Prehypertension and insulin resistance among Mongolian people, Inner Mongolia, China

Abstract

Background. There is little knowledge on association of prehypertension with insulin resistance among Mongolian people. The purpose of the present study is to explore whether there are phenomena of insulin resistance in the phase of prehypertension in the Mongolian population. Methods. 2553 Mongolian people were included in the present analysis. Data on demographic characteristics, lifestyle risk factors, family history of hypertension and medical history were obtained, blood pressure, body weight, height and waist circumference measured, fasting blood samples collected and blood lipids, fast plasma glucose and insulin determined for all individuals. Results. Among participants who are overweight, the means of the homeostatic model assessment of insulin resistance (HOMA-IR) were significantly higher in prehypertensives than those in normotensives. Prehypertension was significantly associated with the higher levels of HOMA-IR after multivariate adjustment. Compared with HOMA-IRs < 1.64, multivariate-adjusted ORs (95% CI) for HOMA-IRs of 1.64–2.32, 2.33–2.84, 2.85–3.76 and ≥3.76 were 1.056 (0.786–1.418), 1.565 (1.158–2.116), 1.381 (1.020–1.870) and 1.435 (1.046–1.970), respectively. Conclusions. Prehypertension was significantly associated with insulin resistance in the Mongolian population, and this study suggest that insulin resistance may play an important role in development of hypertension.

Key Words::

• Hypertension
• insulin resistance
• prehypertension

Introduction

Hypertension is a well established risk factor of cardiovascular disease (CVD). Recently, a new blood pressure (BP) designation of prehypertension has also been suggested as a condition of future risk (1,2). The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High BP [JNC7] (3) had prehypertension defined as a systolic BP (SBP) of 120–139 mmHg and/or a diastolic BP (DBP) of 80–89 mmHg. Some evidence has documented that people with prehypertension have more cardiovascular risk factors (4) and cardiovascular events compared with those with normal BP (2,5,6). Furthermore, prehypertensive individuals are known to be at increased risk of progressing to hypertension (7,8), and prehypertension also is a risk factor of CVD (9,10). As we know, hypertension often co-exists with other multi-metabolism abnormalities including hyperinsulin, insulin resistance, hyperlipidemia and hyperglycemia (11). Insulin resistance may play an important role in leading to multi-metabolism abnormalities and hypertension. Progressing to hypertension from prehypertension is continuous process; it may be a process of gradually appearing of multi-abnormalities and insulin resistance. There may have been the phenomena of insulin resistance in the phase of prehypertension.

There were marked ethical and geographical differences in BP level and the prevalence of hypertension in China (12). Our findings in a pre-study (13) suggested that prevalence of hypertension and rates of risk factors, such as obesity, drinking alcohol, hyperlipemia and hyperglycemia were much high in the Mongolian population of rural and animal husbandry area, Inner Mongolia, China. However, there is little knowledge on association of prehypertension with insulin resistance and difference in extent of insulin resistance between prehypertension and hypertension among Mongolian people of the area. The purpose of the present study was to explore whether there are phenomena of insulin resistance in the phase of prehypertension and compare the extent of insulin resistance between prehypertension and hypertension in the Mongolian population.

Methods

Study participants

A cross-sectional survey was conducted between 2002 and 2003. In the survey, two townships including 32 villages in Kezuohou Banner (county) and Naiman Banner in Inner Mongolia, China, were served as the investigation fields. The two adjacent townships are 100 km from Tongliao, a prefecture-level city in eastern Inner Mongolia, China. Most of the residents in the investigation field are Mongolian, and had lived there for a long time from generation to generation; they have maintained traditional manners and customs of Mongolian ethnicity, their professions are both farmers and herdsmen, and their diets are high in fat and salt. There were a total of 3475 Mongolian people aged 20 or over in the 32 villages. Among them, 2589 people who signed informed consent in the field were included in the present study. A total of 886 did not sign informed consent and were not investigated because they were out of the field or refused to respond at the time of investigation. The study was approved by Soochow University Ethics Committee.

Data collection and examination

Data on demographic characteristics, lifestyle risk factors, family history of hypertension and medical history were obtained using a standard questionnaire administered by trained staff. Cigarette smoker was defined as having smoked at least one cigarette per day for 1 year or more. The amount and type of alcohol consumed during the past year was collected; drinking alcohol was defined as consuming at least 50 g alcohol per day for 1 year or more.

