Relationship Between Metabolic Syndrome and Beta-Cell Function in Nondiabetic Korean Premenopausal and Postmenopausal Women: 2015 Korean National Health and Nutrition Examination Survey

Abstract

Background:

This study was conducted to assess the relationship between metabolic syndrome (MetS) and beta-cell function in nondiabetic Korean women.

Methods:

This study included 2,507 women (premenopausal women, 1,359; postmenopausal women, 1,148) who were aged ≥20 and used 2015 Korean National Health and Nutrition Examination Survey (KNHANES) data.

Results:

Key study results were as follows: first, in both premenopausal and postmenopausal women, after adjusting for related variables [except body mass index (BMI)], MetS (P < 0.001) and metabolic syndrome score (MSS; P < 0.001) were positively associated with the homeostasis model assessment of beta-cell function (HOMA-B) levels. Second, in premenopausal women, when further adjusted for BMI, MetS (P = 0.002) and MSS (P < 0.001) were also positively associated with HOMA-B levels. However, in postmenopausal women, when further adjusting for BMI, the associations of MetS (P = 0.322) or MSS (P = 0.855) and HOMA-B levels were no longer significant.

Conclusions:

Metabolic syndrome was positively associated with beta-cell function in nondiabetic Korean premenopausal women, but not in Korean postmenopausal women.

Introduction

Metabolic syndrome (MetS) is defined as occurring when three or more of its components [abdominal obesity, elevated fasting blood glucose (FBG), elevated blood pressure (BP), elevated triglycerides (TGs), and reduced high-density lipoprotein cholesterol (HDL-C)] are found simultaneously.¹ MetS is characterized by insulin resistance similar to type 2 diabetes mellitus (T2DM), and is a strong risk factor for chronic kidney disease and cardiovascular disease (CVD).² In T2DM onset and progression of T2DM, beta-cell function is very important. Loss of pancreatic beta-cell function leads to worsening glucose tolerance in early T2DM.³ Even if insulin resistance increases in nondiabetics, progression to T2DM cannot develop unless beta-cell dysfunction is present.^4,5

Menopause in women causes many physiological changes, including an increase in osteoporosis and a decrease in sex hormone levels.⁶ The quality of life of postmenopausal women is worsened by an increase in chronic diseases, such as MetS, hypertension, diabetes, and chronic kidney disease (CKD).^7

–10 In particular, the continued reduction of estrogen in postmenopausal women is a major risk factor,^10

–13 and previous studies suggested that hormone replacement therapy (HRT) in postmenopausal women is an important treatment for these chronic diseases.^14,15

To date, studies on the relationship between MetS and beta-cell function have been conducted mainly on patients with diseases, such as obesity and T2DM.^16,17 Studies on nondiabetic premenopausal and postmenopausal women are rare. Therefore, this study aimed to investigate the relationship between MetS and the measured homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-B) in nondiabetic premenopausal and postmenopausal women using data from the Korean National Health and Nutrition Examination Survey (KNHANES), which is representative of Korea.

Methods

Study subjects

This study was based on data from the sixth KNHANES VI-3, which is the most recent data that HOMA-IR and HOMA-B among the KNHANES. In the KNHANES VI-3, 7,380 individuals >1 year of age were sampled. Among the 5,855 subjects who participated in the KNHANES VI-3 (2015), we limited the analyses to adults aged ≥20 years. We excluded 1,873 men and excluded 895 subjects whose data were missing for analytic variables, such as HOMA-IR and B and various blood chemistry tests. After the exclusion of those individuals with missing data or who suffered from diabetes type 1 and 2 (580 subjects diagnosed with FBG level ≥ 126mg/dL or with type 1 diabetes). Finally, 2,507 subjects (premenopausal women, 1,359; postmenopausal women, 1,148) were included in the statistical analysis. The KNHANES VI-3 (2015) study has been conducted according to the principles expressed in the Declaration of Helsinki [Institutional Review Board (IRB) No, 2015–01–02–6C]. All participants in the survey signed an informed written consent form. Further information can be found in “The KNHANES VI-3 (2015) Sample,” which is available on the KNHANES Website. The data from KNHANES VI-3 are available on request by email if the applicant logs onto the “Korea National Health and Nutrition Examination Survey” Website.

