J Endocrinol Invest DOI 10.1007/s40618-015-0302-y
ORIGINAL ARTICLE
Association of metabolic syndrome components with insulin resistance in normal weight population: the Qazvin Metabolic Diseases study S. Hashemipour1 · N. Esmailzadehha1 · H. Hamid1 · S. Oveisi1 · P. Yakhchaliha1 · A. Ziaee1
Received: 7 January 2015 / Accepted: 27 April 2015 © Italian Society of Endocrinology (SIE) 2015
Abstract Purpose Metabolically obese but normal weight (MONW) is associated with higher risk of type 2 diabetes, dyslipidemia, and hypertension. The aim of this study was to evaluate the association of metabolic syndrome components with MONW in each sex in Iranian population. Methods This cross-sectional study was performed on 417 normal weight subjects in Qazvin, Iran between September 2010 and April 2011. MONW was defined by insulin resistance (IR) using the homeostatic model assessment (HOMA). Cut off point for IR was defined as the lower limit of top quintile of HOMA-IR values in normal weight population without any metabolic risk factors. Data were analyzed using T test, Mann–Whitney U test, and multivariant logistic regression analysis. Results Of 417 subjects, 44.3 % were female. The prevalence of MONW was 33.8 % in men and 39.8 % in women. Triglycerides levels were significantly higher in both men and women with MONW. Waist circumference was significantly higher in men with MONW, while high-density lipoprotein cholesterol levels were significantly lower in women with MONW. In logistic regression analysis, hypertriglyceridemia in women (OR 3.398; 95 % CI 1.306– 8.846) and waist circumference (per 5 cm increment) in men (OR 1.653; 95 % CI 1.279–2.136) had independent association with MONW. Conclusion Association of metabolic syndrome components with MONW is different in men and women. Waist
* A. Ziaee [email protected] 1
Metabolic Diseases Research Center, Booali-Sina Hospital, Qazvin University of Medical Sciences, Booali‑Sina Street, Qazvin, Iran
circumference had an independent association with IR in men but not in women. IR and its complications should be considered in lean women with hypertriglyceridemia. Keywords Gender difference · MONW · Insulin resistance · Waist circumference · Hypertriglyceridemia
Introduction Insulin resistance (IR) is not limited to obese subjects. The term metabolically obese but normal weight (MONW) was first introduced by Ruderman et al. [1] in the 1980s for defining a group of patients with normal weight but complications of IR. Individuals with MONW are predisposed to higher cardiovascular disease (CVD) risk and greater severity of coronary artery disease (CAD) [2]. Moreover, greater all-cause mortality during 10 years of follow-up has been reported for them [3]. Unfortunately, individuals with MONW are frequently undetected and untreated for years because of their normal body mass index (BMI) [4, 5]. Therefore, identifying individuals with MONW is important to take early preventive actions. Studying anthropometric characteristics and biochemical abnormalities is a useful method in predicting insulin resistance. In some studies, high systolic and diastolic blood pressure (BP), low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), high lowdensity lipoprotein cholesterol (LDL-C), or changes in its quality were associated with MONW [6–8]. The association of MONW and BMI is inconsistent in different studies. In some studies, BMI and waist circumference (WC) are associated with MONW [6, 7], while other studies have not found such association [4, 5, 8]. Some of these
13
J Endocrinol Invest
inconsistencies could be attributed to race and gender differences in different studies. The aim of this study was to evaluate the association of metabolic syndrome components with MONW in each sex in Iranian population.
defined as Normal subjects based on the diagnostic criteria proposed by national cholesterol education program third adult treatment panel (ATPIII 2004) [13]. The HOMA cut point for IR was 2.482. Subjects with HOMA-IR above 2.482 were considered as MONW.
