| Abstract|| |
Diabetes mellitus (DM) is now considered as the major cause of end-stage kidney failure, and hypertension (HTN) is one of the main determinants of progression of renal disease. The aim of this study was to assess the role of blood pressure (BP) by ambulatory blood pressure monitoring (ABPM) in children and adolescents with type-1 DM and its correlation with micro-albuminuria (MA) and diabetic control. Eighty-one patients with type-1 DM (mean age 13 ± 4 years), whose duration of DM was at least two years, were enrolled in this study. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. The pattern of HTN was as follows: mean systolic HTN 27.2%, mean diastolic HTN 11.2%, daytime systolic HTN 17.3%, daytime diastolic HTN 6.2%, night systolic HTN 30.9%, and night diastolic HTN 29.7%. The systolic and diastolic BP loads were 33.4 and 27.2%, respectively. About 70.4% of the patients were non-dippers, 12.4% had masked HTN, and 3.7% had white coat HTN. The prevalence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. There was no correlation between HTN and both MA and HbA 1 c; also, no correlation was found between the duration of diabetes and HbA 1 c. Moreover, no significant correlation was found between the duration of diabetes and MA (P = 0.080). Despite the high prevalence of abnormal BP profile among diabetic children, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have an impact on the progression to diabetic nephropathy, are recommended.
|How to cite this article:|
Basiratnia M, Abadi SF, Amirhakimi GH, Karamizadeh Z, Karamifar H. Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria. Saudi J Kidney Dis Transpl 2012;23:311-5
|How to cite this URL:|
Basiratnia M, Abadi SF, Amirhakimi GH, Karamizadeh Z, Karamifar H. Ambulatory blood pressure monitoring in children and adolescents with type-1 diabetes mellitus and its relation to diabetic control and microalbuminuria. Saudi J Kidney Dis Transpl [serial online] 2012 [cited 2015 Nov 30];23:311-5. Available from: http://www.sjkdt.org/text.asp?2012/23/2/311/93164
| Introduction|| |
Diabetic nephropathy (DN) is a major complication of type-1 diabetes mellitus (DM) that leads to chronic kidney disease in many pa-tients. , In patients with type-1 DM, diabetic kidney disease almost certainly begins soon after the diagnosis of diabetes and may accelerate during adolescence.  Clinically detectable DN begins with the development of microalbumi-nuria (MA). However, early renal dysfunction may be overlooked despite the use of this parameter and normal-range albuminuria does not exclude nephropathy in diabetic children.  Hypertension (HTN) and MA are considered the major cardiovascular risk factors in young patients with type-1 DM.  Many studies have demonstrated that strict control of blood glucose level and blood pressure (BP) significantly reduces the incidence and progression of diabetic kidney disease.  Ambulatory blood pressure monitoring (ABPM) is the method of choice for the diagnosis and therapeutic monitoring of arterial HTN that permits the observation of BP throughout day and night in a non-medical environment, thereby allowing evaluation not only of casual daytime elevations of BP but also of alterations in the 24hour circadian patterns of BP. , ABPM may help to predict development of DN in pediatric patients with type-1 diabetes of recent onset.  The aim of this study was to assess the mean pressure values and BP parameters by ABPM in children and adolescents with type-1 DM and to assess its correlation with MA and diabetic control.
| Patients and Methods|| |
A total of 106 children and adolescents with type-1 DM with at least two years history of presence of DM, who were on follow-up at the endocrine clinic, Shiraz University of Medical Sciences, were eligible for this study. Out of the 106 patients who fulfilled the enrolment criteria and agreed to participate, 81 (76.4%) completed the study. The exclusion criteria were as follows: duration of diabetes less than two years, age less than seven years or more than 20 years, and chronic systemic diseases other than diabetes. Written informed consent was obtained from the children or their parents before the study. The study was approved by the local ethics committee. Data collected included age, gender, weight, height, and duration of diabetes.
MA was determined from three separate 24hour urine samples collected within at least one month interval. The patients were asked to avoid physical activity and had to be afebrile on the day of urine collection. Urinary albumin excretion was measured by the nephelometric method. Excretion of 30-300 mg/day of albumin in the urine in at least two of three samples was considered as MA. Venous blood for testing HbA 1 c levels was drawn from each study participant three times within at least three months interval. Their mean was considered as an index of long-term glycemic control. The levels above the accepted target, based on the age of the patient, were considered ab-normal. 
