International Journal of Nutrition, Pharmacology, Neurological Diseases

ORIGINAL ARTICLE
Year
: 2011  |  Volume : 1  |  Issue : 1  |  Page : 73--77

Effects of hydrochlorothiazide on K-dependent pancreatic response and the correlations with blood sugar, insulin in patients with essential hypertension


LM Hettihewa 
 Molecular Science and Biomedical Unit and Department of Pharmacology, Faculty of Medicine, University of Ruhuna, Sri Lanka

Correspondence Address:
L M Hettihewa
Molecular Science and Biomedical Unit and Department of Pharmacology, Faculty of Medicine, University of Ruhuna
Sri Lanka

Abstract

Context: To study the onset of the development of glucose intolerance and the mechanism by hydrochlorothiazide (HCT). Settings and Design: Hypertensive patients (n = 120) who were treated with captopril (CP) 25 mg daily were randomly divided into two groups. Materials and Methods: The control group was on captopril (n = 60) and the test group was given 25 mg HCT. They were followed for six months and the levels of fasting blood sugar (FBS), fasting insulin (FI) , and fasting potassium (FK) were analyzed, to calculate the correlation coefficient. Results: There were no significant correlations between FBS and FI or FI, with FK in both groups at baseline. The changes in the FBS or FI levels during the first three months were not significant in both the test and control groups. Reduction of FK was significant (P < 0.05) and had a positive correlation with FBS after three months (r = + 0.78, P < 0.05) in the test group. Correlations between FI and FBS or FK were not significant. FBS was significantly increased (P < 0.05) in the test group after six months. Both FI and FK had developed significant correlations with FBS in the HCT-treated group (r = - 0.71 with FI and r = + 0.77 with FK, respectively, P < 0.05) after six months. Reduction of FI was positively correlated with the FK test group (r = + 0.83, P < 0.05) after six months. Conclusions: HCT induced hypokalaemia in the early phase and developed hyperglycemia and hyperinsulinemia in the late phase. This suggested that HCT initially influenced pancreatic response to glucose, which was dependent on serum K and was probably mediated by hypoinsulinemia. We suggest large scale studies for further investigations on this relationship.



How to cite this article:
Hettihewa L M. Effects of hydrochlorothiazide on K-dependent pancreatic response and the correlations with blood sugar, insulin in patients with essential hypertension.Int J Nutr Pharmacol Neurol Dis 2011;1:73-77


How to cite this URL:
Hettihewa L M. Effects of hydrochlorothiazide on K-dependent pancreatic response and the correlations with blood sugar, insulin in patients with essential hypertension. Int J Nutr Pharmacol Neurol Dis [serial online] 2011 [cited 2022 Jun 24 ];1:73-77
Available from: https://www.ijnpnd.com/text.asp?2011/1/1/73/77536


Full Text

 Introduction



Prescribing diuretic medication especially thiazides (HCT) in the elderly population need special precautions. HCT, especially, leads to hyponatremia, hyperglycemia, and hypokalemia. [1],[2],[3] Various mechanisms for thiazide-induced hyponatremia have been proposed. [4],[5],[6] The principal mechanism is thought to be through a blockage of sodium chloride co-transport in the proximal part of the distal tubule, leading to excess sodium excretion. [7] The ongoing loss of sodium without adequate replacement and also the potassium loss in the urine are other contributory causes. [7],[8] Hyperglycemia due to HCT use is yet thought to be an idiosyncratic reaction. [9]

During the past decade several studies have shown that a large proportion of patients with hypertension, who were given with HCT, had developed hypokalemia and hyperglycemia as common side effects. [10] Treatment with β blockers or HCT had also increased insulin resistance,[5],[11] thereby increasing the risk of developing type 2 diabetes mellitus or impaired glucose tolerance in hypertensive patients. [5],[11]

A review of trials in which HCT was used as an antihypertensive treatment concluded that a definite association existed between diuretic treatment and the development of impaired glucose tolerance. [5],[10],[11] Although the association between glucose intolerance and HCT therapy was established, the exact underlying mechanism has yet not been established. The main objective of this study was to identify the mechanism of action of HCT on the development of glucose intolerance in non-diabetic patients. Medical scientists can plan therapeutic strategies to avoid the development of HCT-induced glucose intolerance in patients. After a literature survey, a hypothesis was made on the mechanism of glucose intolerance - that it could be due to the changes in pancreatic functions. Furthermore, we planned to analyze HCT-induced onset of glucose intolerance and the relationship of the development of glucose intolerance with the insulin and potassium levels in patients.

