The prevalence of hypertension in the general population is 35.5% according to the latest ICMR-INDIAB study with higher prevalence of 40.7% in urban areas and 33% in rural areas [1]. While in T2DM patients, the prevalence increases to 66.3% [1], or by 1.5-16 times [2]. Hypertension (HTN) and diabetes mellitus are two of the leading lifestyle diseases that often co-exist due to overlapping pathophysiological factors. When diabetic patients have HTN, there is an increased risk of Cardiovascular Disease (CVD) fourfold as compared to normotensive nondiabetic controls [3]. In the Framingham heart study, it was shown that the coexistence of hypertension in diabetic patients has increased the risk of cardiovascular events and overall mortality [4].

HTN is the strongest driver of Cardiovascular (CV) outcomes in patients with diabetes. HTN diagnosis and control have emerged as the most important intervention in T2DM patients. Control of blood pressure is as important as glycaemic control in the prevention of DM-related micro and macrovascular complications as demonstrated in the UKPDS study [5]. Reduction of Systolic Blood Pressure (SBP) below 130 mm Hg is associated with a lower risk of stroke, retinopathy, and albuminuria, potentially leading to net benefits for many individuals at high risk for those outcomes as shown by a metanalysis study [6]. Blood Pressure (BP) is the indicator of the person's hemodynamic state and hence is not a static phenomenon. As a result, there are both short-term and long-term variations in BP, referred to as Blood Pressure Variability (BPV). Most hypertensive patients are monitored by clinic-based BP measurement and thus their daily BP variability is not available. Studies have shown that office BP measurement is not ideal for representing 24-hour BP compared with ambulatory blood pressure monitoring [7]. Abnormalities in ABPM parameters were found to be more in diabetic patients as compared to non-diabetic patients in most of the studies. Hypertension aggravates atherosclerotic disease in diabetic patients thus increasing the susceptibility to chronic complications of diabetes [8]. Approximately 35% to 75% of diabetes complications are estimated to be attributed to HTN [6].

As per WHO reports, hypertension affects one in three adults worldwide and four out of every five hypertensive patients are not adequately treated. Uncontrolled hypertension is a major contributory risk factor for heart, brain and kidney-related vascular morbidities and mortalities. In the general population prevalence of hypertension ranges from 25-30% while in Type 2 Diabetic (T2DM) patients it increases to 1.5-1.6 times.2 Not only increased prevalence but a combination of hypertension and T2DM increases cardiovascular morbidities and mortalities significantly. Like other biological clocks, blood pressure has also a circadian rhythm and disturbance in this rhythm may lead to increased cardiovascular risk. Ambulatory Blood Pressure Monitoring (ABPM) is a better tool to assess the dynamic process of blood pressure regulation. ABPM parameters like higher overall mean ABPM blood pressure, nocturnal mean blood pressure, higher morning surge and masked hypertension are reported to result in comparatively adverse cardiovascular outcomes [7]. Diabetic patients are known to have higher overall mean ABPM blood pressure and nocturnal blood pressure in comparison to the non-diabetic population [9]. In type 1 diabetes patients rise in nocturnal blood pressure is reported to precede new onset of Microalbuminuria [10].

There are many ABPM registry data from India and globally highlighting the importance of ABPM in blood pressure monitoring [11, 12]. There are studies about ABPM monitoring in diabetic patients [9, 13]. However, prospective cross-sectional ABPM data comparing diabetic versus non-diabetic patients in India are very sparse. We planned to study ABPM data comparing T2DM and non-diabetic hypertensive patients attending our department in the last 1 year.

We conducted this prospective observational study at our outpatient department. Patients were explained the importance of ABPM and those who wanted to participate in the study were included in the study provided they fulfilled the following inclusion and exclusion criteria. There was no random selection of the patients.

