The interaction between general or abdominal obesity and hypertension on the risk of type 2 diabetes mellitus: a cross-sectional analysis in Iranian adults from the RaNCD cohort study

According to the World Health Organization (WHO), non-communicable diseases (NCDs) are the leading cause of death at global level [1]. Type 2 diabetes Mellitus (T2DM) is one of the most important NCDs responsible for 2.74% of all deaths globally [2]. Iran follows the same pattern, where 3% of all deaths were associated with T2DM in Iran [2]. The age standardized mortality rate for T2DM in Iran has shown a steady trend since 2015 and is expected to increase slightly by 2030 [3].

T2DM is a complex multifactorial disease associated with various risk factors [4, 5]. Scientific evidence has shown that hypertension and T2DM occur together, and the risk of developing T2DM is higher in hypertensive patients than in non-hypertensive [6, 7]. Generally, there is a positive correlation between impaired glucose tolerance and high blood pressure; and hypertension is reported in more than two-thirds of patients with T2DM [7, 8]. In addition, obesity as a major health problem significantly increases the risk of NCDs such as T2DM [9, 10]. Recently, in the study of Hu et al., it was shown that the risk of T2DM in hypertensive and obese individuals was significantly higher compared to those with a normal weight and without hypertension [9]. This relationship indicates that the combined effect of two risk factors together is greater than their effect alone (synergistic interactions). The impact of central obesity on diabetes risk is more significant than that of general obesity [11]. After puberty, fat deposition shifts to the visceral location in males, and in women, this shift occurs at menopause. Additionally, individuals with a normal BMI but a high waist-to-hip ratio (WHR) have a threefold increase in the rate of diabetes [12]. Reducing waist circumference (WC) may lower the risk of developing type 2 diabetes [13]. Our study considers both general and abdominal obesity to account for the complexity of obesity as a condition with diverse manifestations. This comprehensive approach allows for a detailed exploration of the obesity-T2DM relationship and provides a holistic understanding of how different aspects of obesity may interact and influence the risk of Type 2 Diabetes Mellitus in our specific study population.

According to the mentioned facts, the results of association between diabetes and obesity or hypertension should not be explained alone; rather it is essential to consider the interactions happening among them. The interactions between the risk factors may affect the severity of the condition. The study was conducted on 10,000 adults who participated in the first phase of the Ravansar Non-Communicable Disease (RaNCD) cohort study. It is important to note that obesity and overweight are relatively common in this population, especially among women [14], which emphasizes the significance of the present study. Consequently, this research was done to assess the effects of interactions between general or abdominal obesity and hypertension on the risk of T2DM in adults in western Iran.

This research demonstrates that the proportion of hypertension, general and abdominal obesity is higher in diabetics than in non-diabetics. The interaction analysis results revealed there is a synergistic effect between blood pressure and obesity (general/abdominal) in the development of T2DM, and this synergistic effect remained significant after controlling for confounding factors. Briefly, when obesity and hypertension coexist, the risk of T2DM is greater than the sum of obesity and hypertension alone.

The risk of T2DM in those with general/abdominal obesity was 1.65 and 1.69 times greater than in people without general/abdominal obesity, respectively after controlling for confounders. According to some studies [9, 19‐21] obesity is a risk factor for diabetes, which accords with our results. In people with general or abdominal obesity, the accumulation of body fat causes hyperinsulinemia and insulin resistance, which reduces glucose tolerance and the development of T2DM by impairing the use of glucose by muscle and other tissues [9, 19], and obese people have a greater risk of acquiring diabetes than non-obese people do [9]. Losing weight is a crucial first step in lowering occurrence of T2DM, particularly in youthful people, as Studies have demonstrated that more than 80% of the physiological dysfunction of metabolic syndrome is caused by obesity [22]. Therefore, a person who is obese or overweight has a higher likelihood of experiencing diabetic remission the more weight they lose [23]. The association between abdominal obesity and elevated risk of diabetes was significant in the study population; and in women, the association was higher than in men. The higher prevalence of obesity among women can be used to explain this fact. Furthermore, lower levels of physical activity in females than in males, weight increase during pregnancy, and failure to recover to an ideal weight may be contributing factors to the greater occurrence of obesity and incident diabetes in females [20]. In accordance with our study, Wang et al. concluded that BMI-defined general obesity or WHpR-defined central obesity may be contributing factors for females with diabetes and hypertension. The simultaneous presence of hypertension with elevated BMI, WC, WHtR, and WHpR showed associations with the highest risks of developing diabetes [24].

