Association Between Physical Activity and Arterial Stiffness in Patients with Type 2 Diabetes in Ningbo, China: A Cross-Sectional Study

Introduction

Around 140 million people in China have diabetes, and the type 2 diabetes mellitus (T2DM) population in China is the largest in the world.¹ T2DM is a chronic condition, and comorbidities like hypertension and hyperlipidemia are common.² All these are risk factors for cardiovascular diseases (CVD).³ Compared to non-T2DM individuals, CVD risk is two-to-four-fold higher in patients with T2DM.^1,4,5 CVD is one of the primary causes of death in patients with T2DM, accounting for approximately half of all deaths.⁶

Physical activity is an important lifestyle advice given to patients with T2DM.⁷ Regular physical activity can significantly improve insulin sensitivity, glucose metabolism, and body composition.⁸ It can also reduce the risk of developing CVD.^9,10 However, physical activity levels are lower in China.^11,12

Atherosclerosis is a well-known and main pathological basis of CVD.¹³ Arterial stiffness is one of the earliest stages of atherosclerosis¹⁴ and is an independent predictor of CVD even after adjusting for cardiovascular risk factors.¹⁵ Compared to healthy individuals, patients with T2DM have a higher risk of arterial stiffness.¹⁶ The increasing arterial stiffness with accumulating comorbidities like diabetes and hypertension is associated with heart failure with preserved ejection fraction.¹⁷ Brachial-ankle pulse wave velocity (baPWV) is a non-invasive method for detecting atherosclerosis and arterial stiffness in large and medium arteries.¹⁸ Common carotid artery intima-media thickness (CCA IMT) is another safe, simple, inexpensive, and widely used method for detecting atherosclerosis and arterial stiffness.¹⁹ High pulse wave velocity in China is a grave issue.²⁰

Studies have been conducted to determine the relationship between physical activity and arterial stiffness in patients with T2DM, mostly focusing on carotid-femoral pulse wave velocity (cfPWV) or carotid artery thickness with inconsistent results.^21–30 A study conducted in patients with T2DM in China reported that higher sedentary time was associated with higher carotid plaque.²⁷ However, no study has examined the relationship between physical activity and multiple measures of arterial stiffness in patients with T2DM in China. Therefore, the study aimed to determine the association between physical activity and arterial stiffness, based on baPWV and CCA IMT, in patients with T2DM in Ningbo, China.

Materials and Methods

Study Design, Site, Population, Data Source, and Period

A cross-sectional study was conducted using the Metabolic Management Center (MMC) dataset of The First Affiliated Hospital of Ningbo University from 1st March 2018 to 28th February 2023. MMC, led by Ruijin Hospital, Shanghai, is a multi-hospital program on metabolic diseases that is running across mainland China.³¹ In the dataset, there were 5892 patients with metabolic diseases, and 4444 adults (18 to 75 years) with T2DM were included in this study. The rest were excluded due to the following reasons: <18 or >75 years of age (60), not T2DM (606), missing data on T2DM (130), missing or inaccurate physical activity data (49), and missing arterial stiffness data (603).

Data Collection and Study Variables

A standardized questionnaire developed and piloted by MMC is used for data collection, and parameters such as physiological, anthropometric, and biochemical are assessed by trained hospital staff using the MMC standardized protocol.³¹ In this study, the following routinely collected data from the first MMC visit were extracted and used:

