DOI: https://doi.org/10.21203/rs.3.rs-1460082/v1
Background Numerous studies were demonstrated the inverse relationship between all kinds of physical activity (PA) and cardiovascular diseases (CVDs), few of them focus on the new-onset hypertension. Therefore, this study was aimed to determine the impact of long-term PA on the risk of new-onset hypertension in type 2 diabetes mellitus (T2DM) patients with pre-hypertension.
Methods A total of 268 T2DM patients with pre-hypertension were recruited between January and December 2015, and followed them up until December 2020. All patients were took PA self-assessment. Demographic, clinical, laboratory, radiologic, treatments, complications, lifestyle and clinical outcomes data were extracted from electronic medical records or collected through a structured interview.
Results During 5 year follow-up, the incidence of new-onset hypertension was significantly lower in PA group (15.5% vs 35.4%, p<0.01) when compared to the inactivity group. Logistic regression analysis showed that PA (OR 0.337, 95%CI 0.168 to 0.677, p<0.01), body mass index (BMI) (OR 1.138, 95%CI 1.019 to 1.272, p<0.05) and glycosylated hemoglobin (HbA1C) (OR 1.206, 95%CI 1.006 to 1.446, p<0.05) were associated to the incidence of new-onset hypertension in pre-hypertensive T2DM patients. Subgroup analysis found that for those overweight and blood glucose poor controlled pre-hypertensive T2DM patients, long-term PA were less likely to develop hypertension (overweight: OR 0.187, 95%CI 0.063 to 0.558, p<0.01; glucose poor controlled: OR 0.349, 95%CI 0.138 to 0.880, p<0.05).
Conclusion These results suggested that long-term PA might be an important protective factor for new-onset hypertension in overweight and poor blood glucose controlled pre-hypertensive T2DM patients.
Type 2 diabetes mellitus (T2DM) is an important global public health problem with high morbidity and disability. Due to the aging population and unhealthy lifestyles, the prevalence of diabetes tends to continue to rise. The global diabetes prevalence in 2019 was estimated to be 9.3% (463 million people), rising to 10.2% (578 million) by 2030 and 10.9% (700 million) by 2045 [1]. Poorly controlled diabetes can mediate multiple organ damage, leading to microvascular and macrovascular complications, including kidney failure, blindness, amputation, and cardiovascular disease (CVDs) [2] [3]. Despite the medical research of diabetes was already mature and the treatment was comprehensive, T2DM remained considered as an incurable disease, and patients with T2DM still suffered high rates of complications.
Hypertension, as well as diabetes, is another one considered risk factors for CVDs and microvascular complications [4]. Unfortunately, they are frequently present together. It is reported that hypertension is twice more common in diabetics than in non-diabetics. Patients with T2DM more commonly present with isolated systolic hypertension and are more resistant to treatment. Furthermore, the co-existence of T2DM and hypertension significantly increase the risk for coronary heart disease (CHD) [5], left ventricular hypertrophy [6], congestive heart failure [7] and stroke [8] compared with either condition alone. More importantly, both hypertension and T2DM are present in all prediction models for the occurrence of stroke in patients with atrial fibrillation. In addition, microvascular complications are also more common in patients with coexistent hypertension and T2DM, and both retinopathy and nephropathy are more prevalent in those patients [9, 10]. Pre-hypertension, defined as blood pressure 120-139/80-89 mmHg. Blood pressures in the upper half of the pre-hypertensive range also roughly double risk for cardiovascular events, even in the absence of progression to hypertension. Globally, overall CVDs affect approximately 32.2% of all persons with T2DM and are major cause of mortality among T2DM patients, accounting for approximately half of all deaths over the past years. Therefore, among patients with T2DM, prevent hypertension and other CVDs complications are particularly beneficial.
The long-term complications of T2DM can be delayed by taking medications as prescribed along with a healthy lifestyle (i.e., diet and physical activity). Comprehensive lifestyle managements are recommended as the first-line therapy for T2DM in the current guidelines [11, 12]. Along with glycemic control, physical exercise has a number of benefits, such as decreasing insulin resistance and improving aerobic capacity, body composition, endothelial functions and cardiovascular fitness [13]. Patients living with diabetes are recommended to engage in 150 min of moderate-to-vigorous intensity aerobic activity per week to realize benefits on metabolism, fitness, and wellbeing; In addition, resistance and flexibility exercises are recommended two to three times per week [14]. A meta-analysis of 12 aerobic training studies and 2 resistance training studies concluded that exercise training decreases hemoglobin A1c (HbA1c) by 0.66% in individuals with T2DM [15]. Another meta-analysis composing of 27 studies found exercise to be associated with a mean reduction in HbA1c of 0.80% with no difference in magnitude of change in HbA1c between aerobic, resistance, or combination training [16]. Studies with low-volume high intensity training (HIT) in T2DM patients suggested that it can rapidly improve glucose control [17]. One meta-analysis of cohort studies coupled with data from a prospective cohort study have suggested that there is a significant benefit, demonstrating an inverse relationship between physical activity and both cardiovascular disease and all-cause mortality in DM patients [18]. Of important, a randomized controlled trial designed to look at this did not show any difference in a composite cardiovascular endpoint (consisting of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke and hospitalization for angina) with an intensive lifestyle intervention when compared with standard diabetes education over 10 years [19].
