Increased Waist Circumference Is Independently Associated With Hypothyroidism in Mexican Americans

Replicative Evidence From Two Large, Population-Based Studies

Manju Mamtani; Hemant Kulkarni; Thomas D Dyer; Laura Almasy; Michael C Mahaney; Ravindranath Duggirala; Anthony G Comuzzie; Paul B Samollow; John Blangero; Joanne E Curran

Disclosures

BMC Endocr Disord. 2014;14(46)

Abstract

Background. Mexican Americans are at an increased risk of both thyroid dysfunction and metabolic syndrome (MS). Thus it is conceivable that some components of the MS may be associated with the risk of thyroid dysfunction in these individuals. Our objective was to investigate and replicate the potential association of MS traits with thyroid dysfunction in Mexican Americans.

Methods. We conducted association testing for 18 MS traits in two large studies on Mexican Americans – the San Antonio Family Heart Study (SAFHS) and the National Health and Nutrition Examination Survey (NHANES) 2007–10. A total of 907 participants from 42 families in SAFHS and 1633 unrelated participants from NHANES 2007–10 were included in this study. The outcome measures were prevalence of clinical and subclinical hypothyroidism and thyroid function index (TFI) – a measure of thyroid function. For the SAFHS, we used polygenic regression analyses with multiple covariates to test associations in setting of family studies. For the NHANES 2007–10, we corrected for the survey design variables as needed for association analyses in survey data. In both datasets, we corrected for age, sex and their linear and quadratic interactions.

Results. TFI was an accurate indicator of clinical thyroid status (area under the receiver-operating-characteristic curve to detect clinical hypothyroidism, 0.98) in both SAFHS and NHANES 2007–10. Of the 18 MS traits, waist circumference (WC) showed the most consistent association with TFI in both studies independently of age, sex and body mass index (BMI). In the SAFHS and NHANES 2007–10 datasets, each standard deviation increase in WC was associated with 0.13 (p < 0.001) and 0.11 (p < 0.001) unit increase in the TFI, respectively. In a series of polygenic and linear regression models, central obesity (defined as WC ≥ 102 cm in men and ≥88 cm in women) was associated with clinical and subclinical hypothyroidism independent of age, sex, BMI and type 2 diabetes in both datasets. Estimated prevalence of hypothyroidism was consistently high in those with central obesity, especially below 45y of age.

Conclusions. WC independently associates with increased risk of thyroid dysfunction. Use of WC to identify Mexican American subjects at high risk of thyroid dysfunction should be investigated in future studies.

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Table 1. Characteristics of the study subjects.
Characteristic	SAFHS (n = 919)		NHANES 2007–10 (n = 1636)
Characteristic	Value	N	Value	N
Demographics	xx
Age [mean (SE)] y	38.92 (0.54)	907	35.42 (0.81^†)	1636
Females [n (%)]	555 (61.19)	907	842 (47.98^††)	1636
Diabetes at enrolment [n (%)]	126 (13.91)	906	170 (7.35)	1635
Anthropometric indexes [mean (SE)]	xx
Waist cm	94.71 (0.58)	898	95.65 (0.68)	1589
BMI Kg/m²	29.50 (0.23)	900	28.49 (0.27)	1618
WHR	0.89 (0.003)	897	-	-
Blood pressure [mean (SE)]	xx
Systolic mmHg	119.96 (0.61)	899	116.98 (0.75)	1504
Diastolic mmHg	70.56 (0.34)	899	66.84 (0.56)	1504
Biochemical indexes [mean (SE)]	xx
Fasting glucose mmol/L	5.59 (0.07)	907	6.00 (0.11)	805
Fasting insulin μU/mL	16.72 (0.65)	894	15.64 (0.63)	803
Total serum cholesterol mg/dl	189.06 (1.32)	906	190.35 (1.54)	1636
Serum triglycerides mg/dl	151.56 (4.40)	906	141.15 (3.31)	805
HDL cholesterol mg/dl	50.54 (0.43)	905	48.90 (0.31)	1636
LDL cholesterol mg/dl	109.92 (1.10)	906	112.42 (1.52)	785
Thyroid related traits [mean (SE)]	xx
Total thyroxine μg/dl	7.63 (0.07)	839	8.19 (0.08)	1628
Free thyroxine ng/dl	1.38 (0.01)	907	0.80 (0.01)	1636
Total triiodothyronine ng/dl	122.15 (0.92)	845	122.89 (1.03)	1635
Free triiodothyronine pg/ml	3.62 (0.04)	907	3.42 (0.03)	1634
Reverse triiodothyronine ng/dl	23.00 (0.30)	451	-	-
Thyroxine binding globulin μg/ml	19.84 (0.19)	856	-	-
Thyroglobulin ng/ml	11.56 (1.11)	879	11.27 (1.15)	1635
Thyroid stimulating hormone μU/ml	2.96 (0.14)	907	2.00 (0.14)	1635

^†All proportions in NHANES samples are adjusted for survey design variables.
^††For NHANES samples standard errors represent linearized standard errors.

