.2 13.7 6.4 1.8 4.9 0.5* 1.6 0.9 3.9 0.5* 1.1 0.4 265.8 113.5 25 (64.1)* 33 (84.6)** 20 (51.2)* 27 (69.2) 10 (25.6) 14 (35.8)
9 (75.0)** 55.8 16.0 25.8 4.7 93.5 9.4 146.2 45.3* 81.2 15.5 7.1 3.0 3.5 0.5** 1.6 0.7 2.2 0.5* 0.9 0.3* 328.5 82.6** 7 (58.3) 4 (33.3)** 6 (50.0)* 10 (83.3)* 5 (41.6) 4 (33.3)
Data are expressed as mean SD or percentage. * p < 0.05, ** p < 0.01. AO = abdominal obesity, BMI = body mass index, DBP = diastolic blood pressure, FBS = fasting blood sugar, HDL-C = high-density lipoprotein cholesterol, HTG = hypertriglyceridemia, HTN = hypertension, IFG = impaired fasting glucose, LDL-C = low-density lipoprotein cholesterol, MetS = metabolic syndrome, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid, WC = waist circumference.
dysfunction was significantly higher among males 68.7% (n = 11) than females 57.1% (n = 40) (p < 0.001). Among males, 2 had hypothyroidism and 9 had hyperthyroidism. Similarly among females, 37 had hypothyroidism and 3 had subclinical hyperthyroidism. Overall, the prevalence of metabolic syndrome was 48.8% (n = 42) with the gender-wise prevalence of 37.5% (n = 6) in men, and 51.4% (n = 36) in women but not statistically significant (p = 0.409). Comparison of baseline characteristics and components of metabolic syndrome according to thyroid dysfunction type is shown in Table 2. Subjects with hypothyroidism had significantly higher level of BMI, WC, TC, LDL-C, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05). The hyperthyroid group had significantly lower level of TC, LDL-C and HDL-C but a higher level of SBP and UA. Furthermore, abdominal obesity, hypertension and low HDL-C level were the most common metabolic syndrome compounds found in the hyperthyroid group compared to the euthyroid group. Impaired fasting glucose and hypertriglyceridemia were similar in all participants with no significant difference. The relationship of TSH, FT3 and FT4 levels with the presence of MetS components and other cardiometabolic markers was evaluated using Pearson correlation coefficients analysis and is shown in Table 3. LDL-C (r = 0.329, p = 0.002) and TC (r = 0.312, p = 0.003) showed significant positive correlation with TSH level. BMI had negative correlation with free T3 (r = 0.272, p = 0.011) and free T4 (r = 0.351, p = 0.001) and positive correlation with TSH (r = 0.391, p = 0.001). 4. Discussion Thyroid endocrine disorders may be associated with metabolic syndrome. The facts of thyroid function on lipid metabolism, glucose and blood pressure in subjects with thyroid disorder are well known but clinically the changes are not obvious and the relationship between thyroid dysfunction and the components of the metabolic syndrome is ambiguous and remains debatable. This study assesses the prevalence of the metabolic syndrome and its compounds in subjects with different thyroid status. The most common endocrine thyroid disease was hypothyroidism (45.3%), followed by hyperthyroidism (14.0%). Contrary to recent studies [14–16], thyroid dysfunction was more prevalent in men (68.7%) than in women (57.1%), which may be justified by the
difference in race and age of participants as well as the sample size. The prevalence of the MetS in the euthyroid population was estimated at 34.2%, this considerable increase in the rate of metabolic syndrome was reported also by other studies [9–12], may be explicated by the diet and the sedentary lifestyle of Algerian population. According to previous studies [17–19] the prevalence of MetS was significantly more important in hypothyroid patients (64.1%) compared to euthyroid and hyperthyroid (58.3%) population. Furthermore, higher level of BMI, WC, TC, LDLC, and higher prevalence of abdominal obesity (84.6%, p < 0.01) and hypertension (51.2%, p < 0.05) were significantly reported in the hypothyroid group. These findings are consistent with previous studies and indicate that high TSH levels may be a predictive factor of MetS [20–24]. Previous studies demonstrated that thyroid hormones affect lipid metabolism and thus the components of metabolic syndrome, and there is positive relation between TSH and LDL-C, whereas negative relation between TSH and HDL cholesterol [15]. In the present study, no significant relationship between components of metabolic syndrome and thyroid dysfunction parameters were found except for BMI and LDLC. There are contrasting reports about the correlation of thyroid function parameters and cardiometabolic markers.