Numerous studies were demonstrated the inverse relationship between all kinds of physical activity (PA) and CVDs in DM patients, mostly of them were meta-analysis study. However, few of them focus on the impact of long-term PA on the new-onset hypertension in T2DM patients with pre-hypertension. Therefore, this retrospective cohort study aimed to determine the relationship between long-term PA and the incidence of new-onset hypertension in T2DM patients with pre-hypertension.
Study population
This retrospective cohort study included outpatients and inpatients from January 2016 to December 2020. T2DM patients with pre-hypertension were recruited. We defined T2DM as fasting plasma glucose (FPG) ≥7.00 mmol/L or self-reported receipt of antidiabetic treatment [20]. Pre-hypertension was defined as systolic blood pressure /diastolic blood pressure (SBP/DBP) of 120-139/80-89 mm Hg, in participants without a history of hypertension and use of antihypertensive medication [21]. The exclusion criteria were: no available information on characteristics; no available HbA1C value and glucose value; participants diagnosed with hypertension or other CVDs at baseline and participants with undefined CVDs status at follow-up; visit intervals < 1 years; and lost to follow-up. Cohort entry was defined as the date of the initial visit between January and December 2016, and follows them up until December 2020.
The study was approved by the ethics committee of Zhejiang Hospital. The data are anonymous, and the requirement for informed consent was therefore waived. All research procedures are performed according to the criteria of the Declaration of Helsinki.
Data collection
Clinical data (including demographic characteristics, lifestyle, medical history and family history of hypertension and CVDs) and results of laboratory test (including blood glucose, blood lipids, etc) were collected from an electronic clinical information system at baseline or collected through a structured interview.
All patients underwent biochemistry examination were performed on an auto analyzer (Beckman 5800), including fasting plasma glucose (FPG), triglycerides, total cholesterol, high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), serum creatinine (Scr), and alanine aminotransferase (ALT).
Exposure of interest
Regular physical exercise was evaluated by patients themselves. The evaluated standard based on the American Diabetes Association Standards for Diabetes Care 2014 : adults with diabetes should be advised to perform at least 150 minutes per week of moderate-intensity aerobic physical activity (50–70% of maximum heart rate), spread over at least 3 days per week with no more than 2 consecutive days without exercise; In the absence of contraindications, adults with type 2 diabetes should be encouraged to perform resistance training at least twice each week [14]. All patients were took exercise evaluation at initial visit.
Outcome measures and follow-up
The outcomes of interest were incident of new-onset hypertension and other CVDs complications during follow-up period. All subjects participated in physical examinations every year and they would see a doctor in our hospital if there was any discomfort. In addition, almost every surviving patient accepted follow-up for blood pressure and other examinations every 3 months for new-onset hypertension, and other CVDs from the electronic clinical information system in December of each year until 2020.
New hypertension and CVDs were recorded in all patients. Hypertension was defined as either systolic blood pressure ≥140 mmHg, diastolic blood pressure ≥90 mmHg or self-reported receipt of antihypertensive treatment. The CVDs included femoral/carotid atherosclerosis (AS), coronary AS, cerebral ischemic focus, CHD, percutaneous coronary intervention (PCI), and coronary artery bypass graft. Blood pressure value was obtained by trained staff using standard mercury sphygmomanometers through office blood pressure measurements. Femoral/carotid AS was diagnosed by vascular B-ultrasound. Coronary AS and CHD were diagnosed by coronary computed tomography angiography (CTA) or coronary angiography. Cerebral ischemic focus diagnosed by head computed tomography scans (CT) or nuclear magnetic resonance imaging (MRI).
