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Association of three insulin resistance indices with hypertension and body weight among Uyghur adults in rural areas of Xinjiang, China

Abstract Obesity and insulin resistance are significant contributors to hypertension. There is a high prevalence of obesity among Uyghurs in the rural areas of Xinjiang, China. Therefore, this study aimed to explore the association between insulin resistance indices and hypertension according to different body weights in rural Uyghur residents of Xinjiang, China. A total of 12 813 local Uyghur residents were recruited for the study. Excluding those with incomplete data and those using antihypertensive, lipid‐lowering, or glycemic drugs, 9577 permanent residents were eligible for the study. Three insulin resistance indicators were calculated: triglyceride to high‐density lipoprotein cholesterol ratio, product of fasting triglyceride and glucose (TYG), and metabolic score for insulin resistance. Multivariate logistic regression analysis was performed to estimate the association between the three non‐insulin‐based insulin resistance indices and the risk of hypertension for different body weights. TYG was significantly associated with hypertension in the normal‐weight group, particularly in women. In the obese group that was obese, all three indicators were associated with hypertension. Since TYG was associated with hypertension in the groups with normal weight and obesity, it may be useful as a reference indicator for insulin resistance. This indicator may provide a basis for the identification and management of hypertension risk among adults in the Uyghur population.

practical IR index is needed to enable early screening for risk of hypertension.
Recent studies have focused on several non-insulin-based indicators of IR, such as the triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c) ratio (TG/HDL-c), product of fasting TG and glucose level (TYG), and metabolic score of IR (METS-IR), which can be calculated using simple conventional biochemical indicators. 10 Many clinical and epidemiological studies have shown an association between noninsulin-based IR indices and hypertension. 11,12 However, these associations according to different body weights have not been reported in rural Uyghur residents of Xinjiang, China. Xinjiang is located in the far northwest of China and has a disadvantaged economic status. Insulin tests are expensive and difficult to perform in economically disadvantaged regions. Therefore, in rural areas of Xinjiang, it is necessary to identify a simple IR index that is significantly associated with hypertension. The characteristic diet of rural Uyghur residents is rich in salt, fat, and carbohydrates, leading to a high prevalence of obesity. 13 Therefore, we aimed to explore the association between IR indicators and hypertension at different body weights. Especially in normal-weight individuals, these findings are expected to provide an important reference to reduce hypertension risk based on IR and provide a basis for the hierarchical management of hypertension and obesity.

Study participants
A total of 12 813 Uyghur residents from the rural region of Xinjiang were recruited for this study, between 2016 and 2020. A multi-stage (prefecture-county-township-village Interview) stratified cluster random sampling method was used to select participants. The inclusion criteria were as follows: Uyghur residency for at least 6 months; and age ≥18 years. The exclusion criteria were as follows: self-reported use of antihypertensive, lipid-lowering, or glycemic drugs; and incomplete data. A total of 9577 individuals were included in this study. The participant inclusion process is illustrated in Figure 1.
This study was approved by the Ethics Committee. All participants provided informed consent.

Interview
Each participant was interviewed in person. The interview included items on demographic characteristics (age, sex, occupation, and educational level), behavior and lifestyle (smoking and alcohol drinking), and disease history. Smoking was defined as currently smoking more than 100 cigarettes before the interview. 14 Alcohol consumption was defined as drinking alcoholic beverages (beer, red wine, and white wine) at least twice a month or active continuous drinking. 15

Anthropometric and biochemical measurements
Trained examiners measured participant height, weight, and waist circumference (WC). Blood pressure was measured after a 5-min rest using an electronic sphygmomanometer (HEM-7051; Omron, Dalian, China), three times at 30-s intervals. The average value was noted.
Overnight fasting blood samples were collected. Serum levels of fasting plasma glucose (FPG), total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c) were measured using a biochemical autoanalyzer.

Definitions
Hypertension was defined as systolic blood pressure ≥140 mmHg

Population characteristics
This study included 9577 rural Uyghur residents. The participant inclusion process is illustrated in Figure 1. Overall prevalence of hypertension was 29.71%; 31.49% in males and 27.94% in females.