General characteristics and blood chemistry

Research subjects were classified by menopause (premenopausal or postmenopausal women), smoking (non-smoker or current smoker), alcohol drinking (yes or no), and regular exercise (yes or no). Participants who smoked more than one cigarette a day and those who never smoked were classified into the current smoker and nonsmoker groups, respectively. Regular exercise was indicated “yes” for participants who had exercised on a regular basis regardless of outdoor and indoor exercises (regular exercise was defined as 30 min at a time and 5 times/wk in the case of moderate exercise, such as doubles tennis, swimming slowly, badminton, table tennis, volleyball, and carrying light objects; and for 20 min at a time and three times/week in the case of vigorous exercise, such as climbing, running, cycling fast, swimming fast, football, basketball, squash, singles tennis, jump rope, and carrying heavy objects). Alcohol drinking was indicated “yes” for participants who had consumed at least one glass of alcohol every month over the last year. Anthropometric measurements included waist measurement (WM), body mass index (BMI), measurements of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Blood chemistry included measurement of HDL-C, total cholesterol (TC), TGs, high-sensitivity C-reactive protein (hsCRP), insulin, and FBG.

HOMA-IR and HOMA-B

The HOMA-IR and B constitute a method for assessing insulin resistance and beta-cell function from basal insulin and glucose. HOMA-IR and B are also significantly associated with diabetes risk across ethnic groups.¹⁸ The formulae are as follows: HOMA-IR = [fasting insulin (μU/mL) × fasting blood glucose (mg/dL)]/405; HOMA-B = 360 × fasting insulin (μU/mL)/[fasting blood glucose (mg/dL) −63].¹⁹

MetS and metabolic syndrome score

MetS was defined using the diagnostic criteria of the revised National Cholesterol Education Program Adult Treatment Panel III,²⁰ including WM, SBP, DBP, FBG, TGs, and HDL-C. The criteria for abdominal obesity were abdominal circumference measurements of >80 cm for women, according to the Asia-Pacific criteria.²¹ The use of antihypertensive medication or DBP >85 mmHg or SBP >130 mmHg was set as the criterion for the elevated BP. The use of medication for hyperglycemia or FBG >100 mg/dL was set as the criterion for the elevated FBG. Treatments for dyslipidemia or TGs >150 mg/dL were set as the criteria for the elevated TGs. The criteria for treatment for dyslipidemia or reduced HDL-C were HDL-C <50 mg/dL for women. The presence of defined abnormalities in any three of these five measures constitutes a diagnosis of metabolic syndrome (MetS). The metabolic syndrome score (MSS) indicates the presence of elevated BP, abdominal obesity, elevated TGs, reduced HDL-C, or elevated FBG. Subjects without any of the five risk factors received MSS of 0, while those with 1, 2, 3, or ≥4 of the risk factors received an MSS of 1, 2, 3, and ≥4, respectively.²²

Data analysis

The collected data were statistically analyzed using SPSS WIN version 18.0 (SPSS, Inc., Chicago, IL). In statistical analyses, continuous variables were reported as mean ± standard deviation. Categorical variables were reported as percentages (%). Clinical characteristics according to premenopausal and postmenopausal women were analyzed using chi-square and an independent t-test (Table 1). We conducted the multiple linear regression analysis for the HOMA-IR and HOMA-B in premenopausal women (Table 2) and postmenopausal women (Table 3). In the case of analysis of covariance test for HOMA-IR (Table 4) and HOMA-B (Table 5), the 3 models constructed were: (1) adjusted for age; (2) further adjusted for drinking, smoking, regular exercising, TC, and hs CRP; and (3) further adjusted for BMI. The significance level for all of the statistical data was set as P < 0.05.

Table 1.