Three BP measurements were performed by four trained doctors while the study participants were in the sitting position, with a standard mercury sphygmomanometer according to a standard protocol, after the subjects had been resting for 30 min. The first and fifth Korotkoff sounds were recorded as SBP and DBP, respectively; the mean of three BP measurements was used in the analysis. Prehypertension was defined as SBP of 120–139 mmHg and/or DBP of 80–89 mmHg, and no use of antihypertensive medication. Hypertension was defined as SBP≥140 mmHg and/or DBP≥90 mmHg and/or use of antihypertensive medication in preceding 2 weeks. Normotensive was defined as SBP < 120 mmHg and DBP < 80 mmHg without use of antihypertensive medication.

Body weight and height were measured with subjects wearing light clothing and without shoes by trained staff. The body mass index (BMI) was calculated as weight in kilograms divided by the square of the height in meters. The waist circumference (WC) was measured at the level of 1 cm above the umbilicus. Overweight was defined as BMI≥25 kg/m², and central obesity was defined as WC≥90 cm for males and ≥80 cm for females (14). Fasting blood samples were collected in the morning after at least 8 h of fasting for all participants. Serum was subsequently isolated from the whole blood, and all serum samples were frozen at −80°C for testing. Fast plasma glucose (FPG) was examined using a glucose meter (Roche, Basel, Switzerland) in the field; hyperglycemia was defined as FPG≥6.1 mmol/l. Total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and triglycerides (TG) were analyzed enzymatically on a Beckman Synchrony CX5 Delta Clinical System (Beckman Coulter, Fullerton, CA, USA) using commercial reagents, and low-density lipoprotein-cholesterol (LDL-C) concentration was calculated by use of the Friedewald equation for the individuals. Hyperlipidemia was defined as TC ≥ 5.72 mmol/l and/or TG≥1.69 mmol/l and/or LDL-C≥3.64 mmol/l. Metabolic syndrome was defined according to the IDF criteria (14). Insulin was assayed using a radioimmunoassay, and hyperinsulinemia was defined as insulin≥15.05 μU/ml (upper quartile). The hoemeostasis model assessment method was used to calculate insulin resistance index (HOMA-IR) (15):

HOMA-IR = [FPG (mmol/l) × insulin (μU/ml)]/22.5.

Statistical analysis

The prevalence of categorical variables was calculated for normotensive, prehypertensive and hypertensive individuals, respectively. Comparisons of prevalence among groups were performed by using chi-squared tests. The means and standard deviations (SD) of HOMA-IR stratified by various risk factors were calculated for normotensive, prehypertensive and hypertensive individuals, respectively. Analysis of covariance (ANCOVA) was used to compare difference of HOMA-IR between participants with different BP status stratified by risk factors. Multiple logistic regression analysis was used to examine the association between prehypertension and hypertension, and HOMA-IR adjusted for age, gender, alcohol consumption, cigarette smoking, history of hypertension and hyperlipidemia. Patients were divided into even quintiles of HOMA-IR (<1.63, 1.64–2.32, 2.33–2.84, 2.85–3.76 and ≥3.76), and odds ratio (OR) and 95% confident interval (95% CI) of prehypertension and hypertension were calculated for higher quintiles of HOMA-IR compared with the lowest quintile. In the analysis, normotension, prehypertension and hypertension were served as dependent variables, and other factors served as independent variables. All p-values were based on a two-sided test and a significance level of 0.05. Statistical analysis was conducted using SAS statistical software (version 9.1).

Results

A total of 2553 participants aged 20–84 years, including 1047 males and 1506 females, were included in the analysis. There were 953 hypertensives, 981 prehypertensives and 619 normotensives among the participants.

Table I presents the comparisons of demographic characteristics, rates of family history of hypertension, smoking, drinking, overweight, central obesity, hyperlipidemia, hyperglycemia, diabetes, metabolic syndrome and hyperinsulinemia among normotensives, prehypertensives and hypertensives. The results showed that there were significant difference in most of above risk factors among normotensives, prehypertensives and hypertensives. Basically, hypertensives were more likely to be male, older and to have higher rates of family history of hypertension, cigarette smoking, drinking alcohol, overweight, central obesity, hyperglycemia, diabetes and metabolic syndrome compared with prehypertensives, and prehypertensives were more likely to be male, older and to have higher rates of drinking alcohol, overweight, central obesity, hyperlipidemia and metabolic syndrome compared with normotensives.

