Relation between Blood Pressure Control and Insulin Secretion Markers among Elderly Diabetic Females

High geriatric population means a higher number of patients with various chronic diseases and increasing percentage of lifetime health care costs are accounted for this population. Longevity will have a greater chance of developing diseases that occur more commonly during later life; many individuals will also live with chronic illnesses 3 . Of all the diseases, diabetes mellitus is one of the most common diseases affecting a large number of elderly populations along with hypertension which play a major role on the quality of life of the elderly and the healthcare costs. Centers for Disease Control and Prevention (CDC) suggest that the prevalence of diabetes will double in the next 20 years, in part due to the aging of the population 4.


Background
Ageing is a universal phenomenon; almost 5.3% of the entire population is a major concern to health economists 1 .By 2020 it will be 177 million elderly people, aged above 60 years.Ageing process is as such complex and multi-factorial.Chronic morbidities like diabetes and hypertension are becoming common health problems among the geriatric population 2 .
High geriatric population means a higher number of patients with various chronic diseases and increasing percentage of lifetime health care costs are accounted for this population.Longevity will have a greater chance of developing diseases that occur more commonly during later life; many individuals will also live with chronic illnesses 3 .Of all the diseases, diabetes mellitus is one of the most common diseases affecting a large number of elderly populations along with hypertension which play a major role on the quality of life of the elderly and the healthcare costs.Centers for Disease Control and Prevention (CDC) suggest that the prevalence of diabetes will double in the next 20 years, in part due to the aging of the population 4. C-peptide concentrations in the peripheral blood are widely accepted as the most appropriate measure of insulin secretion because it is secreted in equimolar amounts with insulin and is not removed in the first pass through the liver 5,6 Moreover, evidence indicates that Cpeptide is not merely an inactive by-product of insulin biosynthesis but also a hormonally active peptide itself 7- 9 .C peptide index (CPI) could be used as an index of endogenous insulin secretion, it is not affected by exogenous insulin therapy, hence its value in patients with insulin therapy 14 .
The aim of this study was to identify the prevalence of hypertension and to evaluate the relationship between glycemic control and insulin secretion abilities and control of hypertension among Egyptian elderly diabetic female patients.

Method:
This study is a descriptive cross-sectional study.One hundred and sixty three elderly diabetic females were recruited from the first of October 2014 to the end of March, 2016 from Inpatient wards of Ain Shams University Hospital.
After obtaining an informed consent, all participants underwent careful history taking including history of DM and hypertension.All included patients were diabetics on antidiabetic treatment and the associated hypertension was evaluated based on history of hypertension, being on antihypertensive medications and on blood pressure measurement with a calibrated sphygmomanometer at resting state, hypertension was defined as a systolic pressure above or equal 140 mmHg and/or a diastolic pressure above or equal 90 mmHg 15 .Accordingly, participants were divided into 2 groups hypertensive and normotensives, and based on the current blood pressure, hypertensive patients further divided into 4 groups: the first 2 groups included patients with controlled and uncontrolled systolic blood pressure, and the second 2 groups included patients with controlled and uncontrolled diastolic blood pressure.Then comparison was done between each of the 2 groups of patients as regards fasting blood sugar and insulin secretion indicators.
All patients underwent assessment of glycemic control by fasting blood sugar estimation utilizing enzyme technique with gluco-oxidasis.We used fasting serum Cpeptide and CPI as indicators for insulin secretion, accordingly fasting serum C-peptide and CPI measurement were done for each participant.Blood samples were withdrawn during fasting state after about 8 hours fasting, then collected into plain tubes and centrifuged to separate serum that is stored at -70°C until analysis then referred to Ain shams university hospital blood lab for determination of fasting serum C-peptide level using C-peptide kits manufactured by DRG instruments GmbH, Marburg, Germany and were analyzed by ELISA methods.The C-peptide index (CPI) was calculated for all participants with the following formula: fasting C-peptide (ng/ml)/fasting glycemia (mg/dl) × 100 16,17 .