Covariates
Covariates of interest included age, gender, BMI, FPG, triglycerides, total cholesterol, HDL-C, LDL-C, ALT, smoking status, drinking status, family history of hypertension. As for participants’ personal habits, participants were classified by smoking status into current smokers or not. Current smoker was defined as having a current smoking habit regardless of the number of cigarettes smoked per day, and habitual drinker was defined as consuming ≥150 g of alcohol per week.
Statistical analyses
Evaluation of normality was performed with Shapiro-Wilk test. Continuous variables were expressed as the means ±standard deviations (normal distribution) or medians (quartiles) (skewed distribution), and categorical variables were expressed as frequency or percentages. Independent-samples T test was used for normally distributed continuous variables, Mann-Whitney U test for non-normally distributed continuous variables, and chi-square tests for categorical variables. Missing continuous variables were mainly supplemented by means or median. We evaluated the unadjusted and adjusted ORs of incident hypertension using univariate and multivariate logistic regression analyses.
Participants’ characteristics
We identified 268 patients who met our inclusion criteria (Fig.1). The age range of population was 36 to 76 years, the mean age were 58.15±9.17 years. The study population included 208 men (77.6%) and 60 women (22.4%). Table 1 presents the characteristics of the participants. There were 110 subjects (41%) with a physical activity lifestyle and 158 (59.0%) with an inactivity lifestyle. In the regular physical activity group, the mean age was 55.89±8.68 years, with a mean BMI of 24.50±2.41 and the percentages of males were 78 (70.6%).
Meanwhile, compared with those in the inactivity group, those with a regular physical activity lifestyle had significantly younger age. We observed that patients with regular physical activity lifestyle had significantly lower levels of Scr, uric acid, cholesterol, LDL-C, and m-Alb/Cr. We also observed that the proportion of smoking, drinking and family history of hypertension was similar in the two groups.
Table 1 Baseline characteristics of participants
|
Total (N=268) |
Physical activity (N=110) |
Inactivity (N=158) |
P value |
Age (years) |
58.15±9.17 |
55.89±8.68 |
59.77±9.20 |
0.001** |
Gender (Female n,%) |
60 (22.4%) |
32 (29.1%) |
28 (17.7%) |
0.037* |
BMI (kg/m2) |
25.95±12.21 |
24.50±2.41 |
26.92±15.74 |
0.113 |
SBP (mmHg) |
126.21±8.62 |
125.00±8.697 |
127.04±8.49 |
0.057 |
DBP (mmHg) |
78.41±7.91 |
77.68±8.60 |
78.92±7.39 |
0.207 |
Years of T2DM (n,%) |
|
|
|
0.555 |
<5 years |
187 (70.03%) |
80 (72.7%) |
108 (68.4%) |
|
5-10 years |
63 (23.60%) |
25 (22.7%) |
38 (24.1%) |
|
≥10years |
17 (6.37%) |
5 (4.6%) |
12 (7.6%) |
|
HbA1C (%) |
7.56±1.55 |
7.66±1.74 |
7.49±1.42 |
0.392 |
FPG (mmol/L) |
7.47±2.47 |
7.60±2.78 |
7.40±2.24 |
0.509 |
ALT (IU/L) |
28.32±30.62 |
27.36±21.23 |
29.02±35.91 |
0.666 |
Scr (mmol/L) |
69.07±24.70 |
65.11±11.41 |
71.68±30.50 |
0.033* |
Uric acid (mmol/L) |
342.62±88.04 |
326.00±84.56 |
353.82±89.35 |
0.011* |
K+ (mmol/L) |
3.91±0.33 |
3.92±0.30 |
3.91±0.36 |
0.825 |
Na+ (mmol/L) |
145.70±76.81 |
141.04±2.13 |
140.97±2.37 |
0.798 |
Cl- (mmol/L) |
104.49±2.53 |
104.80±2.35 |
104.27±2.64 |
0.092 |
Ca2+ (mmol/L) |
2.34±0.10 |
2.35±0.10 |
2.34±0.10 |
0.830 |
P3+ (mmol/L) |
1.18±0.17 |
1.19±0.17 |
1.18±0.17 |
0.474 |
Triglycerides (mmol/L) |
2.25±2.07 |
2.04±1.34 |
2.40±2.45 |
0.157 |
