Abnormal blood pressure dipping pattern: frequency, determinants, and correlates in Diabetes Mellitus patients in the Cardiovascular Health Risk Assessment in Diabetes Mellitus (CHiD) study

Abstract

Purpose

Non-dipping status is associated with increased total and cardiovascular mortality in many disease conditions including diabetes mellitus. The pattern and its implications are not well described among Africans. This study was done to describe the frequency of abnormal blood pressure (BP) dipping among T2DM subjects, its determinants and correlates in Ogbomoso, Nigeria.

Methods

This was a cross-sectional study done at the LAUTECH Teaching Hospital, Ogbomoso. One hundred individuals diagnosed with T2DM were recruited and they had 24-hour ambulatory BP monitoring, echocardiography, ECG, and carotid Doppler among other evaluations. Statistical analysis was done using SPSS 27.0 (Chicago Ill, USA).

Results

The mean age of the participants was 59.3 ± 10.8 years, mean body mass index 27.7 ± 5.9 kg/m² with a mean duration of diabetes of 7.52 ± 5.54 years. Abnormal BP dipping was present in 89% (consisting of 41% or reverse dippers and 48% non-dippers). T2DM subjects with abnormal dipping pattern were more likely to be females, had higher glycated haemoglobin, lower fractional shortening, higher left atrial volume and left ventricular mass index, and a higher DM duration than those with normal BP dipping status. The major determinants of abnormal dipping pattern were the duration of diabetes and low HDL-C concentration.

Conclusion

Abnormal BP dipping pattern is highly prevalent in T2DM subjects, especially among females. Abnormal BP dipping was also associated with markers of increased cardiovascular risk such as impaired kidney function, left ventricular hypertrophy, postural hypotension, history of intermittent claudication, and presence of plaques on carotid Doppler studies.

Supplementary Information

The online version contains supplementary material available at 10.1007/s40200-023-01337-8.

Keys: Type 2 diabetes, Cardiovascular risks, Ambulatory blood pressure measurement, Dipping pattern.

Introduction

Cardiovascular disease is a major cause of morbidity and mortality in Type 2 Diabetes mellitus (T2DM) subjects and hypertension is a common comorbidity in the clustering of cardiovascular risk factors in T2DM [1, 2]. Diabetes mellitus patients are at increased risk of developing hypertension for many reasons [2, 3] including the fact that T2DM is a common metabolic disorder predisposing to diabetic cardiomyopathy and atherosclerotic cardiovascular disease (CVD) with consequent pressure overload, myocardial ischemia, and increased peripheral resistance, all of which could be mechanisms related to the development of hypertension in T2DM [4, 5].

The underlying insulin resistance involved in the pathogenesis of T2DM subjects can also be interrelated with the development of hypertension [2, 3]. The close association between type 2 DM and CVD has led to the common soil hypothesis, postulating that both conditions share common genetic and environmental factors influencing this association [5, 6].

The relationship between cardiovascular events and mortality in individuals with diabetes is controversial but adverse cardiovascular sequelae of hypertension may not only be related to increased BP values but to circadian variation [7]. Decision on diagnosis, treatment, and evaluation of treatment is based on the average of several BP values. However, BP is characterized by short-term (day-to-night), day-to-day, and long-term (visit-to-visit) fluctuations [8]. These are the results of complex interactions between cardiovascular regulatory mechanisms, environmental and behavioral factors. Several studies have shown that adverse cardiovascular outcomes are independently related to BP variability although its additional predictive value is not very clear [9, 10].

Blood pressure dipping is a physiological drop in blood pressure (10–20%) during sleep which represents an event due to circadian blood pressure variation. The loss of the circadian rhythm variation in blood pressure evidenced by non-dipping status is associated with increased total and cardiovascular mortality in many disease conditions including diabetes mellitus. Other alterations that can be expressed include increased (extreme) dipping, decreased (non-dipping), or a reverse (higher blood pressure during sleep compared to awake state) [11].