Inclusion Criteria

• Patients in the age group of 18-65
• T2DM patients with a history of essential hypertension on regular follow-up and willing to undergo ABPM
• Nondiabetic hypertensive patients on regular anti hypertensives, willing to undergo ABPM

Exclusion Criteria

• Patients with secondary hypertension
• Chronic kidney disease or diabetic kidney disease
• Type 1 DM
• Pregnant women.
• Patients with significant end organ failure.

Detailed clinical history focusing on the duration of hypertension along with the number and type of drug therapy for hypertension control were noted down.

Vital parameters and anthropometric details were obtained. For measurement of height, a standard calibrated stadiometer is used with the individual standing upright with feet together, and placing heels, buttocks, and upper back against the stadiometer after removing the footwear. For weight, a calibrated digital scale is used with the patient standing upright in the centre of the scale with arms at the sides, looking straight ahead and BMI is calculated using the following formula: BMI=Weight (kg)/Height (m)². For office blood pressure measurement, a calibrated aneroid blood pressure device was used. Due precautions for office blood pressure measurement were observed as per WHO guidelines. The patient was asked to sit in a comfortable position for 5 minutes avoiding cross legs and resting arm with the cuff at chest height. An average of 3 office BP records was considered as baseline office BP records.

ABPM was analysed with an automated, Oscillo metric Meditech device (ABPM-05, Hungary) programmed to record BP every 15-20-minute intervals during daytime and 30-minute intervals at night time. ABPM parameters like mean ABPM blood pressure record, maximum systolic and diastolic blood pressure, blood pressure variability (SD), nocturnal mean BP, nocturnal dipping (DI) variables like extent of dipping, exaggerated dipping and non-dipping, morning blood pressure surge/exaggerated surge, white coat hypertension and masked hypertension were studied. The nocturnal fall of 10-20% of the mean ambulatory blood pressure was considered normal dipping, while less than 10% was accepted as reverse dipping and more than 20% as exaggerated dipping.  Blood pressure variability (SD) less than 12 % was defined as normal variability. Less than 20 % surge from mean systolic blood pressure in the morning time was considered a normal morning surge in blood pressure.

Statistics

When a comparison of the simple mean of the two groups was required, the data were analysed by student’s t-test. For comparing the mean of multiple groups, the ANOVA test was used. In the case of categorical data, the difference between observed data and expected data was analysed by a 2×2 chi-square analysis.

Ethical Aspect

The study was conducted with full compliance to the principles of Declaration of Helsinki (2013). The protocol was presented to the institute's ethics committee and due permission was obtained, Ref No- 22120/2023/DNB. Informed consent was obtained from each patient after a detailed explanation of the study.

The mean age of patients was significantly higher in diabetic patients (58.2 ± 9.9 years versus 45.52 ± 8.2 years, p ≤ 0.001). The baseline mean office blood pressure was significantly higher in non-DM patients as compared to diabetic patients (table 1). There was female preponderance in both groups. Other clinical parameters like body mass index, duration of hypertension, and number of patients on monotherapy and multidrug therapy to control hypertension were matched in both groups. Among diabetic patients mean duration of hypertension was 56.46 ±7 months (make it in years) and the mean HbA1C was 7.53 ± 1.5.

Table 1: Clinical profile of DM and NON-DM hypertensive patients.

Among diabetic individuals, 45 are female with an average age of 56.5 years and BMI of 29.6 kg/m², while 30 are male, averaging 60.8 years in age with a BMI of 29.3 kg/m². The mean duration of diabetes is 4 years for females and 7.3 years for males. In non-diabetics, 15 are male with a mean age of 45.8 years and BMI of 28.9, and 60 are female, averaging 45.2 years in age with a BMI of 30.9. Hypertension duration ranges from 3.13 to 6.6 years across groups, and hypothyroidism is present in 15 diabetic females and 4 diabetic males.