Total Cholesterol (mmol/L) |
4.20±1.23 |
4.07±1.27 |
4.40±1.14 |
0.031* |
HDL-C (mmol/L) |
1.08±0.27 |
1.12±0.30 |
1.05±0.26 |
0.051 |
LDL-C (mmol/L) |
2.41±0.91 |
2.30±0.91 |
2.56±0.90 |
0.021* |
m-Alb/Cr |
7.75±22.42 |
3.99±9.08 |
10.41±26.47 |
0.015* |
CRP (mg/L) |
3.66±5.95 |
4.07±8.67 |
3.43±3.57 |
0.591 |
Free T3 (pg/ml) |
3.33±0.45 |
3.34±0.41 |
3.31±0.46 |
0.652 |
Free T4 (ng/dl) |
0.89±0.16 |
0.90±0.19 |
0.89±0.13 |
0.531 |
Total T3 (ng/ml) |
0.88±0.17 |
0.88±0.17 |
0.88±0.17 |
0.971 |
Total T4 (ug/dl) |
7.89±1.45 |
7.88±1.49 |
7.92±1.34 |
0.859 |
TSHu (IU/ml) |
1.93±1.12 |
1.80±1.07 |
2.02±1.11 |
0.102 |
PTH (pg/ml) |
43.20±23.81 |
41.79±8.58 |
44.36±20.54 |
0.218 |
Thyroid nodule (n, %) |
138 (51.5%) |
58 (52.7%) |
80 (50.6%) |
0.804 |
Smoking (n, %) |
85 (31.7%) |
37 (33.6%) |
48 (30.4%) |
0.344 |
Drinking (n, %) |
64 (23.9%) |
24 (21.8%) |
40 (25.3%) |
0.265 |
Depression/anxiety (n, %) |
7 (2.6%) |
3 (2.7%) |
4 (2.5%) |
>0.05 |
Sleep disorders (n, %) |
16 (6.0%) |
7 (6.4%) |
9 (5.7%) |
0.800 |
Family history of hypertension (n, %) |
52 (19.4%) |
21 (19.1%) |
31 (19.6%) |
>0.05 |
Note: BMI, body mass index; SBP, systolic blood pressure; DBP, diastolic blood pressure; T2DM, type 2 Diabetes Mellitus; HbA1C, glycosylated hemoglobin A1c; FPG, fast plasma glucose; ALT, alanine aminotransferase; Scr, Serum creatinine; HDL-C, high density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; m-Alb/Cr: the ratio of urinary micro albumin to creatinine; CRP, C-reactive protein; PTH, parathyroid hormone.
Newly-onset hypertension and related CVDs
As is showed in table 2, during 5 years of follow-up, we recorded a total of 145 coronal AS, which included 46 (42.7%) in the regular physical activity group and 98 (62%) in the physical inactivity group, the risk of coronal AS was obviously lower in the regular physical activity group, compared to the inactivity group (p<0.01). The total prevalence of CHD in this retrospective cohort was 39.9%. Compared to those in the inactivity group, patients in the regular physical activity group had a significantly lower incidence of CHD (30% vs 46.8%, p<0.01). In addition, we observed that the incidence of hypertension had significantly difference in the two groups, patients in the regular physical activity group had significantly lower incidence than those in the inactivity group (15.5% vs 35.4%, p<0.01). We also observed that the incidence of carotid/femoral AS was lower in the regular physical activity group than in the inactivity group, though it had no significance (49.5% vs 61.1%, p=0.051). However, there was no significant difference in terms of the incidence of cerebral ischemic focus, percutaneous coronary intervention (PCI), and myocardial bridge.
Table 2 Newly onset hypertension and related CVDs during follow-up period
|
Total (N=268) |
Physical activity (N=110) |
Inactivity (N=158) |
P value |
Femoral/carotid AS (n, %) |
150 (56.2%) |
54 (49.5%) |
96 (61.1%) |
0.051 |
Coronary AS (n, %) |
145 (54.1%) |
46 (42.7%) |
98 (62%) |
0.002** |
Cerebral ischemic focus (n, %) |
66 (24.6%) |
24 (21.8%) |
42 (26.6%) |
0.591 |
CHD (n, %) |
107 (39.9%) |
33 (30%) |
74 (46.8%) |
0.006** |
Hypertension (n, %) |
73 (27.2%) |
17 (15.5%) |
56 (35.4%) |
0.000** |
PCI (n, %) |
61 (22.8%) |
19 (18.2%) |
41 (25.9%) |
0.142 |
Coronary artery bypass graft (n, %) |
18 (6.7%) |
6 (5.5%) |
12 (7.6%) |
0.622 |
Note: CVDs, cardiovascular diseases; AS, atherosclerosis; CHD, coronary heart disease; PCI, percutaneous coronary intervention.