Several epidemiologic studies have shown that the peak incidence of most types of cardiovascular disease follows a circadian (24 h) pattern. Circadian blood pressure rhythm has been shown to be more independently associated with cardiovascular risks and prognosis than office/clinic blood pressure [12]. The circadian rhythm may be influenced by demographic, neurohormonal, and pathophysiologic factors. The non-dipper profile appears to be of prognostic significance because it is associated with increased target-organ damage and a worsened cardiovascular outcome. Chronotherapy is a new pharmacologic concept whereby medication is delivered at a time and in a concentration that varies according to physiologic need during the dosing period [13]. The prevalence of abnormal dipping pattern in diabetes mellitus subjects have been shown to be substantial. Nandhini recorded that 34% of their subjects in a study in India had non-dipping patterns while 22% were reversed dippers. They also revealed that duration of diabetes > 10 years and long-term poor glucose control as evidenced by abnormal HbA1c were independently associated with the presence of abnormal dipping pattern in. this population [14]. A similar study in Australia showed the frequency of occurrence of non-dipping pattern in their diabetic cohorts to be as high as 55% [15]. These studies concluded that non-dipping, nocturnal systolic hypertension and reversed dipping were strong predictors of end-organ damage. The reliability of OBP for assessing BP in T2DM is only modest. Patients with T2DM are therefore likely to benefit from routine ambulatory blood pressure monitoring.

Despite the mounting evidence of increased cardiovascular risk among T2DM subjects, the use of ambulatory blood pressure monitoring is not yet routinely done in clinical practice. This is in view of the enormous data that can be obtained from ambulatory blood pressure monitoring with diagnostics and therapeutic potentials. The pattern of abnormal blood pressure dipping and its determinants/correlates in Africans have not been well studied. This study aimed to describe the pattern of blood pressure dipping among T2DM subjects in the CHID study, the determinants of non-dipping status among this cohort, and its clinical and demographic correlates.

Materials and methods

This was a cross-sectional study. It was done at the Endocrinology clinic of the Ladoke Akintola University of Technology Teaching Hospital, between August 2019 and June 2022. The COVID-19 Pandemic caused an initial suspension of the recruitment process which was reactivated when the situation improved to allow clinical research. The sample size selection method was by stratified randomization technique. A biodata form was used to collect demographic and clinical data about participants. Clinical parameters including weight(kg), height (meters), waist circumference, hip circumference, systolic blood pressure, and diastolic blood pressure among others were all measured.

Study Population

The study population included adult T2DM patients who met the inclusion criteria. They were recruited by stratified random sampling of all potential participants in the diabetes and metabolism clinic of the Ladoke Akintola University Teaching Hospital, Ogbomoso, Nigeria. Subjects were excluded if they refused to give their consent, were less than 40 years old, had gestational diabetes mellitus, chronic kidney diseases, or any other severe medical illnesses such as heart failure, and cancers among others. These medical complications were excluded because they could by themselves cause abnormal dipping patterns as a result of autonomic neuropathy and they were excluded during routine examination and relevant investigation. Also, patients who were on medical admissions or who has been admitted in the last four weeks were also excluded to avoid the impact of recent medical illness on the outcome of the study.

Sample size determination

The minimum sample size was estimated for the T2DM patients as 100 patients. They were recruited from the clinic if they had been diagnosed with T2DM and were been followed up in the Endocrinology clinic of LAUTECH Teaching Hospital, Ogbomoso, Nigeria. Similar studies from India, Australia, etc. have used smaller sample sizes [14, 15].

Office BP was measured according to standardized procedure with the use of calibrated mercury sphygmomanometer. The mean of the two readings taken 1 min apart was used. The patient was scheduled for 24-hour ambulatory blood pressure monitoring (ABPM) immediately after recruitment and the patient was asked not to change the dosing and/or timing of any antihypertensive treatment if any he/she has been taking. ABPM was performed with a validated, automated, device (CONTEC® device). It was programmed to record BP every 15-minutes interval during the day and 30 min intervals during the night. The daytime interval was set between 6 am and 10 pm and the night interval between 10 pm and 6 am. For analysis, the mean of all valid readings was used and valid measurements had to fulfill pre-specified quality criteria, including the successful recording of at least 70% of programmed measurements corresponding to 20-daytime and 7-nighttime readings during the 24-hour recording period. Reports were generated on all patients in a standard manner and after performing ABPM, categorization of hypertensive phenotypes and sub-categorization was subsequently done. Non-dippers, reversed dipping and normal dipping pattern were identified according to standardized guidelines.