Methods
Statistical analysis
This study was a cross-sectional population-based study that was performed on a representative sample of residents of Mindoodar district of Qazvin which is located 150 km northwest of Tehran, the capital city of Iran from September 2010 to April 2011. The ethics committee of Qazvin University of medical sciences approved the study. The Minoodar district was divided into four main clusters according to the population size. All households had health profiles at Minoodar health center and the sampling unit was the household. 1107 people aged ≥20 years were selected by multistage cluster random sampling methods. Subjects were invited by phone call to attend the study at the Minoodar health center and after face to face explanation of the study details they were free to participate. All subjects gave their written informed consent. Social and demographic data of the subjects were selfreported using a questionnaire. Two practitioners recorded their past medical history, family medical conditions, current medication, and physical examination, using an organized questionnaire. Complete details of the methods have been described elsewhere [9]. Anthropometric data were obtained after 12–14 h overnight fasting. Weight, height, and WC were measured. The WC was measured halfway between the costal margin and the iliac crest at the end of normal expiration. BMI was calculated as weight (kg) divided by the squared height (m). BP was measured three times—on a single occasion—in a seated position using a mercury sphygmomanometer after a 15 min of rest. A venous blood sample of the subjects was taken after 12–14 h overnight fasting and analyzed in the same laboratory. Blood levels of glucose, insulin, total cholesterol, HDL-C, LDL-C, and TGs were measured. The oral glucose tolerance test (OGTT) was performed in each subjects who had never been diagnosed with diabetes. Insulin levels were measured by ELISA using reagent (Monobind Company, USA). A within-run precision CV was 4.9 and total precision CV was 4.9. Subjects with a BMI above 25 and subjects with diabetes were excluded from the present study. MONW was defined by IR using the homeostatic model assessment (HOMA) as fasting serum insulin (μIU/mL) × fasting plasma glucose (mmol/L)/22.5 [10]. The optimal cut point of HOMA to determine IR was evaluated by the lower limit of top quintile of HOMA-IR values in normal subjects [11, 12]. Subjects without any component of metabolic syndrome were
Kolmogorov–Smirnov test was used to examine the normality of variables of interest. Data were recorded as mean ± SD or median (minimum–maximum) where appropriate. T-test was used for analysis of continuous variables and non-normally distributed variables were compared by Mann–Whitney U test. The independent associations of age, the components of metabolic syndrome, and insulin resistance were assessed by multivariant logistic regression. The odds ratio (OR) and 95 % confidence intervals (CI) are expressed per 5 cm increment of WC due to inconsistency of WC cut off in different studies. p values less than 0.05 were considered statistically significant.
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Results The study was performed on a total of 417 subjects with a BMI lower than 25 kg/m2 and aged 20–72-year old (35.71 ± 11.04). Of 417 subjects, 44.3 % were female. The prevalence of MONW was 33.8 % in men and 39.8 % in women. No significant differences were found for HOMAIR according to gender (2.27 ± 1.2 in men vs. 2.42 ± 1.43 in women). Table 1 presents clinical and biochemical characteristics of the study subjects by gender. WC and BMI were not different between women with and without MONW. WC and BMI in men with MONW were higher than men without MONW (p
ORIGINAL ARTICLE
Association of metabolic syndrome components with insulin resistance in normal weight population: the Qazvin Metabolic Diseases study S. Hashemipour1 · N. Esmailzadehha1 · H. Hamid1 · S. Oveisi1 · P. Yakhchaliha1 · A. Ziaee1
Received: 7 January 2015 / Accepted: 27 April 2015 © Italian Society of Endocrinology (SIE) 2015
Abstract Purpose Metabolically obese but normal weight (MONW) is associated with higher risk of type 2 diabetes, dyslipidemia, and hypertension. The aim of this study was to evaluate the association of metabolic syndrome components with MONW in each sex in Iranian population. Methods This cross-sectional study was performed on 417 normal weight subjects in Qazvin, Iran between September 2010 and April 2011. MONW was defined by insulin resistance (IR) using the homeostatic model assessment (HOMA). Cut off point for IR was defined as the lower limit of top quintile of HOMA-IR values in normal weight population without any metabolic risk factors. Data were analyzed using T test, Mann–Whitney U test, and multivariant logistic regression analysis. Results Of 417 subjects, 44.3 % were female. The prevalence of MONW was 33.8 % in men and 39.8 % in women. Triglycerides levels were significantly higher in both men and women with MONW. Waist circumference was significantly higher in men with MONW, while high-density lipoprotein cholesterol levels were significantly lower in women with MONW. In logistic regression analysis, hypertriglyceridemia in women (OR 3.398; 95 % CI 1.306– 8.846) and waist circumference (per 5 cm increment) in men (OR 1.653; 95 % CI 1.279–2.136) had independent association with MONW. Conclusion Association of metabolic syndrome components with MONW is different in men and women. Waist
* A. Ziaee [email protected] 1
Metabolic Diseases Research Center, Booali-Sina Hospital, Qazvin University of Medical Sciences, Booali‑Sina Street, Qazvin, Iran
circumference had an independent association with IR in men but not in women. IR and its complications should be considered in lean women with hypertriglyceridemia. Keywords Gender difference · MONW · Insulin resistance · Waist circumference · Hypertriglyceridemia
Introduction Insulin resistance (IR) is not limited to obese subjects. The term metabolically obese but normal weight (MONW) was first introduced by Ruderman et al. [1] in the 1980s for defining a group of patients with normal weight but complications of IR. Individuals with MONW are predisposed to higher cardiovascular disease (CVD) risk and greater severity of coronary artery disease (CAD) [2]. Moreover, greater all-cause mortality during 10 years of follow-up has been reported for them [3]. Unfortunately, individuals with MONW are frequently undetected and untreated for years because of their normal body mass index (BMI) [4, 5]. Therefore, identifying individuals with MONW is important to take early preventive actions. Studying anthropometric characteristics and biochemical abnormalities is a useful method in predicting insulin resistance. In some studies, high systolic and diastolic blood pressure (BP), low high-density lipoprotein cholesterol (HDL-C), high triglycerides (TGs), high lowdensity lipoprotein cholesterol (LDL-C), or changes in its quality were associated with MONW [6–8]. The association of MONW and BMI is inconsistent in different studies. In some studies, BMI and waist circumference (WC) are associated with MONW [6, 7], while other studies have not found such association [4, 5, 8]. Some of these
13
J Endocrinol Invest
inconsistencies could be attributed to race and gender differences in different studies. The aim of this study was to evaluate the association of metabolic syndrome components with MONW in each sex in Iranian population.