General Clinical Characteristics of Nondiabetic Subjects

Variables	Category	Total (n = 2,507)	Premenopausal women (n = 1,359)	Postmenopausal women (n = 1,148)	P
Age (years)		50.43 ± 15.85	39.80 ± 12.23	63.01 ± 8.89	<0.001
Smoking	Current smoker	110 (4.4)	72 (5.3)	38 (3.3)	<0.001
Alcohol drinking	Current drinker	1,019 (40.6)	682 (50.2)	337 (27.4)	<0.001
Regular exercise	Yes	246 (9.8)	165 (12.1)	81 (7.1)	<0.001
MetS	MSS <3	1,874 (74.8)	1,155 (85.0)	719 (62.6)	<0.001
	MSS ≥3	633 (25.5)	204 (15.0)	429 (37.3)
MSS	0	736 (29.4)	583 (42.9)	153 (13.3)	<0.001
	1	621 (24.8)	353 (26.0)	268 (23.3)
	2	517 (20.6)	219 (16.1)	298 (26.1)
	3	392 (15.6)	130 (9.6)	262 (22.8)
	≥4	241 (9.6)	74 (5.4)	167 (14.5)
SBP (mmHg)		116.34 ± 17.83	109.77 ± 15.03	124.12 ± 17.76	<0.001
DBP (mmHg)		73.57 ± 9.80	72.06 ± 9.63	75.35 ± 9.70	<0.001
BMI (kg/m²)		23.38 ± 3.46	21.72 ± 3.46	24.17 ± 3.29	<0.001
WM (cm)		79.26 ± 9.42	76.80 ± 9.03	82.17 ± 9.04	<0.001
TC (mg/dL)		193.51 ± 34.83	186.63 ± 32.68	201.65 ± 35.55	<0.001
TGs (mg/dL)		112.31 ± 70.21	98.69 ± 62.96	128.43 ± 74.81	<0.001
HDL-C (mg/dL)		54.56 ± 13.13	56.39 ± 12.83	52.39 ± 13.16	<0.001
hsCRP (mg/dL)		1.13 ± 2.18	1.08 ± 2.29	1.18 ± 2.05	0.250
FBG (mg/dL)		93.64 ± 9.36	91.60 ± 8.69	96.06 ± 9.55	<0.001
Insulin (μU/mL)		7.47 ± 4.96	7.41 ± 5.15	7.55 ± 4.73	0.455
HOMA-IR		1.77 ± 1.29	1.71 ± 1.32	1.83 ± 1.25	0.021
HOMA-B		90.15 ± 55.44	95.39 ± 60.73	83.95 ± 55.44	<0.001

Values are n (%) or mean ± SD.

BMI, body mass index; DBP, diastolic blood pressure; FBG, fasting blood glucose; HDL-C, high-density lipoprotein cholesterol; HOMA-B, homeostasis model assessment of beta-cell function; HOMA-IR, homeostasis model assessment of insulin resistance; hsCRP, high-sensitivity C-reactive protein; MetS, metabolic syndrome; MSS, metabolic syndrome score; SBP, systolic blood pressure; SD, standard deviation; TC, total cholesterol; TGs, triglycerides; WM, waist measurement.

Table 2.

Multiple Linear Regression Analysis for the Independent Factors Determining Homeostasis Model Assessment of Insulin Resistance in Premenopausal and Postmenopausal Women (n = 2,507)

Variables	HOMA-IR
	Premenopausal women (n = 1,359)					Postmenopausal women (n = 1,148)
	β	SE	t	95% CI	P	β	SE	t	95% CI	P
Age (years)	−0.282	0.003	−11.055	−0.036 to −0.025	<0.001	0.009	0.004	0.291	−0.007 to 0.009	0.771
SBP (mmHg)	0.095	0.003	2.635	0.002 to 0.015	0.009	−0.028	0.003	−0.791	−0.007 to 0.003	0.429
DBP (mmHg)	−0.089	0.004	−2.723	−0.021 to −0.003	0.007	0.047	0.004	1.396	−0.002 to 0.016	0.163
BMI (kg/m²)	0.227	0.017	5.053	0.053 to 0.121	<0.001	0.108	0.018	2.256	0.005 to 0.077	0.024
WM (cm)	0.141	0.007	3.050	0.007 to 0.034	0.002	0.248	0.007	4.976	0.021 to 0.048	<0.001
TGs (mg/dL)	0.183	0.001	7.677	0.003 to 0.005	<0.001	0.076	0.001	2.892	0.000 to 0.002	0.004
HDL-C (mg/dL)	−0.060	0.002	−2.574	−0.011 to −0.001	0.010	−0.034	0.002	−1.304	−0.008 to 0.002	0.193
FBG (mg/dL)	0.360	0.004	15.342	0.048 to 0.062	<0.001	0.364	0.003	14.611	0.041 to 0.054	<0.001

CI, confidence interval; SE, standard error.