Among other investigations that were done for participants include Electrocardiography (ECG), Echocardiography, Carotid Doppler studies for carotid intima-media thickness and to determine carotid stenosis, urinalysis, glycated hemoglobin, serum lipid profile, inflammatory markers such as interleukin-1, high sensitive-C-reactive protein (hs-CRP), full blood count, electrolytes, urea, and creatinine. The estimated glomerular filtration rate was determined using the MDRD formula.

Ethical considerations

Institutional Ethical clearance was obtained from the Research ethics Committee of Ladoke Akintola University of Technology Teaching Hospital, Ogbomoso, Nigeria. Written informed consent was obtained from all study participants.

Statistical analysis

Statistical analysis was done using the Statistical Package for Social Sciences (SPSS) version 27.0 (Chicago Ill. USA). The data were presented in appropriate tabulations; descriptive statistics was generated to describe the sample in relation to demographic and clinical characteristics. Mean and standard deviation were computed for continuous variables. The Chi-square test was employed to compare differences in the distribution of categorical, socio-demographic and clinical characteristics between dippers and non-dippers diabetic participants. Fisher’s exact test was used as an alternative whenever the expected frequency counts violates the assumption required for Chi-square test. Furthermore, the student t-test or Mann-Whitney test was used for the comparison of continuous variables. Logistic regression analysis was used to determine the determinants of non-dipping status among T2DM subjects. P value less than 0.05 was considered as significant level. Pearson correlation coefficient, two-independent samples t-test, and ANOVA were also used for statistical analysis.

Results

Abnormal dipping patterns were documented in 89(89%) of the study participants consisting of reverse dippers (41%) and a non-dipping pattern in 48(48%). Only 11(11%) of study participants had normal blood pressure dipping pattern in the cohort of T2DM in this study. This is shown in Fig. 1.

Fig. 1.

shows the pattern of non-dipping status in a cohort of Type 2 diabetes mellitus patients in this study

The clinical, demographic, and echocardiographic parameters between participants with normal dipping status and abnormal dipping status are shown in Table 1. T2DM subjects who are normal dippers were similar in age (61.9 ± 13.3years vs. 58.9 ± 10.5 years, p > 0.05) respectively), body mass index (26.8 ± 6.1 vs. 28.6 ± 6.3 kg/m² years, respectively, p > 0.05), waist-hip ratio (0.96 ± 0.03 vs. 0.93 ± 0.09 respectively, p > 0.05) and neck circumference (38.2 ± 3.3 vs. 37.2 ± 3.1 cm respectively, p > 0.05) compared to those with abnormal dipping status.

Table 1.

Some cardiovascular risks/diseases between dippers and non-dippers in study participants

variables	Normal Dippers (11)	Abnormal dippers (89)	P value
eGFR < 60mls/min (n)	1(9.1%)	24(27.0%)	0.014*
LVH	3(27.3%)	82(92.1%)	0.032*
Dyslipidaemia Elevated TC > 5.2mmol/l Elevated TG > 1.7mmol/l Low HDL < 1.03mmol/l Increased LDL > 2.58mmol/l	1(9.1%) 2(18.2%) 9(81.8%) 4(36.4%)	19(21.3%) 11(12.4%) 74(83.1%) 8(9.0%)	0.132 0.324 0.912 0.098
Hx of stroke/CVD	1(9.1%)	7(7.9%)	0.973
Proteinuria	1(0.0%)	8(9.0%	0.349
Postural hypotension	0(0.0%)	14 (15.7%)	0.016*
Intermittent claudication	8(72.7%)	34(38.2%)	0.015*
History of Smoking	1(9.1%)	5(56.2%)	0.067
Carotid Plaques	4(36.4%)	40(44.9%)	0.035*