Univariate and multivariate logistic regressions for new-onset hypertension in pre-hypertension patients with T2DM
Unadjusted and adjusted ORs for new-onset hypertension of the whole cohort are shown in Table3. The univariate and multivariate analysis showed that BMI (univariate: OR 1.126, 95% CI: 0.504 to 1.842, P<0.05; multivariate: OR 1.138, 95% CI: 1.019 to 1.272, p<0.05), HbA1C (univariate: OR=1.129, 95% CI: 1.016–1.253,P<0.05; multivariate: OR 1.206, 95% CI: 1.006 to 1.446, p<0.05), and physical exercise (univariate: OR 0.333, 95% CI: 0.181 to 0.613, P<0.01; multivariate: OR 0.337, 95% CI: 0.168 to 0.677, p<0.01), were independently associated with new-onset hypertension in T2DM patients.
Table 3 Univariate and multivariate ORs for new-onset hypertension in pre-hypertension T2DM participants
Variables |
Univariate |
Multivariate |
||
OR (95%CI) |
P-Value |
OR (95%CI) |
P-Value |
|
Age |
1.029 (0.998-1.060) |
0.067 |
1.032 (0.990-1.076) |
0.136 |
Gender (Female) |
0.963 (0.504-1.842) |
0.910 |
1.739 (0.729-4.146) |
0.212 |
BMI |
1.126 (1.023-1.240) |
0.015 * |
1.138 (1.019-1.272) |
0.022 * |
FPG |
1.121 (0.945-1.331) |
0.190 |
0.971 (0.724-1.302) |
0.845 |
Scr |
1.008 (0.997-1.018) |
0.159 |
1.012 (0.999-1.024) |
0.070 |
Triglycerides |
1.033 (0.913-1.169) |
0.604 |
0.940 (0.806-1.097) |
0.434 |
Total cholesterol |
1.108 (0.891-1.378) |
0.358 |
1.242 (0.939-1.643) |
0.128 |
HbA1C |
1.129 (1.016-1.253) |
0.024 * |
1.206 (1.006-1.446) |
0.043 * |
Years of diabetes |
1.052 (0.972-1.138) |
0.206 |
1.051 (0.952-1.159) |
0.325 |
Drinking |
1.571 (0.858-2.879) |
0.143 |
1.551 (0.731-3.291) |
0.253 |
Smoking |
1.172 (0.662-2.074) |
0.586 |
1.171 (0.569-2.407) |
0.668 |
Regular physical activity |
0.333 (0.181-0.613) |
<0.001** |
0.337 (0.168-0.677) |
0.002** |
Note:T2DM, type 2 Diabetes Mellitus; BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.
Univariate and multivariate logistic regressions for new-onset hypertension in the subgroup analysis by BMI
To further identify the impact of baseline overweight on the risk of new-onset hypertension in pre-hypertension patients with T2DM, univariate and multivariate logistic regressions analysis was performed (Table 4). We defined overweight as BMI ≥25 kg/m2 and used this to subdivide the T2DM patients into an overweight group (n=142) and a non-overweight group (n=126). In the overweight group, univariate logistic regression analysis found that the risk of new-onset hypertension was significantly associated with age (OR 1.041; 95% CI 1.001 to 1.083; p<0.05) and regular physical exercise (OR 0.219; 95% CI 0.085 to 0.567; p<0.01). And we found that regular physical exercise (OR 0.187; 95% CI 0.063 to 0.558; p<0.01) remained as the protective factor for new-onset hypertension in the multivariate logistic regressions analysis. In the non- overweight group, there was no significantly association between regular physical exercise and new-onset hypertension in T2DM patients.