Table 3.

Multiple Linear Regression Analysis for the Independent Factors Determining Homeostasis Model Assessment of Beta-Cell Function in Premenopausal and Postmenopausal Women (n = 2,507)

Variables	HOMA-B
	Premenopausal women (n = 1,359)					Postmenopausal women (n = 1,148)
	β	SE	t	95% CI	P	β	SE	t	95% CI	P
Age (years)	−0.346	0.137	−12.548	−4.990 to −1.452	<0.001	0.010	0.175	0.292	−0.292 to 0.395	0.770
SBP (mmHg)	0.119	0.158	3.038	0.170 to 0.789	0.002	−0.023	0.107	−0.571	−0.272 to 0.149	0.568
DBP (mmHg)	−0.088	0.222	−2.505	−0.993 to −0.121	0.012	0.051	0.187	1.341	0.116 to 0.618	0.180
BMI (kg/m²)	0.210	0.854	4.325	2.018 to 5.369	<0.001	0.135	0.777	2.513	0.428 to 3.476	0.012
WM (cm)	0.197	0.336	3.948	0.667 to 1.984	<0.001	0.277	0.0294	4.972	0.884 to 2.037	<0.001
TGs (mg/dL)	0.255	0.025	9.853	0.197 to 0.295	<0.001	0.129	0.019	4.388	0.045 to 0.119	<0.001
HDL-C (mg/dL)	−0.055	0.120	−2.181	−0.496 to 0.026	0.029	−0.036	0.106	−1.236	−0.339 to 0.077	0.217
FBG (mg/dL)	−0.231	0.177	−9.092	−1.961 to −1.265	<0.001	−0.266	0.139	−9.573	−1.603 to −1.058	<0.001

Table 4.

Comparisons of the Homeostasis Model Assessment of Insulin Resistance Levels According to Metabolic Syndrome and Metabolic Syndrome Scores in Premenopausal and Postmenopausal Women (n = 2,507)

	Variables	Category	HOMA-IR
	Variables	Category	Model 1	Model 2	Model 3
Premenopausal women	MSS	0	1.23 ± 0.05 (1.14–1.32)	1.14 ± 0.05 (1.05–1.24)	1.38 ± 0.05 (1.28–1.48)
(n = 1,359)		1	1.55 ± 0.06 (1.43–1.67)	1.56 ± 0.06 (1.44–1.67)	1.57 ± 0.06 (1.46–1.68)
		2	2.01 ± 0.08 (1.85–2.16)	2.06 ± 0.08 (1.91–2.21)	1.82 ± 0.08 (1.67–1.97)
		3	2.59 ± 0.10 (2.39–2.78)	2.77 ± 0.10 (2.57–2.97)	2.36 ± 0.10 (2.15–2.56)
		≥4	3.89 ± 0.13 (3.63–4.15)	4.06 ± 0.13 (3.80–4.32)	3.56 ± 0.13 (3.29–3.82)
		P	<0.001	<0.001	<0.001
	MetS	MSS <3	1.47 ± 0.04 (1.41–1.54)	1.46 ± 0.04 (1.39–1.53)	1.54 ± 0.03 (1.48–1.61)
		MSS ≥3	3.06 ± 0.08 (2.90–3.23)	3.15 ± 0.09 (2.98–3.32)	2.67 ± 0.09 (2.49–2.84)
		P	<0.001	< 0.001	<0.001
Postmenopausal women	MSS	0	1.07 ± 0.09 (0.89–1.25)	1.07 ± 0.10 (0.88–1.25)	1.42 ± 0.10 (1.23–1.61)
(n = 1,148)		1	1.38 ± 0.07 (1.24–1.52)	1.39 ± 0.07 (1.25–1.52)	1.55 ± 0.07 (1.41–1.68)
		2	1.90 ± 0.07 (1.77–2.03)	1.91 ± 0.07 (1.77–2.04)	1.87 ± 0.06 (1.74–1.99)
		3	2.13 ± 0.07 (1.99–2.27)	2.13 ± 0.07 (1.99–2.27)	1.99 ± 0.07 (1.85–2.13)
		≥4	2.67 ± 0.09 (2.50–2.85)	2.66 ± 0.09 (2.48–2.84)	2.37 ± 0.09 (2.19–2.54)
		P	<0.001	<0.001	<0.001
	MetS	MSS <3	1.53 ± 0.04 (1.44–1.62)	1.54 ± 0.05 (1.45–1.63)	1.68 ± 0.04 (1.59–1.76)
		MSS ≥3	2.34 ± 0.06 (2.23–2.45)	2.32 ± 0.06 (2.21–2.44)	2.10 ± 0.06 (1.99–2.21)
		P	<0.001	<0.001	<0.001