Key to table: TC-Total cholesterol, TG-triglycerides, HDL-high density lipoprotein, LDL-low density lipoprotein, CVD-cardiovascular disease

Abnormal dippers were more likely to be females as 65 (73%) of those with abnormal dipping pattern were females compared to 4(36.4%) of those with normal dipping pattern who were females. Similarly, glycated haemoglobin, a measure of long-term glucose control and variability was significantly higher among those with abnormal dipping pattern compared to those with normal dipping pattern (11.1 ± 9.4 vs. 8.3 ± 2.4% respectively, p < 0.05). Out of the echocardiographic parameters, fractional shortening was significantly lower among those with abnormal dipping pattern compared to those with normal dipping pattern (30.9 ± 5.1 vs. 34.1 ± 4.5% respectively, p < 0.05). Some echocardiographic parameters such as left ventricular internal dimension in diastole, ejection fraction, interventricular septal thickness in diastole, posterior wall thickness in diastole, right ventricular dimension, aortic root dimension, left atrial dimension, tricuspid Annular systolic pulmonary excursion, and right atrial volume were not significantly different between those with normal and abnormal dipping pattern in the study group as shown in Table 2. Those with abnormal dipping pattern had significantly higher left atrial volume (22.2 ± 4.4 vs. 19.7 ± 4.6 mm² respectively, p < 0.05), left ventricular mass index (144.0 ± 62.7 vs. 75.4 ± 35.2 g/m^2.7 respectively, p < 0.05) than those with normal BP dipping status. Those with abnormal dipping status in the T2DM cohorts were shown to have a longer duration of diabetes mellitus diagnosis compared to those with normal dipping status (7.9 ± 5.5 vs. 4.4 ± 4.7 years, respectively, p < 0.05) as shown in Table 2.

Table 2.

; Clinical, demographic, and related parameters between T2M dippers and non-dippers

Variable	Normal Dippers(11)	Abnormal Dippers(89)	P value
Age(years)	61.9 (13.3)	58.9 (10.5)	0.392
GENDER(F) (n) (%)	4(36.4%)	65(73.0%)	0.013*
BMI (kg/m2)	26.8(6.1)	28.6(6.3)	0.376
WHR	0.96(0.03)	0.93(0.09)	0.208
Neck Circum (cm)	38.2(3.3)	37.2(3.1)	0.32
HbA1c (%)	8.3(2.4)	11.1(9.4)	0.0416*
LVDD(mm)	46.1(5.7)	44.2(6.9)	0.408
FS (%)	34.1(4.5)	30.9(5.1)	0.047*
EF (%)	63.3(5.7)	60.1(5.5)	0.072
IVST (mm)	13.3(1.6)	12.5(2.2)	0.232
PWTD (mm)	11.3(1.7	11.8(2.0)	0.481
RVD (mm)	24.9(3.2)	26.8(4.4)	0.171
AOD (mm)	31.2(6.5)	32.1(4.9)	0.579
TAPSE (mm)	22.2(4.0)	22.0(3.3)	0.865
LAD (mm)	38.9(3.9)	38.5(5.1)	0.793
LAV (m2)	19.7(4.6)	22.2(4.4	0.047*
RAV (m2)	16.4(3.1)	17.2(3.4)	0. 341
MITRAL E-A RATIO	0.81(0.3)	0.72(0.21)	0.03*
EST PASP (mmHg)	7.2(3.4)	9.0(5.3)	0.353
LVMI (g/m2.7)	75.4(34.2)	144.0(62.7)	0.034*
DURATION OF DM (years)	4.4(4.7)	7.9(5.5)	0.045*

Key to table: BMI- body mass index, F-female, WHR-waist-hip ratio, HBA1c-glycated haemoglobin, LVDD-left ventricular internal dimension in diastole, FS-fractional shortening, EF-ejection fraction, IVST-Interventricular septal thickness in diastole, PWTd-Posterior wall thickness in diastole, RVD-right ventricular dimension, AOD-aortic root dimension, TAPSE-Tricuspid Annular Systolic Plane Excursion, LAD-left atrial dimension, LAV-left atrial volume, RAV-right atrial volume, MITRALE-A rat-Mitral valve E/A ratio, EST PASP-estimated pulmonary arterial systolic pressure, LVMI-left ventricular mass index, DM-diabetes mellitus