The association between hypertension and T2DM was significant and there was 1.5 times increased risk of T2DM in hypertensive individuals compared to non-hypertensive individuals, which is consistent with a previous study [9, 25, 26]. It shows the importance of managing blood pressure and BMI effectively to prevent the onset and progression of diabetes [9].

However, there are limited finding on the interaction between general/abdominal obesity, hypertension, and the risk of T2DM. The findings of this research showed that the interactive effect of hypertension and abdominal obesity in men and women was 2.46 and 3.97 times the risk of T2DM. Interactive effect of hypertension and general obesity in men and women was 2.66 and 2.87, respectively. This result is in line with the findings from investigations by Conghui Hu et al. [9]. Several studies have investigated the interaction effects of two risk factors in increasing of risk of disease and have found similar results. Previous research has found that a family history of dyslipidemia and diabetes [27], a history of diabetes and high blood pressure in the family [28], and Having a family history of diabetes, as well as the waist-to-height ratio all work synergistically to impact the development of diabetes [29, 30]. In another study, it was shown that family history and overweight had a synergistic relationship with the pathogenesis of diabetes and that the impacts of the two factors independently were not insignificant [29]. When hyperlipidemia and familial history of diabetes coexist in normotensive populations, there may potentially be a synergistic influence on diabetes [9]. Studies like the ones described above have demonstrated that conditions like dyslipidemia, high blood pressure, and family history may increase or decrease a person’s chance of developing diabetes and that the cumulative incidence of illnesses has a higher effect on diabetes than the harm caused by a single complicating condition.

Obesity may impact blood pressure through various mechanisms, including leptin-mediated increased sympathetic activity and activation of the renin-angiotensin system. Additionally, insulin resistance is associated with greater sodium retention and increased blood pressure on a high-sodium diet [31]. The link between hypertension and T2DM can be explained by factors such as elevated blood sugar levels, insulin resistance, and dyslipidemia, all of which contribute to the development of atherosclerosis—a condition that can lead to vascular stenosis and heightened peripheral arterial resistance, both characteristic features of hypertension [32].

The interaction effect between obesity and hypertension on diabetes has important implications for clinical practice, as it indicates that these conditions should not be considered in isolation but rather as interrelated components of the metabolic syndrome. Therefore, it is necessary to implement comprehensive strategies to prevent and treat obesity, blood pressure, and diabetes, and to reduce the complications and deaths caused by them. Evidence-based strategies include lifestyle modifications such as weight loss, physical activity, dietary intervention, as well as pharmacological therapy [12].

The relationship between the two risk factors of obesity and hypertension on T2DM in a sizable group of Iranian people is being examined for the first time in this study. In our study, potential confounding variables (except genetic status) were controlled. The present study has a number of limitations, one of which is that it is cross-sectional in design and cannot demonstrate a causal association between risk factors and disease. Therefore, longitudinal studies are recommended to confirm the findings of this study.

We found that general/abdominal obesity and hypertension have a synergistic effect on the risk of T2DM. To prevent the increasing incidence of T2DM, preventive strategies should be created that focus on these modifiable lifestyle factors. In order to avoid the occurrence and progression of T2DM, it is advised that people manage their hypertension and BMI through strategies like sensible exercise, a healthy diet, quitting smoking, and abstaining from alcohol.