Office BP was measured by the auscultation method using a mercury sphygmomanometer (three recordings after five min rest in sitting position from the right arm with appropriately sized cuff), on the day of ABPM. The mean of the three readings was recorded as the office BP.
To compensate for the differences in age and body size, the BP records were indexed by dividing the measured value into age-, sex-, and height-specific 95 th BP percentile, using standardized tables.  The subjects were considered hypertensive when the indexed BP was equal to or more than 1.0. For patients older than 18 years of age, the normal systolic BP (SBP) and diastolic BP (DBP) were set at 140 and 90 mmHg, respectively. Ambulatory recordings were taken with Suntech Oscar II (Morrisville, NC, USA). Cuff size was determined by the measurement of mid-arm circumference. The device was set to take the measurements every 20 min during the day (07:00 to 22:00 hours) and every 30 min during sleep (22:00 to 07:00 hours). The patients were instructed to rest or sleep between 22:00 and 07:00 hours and to maintain their usual activities between 07:00 and 22:00 hours and to avoid heavy physical exercise. The patient or parents were asked to keep a diary to record the 24-hour events including the awake and asleep times. At least 40 readings were considered satisfactory for analysis. Ambulatory BP data (24-hour systolic and diastolic, daytime, and nighttime) were compared with European norms  and indexed by dividing each value into gender- and height-specific 95 th BP percentile. The BPI ≥1 means that the systolic or diastolic value is more than 95 th percentile for gender and height. HTN was defined as daytime and/or nighttime SBP or DBP ≥95th percentile for healthy children based on sex and height using standardized tables.  Elevated BP load was defined as more than 30% of the recordings of systolic/diastolic measurements equal to or more than the 95th percentile for sex and height, respectively. The patients were classified as dippers if the mean SBP and/or DBP decreased 10% or more during the sleep period and this was calculated as follows: (mean daytime - mean nighttime/ mean daytime) × 100. The subjects with a nighttime drop of SBP or DBP less than 10% of daytime values were considered non-dippers.
| Statistical Analysis|| |
Data analysis was performed by SPSS-15. The results were expressed as frequencies or mean and standard deviation. Comparison of means and proportions was performed by Student's t-test and Chi-square, respectively. Pearson correlation coefficient was used to determine the association between the subgroups. A P value of 0.05 was considered as statistically significant.
| Results|| |
Data of 81 patients (32 males, 49 females) were analyzed. The mean age of the patients was 14.3 ± 4 years (7-20 years), and duration of diabetes was 5.7 ± 3.2 years (2-16 years). The prevalence of MA was 34.6% and that of abnormal HbA 1 c was 82.7%. The prevalence of HTN based on ABPM was 28.4%, while by casual method it was 32.1%. Among the 26 patients (32.1%) who were hypertensive with the casual method, systolic HTN was seen in 15, diastolic HTN in two, and both systolic and diastolic HTN were seen in nine patients. ABPM identified 23 patients (28.4%) with high BP. Fifty-eight patients (71.6%) were normotensive by ambulatory measurement. The pattern of HTN was as follows: mean systolic HTN in 27.2%, mean diastolic HTN in 11.2%, day systolic HTN in 17.3%, day diastolic HTN in 6.2%, night systolic HTN in 30.9%, and night diastolic HTN in 29.7%. The SBP and DBP loads were 33.4 and 27.2%, respectively. Non-dipping was identified in 57 patients (70.4%). Fifty-six patients (69.1%) were systolic non-dippers and 33 (40.7%) were dias-tolic non-dippers. The prevalence of masked HTN (office normotensive and ambulatory hypertensive) was 12.4% and that of white coat HTN (WCH) (office hypertensive and ambulatory normotensive) was 3.7%. No correlation was found between HTN and MA or HbA 1 c. Also, no correlation was observed between non-dippers and MA or HbA 1 c. Similarly, no correlation was found between duration of diabetes and HbA 1 c and also between duration of diabetes and MA (P = 0.080).
| Discussion|| |
Our study showed a high prevalence of both casual and ambulatory HTN (32.1 and 28.4%, respectively) and non-dipping (70.4%) in children and adolescents with DM. There was no difference between normotensive and hypertensive patients regarding diabetic control and presence of MA.