Table 1 shows the pattern of some identified CV risk factors/diseases or markers of CVD in the study population. Impaired kidney function defined by estimated glomerular filtration rate < 60ml/min was present in 27% of those with abnormal dipping pattern compared to 9.1% of those with normal dipping pattern, p < 0.05. Similarly, those with abnormal dipping pattern had a greater frequency of left ventricular hypertrophy (92.1% vs. 27.3%, p < 0.05), postural hypotension (15.7% vs. 0.0% respectively, p < 0.05), and presence of carotid plaques (44.9% vs. 36.4% respectively, p < 0.05) on carotid Doppler studies compared with those with normal dipping pattern as shown in Table 1.

The circadian ambulatory blood pressure monitoring rhythm profile and blood pressure averages are shown in Table 3. 24-hour average systolic blood pressure was significantly lower among non-dippers compared to those with normal dipping pattern and reverse dippers. Similarly, average daytime systolic and diastolic blood pressures were significantly lower among non-dippers and reverse dippers compared to those with normal dipping pattern as shown in Table 3. Average night systolic and diastolic blood pressure were significantly higher among reverse dippers compared to those with normal dipping pattern and non-dippers. Night-time average systolic and diastolic blood pressures were significantly higher among reverse dippers compared to those with a non-dipping pattern and normal dipping pattern. Similarly, nighttime systolic blood pressure load > 120mmHg and night-time diastolic blood pressure load > 70mmHg were significantly higher among reverse dippers compared to others. In a similar vein, circadian systolic and diastolic blood pressure nights were significantly different between the three groups. Average daytime and nighttime pulse rate were not significantly different between the three study groups likewise, maximum systolic and diastolic blood pressures, and minimum systolic and diastolic blood pressure. as shown in Table 3.

Table 3.

Circadian ABPM profiles and BP values of study patients

variables	normal dippers(11)	non dippers (48)	reverse dippers (41)	ALL (n = 100)	P value
Age(years)	61.9(13.3	56.94(10.3)	61.3(10.5)	59.3(10.8)	0.117
BMI (kg/m2)	27.8(6.3)	27.4(5.3)	28.0(6.5)	27.7(5.9)	0.900
ALL BP AVR SBP	130.2(11.9)	122.9(12.0)	129.8(12.6)	126.5(12.6)	0.019*
ALL BP AVR DBP	79.3(8.6)	74.0(7.0)	75.8(7.1)	75.3(7.4)	0.085
DAY SYST BP AVR	136.3(12.1)	124.8(12.3)	125.0 (4.1)	126.2(13.8)	0.034*
DAY DIAST BP AVR	83.7(8.3)	76.4(7.8)	74.8(7.3)	76.5(8.0)	0.004*
NIGHT AVR SYST	116.8(9.8)	119.3(12.0)	135.6(14.0)	125.7(15.0)	0.000*
NIGHT AVR DIAST	69.8(7.3)	69.6(6.8)	77.0(7.9)	72.7(8.1)	0.000*
DAY SBP LOAD > 135	48.4(30.8)	28.3(23.9)	31.9(25.5)	32.0(25.8)	0.066
DAY DBP LOAD > 85	42.9(24.4)	21.8(20.0)	20.3(19.5)	23.5(21.2)	0.005*
NIGHT SBP LOAD > 120	42.3(26.5)	42.8(34.2)	72.8(29.0)	55.1(34.5)	0.000*
NIGHT DBP LOAD > 70	36.0(13.7)	42.6(25.8)	69.7(23.9)	53.0(27.7	0.000*
MAX SBP	178.5(28.7)	170.9(23.0)	177.7(20.7)	174.5(22.8)	0.315
MAX DBP	125.5(26.4)	122.4(25.9)	119.6(22.7)	121.6(24.5	0.743
MIN SBP	93.2(12.7)	91.0(26.0)	87.2(21.4)	89.7(23.0)	0.643
MIN DBP	51.2(9.9)	44.8(13.1)	44.0(14.6)	45.2(13.5)	0.283
CIRC RHYTHM BP SYST NIGHT	14.3(1.9)	7.6(12.2)	(-)5.5(5.0	3.2(11.7)	0.000*
CIRC RYTH DBP NIGHT	16.5(3.6)	10.0(7.7)	(-)1.6(7.9)	6.1(9.9)	0.000*
BP CV ALL SYST	13.3(1.9)	12.7(3.6)	13.1(3.2)	12.9(3.2)	0.802
BP CV ALL DIAST	20.0(3.6)	18.5(5.8)	18.2(5.6)	18.6(5.5)	0.633
BP CV DAY SBP	11.2(2.4)	13.7(4.7)	13.8(3.6)	13.5(4.1)	0.149
BP CV DAY DBP	18.0(4.1)	19.9(6.8)	19.4(6.4)	19.5(6.4)	0.691
BP CV NIGHT SBP	11.2(3.9)	8.7(2.3)	9.4(4.2)	9.3(3.4)	0.086
BP CV NIGHT DBP	18.6(7.6)	11/4(2.6)	12.6(5.5)	12.7(5.1	0.000*
AVR PULSE RATE DAY	85.4(5.7)	85.3(9.8)	81.9(10.3)	75.5(10.3)	0.229
AVR PULSE RATE NIGHT	72.3(6.0)	76.9(9.3)	74.8(12.3)	75.5(10.3)	0.353