Table 3 Correlation of thyroid function parameters and cardiometabolic markers. TSH
Age (years) BMI (kg/m2) WC (cm) SBP (mmHg) DBP (mmHg) FBG (mmol/L) TC (mmol/l) TG (mmol/L) LDL-C (mmol/L) HDL-C (mmol/L) UA (mmol/L)
FT3
FT4
R
P value
R
P value
R
P value
0.041 0.396** 0.149 0.030 0.008 0.024 0.312** 0.088 0.329** 0.068 0.126
0.632 0.001 0.170 0.832 0.955 0.828 0.003 0.420 0.002 0.531 0.281
0.006 0.272* 0.116 0.087 0.013 0.010 0.108 0.025 0.113 0.000 0.284*
0.896 0.011 0.289 0.544 0.929 0.930 0.322 0.821 0.302 1.0 0.013
0.123 0.351** 0.154 0.010 0.005 0.005 0.166 0.067 0.158 0.116 0.268*
0.291 0.001 0.156 0.943 0.973 0.965 0.127 0.540 0.145 0.287 0.020
Data are expressed as mean SD or percentage. * p < 0.05, ** p < 0.01. BM I = body mass index, DBP = diastolic blood pressure, FBS = fasting blood sugar, FH = fasting hyperglycemia, HDL-C = high-density lipoprotein cholesterol, LDLC = low-density lipoprotein cholesterol, SBP = systolic blood pressure, TC = total cholesterol, TG = triglycerides, UA = uric acid, WC = waist circumference.
Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001
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A few studies showed a positive relation between TSH levels within the reference range and prevalent MetS [24–26]. Recently, Bojin Xu et al. have found no linear association between SBP or DBP and TSH level and no difference in the prevalence of hypertension between the high- and low-TSH groups [15]. The inconsistent results between TSH levels and MetS may be due to differences in study populations, in the categorization of thyroid function, in the factors included for adjustments in the analyses and in crosssectional or longitudinal approaches. Furthermore, inverse associations between FT4 levels within reference range and metabolic parameters have been reported in several studies [27–30]. Mehran et al. [31] found that lower normal fT4 levels were significantly related to a higher risk of insulin resistance and MetS. In contrast, high normal total T3 or FT3 levels have been positively correlated with components of MetS [28,30,32]. Our findings, showed a significant inverse relationship between BMI level and the thyroid hormones levels, whereas, serum uric acid level (UA) was positively correlated with FT3 (r = 0.284, p = 0.013) and FT4 (r = 0.268, p = 0.020) levels. The main limitation of our study is the small sample size that may influence the correlation of metabolic syndrome components with different statuses thyroid, the short duration of follow-up of thyroid patients with the metabolic syndrome does not allow a proper assessment. In conclusion, this study gives, for the first time, an idea on the prevalence of MetS among Algerian patients with thyroid endocrine dysfunction, and its relationship with thyroid parameters. Conflicts of interest All the authors declare no conflict of interest with regard to this study. Acknowledgments The authors acknowledge the laboratory technical staff; Bouchareb Mohamed, Chiakha Aziz and al for their cooperation and assistance. References [1] Grundy SM. Metabolic syndrome: connecting and reconciling cardiovascular and diabetes worlds. J Am Coll Cardiol 2006;47:1093–100. [2] Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications: part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabetic Med 1998;15:539–53. [3] Walsh JP, Bremner AP, Bulsara MK, et al. Thyroid dysfunction and serum lipids: a community-based study. Clin Endocrinol 2005;63:670–5. [4] Wang F, Tan Y, Wang C, et al. Thyroid-stimulating hormone levels within the reference range are associated with serum lipid profiles independent of thyroid hormones. J Clin Endocrinol Metab 2012;97:2724–31. [5] Xu C, Yang X, Liu W, et al. Thyroid stimulating hormone, independent of thyroid hormone, can elevate the serum total cholesterol level in patients with coronary heart disease: a crosssectional design. Nutr Metab 2012;9:44. [6] Waring AC, Rodondi N, Harrison S, Kanaya AM, Simonsick EM, Miljkovic I, et al. Thyroid function and prevalent and incident metabolic syndrome in older adults: the health, ageing and body composition study. Clin Endocrinol (Oxf) 2012;76:911–8. [7] Alexander CM, Landsman PB, Teutsch SM, Haffner SM. NCEP-defined metabolic syndrome, diabetes, and prevalence of coronary heart disease among NHANES III participants age 50 years and older. Diabetes 2003;52:1210–4. [8] Cameron AJ, Magliano DJ, Zimmet PZ, Welborn TA, Colagiuri S, Tonkin AM, et al. The metabolic syndrome as a tool for predicting future diabetes: the AUSDIAB study. J Intern Med 2008;264:177–86. [9] Yahia-Berrouiguet A, Benyoucef M, Meguenni K, Brouri M. Enquête sur la prévalence des facteurs de risque de maladies cardiovasculaires à Tlemcen (Algérie) Médecine des maladies. Médecine des maladies Métaboliques 2009;3(mai–juin(3)):313–9.
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Please cite this article in press as: M.L. Hamlaoui, et al., Relationship of metabolic syndrome and its components with thyroid dysfunction in Algerian patients, Diab Met Syndr: Clin Res Rev (2017), http://dx.doi.org/10.1016/j.dsx.2017.08.001