Statistical method
Values were presented as means + SD or as numbers and proportions, as appropriate.The relations between qualitative variables were evaluated by Chi-square test or Fisher's exact test, as indicated.Means were compared with Student's test or analysis of variance.Quantitative variables were correlated with the use of coefficient of correlation "r".All tests were bilateral and a P value of 0.05 was the limit of statistical significance.Analysis was performed by statistical package software IBM-SPSS for MAC, version 24.
Based on blood pressure control, there was statistically significant difference between controlled and uncontrolled diastolic blood pressure as regard means of serum C peptide level and CPI (p<0.001).The mean serum levels of C peptide ng/ml and CPI were (3.33±3.91 and 2.25±3.13)versus (2.02±2.86 and 1.35± 1.84), respectively.Patients with controlled diastolic blood pressure had significantly higher C peptide (P=0.036) and CPI values (P=0.037),compared to uncontrolled patients (Table 4).
Upon comparison between means of serum C peptide level and CPI in both groups of systolic blood pressure, there was statistically significant difference between controlled and uncontrolled systolic blood pressure (p<0.001).The mean serum levels of C peptide (ng/ml) and CPI were (3.44±4.07and1.80±2.31)vs (2.02±3.19 and 1.13± 1.44), respectively (Table 5).

Discussion
Hypertension is a common comorbidity among persons with diabetes and its prevalence increases with advancing age.In diabetic people, hypertension is a major risk factor for cardiovascular disease.Elderly patients with hypertension and DM have an increased mortality risk than similarly aged controls without DM.The United Kingdom Prospective Diabetes Study blood-pressure trial demonstrated the benefits of more intensive blood pressure control in individuals with type 2 diabetes.Hence, detection of hypertension amongst the diabetics and maintaining its control is essential for reducing mortality of these patients 18,19 In this study, the concentrations of fasting serum C peptide level and CPI value were used as surrogate markers of beta-cell function, as serum C-peptide level is   commonly considered an index of insulin secretion, it is higher in the elderly persons than young population 20 that is consistent with our finding of the statistically significant positive correlation between serum C peptide and age.We have 82.8% elderly diabetic female patients who are hypertensive, and about 66.3% had uncontrolled blood pressure which is consistent with Jain and Paranjape, 2013 who found that 80% of studied diabetic elderly population were hypertensive 4 .
This study examined difference between hypertensive and normotensive elderly diabetic female patients in fasting serum blood sugar, C peptide level and CPI value, in addition to the association between poor blood pressure control and poor glycemic status and / or lower insulin secretion markers.Both serum C peptide and CPI could be used as surrogate markers for endogenous insulin secretion and pancreatic beta cells function 14 that is supported by our finding of the statistically significant positive correlation between serum C peptide and CPI.
We could not demonstrate significant association between control of blood pressure and glycemic status assessed by FBS.While other studies showed significant association between glycemic control and blood pressure in elderly diabetic patients such as Yoda et al. 24 who examined association between glycemic control and morning blood pressure in 50 elderly diabetic patients and showed significant association between morning blood pressure surge and poor glycemic control including higher fasting blood sugar and HbA1c.This study did not show significant difference between hypertensive and normotensive elderly diabetic female patients as regards glycemic control and insulin secretion markers, but showed significant differences between elderly patients with uncontrolled and controlled systolic and diastolic blood pressure in fasting serum C peptide level and CPI value this agreed with a population based study that found that elderly diabetic female patients with controlled systolic and diastolic blood pressure had significantly higher fasting serum c peptide level and CPI value indicating better pancreatic beta cells function and higher insulin secretory abilities , supporting the beneficial effects of C-peptide in attenuating the proatherogenic risk in diabetes by inhibiting insulin-induced neo-intima formation 9 .
Although some previous studies showed that increases in serum C-peptide are related to increases blood pressure 11, 13 .In a recent cross sectional study, 471 type 1 diabetic patients were followed from 1994 to 2004, subjects with the lowest fasting C-peptide levels were found to have the highest rate of micro vascular complications 10 .
In a large community-based survey of adults in china, was conducted by the Yang-Ming Crusade in 1992 and 1994 among a total of 1,447 men and 1,800 women (mean age 46.7 years), found that fasting C-peptide was significantly higher among hypertensive subjects in comparison to normotensives (p= 0.00) 22 .
Similarly, Gonzalez-Mejia et al. 23 found that C-peptide was significantly higher in insulin resistance syndrome subjects (P < 0.05) and C-peptide correlated with all components of insulin resistance syndrome including hypertension.
Further prospective studies are needed to confirm the association of C-peptide and hypertension, other micro and macro vascular complications in patients with diabetes and to elucidate the causal relationship between C-peptide and blood pressure in diabetes mellitus.Corresponding Author: Khalid E. Elsorady: khalid_elsorady1987@yahoo.com