Model 1 [mean ± SE (95% CI)], adjusted for age; Model 2 [mean ± SE (95% CI)], Model 1 further adjusted for smoking, alcohol drinking, regular exercise, TC, and hsCRP; Model 3 [mean ± SE (95% CI)], Model 2 further adjusted for BMI.

Table 5.

Comparisons of the Homeostasis Model Assessment of Beta-Cell Function Levels According to Metabolic Syndrome and Metabolic Syndrome Scores in Premenopausal and Postmenopausal Women (n = 2,507)

	Variables	Category	HOMA-B
	Variables	Category	Model 1	Model 2	Model 3
Premenopausal women (n = 1,359)	MSS	0	76.37 ± 2.40 (71.66–81.09)	77.84 ± 2.42 (73.10–82.59)	89.32 ± 2.55 (84.32–94.32)
Premenopausal women (n = 1,359)		1	89.27 ± 2.97 (83.45–95.09)	89.46 ± 2.96 (83.66–95.26)	90.14 ± 2.84 (84.57–95.70)
		2	117.97 ± 3.79 (110.53–125.41)	116.54 ± 3.79 (109.10–123.98)	105.03 ± 3.79 (97.60–112.47)
		3	129.03 ± 5.08 (119.06–139.00)	125.92 ± 5.10 (115.92–135.92)	105.93 ± 5.23 (95.68–116.18)
		≥4	148.40 ± 6.61 (135.42–161.37)	145.61 ± 6.61 (132.65–158.57)	121.12 ± 6.73 (107.92–134.31)
		P	<0.001	<0.001	<0.001
	MetS	MSS <3	88.74 ± 1.71 (85.38–92.09)	89.36 ± 1.70 (86.03–92.68)	93.20 ± 1.62 (90.03–96.37)
		MSS ≥3	133.04 ± 4.25 (124.71–141.37)	129.52 ± 4.25 (121.19–137.86)	107.75 ± 4.30 (99.32–116.18)
		P	<0.001	<0.001	0.002
Postmenopausal women (n = 1,148)	MSS	0	68.67 ± 3.86 (61.10–76.25)	68.43 ± 3.88 (60.82–76.04)	82.48 ± 3.94 (74.76–90.21)
Postmenopausal women (n = 1,148)		1	76.30 ± 2.88 (70.66–81.95)	76.30 ± 2.88 (70.65–81.95)	82.63 ± 2.82 (77.10–88.15)
		2	84.68 ± 2.72 (79.34–90.01)	84.76 ± 2.72 (79.43–90.09)	83.22 ± 2.60 (78.12–88.32)
		3	92.08 ± 2.92 (86.36–97.81)	92.27 ± 2.92 (86.53–98.00)	86.79 ± 2.84 (81.22–92.36)
		≥4	96.17 ± 3.65 (89.00–103.34)	95.95 ± 3.68 (88.73–103.17)	84.27 ± 3.68 (77.04–91.49)
		P	<0.001	<0.001	0.855
	MetS	MSS <3	78.27 ± 1.77 (74.80–81.75)	78.30 ± 1.77 (74.82–81.78)	82.84 ± 1.73 (79.44–86.24)
		MSS ≥3	93.46 ± 2.30 (88.95–97.98)	93.42 ± 2.31 (88.89–97.96)	85.82 ± 2.30 (81.31–90.32)
		P	<0.001	<0.001	0.322