Table 2. Association of metabolic syndrome related traits with thyroid function index in the SAFHS participants.
Metabolic syndrome-related trait	All subjects				Males				Females
	Unadjusted		Adjusted^†		Unadjusted		Adjusted^††		Unadjusted		Adjusted^††
	β	p	β	p	β	p	β	p	β	P	β	p
Fasting glucose	0.08	0.03	-0.02	0.62	0.07	0.19	0.01	0.91	0.07	0.14	-0.03	0.53
2-hour glucose	0.14	<0.0001	0.05	0.15	0.16	<0.01	0.11	0.05	0.09	0.06	-0.01	0.82
Fasting insulin	0.04	0.27	0.00	0.96	0.03	0.62	0.01	0.78	0.03	0.52	-0.01	0.77
2-hour insulin	0.08	0.02	0.04	0.22	0.07	0.18	0.04	0.43	0.07	0.13	0.03	0.47
HOMA-IR	0.06	0.12	0.00	0.94	0.04	0.41	0.02	0.78	0.05	0.33	-0.02	0.68
HOMA-β	-0.07	0.06	0.02	0.58	-0.05	0.38	0.01	0.86	-0.06	0.1763	0.04	0.47
WC	0.19	<0.0001	0.13	<0.001	0.12	0.04	0.08	0.18	0.20	<0.0001	0.14	0.001
BMI	0.15	<0.0001	0.11	<0.01	0.04	0.45	0.02	0.76	0.18	<0.0001	0.13	<0.01
WHR	0.15	<0.0001	0.09	0.01	0.23	<0.001	0.20	<0.01	0.16	0.0001	0.10	0.02
Total serum cholesterol	0.12	0.0001	0.06	0.06	0.08	0.10	0.07	0.19	0.11	0.0101	0.03	0.46
Serum triglycerides	0.15	<0.0001	0.08	0.02	0.12	0.02	0.09	0.07	0.14	<0.01	0.07	0.14
Serum HDL cholesterol	0.05	0.11	0.06	0.06	0.05	0.32	0.07	0.15	0.02	0.67	0.02	0.69
Central obesity	0.30	<0.0001	0.20	<0.01	0.16	0.14	0.13	0.26	0.33	0.0001	0.20	0.02
Raised triglycerides	0.16	0.02	0.05	0.42	0.13	0.19	0.09	0.39	0.19	0.03	0.06	0.49
Low HDL cholesterol	-0.02	0.81	-0.05	0.46	0.12	0.28	0.08	0.49	-0.11	0.20	-0.11	0.17
High blood pressure	-0.25	<0.01	-0.05	0.61	-0.10	0.44	0.06	0.65	-0.26	0.01	-0.06	0.61
Type 2 diabetes	0.15	0.04	-0.04	0.60	0.14	0.22	-0.01	0.95	0.15	0.14	-0.04	0.70
Metabolic syndrome	0.27	<0.0001	0.16	0.02	0.28	0.02	0.25	0.04	0.24	<0.01	0.11	0.24

^†Adjusted for age, age², sex, age x sex interaction and age² x sex interaction; ^††, adjusted for age and age²; numbers in bold face indicate statistically significant associations after correcting for multiple testing.

Table 3. Association of metabolic syndrome related traits with thyroid function index in NHANES 2007–2010 participants.*
Metabolic syndrome-related trait	All subjects				Males				Females
	Unadjusted		Adjusted^†		Unadjusted		Adjusted^††		Unadjusted		Adjusted^††
	β	p	β	p	β	p	β	p	β	P	β	p
Fasting glucose	0.09	0.08	0.01	0.78	0.15	<0.01	0.12	0.03	0.08	0.25	-0.02	0.76
Fasting insulin	0.05	0.13	0.06	0.07	0.12	<0.01	0.12	<0.01	-0.05	0.32	-0.03	0.56
HOMA-IR	0.07	0.02	0.06	0.04	0.15	<0.001	0.14	<0.001	-0.02	0.70	-0.03	0.52
HOMA-β	0.00	0.98	0.05	0.20	0.05	0.30	0.08	0.12	-0.09	0.16	0.00	0.98
WC	0.16	<0.0001	0.11	<0.001	0.21	<0.0001	0.20	<0.0001	0.13	<0.001	0.06	0.17
BMI	0.15	<0.0001	0.12	<0.001	0.20	<0.0001	0.20	<0.0001	0.11	<0.01	0.03	0.40
Total serum cholesterol	0.16	<0.0001	0.11	<0.01	0.13	<0.001	0.13	<0.001	0.20	<0.001	0.11	0.04
Serum triglycerides	0.13	<0.001	0.09	0.04	0.11	<0.01	0.10	0.02	0.20	0.001	0.12	0.07
Serum HDL cholesterol	0.00	0.98	0.00	0.85	-0.10	<0.001	-0.10	<0.001	0.05	0.09	0.04	0.11
Central obesity	0.32	<0.0001	0.22	<0.001	0.36	<0.0001	0.30	<0.0001	0.22	<0.01	0.05	0.58
Raised triglycerides	0.17	<0.01	0.01	0.90	0.09	0.17	-0.01	0.88	0.31	<0.01	0.13	0.20
Low HDL cholesterol	0.10	<0.01	0.04	0.12	0.14	0.02	0.10	0.08	0.02	0.69	-0.03	0.52
High blood pressure	0.31	<0.0001	0.08	0.16	0.32	<0.01	0.17	0.13	0.34	<0.001	0.02	0.83
Type 2 diabetes	0.30	<0.0001	0.04	0.55	0.24	0.02	0.00	0.98	0.33	0.001	0.07	0.47
Metabolic syndrome	0.32	<0.0001	0.16	0.05	0.29	0.01	0.19	0.11	0.29	0.06	0.09	0.62

*In this set, data on 2-hour glucose, 2-hour insulin and WHR were not available; ^†, adjusted for age, age², sex, age x sex interaction and age² x sex interaction; ^††, adjusted for age and age²; numbers in bold face indicate statistically significant associations after correcting for multiple testing.