Table I. Baseline characteristics of participates according to different blood pressure status.

Factors	Normotensive (619)	Prehypertensives (981)	Hypertensives (953)	p-value
Male, %	27.3 (169)	40.9 (401)^a	50.1 (477)^ab	<0.01
Age
20–	10.2 (63)	6.5 (64)	1.5 (14)
30–	40.9 (253)	32.3 (317)	13.2 (126)
40–	27.8 (172)	29.7 (291)	29.7 (283)
50–	16.0 (99)	20.4 (200)	29.7 (283)
60–	5.2 (32)	11.1 (109)^a	25.9 (247)^ab	<0.01
FHH	3.9 (24)	7.4 (73)	24.8 (236)^ab	<0.01
Smoking, %	41.2 (255)	42.7 (419)	48.3 (460)^ab	<0.01
Drinking, %	20.4 (126)	31.1 (305)^a	44.4 (423)^ab	<0.01
BMI ≥25, %	10.2 (63)	17.5 (172)^a	29.8 (284)^ab	<0.01
WC, male ≥90, female ≥80, %	26.5 (164)	32.6 (320)^a	45.2 (431)^ab	<0.01
Hyperlipidemia, %	36.8 (228)	41.7 (409)^a	46.1 (439)^a	<0.01
Hyperglycemia, %	6.8 (42)	9.5 (93)	14.8 (141)^ab	<0.01
Diabetes, %	2.9 (18)	2.3 (23)	5.6 (53)^ab	<0.01
Metabolic syndrome,%	3.2 (20)	13.1 (129)^a	28.3 (270)^ab	<0.01
Hyperinsulinemia, %	23.9 (148)	23.5 (231)	27.1 (258)	>0.05

The number in parentheses are numbers of cases. FHH, family history of hypertension; BMI, body mass index; WC, waist circumference.

^aCompared with normotensives, p < 0.05

^bCompared with prehypertensives, p < 0.05.

Table II presents comparison of HOMA-IR between participants with different BP status stratified by risk factors including age, gender, family history of hypertension, smoking, drinking, overweight, central obesity, hyperlipidemia and diabetes. The results showed that the means of HOMA-IR were higher in hypertensives than those in normotensives in both males and females, and the means of HOMA-IR were higher in hypertensives than those in male prehypertensives. In age 30–49 years, the means of HOMA-IR was significantly higher in hypertensives than those in normotensives, and in 40–49 years, the means of HOMA-IR was significantly higher in prehypertensives than those in normotensives. In most of sub-groups stratified by risk factors, the means of HOMA-IR were significantly higher in hypertensives than those in normotensives, and in those with non-family history, smoking, non-alcohol drinking and hyperlipidemia, the means of HOMA-IR were significantly higher in hypertensives than those in prehypertensives. Among those with family history of hypertension, drinking alcohol, overweight, central obesity, hyperlipidemia and diabetes, the means of HOMA-IR were significantly higher in prehypertensives than those in normotensives.

Table II. Comparison of the homeostatic model assessment of insulin resistance (HOMA-IR, mean±SD) between participants with different blood pressure status stratified by risk factors.