Table 4 Univariate and multivariate ORs for new-onset hypertension in the Subgroup by BMI
Variables |
Univariate |
Multivariate |
||
OR (95%CI) |
P-Value |
OR (95%CI) |
P-Value |
|
BMI<25 (N=126) |
||||
Age |
1.021 (0.972-1.073) |
0.403 |
1.026 (0.956-1.100) |
0.482 |
Gender (Female) |
1.268 (0.509-3.156) |
0.610 |
4.043 (0.923-17.716) |
0. 064 |
FPG |
1.092 (0.938-1.270) |
0.256 |
1.173 (0.867-1.586) |
0.302 |
Scr |
1.004 (0.992-1.016) |
0.490 |
1.014 (1.000-1.029) |
0.046 * |
Triglycerides |
1.104 (0.927-1.315) |
0.267 |
0.992 (0.774-1.270) |
0.947 |
Total cholesterol |
1.457 (1.054-2.015) |
0.023 * |
1.611 (1.012-2.565) |
0.045 * |
HbA1C |
1.014 (0.778-1.320) |
0.920 |
0.764 (0.468-1.249) |
0.283 |
Years of diabetes |
0.199 (0.967-1.249) |
0.150 |
1.100 (0.940-1.289) |
0.235 |
Drinking |
3.036 (1.140-8.086) |
0.026 * |
2.695 (0.702-10.347) |
0.149 |
Smoking |
2.035 (0.834-4.963) |
0.118 |
4.149 (1.106-15.561) |
0.035 * |
Regular physical activity |
0.573 (0.242-1.359) |
0.206 |
0.627 (0.217-1.812) |
0.389 |
BMI≥25 (N=142) |
||||
Age |
1.041 (1.001-1.083) |
0.044 * |
1.039 (0.984-1.096) |
0.170 |
Gender (Female) |
0.897 (0.341-2.361) |
0.826 |
1.980 (0.514-7.625) |
0.231 |
FPG |
1.158 (0.995-1.348) |
0.059 |
1.298 (0.997-1.691) |
0.053 |
Scr |
1.016 (0.996-1.037) |
0.113 |
1.023 (0.996-1.051) |
0.101 |
Triglycerides |
0.954 (0.789-1.154) |
0.629 |
0.924 (0.739-1.155) |
0.487 |
Total cholesterol |
0.864 (0.632-1.178) |
0.356 |
1.051 (0.713-1.549) |
0.802 |
HbA1C |
1.207 (0.958-1.521) |
0.110 |
1.076 (0.722-1.605) |
0.718 |
Years of diabetes |
1.028 (0.930-1.135) |
0.594 |
0.987 (0.865-1.126) |
0.847 |
Drinking |
0.957 (0.439-2.083) |
0.911 |
1.374 (0.511-3.692) |
0.529 |
Smoking |
0.763 (0.359-1.619) |
0.480 |
0.726 (0.274-1.926) |
0.520 |
Regular physical activity |
0.219 (0.085-0.567) |
0.002** |
0.187 (0.063-0.558) |
0.003** |
Note: BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.
Univariate and multivariate logistic regressions for new-onset hypertension in the subgroup analysis by HbA1C
HbA1C level is utilized clinically as an indicator of the adequacy of glycemic control over several months prior to testing. To explore the impact of baseline HbA1C on the risk of new-onset hypertension in the T2DM patients, we performed subgroup analysis according to HbA1C level. The American Diabetes Association has recommended that an HbA1C breakpoint of 7% would realize the greatest cardiovascular benefit [22]. As is showed in Table 5, our results revealed that in the glucose well controlled group (HbA1C<7%), regular physical exercise (OR=0.309, 95% CI: 0.114-0.834, p<0.05) was associated with the incidence of new-onset hypertension in T2DM patients. After adjusting for confounding factors, regular physical exercise (OR=0.385, 95% CI: 0.118-1.261, p=0.115) was no longer the related factor. In the glucose poorly controlled group (HbA1C³7%), both univariate and multivariate analysis suggested that regular physical exercise (univariate: OR 0.349; 95% CI 0.160 to 0.760; p<0.01; multivariate: OR 0.349; 95% CI 0.138 to 0.880; p<0.05) was the independent associated factor of the incidence of new-onset hypertension in T2DM patients.
Table 5 Univariate and multivariate ORs for new-onset hypertension in the subgroup by HbA1C level
Variables |
Univariate |
Multivariate |
||
OR (95%CI) |
P-Value |
OR (95%CI) |
P-Value |
|
HbA1C level<7 (N=111) |
|
|
|
|
Age |
1.070 (1.019-1.124) |
0.007 ** |
1.087 (1.008-1.172) |
0.029 * |
Gender (Female) |
0.936 (0.349-2.512) |
0.896 |
0.959 (0.241-3.818) |
0.953 |
BMI |
1.036 (0.890-1.206) |
0.646 |
1.112 (0.907-1.362) |
0.308 |
Glucose |
0.999 (0.703-1.418) |
0.994 |
0.941 (0.603-1.469) |
0.789 |
Scr |
1.006 (0.994-1.019) |
0.302 |
1.006 (0.993-1.020) |
0.354 |
Triglyceride |
1.049 (0.766-1.436) |
0.765 |
1.023 (0.684-1.530) |
0.911 |
Cholesterol |
1.178 (0.805-1.724) |
0.398 |
1.816 (1.048-3.148) |
0.034 * |
Years of diabetes |
1.163 (1.036-1.304) |
0.010 * |
1.094 (0.951-1.260) |
0.210 |
Drinking |
1.227 (0.486-3.098) |
0.665 |
1.081 (0.319-3.659) |
0.901 |
Smoking |
1.255 (0.511-3.084) |
0.620 |
1.422 (0.423-4.779) |
0.569 |
Regular physical activity |
0.309 (0.114-0.834) |
0.020 * |
0.385 (0.118-1.261) |
0.115 |
HbA1C level³7 (N=157) |
|
|
|
|
Age |
1.000 (0.962-1.040) |
>0.05 |