Hypertension groups
People with hypertension (hypertension group) were older than those without (non-hypertension group) (mean ± standard deviation, 52.85

Weight, hypertension, and insulin resistance indices
The prevalence of hypertension increased with increasing non-insulin-    Table S1.
The number of participants with hypertension in each quartile is presented in Table S2.
The ORs for the continuous variables and the second and third quartiles are shown in Table S3.
The results of the multiple linear regression of the relationship between the three non-insulin-based IR indices and blood pressure, in the different BMI and WC groups, are shown in Table S4.
The clinical conditions of the different BMI and WC groups are presented in Table S5.

DISCUSSION
In this cross-sectional study, we evaluated the association between three non-insulin-based IR indices and hypertension for different body weights. TYG was significantly associated with hypertension in the normal-weight group, particularly in women. In the group that was obese, all three indicators were associated with hypertension. TYG was distribution, and subclinical atherosclerosis. 22 The TG/HDL-c ratio is associated with hyperinsulinemia 23 and has been proposed as a simple marker of IR in clinical practice. 24 The METS-IR is a novel alternative IR index validated for essential hypercholesterolemia. It also has good diagnostic and predictive performance for detecting type 2 diabetes and prehypertension. 25 Previous studies explored the associations between hypertension, IR, and obesity. However, only a few have focused on the relationship between IR and hypertension at different body weights. 26 This study explored the association between three non-insulin-based IR indices and hypertension according to body weight in the Uyghur > population.
We found that TYG was significantly associated with hypertension in the group with normal weight. Similar results were reported by a large cohort study in which TYG was significantly associated with subsequent risk of cardiovascular disease in individuals with normal weight. 27 TYG was also associated with cardiovascular risk factors in a cross-sectional study of children with normal weight and adolescents. 28 Another important finding of our study was that the association between TYG and hypertension in the group with normal weight was more common in women than in men, which is consistent with previous findings. A cohort study showed that IR was associated with the development of hypertension in women but not men. 29 This sex difference may be related to estrogen levels. 30 Our study found no differences in HDL-c level between the non-and hypertension groups in the rural Xinjiang population with normal weight. Therefore, HDL-crelated indicators, TG/HDL-c ratio, and METS-IR were not associated with hypertension in this population.
Current public health strategies focus on reducing the risk of hypertension in overweight and individuals who are obese. The risk of hypertension in individuals with normal weight is often ignored. 31 Since metabolic abnormalities in individuals with normal weight are more likely to be overlooked, it is crucial to accurately identify IR to reduce the risk of hypertension in this population.
Our study demonstrated significant associations between the three non-insulin-based IR indices and hypertension in the group with obesity. This suggests that IR plays a more critical role in the development of hypertension in individuals who are obese than in individuals with normal weight. This result is consistent with those of previous reports. 32 Obesity and hypertension are characterized by increased spill over from the kidneys. 33 Recent evidence has shown that IR, particularly in the presence of visceral fat, can stimulate and increase sodium and urate reabsorption at the tubular level, leading to increased blood pressure. 34 This may provide an etiological basis for the management of hypertension, specifically targeting IR-driven metabolic abnormalities among individuals who are obese. In our study, TYG was significantly associated with hypertension in participants who are obese. Therefore, the measurement of TYG in the whole population of rural areas of Xinjiang is of great significance for the management of hypertension.
To the best of our knowledge, this is the first large-scale populationbased study to examine the relationship between three non-insulinbased IR indices and hypertension according to body weight in the rural areas of Xinjiang. This study provides a reference for screening for hypertension in rural residents of Xinjiang.
Our study had some limitations. First, it was a cross-sectional study; thus, it was not possible to determine the causal time series for the three indicators of hypertension. Second, we were unable to perform direct hyperinsulinemic/euglycemic clamp for IR measures.
Third, there may be some recall bias in the self-reports of drug use.
Therefore, further prospective studies are required to confirm our findings.

AUTHOR CONTRIBUTION
All authors were involved in developing the study design, data acqui-