Factors	Normotensives (619)	Prehypertensives (981)	Hypertensives (953)
Gender
Male	2.73 ± 1.81	2.99 ± 2.03	3.31 ± 2.38^ab
Female	2.83 ± 1.89	3.00 ± 2.34	3.24 ± 2.15^a
Age
20–	3.17 ± 1.75	2.95 ± 2.44	3.56 ± 1.61
30–	2.81 ± 1.88	2.99 ± 1.95	3.34 ± 2.13^a
40–	2.53 ± 1.51	2.90 ± 2.01^a	3.14 ± 2.13^a
50–	2.95 ± 2.07	3.19 ± 2.55	3.35 ± 2.61
60–	3.04 ± 2.78	2.92 ± 2.66	3.32 ± 2.08
FHH
No	2.79 ± 1.86	2.96 ± 2.19	3.28 ± 2.19^ab
Yes	3.17 ± 1.97	3.49 ± 2.50^a	3.29 ± 2.48
Smoking
No	2.90 ± 1.88	3.13 ± 2.49	3.40 ± 2.27^a
Yes	2.66 ± 1.84	2.82 ± 1.79	3.16 ± 2.26^ab
Drinking
No	2.85 ± 1.93	3.02 ± 2.34	3.36 ± 2.27^ab
Yes	2.62 ± 1.56	2.95 ± 1.93^a	3.18 ± 2.25^a
BMI
<25	2.77 ± 1.86	2.79 ± 1.77	3.05 ± 2.13^a
≥25	3.06 ± 1.86	3.99 ± 3.49^a	3.86 ± 2.46^a
WC
Male < 90, female < 80	2.73 ± 1.79	2.75 ± 1.76	3.08 ± 2.16
Male ≥ 90, female ≥ 80	3.01 ± 2.05	3.51 ± 2.89^a	3.52 ± 2.37^a
Hyperlipidemia
No	2.75 ± 1.94	2.84 ± 2.03	3.08 ± 2.30^a
Yes	2.89 ± 1.74	3.21 ± 2.44^a	3.51 ± 2.21^ab
Diabetes
No	2.71 ± 1.71	2.86 ± 1.83	3.03 ± 1.79
Yes	5.86 ± 3.77	8.91 ± 6.13^a	7.56 ± 4.33^a

*Compared with normotensives, p < 0.05; ^bcompared with prehypertensives, p < 0.05. FHH, family history of hypertension; BMI, body mass index; WC, waist circumference.

Normotensives served as the control; the unadjusted and multivariable-adjusted ORs of prehypertension and hypertension associated with higher quintiles of HOMA-IR compared with the lowest quintile were estimated in the logistic analysis, and the ORs and 95% CIs are presented in Table III. The higher quintiles of HOMA-IR were significantly associated with prehypertension and hypertension before and after multivariate adjustment. For example, the unadjusted ORs of prehypertension associated with HOMA-IR of 1.64–2.32, 2.33–2.84, 2.85–3.76 and ≥3.76 were statistically positive and significant; multivariate-adjusted ORs for HOMA-IRs of 2.32–2.84, 2.85–3.76 and ≥3.76 were still statistically positive and significant. The unadjusted ORs of hypertension associated with HOMA-IR of 1.64–2.33, 2.33–2.85, 2.85–3.76 and ≥3.76 were statistically positive and significant; multivariate-adjusted OR for HOMA-IRs ≥3.76 was still statistically positive and significant.

Table III. Odds ratios (OR) and 95% confident intervals (CI) of prehypertension and hypertension associated with the homeostatic model assessment of insulin resistance (HOMA-IR).

HOMA-IR	Unadjusted OR (95% CI)	p-value	Multivariate adjusted OR^a (95% CI)	p-value
Prehypertension
<1.64	1.00 (ref)		1.00 (ref)
1.64–2.32	1.290 (1.038,1.602)	0.022	1.056 (0.786,1.418)	0.717
2.33–2.84	1.929 (1.537,2.421)	<0.001	1.565 (1.158,2.116)	0.004
2.85–3.76	1.707 (1.357,2.147)	<0.001	1.381 (1.020,1.870)	0.037
≥3.76	1.760 (1.377,2.250)	<0.001	1.435 (1.046,1.970)	0.025
Hypertension
<1.64	1.00 (ref)		1.00 (ref)
1.64–2.32	1.214 (0.974,1.512)	0.084	0.855 (0.612,1.195)	0.359
2.33–2.84	1.619 (1.281,2.047)	<0.001	1.052 (0.743,1.488)	0.777
2.85–3.76	1.681 (1.336,2.115)	<0.001	1.189 (0.846,1.672)	0.319
≥3.76	2.370 (1.876,2.994)	<0.001	1.803 (1.277,2.546)	0.001

^aAdjusted for age, gender, alcohol consumption, cigarette smoking, history of hypertension, and hyperlipidemia.

Discussion

Our findings showed that there had been insulin resistance in the phase of prehypertension. Although the means of HOMA-IR were significantly lower in prehypertensives than those in hypertensives in some groups stratified by some risk factors, almost all were higher in prehypertensives compared with normotensives, and there was statistical significance for means of HOMA-IR between prehypertension and normotensives among individuals with family history of hypertension, drinking alcohol, overweight, central obesity, hyperlipidemia and diabetes. The ORs of prehypertension associated with higher levels of HOMA-IR were greater and statistically significant compared with lowest quintile of HOMA-IR. These findings implied that individuals with prehypertension had been influenced by cardiovascular risk factors, and insulin resistance had strongly existed in the stage of prehypertension and might play an important role in the development of hypertension.