Our data are in accordance with those of Glowinska et al  who reported the presence of HTN in about one-third of the diabetic patients. Balkau et al  demonstrated a lower prevalence of HTN in patients (2% in boys and 7% in girls) with type-1 DM. Although Darcan et al  demonstrated a higher prevalence of HTN by ABPM compared with casual method, Sulakova et al  detected higher numbers of hypertensive patients by the casual method (51% vs 29%), and it was the same in our study (32.1% vs 28.4%). This difference could be due to the white coat effect in the last two studies. The prevalence of WCH and masked HTN was 3.7 and 12.4%, respectively, in our study. Sulakova et al  and Kotsis et al  found more patients (32 and 17.9%, respectively) with WCH as compared with our results, but the frequency of masked HTN in the present study was not much different from that reported by others. ,, WCH is a risk factor for the development of future persistent HTN and masked HTN is an independent risk factor for cardio-vascular morbidity, and neither can be evaluated by office BP measurements. ,
We noticed a higher prevalence of nocturnal HTN compared to daytime HTN (37% vs 17.3%). Similar findings have been reported by Sulakova et al  and Dost et al.  This feature shows the advantage of ABPM for demonstrating the abnormal BP during sleep. Nocturnal HTN is a risk factor for DN as shown by Guntsche et al  and Darcan et al. 
In our study, the nighttime BP load was higher compared to daytime load (55.6% vs 28.4%). Higher nocturnal BP load leads to serious consequences such as progression of DN. Darcan et al  have shown that DBP load has a positive correlation with MA, HbA 1 c, and duration of diabetes. Guntsche et al  have demonstrated the changes in nocturnal BP before the development of MA, and this event again emphasizes the superiority of detection of nocturnal BP by ABPM.
Our study showed a high incidence of non-dipping in patients with type-1 DM (81.5%). Numerous studies have shown that non-dipping is highly prevalent in patients with type-1 DM. ,,,, Non-dipping has been related to an increase in target organ damage such as DN and cardiovascular events.  Auto-nomic neuropathy is a factor of importance for the reduced dipping at night, which results in an increase in intra-glomerular pressure. Long-term increase in intra-glomerular pressure might damage the glomerular basement membrane and cause mesangial expansion. The final result is nephropathy. 
Several studies have shown a correlation between MA and non-dipping ± HTN. ,,, Guntsche et al  showed that DBP load was higher in children with MA. This was in line with other studies that evaluated the relationship between MA and HTN. ,, Darcan et al  found a greater degree of MA in non-dippers versus dipper patients (63.6% vs 41.2%). However, in the present study, we could not confirm the above correlations, and one should take into account that HTN is not the only risk factor for development of DN and other important risk factors such as genetic factors have considerable impact on the development of DN.
Kowalewski et al  and Chatterjee et al  have reported more abnormal ABP profiles in patients with poor glycemic control, but we could not demonstrate this association. This discrepancy might be the result of not taking into account the impact of parental history of HTN and different hereditary patterns among our patients in comparison with the earlier studies. Guntsche et al  have shown that hy-perglycemia accelerates the phenotypic expression of hypertensive inheritance in diabetic children.
The current study has some limitations; it is not a prospective longitudinal trial showing the evolution of MA, has a small sample size, and did not consider the other risk factors for DN and parental HTN.
In conclusion, the current study revealed a high prevalence of abnormal BP profile, poor diabetic control, and MA in diabetic patients. Regarding the finding of lack of association between HTN, HbA 1 c, and MA, prospective longitudinal studies considering the other major risk factors, particularly genetic factors, which have impact on tracking the progression to DN are recommended.