 Materials and Methods



The protocol for this study was approved by the Ethical Committee of the Faculty of Medicine, University of Ruhuna. Hypertensive patients (n = 120) who were treated with captopril (CP) 25 mg daily were randomly divided into two groups. The control group was only on captopril (n = 60) and the other group was given 25 mg HCT. The participants underwent a physical examination, including measurement of height, weight, and radial pulse rate. Overnight fasting blood samples were drawn for the analysis of FBS, FI, and FK. All the patients were given verbal and written information about the study. Clinical history, including age, sex, drugs, smoking and alcohol consumption, level of physical exercise, previous history of diabetes, coronary artery disease, and peripheral vascular disease were obtained. Family history of diabetes was ascertained. The exclusion criteria were age outside the range of 30 - 65 years, hypothyroidism, liver, kidney or heart failure, and neoplasm. They were followed for six months and the FBS (Diagnostica-merck), FI (ELISA - diagnostic automation), and FK Diagnostica-merck) were analyzed at monthly intervals.

Statistical analysis

For the descriptive statistics, after having checked the normality of the variables using the Kolmogorov-Smirnov test, the usual central and dispersion methods were used: average, standard deviation (SD), and 95% confidence interval (CI) power were carried out based on the results of the current study, comparing changes in FI, FK, and FBS for six months, allowing a declaration of the difference before and after, in same treatment group, at a significant level of alpha = 0.05, with a power of 80%. The statistical significance of differences between the means were evaluated using the paired Student's T-test in case of the normal distribution of data sets, and the Kolmogorov-Smirnov test when the normal distribution was excluded in at least one of the data sets. Correlation between two variables was studied with the Spearman rank-order. All statistical analyses were performed using Microcal origin 4.1 (2005) and Microsoft Excel, whenever applicable.

 Results



The changes in FBS and FI after the first three months of HCT therapy were not statistically significant both in the test and control groups [P > 0.05, [Table 2]]. In contrast, reduction of FK was statistically significant (P < 0.05) within three months.

[Table 1]. [Table 2] presents the means and standard deviations for baseline metabolic characteristics and changes in FBS, FI, and FK with 25 mg of HCT therapy in our study participants. There was no significant difference in weight, FBS, FI, or FK in the control or test groups.{Table 1}{Table 2}

Correlation between these parameters was also assessed after three months and there was no significant correlation between either FBS and FI or FI and FK, in both groups [Figure 1]a and b. {Figure 1}

In contrast, [Figure 2] shows the reduction of FK concentration in the HCT test group after three months. It was statistically significant (P < 005).

The reduction of FK in the study group was also statistically significant [Figure 3]b. In addition to that, FK also had a significant positive correlation with FBS at the end of three months in the HCT-treated group (r = +0.78, P < 0.001, [Figure 3]a). There was no significant correlation in the control group of patients (data not shown).{Figure 2}{Figure 3}

There was a significant reduction in FI and FK (P < 0.05, [Table 3]), and FBS was increased significantly in the HCT group after six months [Table 3]. On account of these observations, we extended our study to analyze any correlation between FK and FBS or FK andFI after six months of HCT therapy.

[Figure 4]a and b show that both FI and FK had significant correlations with FBS in the HCT-treated group (r = - 0.71 with FI and r = + 0.77 with FK, respectively. P < 0.05) at six months. Reduction of FI also had a positive correlation with the FK levels in the HCT-treated group (r = + 0.83, P < 0.05, [Figure 4]C), but not in the control.{Figure 4}{Table 3}

 Discussion



In this article we investigated the role of HCT therapy on FBS, FI, and FK levels in hypertensive patients. We observed that HCT therapy caused early reduction of FK before development of GI in the early phase. Changes in FBS and FI were not significant at the end of the third month. Our results showed that HCT-induced GI initially had a negative correlation with FK and later GI had a positive correlation with both FI and FBS.

The present experience suggests that HCT has caused early hypokalemia and late insulinopenia, which has reciprocally induced hypoglycemia. Although there are several original research data available on thiazide diuretic therapy, the correlation and mechanism of the development have not been analyzed by any other researchers. [12] Therefore, it is yet impossible to find out either supporting or contrasting data, for a comparison with our study.

We hereby strongly suggest that HCT first induced an initial pancreatic response in glucose, which could be dependent on serum K. It had led to the development of late hypoinsulinemia and hyperglycemia during the treatment of hypertensive non-diabetic patients.

In conclusion, the present study indicates that early reduction of FK levels can influence the metabolism of insulin in the pancreas and that initiates a disturbance in the glucose metabolism caused by hypoinsulinemia in the late stages. These disturbances of FK, FI, and FBS induced by HCT are inter-related. A number of patients in our study are limited, for the application of our results on the general population. Related studies are also limited in this area. We are in the progress of conducting large scale studies for confirmation of our results, and strongly recommend others to conduct similar studies.

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