1. Self-reported sociodemographic factors:
   1. Age (18 to 39 years, 40 to 59 years, or ≥60 years)
   2. Sex (male or female)
2. Self-reported lifestyle factors:
   1. Smoking (current status)
   2. Alcohol drinking (current status)
   3. Physical activity (high, moderate, or low, assessed using the International Physical Activity Questionnaire (IPAQ)-Short)³²
   4. Sedentary time (assessed using IPAQ-Short)³²
3. Health-related conditions:
   1. Overweight/obesity (ie, body mass index (BMI) ≥24kg/m²,³³ body weight and height were measured with light clothes and without shoes in standing position using a calibrated automatic digital body weight and height scale (HNH-318, Omron, Japan), body weight was measured to the nearest 0.1 kg, height was measured to the nearest 0.5 cm, and BMI was calculated as weight in kg divided by height in m²)
   2. High blood pressure (ie, systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥80 mmHg on the day of visit using an automated blood pressure monitor (HBP-1100U, Omron, Japan) in a seated position, self-reported history of hypertension, or use of antihypertensive medicines)
   3. Hyperlipidemia (ie, low-density lipoprotein cholesterol ≥2.6 mmol/L or non-high-density lipoprotein cholesterol ≥2.6 mmol/L,³⁴ determined by the enzymatic assays (AU5400, Beckman Coulter, USA), self-reported history of hyperlipidemia, or use of antihyperlipidemic medicines)
   4. Self-reported duration of T2DM (<5 years, ≥5 to <10 years, or ≥10 years)
   5. Glycosylated hemoglobin (HbA1c, <7% or ≥7%,³⁵ measured using the high-performance liquid chromatographic method (D-10 Hemoglobin Analyzer, Bio-Rad, USA))
   6. Arterial stiffness (ie, baPWV ≥1800cm/s³⁶ or CCA IMT ≥1mm³⁷). BaPWV was measured by a specially trained nurse, using the plethysmography apparatus (BP-203RPE III, Omron, Japan). The assessment was conducted in a well-controlled room (with temperature around 22–25°C) and after resting for at least 5 minutes. Patients were requested not to smoke for at least 2–4 hours before the test. They were requested to wear light clothes, lie down on the examination bed in the supine position, and remain quiet during the test. Blood pressure cuffs were wrapped on both the arms and ankles. The lower edge of the arm cuff was positioned 2–3 cm above the cubital fossa transverse striation, and the lower edge of the ankle cuff was positioned 1–2 cm above the medial malleolus. The heartbeat monitor was placed on the left edge of the sternum, and electrocardiogram electrodes were placed on the wrists. BaPWV measurements on the left and right sides were taken, and the average of these was recorded.³⁸ CCA IMT was assessed using the B-mode ultrasound (Resona R9T, Mindray, China), by an ultrasound doctor. CCA IMT was observed as a double line pattern visualized between the intimal-luminal and the medial-adventitial interfaces of the carotid wall in a longitudinal view. CCA IMT was measured near the carotid bifurcation in a region that was free of plaque (usually found in a segment of the distal CCA). The arterial wall was assessed in a lateral probe position with an insonification angle of 90° to acquire high-quality images. CCA IMT was measured along a 10 mm length, preferably on the posterior wall of the CCA at least 5 mm below its termination to avoid inter-individual variability. Manual measurements on the left and right sides were taken three times, and the average of these was recorded.³⁹

Statistics Analyses

IBM SPSS Statistics version 28.0 for Windows was used for data analyses. Numbers and percentages are reported for categorical data and mean (standard deviation (SD)) and median (interquartile range (IQR)) are reported for normally distributed and skewed continuous data, respectively. Chi-square test was used to assess the correlations between physical activity and arterial stiffness (based on baPWV and CCA IMT) in patients with T2DM. To identify any association between physical activity and arterial stiffness, the following models were created:

1. Unadjusted: Simple logistic regression analyses were performed.
2. Adjusted: Multiple logistic regression analyses were performed, and the adjustment was done for age, sex, current smoker, current alcohol drinker, sedentary time, overweight/obesity, high blood pressure, hyperlipidemia, duration of T2DM, and HbA1c. Data missing (unknown) on the adjusted variables were included in the models.

Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. A P value of ≤0.05 was considered statistically significant.

Ethics

Ethics approval was obtained from the Research Ethics Committees of Ruijin Hospital (2017-42) and The First Affiliated Hospital of Ningbo University (2019-R057). The study was conducted in accordance with the Declaration of Helsinki. All the patients gave written informed consent to use the routinely collected data on them for research purposes.