| References|| |
|1.||Lengel Z, Rosivall L, Nemeth C, et al. Diurnal blood pressure pattern may predict the increase of urinary albumin excretion in normotensive normoalbuminuric type 1 diabetes mellitus patients. Diabetes Res Clin Pract 2003;262: 159-67. |
|2.||Torun B, Georg A, Ulla B. Nondipping and Its Relation to Glomerulopathy and Hyperfiltra-tion in Adolescents with Type 1 Diabetes. Diabetes Care 2004;27:510-6. |
|3.||Zachwieja J, Soltysiak J, Fichna P, et al. Normal range albuminuria does not exclude neph-ropathy in diabetic children. Pediatr Nephrol 2010;25:1445-51. |
|4.||Cobuz C, Datcu G. Relationship of hypertension and microalbuminuria in type 1 diabetes. Rev Med Chir Soc Med Nat Lasi 2010;114:52-8. |
|5.||Atkins RC, Zimmet P. Diabetic kidney disease: act now or pay later. Pediatr Nephrol 2010;25: 181-4. |
|6.||Wuhl E, Witte K, Soergel M, Mehls O, Schaefer F. Distribution of 24-h ambulatory blood pressure in children: normalized reference values and role of body dimensions. J Hypertens 2002;20:1995-2007. |
|7.||Ruiz Pons M, Garcia Nleto V, Garcia MG, Garcia Merida M, Valenzuela Hdez C, Aguirre-Jaime A. Reduced nocturnal systolic blood pressure dip in obese children. Nephrologia 2008;28:517-24. |
|8.||Guntsche Z, Saravi FD, Reynalds EA, Rauek B, Rauek M, Guntsche EM. Parentral hypertension and 24 h-blood pressure in children prior to diabetic nephropathy. Pediatr Nephrol 2002;17:157-64. |
|9.||Alemzade R, Wyatt DT. Diabetes Mellitus in Children. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF. Nelson textbook of Pediatrics. Saunders, Philadelphia, 2007; 2404-31. |
|10.||Glowinska B, Urban M, Peczynska J, Florys B, Szydlowska E. Elevated concentration of homocysteine in children and adolescents with arterial hypertension accompanying type I diabetes. Med Sci Monit 2001;7:1242-9. |
|11.||Balkau B, Tichet J, Caces E, Vol S, Eschwege E, Cahance M. Insulin dose and cardiovascular risk factors in type I diabetic children and adolescents. Diabetes Metab 1998;24:143-50. |
|12.||Darcan S, Goksen D, Mir S, et al. Alteration of blood pressure in type I diabetic children and adolescents. Pediatr Nephrol 2006;21:672-6. |
|13.||Sulakova T, Janda J, Cema J, et al. Arterial HTN in children with T1DM frequent and not easy to diagnose [abstract]. Pediatr Diabetes 2009;10:441-8. |
|14.||Kotsis V, Stabouli S, Toumanidis S, et al. Target organ damage in white coat hypertension and masked hypertension. Am J Hypertens 2008; 21:393-9. |
|15.||Markuszewski L, Ruxer M, Szadkowska A, Bodalska J, Bissiger A. Evaluation of blood pressure changes by 24-hours ABPM in young, normotensive patients with diabetes mellitus type 1. Pol Merkur Lekarski 2006;20:32-5. |
|16.||Marcovecchio ML, Dalton RN, Schwarze CP, et al. Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes. Diabetologia 2009;52:1173-81. |
|17.||Sulakova T, Janda J. Ambulatory blood pressure in children with diabetes 1. Pediatr Nephrol 2008;23:2285-6. |
|18.||Dost A, Klinkert C, Kapellen T, et al. Arterial hypertension determined by ambulatory blood pressure profiles: Contribution to microalbu-minuria risk in a multicenter investigation in 2105 children and adolescents with diabetes mellitus type 1. Diabetes care 2008;31:720-5. |
|19.||Cuspidi C, Vaccarella A, Leonetti G, Sala C. Ambulatory blood pressure and diabetes: targeting nondipping. Curr Diabetes Rev 2010; 6:111-5. |
|20.||Kowalewski M, Peczvnska J, Glowinska B, Urban M, Urban B, Florys B. The assessment of 24-hour ABPM, microalbuminuria and diabetic autonomous neuropathy in children with type 1 diabetes and hypertension. Endokrynol Diabetol Chor Przeminay Materii Wicku Rozw 2006;12:103-6. |
|21.||Chatterjee M, Speiser PW, Pellizzarri M, et al. Poor glycemic control is associated with abnormal changes in 24-hour ambulatory blood pressure in children and adolescents with type I diabetes mellitus. J Pediatr Endocrinol Metab 2009;22:1061-7. |
Pediatric Nephrology Ward, Nemazee Hospital, Shiraz University of Medical Sciences, Shiraz