Key to table: BMI-body mass index, BP-Blood pressure, AVR-Average, SYST-systolic, DIAST-Diastolic, SBP-systolic blood pressure, DBP-diastolic blood pressure, CIRC-circadian

Table 4 shows the multiple regression analysis of the determinants of non-dipping status in the study participants. The major determinants of abnormal blood pressure dipping pattern in the study population were shown to be the duration of diabetes diagnosis in years) and low high-density lipoprotein concentration.

Table 4.

Multiple regressions analysis of the determinants of non-dipping status

Variables	B	S.E.	Wald	df	Sig.	Exp(B)	95% C.I.for EXP(B)Lower	Upper
AGE(YRS)	-0.108	0.073	2.212	1	0.137	0.898	0.779	1.035
BMI	0.172	0.109	2.51	1	0.113	1.188	0.96	1.47
duration of dm(years)	0.725	0.35	4.289	1	0.038*	2.066	1.04	4.104
PULSE RATE	-0.096	0.077	1.538	1	0.215	0.908	0.781	1.057
Postural SBP Drop	0.083	0.081	1.062	1	0.303	1.087	0.928	1.273
Postural DBP Drop	-0.023	0.11	0.046	1	0.831	0.977	0.788	1.211
HbA1c	0.069	0.331	0.043	1	0.835	1.071	0.56	2.048
LDL-C	-0.299	0.501	0.356	1	0.551	0.742	0.278	1.979
HDL-C	-1.173	0.534	4.831	1	0.028*	0.309	0.109	0.881
TOTAL-C	0.413	0.406	1.035	1	0.309	1.511	0.682	3.35
SERUM CR	0.034	0.029	1.412	1	0.235	1.035	0.978	1.094
LVDD(mm)	-0.25	0.149	2.801	1	0.094	0.779	0.582	1.044
IVST(mm)	-0.046	0.348	0.018	1	0.894	0.955	0.483	1.887
RAV (cm2)	0.003	0.193	0	1	0.987	1.003	0.688	1.463
Constant	17.544	13.84	1.608	1	0.205	41622143.7

Variable(s) entered on step 1: AGE(YRS), BMI, duration of dm(years), PULSE RATE, Postural SBP Drop, Postural DBP Drop, HbA1c, LDL-C, HDL-C, TOTAL-C, SERUM CR, LVDD (mm), IVST(mm), RAV (cm2)