Insulin resistance and hyperinsulinemia have been showed to be associated with hypertension or elevated BP, especially in obese individuals (16–18). There are a few reports about association of insulin resistance with prehypertension. Cordero et al. (19) reported that prehypertension was associated with insulin resistance; in their study, the ratio of triglycerides to HDL was served as surrogate markers of insulin resistance. Recently, Kawamoto et al. (20) examined the cross-sectional relationship between insulin resistance evaluated by HOMA-IR and prehypertension among 1269 Japanese people without a clinical history of CVD in the community; their findings were consistent with ours, in which insulin resistance was significantly associated with prehypertension as well as hypertension. In Player et al.'s study (21), insulin resistance was associated with prehypertension only in men in a nationally representative adult population.

Some studies (11) have showed that insulin resistance and hyperinsulinemia often occur with many cardiovascular risk factors. Guo & Xu (22) investigated the relationship between the insulin sensitivity and cardiovascular risk factors in 106 patients with hypertension or coronary heart disease and 32 normal subjects in China; their findings showed that as the number of risk factors increased from 1 to ≥3, the insulin sensitivity index decreased from −1.69 ± 0.24, −1.95 ± 0.17 to −2.14 ± 0.21, respectively. Some investigations (23,24) also showed that dyslipidemia and elevated FPG tended to coexist with hypertension and prehypertension.

Our findings implied that insulin resistance might occur in phase of prehypertension and promote development of prehypertension to hypertension. These findings appear to show that correlation between insulin resistance and hypertension may not be explained by the concept that insulin resistance occurs secondarily to hypertension. Although insulin resistance and hyperinsulinemia may not be directly linked to hypertension, there is increasing evidence that metabolic abnormalities associated with insulin resistance may increase the risk of CVD (e.g. coronary artery disease) associated with hypertension and type 2 diabetes (25).

Insulin resistance frequencies varied among different ethnic groups (26). Pima Indians and Asian Indians are more insulin resistant than European Caucasians of similar age and BMI, as assessed by the euglycemic–hyperinsulinemic clamp (27,28). Dickinson et al. (29) examined difference in post-prandial blood glucose and insulin sensitivity among healthy young adults of different ethnic origins subjects from five ethnic groups (European Caucasians, Chinese, South East Asians, Asian Indians and Arabic Caucasians); the subjects were matched for age, BMI, waist circumference, birth weight and current diet. Both post-prandial hyperglycemia and insulin sensitivity showed a twofold variation among the groups. South East Asians had the highest post-prandial blood glucose and lowest insulin sensitivity, whereas European and Arabic Caucasian subjects were the most insulin sensitive and carbohydrate tolerant.

In the present study, the Mongolian subjects are a minority differing from the Chinese Han people in China; our findings showed that insulin resistance was significantly associated with prehypertension, and maybe these findings imply that insulin sensitivity is low among Mongolians with prehypertension. However, at present, there have been no reports about variation in insulin resistance between the Mongolian and Han people in China.

There are some limitations in the present study. First, it was a cross-sectional study, in which progressing to hypertensives from prehypertensives with insulin resistance could not be precisely delineated. Second, approximately 25% individuals who were eligible for the inclusion did not participate in the study, which would unavoidably cause some selection bias. However, the study site is a remote area from the city, inhabitants here knew little about their BP and FPG values, and it was not likely that they did not participate in the study because they knew their BP and FPG values, which might have partly retrieved the above deficiency.

In summary, our study found that hypertensives and prehypertensives had higher levels of HOMA-IR compared with normotensives, and there was insulin resistance in the phase of prehypertension. This study suggests that insulin resistance may play an important role in the development of hypertension.

Acknowledgements

We are deeply appreciative of the participants in the study, and thank the Kezuohou Banner Center for Disease Prevention and Control, and the Naiman Banner Center for Disease Prevention and Control, for their support and assistance.

This study was supported by National Natural Science Foundation of China (Grant No. 30972531).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.