1.016(0.963-1.072) |
0.566 |
Gender (Female) |
0.982 (0.415-2.320) |
0.967 |
2.656 (0.793-8.900) |
0.113 |
BMI |
1.1195 (1.053-1.357) |
0.006 ** |
1.193 (1.033-1.033) |
0.017 * |
Glucose |
1.218 (1.064-1.393) |
0.004 ** |
1.304 (1.096-1.550) |
0.003 ** |
Scr |
1.010 (0.991-1.030) |
0.296 |
1.024 (0.998-1.051) |
0.067 |
Triglyceride |
1.035 (0.902-1.186) |
0.625 |
0.946 (0.793-1.129) |
0.540 |
Cholesterol |
1.080 (0.825-1.414) |
0.575 |
1.096 (0.763-1.574) |
0.620 |
Years of diabetes |
0.942 (0.832-1.067) |
0.350 |
0.949 (0.819-1.101) |
0.492 |
Drinking |
1.895 (0.849-4.228) |
0.118 |
2.503 (0.887-7.070) |
0.083 |
Smoking |
1.126 (0.536-2.362) |
0.754 |
0.815 (0.303-2.188) |
0.684 |
Regular physical activity |
0.349 (0.160-0.760) |
0.008 ** |
0.349 (0.138-0.880) |
0.026 * |
Note: BMI, body mass index; FPG, fast plasma glucose; Scr,Serum creatinine;HbA1C, glycosylated hemoglobin A1c.
T2DM and hypertension often coexist, and there is a considerable overlap between their complications and mechanisms. Most patients with T2DM display dyslipidemia, hypertension and hyperinsulinemia, which are associated with metabolic syndrome and will lead to an increased risk of premature CVDs [23]. Comorbid conditions and complications are considered to determine the quality of life of patients with T2DM [24]. Standards of medical care in diabetes recommended that patients living with diabetes were engaged in regular aerobic activity, resistance or flexibility exercises to realize benefits on metabolism, fitness, and wellbeing. Many studies have elucidated the effects of different exercises on glycemic control, and cardiovascular risk factors in patients with T2DM. However, no cohort study assessed the influence of long-term regular physical activity on new-onset hypertension in T2DM population with pre-hypertension. To the best of our knowledge, this is the first study to investigate the relationship between long-term regular physical exercise and new-onset hypertension in pre-hypertension patients with T2DM.
So far, research concerning the relationship between physical activity and diabetic CVDs were numerous. A meta-analysis study conducted by Bei Pan including total of 37 studies with 2208 patients with T2DM was summarized that aerobic, resistance exercise, and combined exercise have pronounced improvement in HbA1c levels and reduction of CVDs risk factors, including TC, TG, LDL and HDL [25]. Another meta-analysis showed that exercise training, in particular aerobic and combined exercise, improved endothelial function, the indicator of CVDs, in T2DM patients [26]. In these studies the meta-analysis included, the duration of exercise was not long, ranged of 8 weeks to 6 months. That’s not long enough to evaluate the long-term influence of physical activity on diabetic complications. More recently, this point also confirmed by a randomized controlled trials, which reporting that combined (resistance-aerobic) exercise training for eight weeks showed a negative result on the serum kinesin-1 level in T2DM patients with diabetic peripheral neuropathy [27]. Hypertension is a major risk factor for CAD, stroke, kidney disease, and mortality. However, the evaluate indicators in these studies were CVDs related factors, such as TC, TG, HDL and endothelial function, et al. Compared with the indicators of new cases of hypertension, these indicators are not intuitive. This study included 268 subjects with a 5-year follow-up provided evidence that there was a significant association between long-term regular physical activity and the incidence of new-onset hypertension among pre-hypertension patients with T2DM. We also found that pre-hypertension T2DM patients with a long-term regular physical activity lifestyle were less likely to have hypertension when compared to the inactivity population (15.5% vs 35.4%, p<0.01). Of note, physical exercise (OR 0.337, 95% CI: 0.168 to 0.677, p<0.01), BMI (OR 1.138, 95% CI: 1.019 to 1.272, p<0.05) and HbA1C (OR 1.206, 95% CI: 1.006 to 1.446, p<0.05) were the main associated factors for incidence of new-onset hypertension in pre-hypertension patients with T2DM. In this study, long-term regular physical activity might be advantageous in the prevention of new-onset hypertension among T2DM patients with pre-hypertension.