Ambulatory Blood Pressure Parameters

All ambulatory blood pressure parameters including mean systolic and diastolic ambulatory blood pressure and mean nocturnal systolic and diastolic blood pressure were significantly higher in non-DM patients (figure 1). The mean of maximum systolic and diastolic ambulatory blood pressure was also significantly higher in non-DM patients as compared to DM patients (figure 1, 167/107 versus 155/94 mm of Hg, p ≤ 0.001). The mean of nocturnal systolic and diastolic BP was higher in non-DM patients as compared to DM patients (128/75 versus 121/66 mm of Hg, p = 0.017). However, there was no significant difference in minimum systolic and diastolic BP (98.5/50 versus 99.8/56).

Figure 1: Comparison of Ambulatory blood pressure parameters in diabetic versus nondiabetic patients.

Blood Pressure Variability and Nocturnal Dipping

Blood pressure variability was seen more in non-diabetic patients in comparison to diabetic patients (figure 2). Normal blood pressure variability was seen in 9/75 (12%) non-DM patients in contrast to 34/75 (45%) DM patients (figure2, p ≤ 0.001). Nocturnal dipping was not significantly different in both groups (figure 3). The number of non-dippers (43 versus 41) and extreme dippers (3 versus 2) were higher among diabetic patients as compared to the non-diabetic group. However, this difference was not significant (figure 3, p = 0.9).

Figure 2: Morning surge and BP variability in DM versus Non-DM patients.

Figure 3: Nocturnal dipping pattern in DM versus Non-DM patients.

Morning Surge in Blood Pressure

There was a marginal difference in morning surge BP data among both the groups, but not significant. Normal morning surge in systolic blood pressure (less than 20% of mean ambulatory blood pressure) was seen in higher number of non-diabetic patients than diabetic group (62/75- 82% versus 58/75 - 77%, figure 2, p = 0.5). Exaggerated surge was higher in diabetic patients versus non-diabetic patients, but not significant (17 versus 13, p=0.5).

White Coat and Masked Blood Pressure Effects

Among 75 patients in each group, the white coat hypertension effect (Mean office blood pressure higher than mean ambulatory blood pressure) was seen in 20 (27%) diabetic patients versus 25 (33%) non-diabetic patients (p = 0.50). Masked hypertension effect (Mean office systolic blood pressure lower than mean ambulatory systolic blood pressure) was seen in 7 patients in each group.

Overall Results

In both groups, there was a female preponderance. Mean age was significantly higher in diabetic patients as compared to non-diabetic patients (58.23 ± 9.9 versus 45.5 ± 8.2, p < 0.001 or simply mention Table 1). Mean body mass index and mean duration of hypertension were not significantly different in both groups. Number of patients using multiple anti-hypertensive drugs and RAS blocking agents was also not different in both groups (Table1). Baseline office blood pressure, mean ambulatory blood pressure, mean nocturnal blood pressure, and blood pressure variability indices were significantly higher in non-diabetic patients in comparison to diabetic patients (Table1). The number of non-dippers, extreme dippers, and patients with extreme morning surges in systolic blood pressure was marginally higher among diabetic patients (p= 0.5).

Table 2: ABPM analysis in NON-DM Males and Females.

Table 3: ABPM analysis in DM Males and Females.

Several studies on ABPM highlight it as a better monitoring tool for assessing hypertension control than office blood pressure monitoring [7, 11].  Majority of these studies are retrospective analysis of ABPM registry. ABPM parameters like mean nocturnal blood pressure, nocturnal systolic blood pressure dipping and early morning exaggerated surge in systolic bp correlate more with future cardiovascular risk which cannot be assessed by office bp monitoring [9,14,15]. All these studies are largely based on multicentric retrospective ABPM registry data. Most of them have reported poor ABPM parameters in diabetic patients than in non-diabetic hypertensive patients [13, 16]. There are very few dedicated prospective studies comparing diabetic and non-diabetic hypertensive populations [13, 16]. Indian studies comparing both groups for ABPM parameters are sparse.