Results

General characteristics of research subjects

General clinical characteristics of the research subjects are shown in Table 1. In premenopausal women, the mean HOMA-IR and B levels of subjects were 1.71 ± 1.32 and 95.39 ± 60.73, respectively. According to the classification of MSS guidelines, 583 (42.9%), 353 (26.0%), 219 (16.1%), 130 (9.6%), and 74 (5.4%) subjects were classified as MSS 0, MSS 1, MSS 2, MSS 3, and MSS ≥4, respectively, while MetS was reported for 204 of the 1,359 patients (15.0%). In postmenopausal women, the mean values of HOMA-IR and B levels of subjects were 1.83 ± 1.25 and 83.95 ± 55.44, respectively. According to the classification of MSS guidelines, 153 (13.3%), 268 (23.3%), 298 (26.1%), 262 (22.8%), and 167 (14.5%) subjects were classified as MSS 0, MSS 1, MSS 2, MSS 3, and MSS ≥4, respectively, while MetS was reported for 429 of the 1,148 patients (37.3%).

The associations of the HOMA-IR and HOMA-B and MetS risk factor in premenopausal and postmenopausal women

The associations of the HOMA-IR and HOMA-B and MetS risk factor in premenopausal and postmenopausal women are shown in Tables 2 and 3. HOMA-IR was positively associated with SBP, BMI, WM, and TGs in premenopausal women but was inversely associated with age, DBP, and HDL-C. In postmenopausal women, HOMA-IR was positively associated with BMI, WM, and TGs (Table 2). HOMA-B was positively associated with SBP, BMI, WM, and TGs in premenopausal women but was inversely associated with age and DBP. In postmenopausal women, HOMA-B was positively associated with BMI, WM, and TGs (Table 3).

Comparisons of the HOMA-IR and HOMA-B levels according to MetS and MSS in premenopausal and postmenopausal women

Comparisons of the HOMA-IR and B levels according to MetS in premenopausal and postmenopausal women are shown in Tables 4 and 5. In premenopausal and postmenopausal women, MetS and MSS were positively associated with HOMA-IR levels (P < 0.001) after adjustment for related variables (Table 4). In both premenopausal and postmenopausal women, after adjustment for related variables (except BMI), MetS (P < 0.001) and MSS (P < 0.001) were positively associated with HOMA-B levels (Model 2). However, when further adjusted for BMI (Model 4), MetS (P < 0.001) and MSS (P = 0.002) were positively associated with HOMA-B levels in premenopausal women, but the associations of MetS (P = 0.855) or MSS (P = 0.322) and HOMA-B levels in postmenopausal women were not significant (Table 5).

Discussion

In our study population involving nondiabetic Korean women, MetS and MSS were positively associated with HOMA-B after adjusting for the related variables (except BMI) in both premenopausal and postmenopausal women. However, when further adjusted for BMI, MetS and MSS were positively associated with HOMA-B in premenopausal women, but not in postmenopausal women.

The prevalence of MetS in nondiabetic women (25.5%) in our study was higher than that in nondiabetic Taiwanese women (8.9%),²³ Chinese women (16.2%),²⁴ and European women (14.2%),²⁵ but was similar to the prevalence in nondiabetic American Indian women (20.3%).²⁶ Most previous studies have reported that the cardiovascular risk factors in postmenopausal women are higher than those in premenopausal women.^27
–29 In this study, BMI, WM, SBP, DBP, FBG, TGs, HOMA-IR, and MetS in postmenopausal women were higher than those in premenopausal women, and HDL-C and HOMA-B were lower. It has been recognized that the increase of CVD risk factors in postmenopausal women is due to a difference in fat distribution and a reduction of sex hormones caused by menopause. Premenopausal women tend to accumulate fat primarily in the subcutaneous regions; however, after menopause, adiposity shifts from subcutaneous regions to the visceral area, which is positively correlated with risk of MetS and CVD.³⁰ Munoz et al. reported that HRT in postmenopausal women has been shown to lower adipose tissue mass as well as FBG and insulin level.^14,31