T2DM is a disease that needs long-term lifestyle management. Estimate 80% of people with T2DM are overweight or obese, and many have mobility problems. It has been reported that overweight and obesity are highly prevalent in T2DM patients with high CVD risk and that BMI and waist circumference are related to major cardio metabolic risk factors such as hypertension and elevated LDL-C [28]. In this study, BMI and HbA1C were the independent risk factor for new-onset hypertension in T2DM patients. Further, the confounding effects of BMI and HbA1C on the incidence of new-onset hypertension in T2DM patients with pre-hypertension were analysis in the subgroup. Subgroup analysis indicated that for the overweight T2DM patients, regular physical activity (univariate: OR 0.219; 95% CI 0.085 to 0.567; p<0.01; multivariate: OR 0.187; 95% CI 0.063 to 0.558; p<0.01) was the independent protective factor for the incidence of new-onset hypertension. But it was not in the non-overweight group.
HgbA1c level is utilized clinically as an indicator of the adequacy of glycemic control over several months prior to testing. Thus, it is felt to reflect the effectiveness of long-term glucose control in diabetes patients. Several studies have shown that HgbA1c is associated with the severity and progression of coronary atherosclerosis [29, 30]. One clinical study conducted by R. Huang et al. aiming to scrutinize the relationship between HbA1c and myocardial perfusion in patients with T2DM showed that optimal glycemic control is associated with a preservation of myocardial blood flow reserve (MBFR) in T2DM patients who are at risk for CAD[31]. In this study, HbA1C was the independent risk factor for new-onset hypertension in T2DM patients. Furthermore, subgroup analysis suggested that in the glucose poorly controlled population, regular physical activity (univariate: OR 0.349; 95% CI 0.160 to 0.760; p<0.01; multivariate: OR 0.349; 95% CI 0.138 to 0.880; p<0.05) was significantly related to the lower incidence of new-onset hypertension compared with the T2DM patients with inactivity lifestyle. These results suggested that regular physical activity was the main protective factor for new-onset hypertension in overweight and glucose poorly controlled T2DM patients with pre-hypertension, rather than whose well controlled.
This study has some limitations. First, because of retrospective cohort study design, the present findings should be confirmed by future prospective cohort studies. Second, hypertension was defined as taking antihypertensive medications and/or having systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg based on a one-time blood pressure measurement, although current clinical guidelines recommend the mean value of two measurements on at least two different occasions. Third, the follow-up period was only 5 years, and absence of data regarding changes in lifestyle during follow-up. However, our study was consisted only long-term regular physical activity population, suggesting that the impact of lifestyle changes during follow-up period was minimal in our study. Fourth, we cannot obtain other important variables from the electronic database, such as the history of hypertension, change trajectory of blood pressure, fat distribution and weight changes (waist circumference and waist–hip ratio). It is worth mentioning that this study has several highlights. All subjects in this study were T2DM patients with pre-hypertension, which is the high risk stage of developing hypertension.
In conclusion, in this study, long-term regular physical activity may be an important protective factor for new-onset hypertension in pre-hypertension patients with overweight, poor blood glucose control and T2DM at baseline. Our findings suggested that diabetes pre-hypertensive patients should be advised to take physical activity and long-term implementation in order to achieve great cardiovascular benefits.
Ethics approval and consent to participate
The study was approved by the ethics committee of Zhejiang Hospital. The data are anonymous, and the requirement for informed consent was therefore waived. All research procedures are performed according to the criteria of the Declaration of Helsinki.
Consent for publication
Not applicable.
Availability of data and materials
The data that support the findings of this study are available from the ethics committee of Zhejiang Hospital, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the ethics committee of Zhejiang Hospital.
Competing interests
The authors declare that they have no competing interests.
Funding
This work was supported by funds from Health Bureau of Zhejiang Province (2021KY013).
The conception and design of the study (Q. Wu, J.M. Zhou), acquisition and analyze of data (X.L. Lv, R.F. Zhou), draft, revised article and finished the submission (Q. Wu), collected literature and polished the language for revised manuscript (B.Z. Wang). The other co-authors do not have any conflict of interest. All authors read and approved the final manuscript
Acknowledgements
We would like to thank the assistance of Ms. Yi Yang (Zhejiang Hospital, China.) for her helpful advice on clinical data collection.