Based on this, we decided to prospectively study the ABPM parameters in our hypertensive diabetic and non-diabetic hypertensive patients. Ours was a single centre prospective observational study conducted over a period of 1 year. All hypertensive patients were explained about importance of ABPM and those willing for it were included in the study after their consent. There was no randomisation process followed in selecting the patients. Our non-diabetic hypertensive patients had significantly higher baseline mean office bp along with higher mean ABPM systolic (p≤0.001) and mean nocturnal bp (p=0.017). They also had higher ABPM variability index (SD). This contrasts with the results of previous studies [9, 13]. Some of the ABPM parameters like exaggerated morning surge, number of nocturnal non-dippers and reverse dippers were relatively more in diabetic patients as compared to non-diabetic patients (p=0.4).

Introspecting our findings, we had a significantly higher number of non-diabetic patients with multiple ABPM parameters abnormalities in comparison to diabetic individuals. We feel few reasons responsible for the same. It might have happened that diabetic patients opted for ABPM as an important health monitoring tool along with other monitoring parameters while non-diabetic patients opted for ABPM only when hypertension was a major troubling health problem for them due to poor control. Hence right from the beginning hypertension parameters were higher in non-diabetic patients and same was reflected in ABPM analysis. Baseline high mean office systolic blood pressure and higher mean nocturnal blood pressure in non-diabetic patients, could be responsible for higher ambulatory blood pressure parameters in non-diabetic patients. The number of patients having baseline blood systolic blood pressure was also higher in non-diabetic patients as compared to the diabetic population (57% versus 45.3%, p ≤ 0.001). The mean duration of hypertension, age, body mass index and number of antihypertensive drugs required to control hypertension were similar in both groups. More than 90% of patients in both groups used RAS blockade agents as one of their antihypertensive drug therapies. Another important reason for unexpected results could be the small cohort in our study in comparison to large-scale ABPM registry data reported in previous studies [9, 13]. Ours was a prospective observational study and hence each patient was given a choice to undergo ABPM as an additional tool to monitor hypertension.

The patient selection process also might have played a role. After explaining about ABPM, any hypertensive patient who was willing to undergo an ABPM test was included. No patient was excluded just to match the demographic data. It seems that diabetic patients have undergone ABPM as they understood hypertension as an important co-morbidity along with diabetes while non-diabetic patients have opted for ABPM when hypertension control was the main concern. Awareness and seriousness about controlling hypertension might be more in diabetic patients as compared to non-diabetic patients. Masked hypertension and white coat hypertension effects were not different in both groups (p = 0.84).

Overall, in our study higher baseline office BP and higher nocturnal mean systolic blood pressure resulted in poor ABPM parameters among non-diabetic patients in comparison to the diabetic group. However, our findings emphasise that hypertension control in non-diabetic patients is equally important, and it should be taken seriously. Aggressive hypertension control must be emphasised in all patients irrespective of the presence or absence of diabetes.

In contrast to retrospective analysis of ABPM registry, this unique study highlights the prospective cross-sectional comparison of ABPM parameters in type 2 diabetic patients versus non-diabetic hypertensive patients. Many of the ABPM abnormalities were more common in non-diabetic patients in comparison to diabetic patients. A small cohort, selection process, higher baseline BP and less seriousness about the disease could be possible reasons for the difference. It also highlights the importance of ABPM as a monitoring tool in both diabetic as well as non-diabetic patients and a need for stricter blood pressure control even in non-diabetic patients.

Abbreviations

ABPM- Ambulatory Blood pressure monitoring; HTN- Hypertension; BPV- Blood pressure variability

Authors Contribution

• Study concepts and design – Author 1, 5
• Literature search – Author 1,2,5
• Data acquisition and analysis – Author 1,3
• Manuscript preparation – Author 1,2,5
• Manuscript review and editing – Author 1,4,5
• Final approval – Author 2, 4,5

The final manuscript has been read and approved by all the authors.