Discussion

Ambulatory blood pressure monitoring (ABPM) seems to be a stronger prognostic tool than clinic measurement and predicts mortality better than clinic measurement [2, 4, 8]. This study revealed that abnormal BP dipping status is very common among T2DM patients in Ogbomoso, Nigeria as more than four-fifths (89%) were abnormal dippers consisting of 41% reverse dippers and 48% non-dippers. Abnormal BP dipping status was frequently more associated with the female gender and those with abnormal BP dipping pattern has significantly reduced left ventricular fractional shortening, and a higher degree of left ventricular diastolic dysfunction evidenced by significantly reduced E/A ratio and left atrial volume. They also had a significantly higher left ventricular mass index compared to those with normal blood pressure dipping status. This study also showed a significant association between the duration of diagnosis of diabetes mellitus and abnormal blood pressure dipping pattern suggesting that as the duration of diagnosis increases, the likelihood of developing abnormal blood pressure dipping pattern increases substantially. The frequency of abnormal BP dipping status reported in this study is far higher than what has been reported among other populations where prevalence varies between 54.2% and 64.2% were reported from various parts of the world [15–18]. The very high preponderance of abnormal BP dipping status may be an underlying risk factor for the increased cardiovascular risk associated with the Black race and may likely be genetic. In the CREOLE study, a prevalence of non-dipping of 78% was also reported among hypertensive subjects [19].

Abnormal BP dipping status is associated with blood pressure-related organ damage and poorer long-term outcomes [20–22]. The presence of a non-dipping pattern may be useful to assess risk, initiate specific treatment, or the use of specific pharmacotherapy. Diabetes is associated with abnormal BP dipping status than many other cardiovascular diseases as it has been shown to be more prevalent in DM than many other CV risk factors such as hypertension.;22]. This is because autonomic neuropathy is a significant complication of long-term Type 2 DM which contributes to the diurnal variation of BP. Diabetic neuropathy has been shown to be closely associated with abnormal ambulatory blood pressure profile in diabetes mellitus patients including abnormal blood pressure dipping status [23]

Hypertension is a common comorbidity in diabetes mellitus patients present in up to 75% of all patients in Nigeria [24, 25] Strict blood pressure control in addition to blood glucose control in accordance with conventional guidelines remains the major cornerstone for the management of micro and macrovascular complications of diabetes [26]. Ambulatory blood pressure monitoring gives information on nocturnal blood pressure and circadian blood pressure rhythm, which have been shown to have prognostic significance independent of BP control [27, 28].

De la Sierra et al. demonstrated that type 2 diabetes mellitus was independently associated with non–dipping in a cohort of 34,563 treated and 8384 untreated hypertensive patients in a registry-based study [29]. Ukkola et al. also demonstrated this association in patients with impaired glucose tolerance [30] and Lyhne et al. in newly diagnosed type 2 diabetics [31]. A similar pattern in prevalence was demonstrated in a study by Ayala et al [32].

The pattern seen in this study was underpinned by many specific ambulatory blood pressure monitoring values. Those with blunted dipping pattern and reversed dipping pattern were different in many ABPM values including 24-hour average systolic blood pressure, daytime average systolic and diastolic blood pressure, nighttime blood pressure load > 120mmHg and > 70mmHg diastolic blood pressure. These are also independent determinants of cardiovascular risk and collectively add further information to cardiovascular risk stratification and monitoring [3, 12].

The etiology of non-dipping has been linked to hypertension, renal function impairment and altered nocturnal sympathovagal balance associated with cardiovascular autonomic neuropathy (CAN) [33, 34] CAN is an independent predictor of CVD mortality and CVD events in diabetes [34]. Poor glucose control, as documented by HbA1clevels is considered the main factor driving the development of diabetic complications including CAN in patients with diabetes. Emerging evidence suggests that wide glucose fluctuations may play an important role in the development of chronic complications, including CAN, independent of HbA1c. This study also demonstrated that abnormal dippers are more likely to be females, and had a higher glycated haemoglobin suggesting poorer glucose control, lower ejection fraction, and a higher chance of left ventricular diastolic dysfunction due to the significantly lower E/A ratio and increased left atrial volume.