defined as Normal subjects based on the diagnostic criteria proposed by national cholesterol education program third adult treatment panel (ATPIII 2004) [13]. The HOMA cut point for IR was 2.482. Subjects with HOMA-IR above 2.482 were considered as MONW.
Methods
Statistical analysis
This study was a cross-sectional population-based study that was performed on a representative sample of residents of Mindoodar district of Qazvin which is located 150 km northwest of Tehran, the capital city of Iran from September 2010 to April 2011. The ethics committee of Qazvin University of medical sciences approved the study. The Minoodar district was divided into four main clusters according to the population size. All households had health profiles at Minoodar health center and the sampling unit was the household. 1107 people aged ≥20 years were selected by multistage cluster random sampling methods. Subjects were invited by phone call to attend the study at the Minoodar health center and after face to face explanation of the study details they were free to participate. All subjects gave their written informed consent. Social and demographic data of the subjects were selfreported using a questionnaire. Two practitioners recorded their past medical history, family medical conditions, current medication, and physical examination, using an organized questionnaire. Complete details of the methods have been described elsewhere [9]. Anthropometric data were obtained after 12–14 h overnight fasting. Weight, height, and WC were measured. The WC was measured halfway between the costal margin and the iliac crest at the end of normal expiration. BMI was calculated as weight (kg) divided by the squared height (m). BP was measured three times—on a single occasion—in a seated position using a mercury sphygmomanometer after a 15 min of rest. A venous blood sample of the subjects was taken after 12–14 h overnight fasting and analyzed in the same laboratory. Blood levels of glucose, insulin, total cholesterol, HDL-C, LDL-C, and TGs were measured. The oral glucose tolerance test (OGTT) was performed in each subjects who had never been diagnosed with diabetes. Insulin levels were measured by ELISA using reagent (Monobind Company, USA). A within-run precision CV was 4.9 and total precision CV was 4.9. Subjects with a BMI above 25 and subjects with diabetes were excluded from the present study. MONW was defined by IR using the homeostatic model assessment (HOMA) as fasting serum insulin (μIU/mL) × fasting plasma glucose (mmol/L)/22.5 [10]. The optimal cut point of HOMA to determine IR was evaluated by the lower limit of top quintile of HOMA-IR values in normal subjects [11, 12]. Subjects without any component of metabolic syndrome were
Kolmogorov–Smirnov test was used to examine the normality of variables of interest. Data were recorded as mean ± SD or median (minimum–maximum) where appropriate. T-test was used for analysis of continuous variables and non-normally distributed variables were compared by Mann–Whitney U test. The independent associations of age, the components of metabolic syndrome, and insulin resistance were assessed by multivariant logistic regression. The odds ratio (OR) and 95 % confidence intervals (CI) are expressed per 5 cm increment of WC due to inconsistency of WC cut off in different studies. p values less than 0.05 were considered statistically significant.
13
Results The study was performed on a total of 417 subjects with a BMI lower than 25 kg/m2 and aged 20–72-year old (35.71 ± 11.04). Of 417 subjects, 44.3 % were female. The prevalence of MONW was 33.8 % in men and 39.8 % in women. No significant differences were found for HOMAIR according to gender (2.27 ± 1.2 in men vs. 2.42 ± 1.43 in women). Table 1 presents clinical and biochemical characteristics of the study subjects by gender. WC and BMI were not different between women with and without MONW. WC and BMI in men with MONW were higher than men without MONW (p