In this study, in non-MetS populations, insulin levels in premenopausal and postmenopausal women were not significant (P = 0.594) but in MetS populations, insulin level in premenopausal women was higher than those in postmenopausal women (P < 0.001) (Fig. 1). In addition, MetS and MSS were positively associated with HOMA-B in nondiabetic premenopausal women, but there was no significant association with HOMA-B and MetS and MSS in nondiabetic postmenopausal women (Table 5). We think these results may be explained by the reduction in levels of sex hormones such as estrogens. According to increase in age, the ability of pancreatic beta cells to maintain an insulin secretion function adequate for metabolic demand is impaired.^32,33 In our results, HOMA-B levels were decreased with an increasing age (Table 3). Menopause in women causes a sharp decline in the indices related to sex hormones such as estrogens and the estrogen receptor alpha (ER-α). In terms of blood glucose homeostasis in women, the estrogen receptor and estrogen play an important role in the activation of beta-cell function. Estrogen-deficient women exhibit insulin resistance and impaired glucose metabolism.³⁴ Yuchi et al. reported that estradiol (E2) and ER-α signaling lead the replication and formation of beta cells in mouse pancreas.³⁵ ER-α promotes beta-cell survival and insulin secretion through the maintenance of mitochondrial fission–fusion–mitophagy dynamics and mitochondrial–endoplasmic reticulum function.³⁶ They suggested that ER-α regulates autophagy in pancreatic beta cells and protects beta cells from apoptosis. In the distribution of fat storage in women, visceral adipose tissue is increased with menopause and increasing age and BMI.^37,38 Toth et al. reported that postmenopausal women had 22% greater subcutaneous abdominal fat area (P < 0.05), 36% more trunk fat (P < 0.01), and 49% greater intra-abdominal fat area (P < 0.01) than premenopausal women.³⁹ Abdominal fat was inversely associated with beta-cell function.⁴⁰ Menopause in women causes a sharp decline in sex hormones. Therefore, several studies suggested that HRT in postmenopausal women can represent beneficial effects of improved distribution of abdominal fat, fasting lipid levels, and the prevention of CVD and T2DM.^14,41,42

FIG. 1.

Comparisons of insulin according to premenopausal and postmenopausal women in non-MetS and MetS. In non-MetS, insulin levels in premenopausal and postmenopausal women were not significant (P = 0.594). In MetS, insulin levels in premenopausal women were higher than those in postmenopausal women (P < 0.001). MetS, metabolic syndrome.

This study has a few limitations. First, estrogens are important factors in beta-cell function. However, the data of the KNHANES study failed to measure estrogens. Second, the measurement methods of beta-cell function vary (clamp studies, insulin sensitivity derived from an oral glucose tolerance test, insulin secretion-sensitivity index, the intravenous glucose tolerance test, or HOMA indices). HOMA indices are not the “gold-standard” method (the hyperglycemic clamp test and hyperinsulinemic-euglycemic clamp), but HOMA may be more appropriate for use in large amount epidemiological studies.⁴³ Third, because this study was a cross-sectional study, the ability to establish a causal association of MetS and beta-cell dysfunction was limited. Nevertheless, this is the first reported study to determine the association of MetS and MSS and beta-cell function in nondiabetic Korean premenopausal and postmenopausal women. More accurate results might be obtained by performing a cohort study.

In conclusion, we investigated the relationship between MetS and MSS and HOMA-IR and B in nondiabetic Korean women. MetS and MSS were positively associated with beta-cell function in nondiabetic premenopausal women but were not associated with beta-cell function in nondiabetic postmenopausal women.

Footnotes

Author Disclosure Statement

No conflicting financial interests exist.

Funding Information

This study was supported by Wonkwang Health Science University in 2019.

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