Morning blood pressure surge (MBPS) is another component of BP variability. High values have been shown to independently increase the risk of cardiovascular diseases (CVDs). This was evident in the study population where a nocturnal increase in blood pressure was demonstrated and a significant proportion of night-time systolic/diastolic blood pressure was greater than the cut-off of 120/70mmHg [35, 36]. There are 3 definitions for MBPS including sleep-trough surge, pre-waking surge, and rising surge. Sleep trough surge is one of the dynamic diurnal surges during the specific period from sleep to early morning. Prewaking surge is the BP change occurring 4 h before and after arising. The rising surge may detect the morning risk just after arising [37].

24-hour ambulatory blood pressure monitoring can detect early stages of cardiovascular target organ damage in patients with T2DM. Left ventricular hypertrophy and functional vascular organ damage has been reported in diabetic patients with abnormal dipping status in ABPM profile [38]. This was evident in this study as the frequency of left ventricular hypertrophy, and impaired kidney function were significantly higher among those with abnormal dipping patterns compared with normal dippers. In a similar vein, postural hypotension, history of intermittent claudication, and the presence of carotid plaques on carotid Doppler studies were significantly higher among those with abnormal dipping patterns compared to those with normal dipping pattern in the study group. Atherosclerotic disease of the coronary and carotid arteries is the primary global cause of significant mortality and morbidity [39].

Postural (Orthostatic) hypotension is a cardinal sign of cardiovascular (CV) autonomic dysfunction as a result of autonomic nervous system failure to control the postural hemodynamic homeostasis. The proportion of individuals with OH increases with aging and chronic conditions including diabetes and hypertension [40]. These among others, further suggest that T2DM subjects with abnormal dipping patterns are at increased cardiovascular risk compared to those with normal dipping pattern.

The two most important determinants of abnormal dipping pattern in this study were found to be the duration in years of diabetes, the longer the duration the more likely the chance of developing abnormal BP dipping pattern and the HDL-C concentration. There was an inverse relationship between HDL-C and the risk of abnormal BP dipping in this population. While low HDL-c is an established cardiovascular risk, [41] its association with abnormal dipping pattern is not well described in the literature and this study may provide the first set of information as to the relationship between low HDL-C and abnormal dipping patterns in T2DM subjects. The conclusions from this study are similar to what was shown in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, a randomized controlled trial in patients with type 2 diabetes, age or age at diagnosis and diabetes duration were independently associated with macrovascular events and death whereas only diabetes duration is independently associated with microvascular events and this effect is greater in the youngest patients [42]. The import of this study revealed that the majority of diabetes mellitus patients in this environment may be at poor cardiovascular risk based on the abnormal blood pressure dipping pattern and may be at future risk of cardiovascular disease if care is not taken. It is therefore essential that ambulatory blood pressure monitoring be routinely advocated to identify diabetics at increased risk for early intervention with the aim of improving the prognosis of diabetes mellitus especially in sub-Saharan Africa. This study is not without some limitations, firstly is the fact that the study design may not directly confer a causality effect on the observed cardiovascular risk factor markers and for this, a prospective longitudinal study may be more relevant. It is also a hospital-based study and the tendency to have seen the larger spectrum of patients with increased risk is without doubt a limiting factor in generalizing the result totally to the general population. Similarly, the impact of drugs on these observed differences were also not studied.

Conclusion: This study revealed that abnormal blood pressure dipping pattern is highly prevalent in T2DM subjects, especially among females. It also revealed that abnormal dipping pattern was associated with markers of increased cardiovascular risk among diabetes mellitus subjects which include impaired kidney function, left ventricular hypertrophy, postural hypotension, history of intermittent claudication, and presence of plaques on carotid Doppler studies. The study further revealed that the duration of diabetes and low HDL-C concentration were the major determinants of abnormal dipping patterns. The implication of these findings is that diabetics with abnormal dipping patterns are at increased cardiovascular risk and should be screened for and appropriately intervened to wholistically reduce the burden of cardiovascular disease in Type 2 diabetes mellitus patients. Further prospective studies to demonstrate the prognostic impact of abnormal dipping status in T2DM subjects and further highlight the associations with cardiovascular risk are therefore necessary.

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Declarations

Competing interests

None.