Declaration of patient consent

The authors certify that they have obtained all appropriate patients’ consent to participate in the study. In the form, the patient(s) has/have given his/her/their consent for his/her/blood tests and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial Support and Sponsorship

NIL

Acknowledgments

We thank all the patients who participated in the study. We acknowledge the support from clinic assistant B Christina for data entry and Eris Life science company for providing ABPM device. We also acknowledge the help and support from all consultants from various other departments of Care hospitals.

Conflicts of Interest: There are no conflicts of interest.

Data Availability: The Excel sheet with study data will be shared if required.

1. Anjana RM, Unnikrishnan R, Deepa M, Pradeepa R, Tandon N, Das AK, et al. Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17). Lancet Diabetes Endocrinol. 2023; 11: 474-489.
2. Viswanathan V, Smina TP. Blood pressure control in diabetes—the Indian perspective. J Hum Hypertension. 2019; 33: 588-593.
3. Kengne AP, Patel A, Barzi F, et al. Systolic blood pressure, diabetes and the risk of cardiovascular diseases in the Asia-Pacific region. J Hypertension. 2007; 25: 1205-1213.
4. Chen G, McAlister FA, Walker RL, Hemmelgarn BR, Campbell NRC. Cardiovascular outcomes in framingham participants with diabetes: The importance of blood pressure. Hypertension. 2011; 57: 891-897.
5. Adler AI, Stratton IM, Neil HAW, Yudkin JS, Matthews DR, Turner RC, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study.
6. Emdin CA, Rahimi K, Neal B, Callender T, Perkovic V, Patel A. Blood pressure lowering in type 2 diabetes: A systematic review and meta-analysis. JAMA. American Medical Association; 2015; 313: 603-615.
7. Niiranen TJ, Maki J, Puukka P, Karanko H, Jula AM. Office, Home, and Ambulatory Blood Pressures as Predictors of Cardiovascular Risk. Hypertension. 2014; 64.
8. Oparil S, Zaman MA, Calhoun DA. Pathogenesis of hypertension. Ann Intern Med. 2003; 139: 761-776.
9. Gorostidi M, de la Sierra A, Gonzalez-Albarran O, Segura J, de la Cruz JJ, Vinyoles E, et al. Abnormalities in ambulatory blood pressure monitoring in hypertensive patients with diabetes. Hypertension Research. 2011; 34: 1185-1189.
10. Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002; 347: 797-805.
11. Kaul U, Arambam P, Rao S, Kapoor S, Swahney JPS, Sharma K, et al. Usefulness of ambulatory blood pressure measurement for hypertension management in India: the India ABPM study. J Hum Hypertens. 2020; 34: 457-467.
12. Banegas JR, Ruilope LM, de la Sierra A, Vinyoles E, Gorostidi M, de la Cruz JJ, et al. Relationship between Clinic and Ambulatory Blood-Pressure Measurements and Mortality. New England J Medicine. 2018; 378: 1509-1520.
13. Sun L, Yan B, Gao Y, Su D, Peng L, Jiao Y, et al. Relationship between blood pressure reverse dipping and type 2 diabetes in hypertensive patients. Sci Rep. 2016; 6.
14. Najafi MT, Khaloo P, Alemi H, Jaafarinia A, Blaha MJ, Mirbolouk M, et al. Ambulatory blood pressure monitoring and diabetes complications. Medicine. 2018; 97: e12185.
15. Staessen JA, Yang WY, Melgarejo JD, Thijs L, Zhang ZY, Boggia J, et al. Association of Office and Ambulatory Blood Pressure with Mortality and Cardiovascular Outcomes. JAMA - J American Medical Association. 2019; 322: 409-420.
16. Ozawa M, Tamura K, Iwatsubo K, Matsushita K, Sakai M, Tsurumi-Ikeya Y, et al. Ambulatory Blood Pressure Variability Is Increased in Diabetic Hypertensives. Clin Exp Hypertens. 2008; 30: 213-224.