Results

Table 1 shows the characteristics of patients with T2DM in the study. Their mean age was 51.0 years (SD ±11.9), and 63.4% were men. 6.5%, 47.0%, and 46.5% of patients with T2DM had high, moderate, and low physical activity, respectively. 18.8% and 17.5% of patients had arterial stiffness based on baPWV and CCA IMT, respectively.

Table 1 Characteristics of Patients with T2DM in the Study

Table S1 shows the correlations between physical activity and arterial stiffness (based on baPWV and CCA IMT) in patients with T2DM. The proportion of arterial stiffness was found to be lower in patients having high physical activity, employing a p-value threshold of 0.05.

Table 2 reports the association between physical activity and arterial stiffness (based on baPWV) in patients with T2DM. In the adjusted model, the odds of arterial stiffness were lower in patients having moderate to high physical activity (OR 0.82, 95% CI 0.68 to 0.98 and OR 0.58, 95% CI 0.39 to 0.87, respectively).

Table 2 Association Between Physical Activity and Arterial Stiffness (Based on baPWV) in Patients with T2DM

Table 3 shows the association between physical activity and arterial stiffness (based on CCA IMT) in patients with T2DM. In the adjusted model, the odds of arterial stiffness were found to be lower in patients having high physical activity (OR 0.49, 95% CI 0.33 to 0.74).

Table 3 Association Between Physical Activity and Arterial Stiffness (Based on CCA IMT) in Patients with T2DM

Discussion

In the present study, higher physical activity was found to be associated with lower arterial stiffness in patients with T2DM in Ningbo, China. The finding is consistent with existing observational epidemiological studies conducted in Denmark, Canada, and Finland.^23–25 A large cross-sectional study in China reported an association between sedentary time and arterial stiffness.²⁷ Some randomized controlled trials (RCTs) conducted in Portugal and Greece reported a beneficial effect of physical activity on arterial stiffness,^28,30 whereas no effect of the intervention was found in other RCTs conducted in the USA, Canada, Finland, and Norway.^21,22,26,29 It is difficult to generalize the RCT findings due to several factors, including trial-related issues (eg, small sample sizes, shorter trial durations) and intervention-related issues (eg, heterogeneous content, structure, and delivery characteristics of interventions).

The underlying mechanism of how physical activity delays arteriosclerosis is still unclear and the following pathways are proposed: (i) physical activity improves blood glucose, blood pressure, and blood lipids, which are well-known risk factors of arterial stiffness,⁴⁰ (ii) physical activity improves body composition, leading to fat mass reduction, which in turn inhibits the secretion of various inflammatory mediators (eg, interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α)) that are known to cause atherosclerosis,^41,42 and (iii) physical activity improves blood circulation and releases vasodilators (eg, nitric oxide) to improve blood and oxygen supply to the tissues and protects vascular endothelial cells, which in turn delays arteriosclerosis.^43–45

To the best of the authors’ knowledge, this was the first study to investigate the association between physical activity and multiple measures of arterial stiffness in patients with T2DM in China. The study included a relatively large number of patients with T2DM, and the routinely collected data quality was high. Missing data on the adjusted variables were low in the study and were included in the adjusted models. However, the physical activity assessment was subjective, and IPAQ-Short was used for this purpose. Although IPAQ-Short is a well-tested tool,³² in the future, there is a need to assess physical activity objectively. Similarly, some other variables were self-reported (eg, other lifestyle factors, some health-related conditions), and social desirability bias and recall bias could have been an issue. Since it was a cross-sectional study, the causal relationship between physical activity and arterial stiffness could not be determined, and there is a need for longitudinal studies.

In conclusion, higher physical activity was found to be associated with lower arterial stiffness in patients with T2DM in Ningbo, China. This was a cross-sectional study, and there is a need to conduct cohort or case-control studies on this topic.