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Incidence of hyperkalemia in patients of type 1 and type 2 diabetes mellitus in Saudi Arabia

 


Abdulrazak Abyad
MD, MPH, MBA, AGSF, AFCHSE

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Incidence of hyperkalemia in patients of type 1 and type 2 diabetes mellitus in Saudi Arabia

 
AUTHOR

Abdul Rahman Al-ajlan PhD
Associate Professor of Clinical Biochemistry
Dean, Riyadh College of Health Sciences,(Men)

CORRESPONDENCE

Dr Abdul Rahman Al-Ajlan
Dean, Riyadh College of Health Sciences (Men)
P. O. Box 22637 Riyadh 11416 Kingdom of Saudi Arabia
Tel: 01-4484964; Fax: 01-4481033
Email: aalajl@hotmail.com


ABSTRACT

Background & Objective: The objective of this study is to determine the level of hyperkalemia in Saudi patients of Type 1 and Type 2 diabetes mellitus, since the patients of diabetes mellitus with hyperkalemia are at a higher risk.

Methods: In the present study, 362 male and female known diabetic patients of Type 1 and Type 2 and 158 non diabetic control subjects visiting Al Iman General and Prince Salman hospitals of Riyadh were studied from October 2003 to August 2005. The diabetics were classified into Type 1 and Type 2 on the latest criteria laid down by the International expert committee on Diabetes Mellitus. None of the diabetics included in our study had shown signs of renal failure. Both types of diabetics were subdivided on the basis of their fasting plasma glucose levels (FPG) in three groups, group 1(7.1 -10.0) group 2 (10.1 -20.0) and group3 (>20.0) mmol / L and their serum potassium levels were estimated.
In the control and test groups the plasma glucose level (FPG) and the serum potassium level were measured after twelve hours of night fasting.

Results: Hyperkalemia was not detected in the group 1 diabetics of Type1 and females of Type 2. The group 2 diabetics of Type 1 and Type 2 showed serum potassium levels of 5.9+1.1 and 7.2 + 1.4 mmol /L ( P <0.001). The serum potassium levels in the group 3 of Type 1 and Type 2 diabetics carrying a FPG of > 20 mmol /L were 6.8 + 1.2 ( r = 0.56) and 8.1+ 1.7 mmol /L ( r =0.68 ) P< 0.05.

Conclusion: It was observed that there is a strong association between hyperglycemia and hyperkalemia in Saudi diabetes mellitus patients of Type 1 and Type 2. The elderly uncontrolled diabetics are at a higher risk of hyperkalemia. Hyperkalemia in uncontrolled diabetics can lead to kidney and liver damage and cardiac arrest. The physicians, while prescribing ACE inhibitors to diabetics, must take precautions to avoid complications of hyperkalemia.

Key Words: Diabetes Mellitus, Hyperkalemia, Saudi Arabia

INTRODUCTION

Potassium is the most abundant cation in the body. 98% of the total 4000 mmol is in the intracellular fluid compartment; with only 60 mmol being in the extracellular fluid of an adult. The kidneys regulate long term balance of potassium.1 Cellular uptake of potassium is regulated by insulin, acid base status aldosterone and adrenergic activity. Hyperkalemia is caused by redistribution of potassium from the intracellular to the extracellular fluid compartment due to the factors leading to impaired cellular uptake, like insulin insufficiency 2. Decreased renal excretion adds to further retention of potassium.2,3

Hyperkalemia is a life threatening emergency and warrants immediate treatment because of its deleterious cardiac consequences4. In general physiological and pathological changes that occur in patients as they grow older may result in distal renal tubular dysfunction, as well as decreased level of plasma aldosteron. Such alterations result in a tendency toward hyperkalemia.5-7 Abnormalities of potassium homeostasis in diabetes are probably related to insulin and mineral corticoid deficiency.8 Chronic hyperkalemia in elderly diabetics is most often attributable to hyporeninemic hypoaldosteronism 9. In the diabetic with ketoacidosis hyperkalemia in the face of potassium depletion may be attributed to reduced renal function, acidosis and release of potassium from cells due to glycogenolysis.9

Generally diabetes is considered as an independent cause of hyperkalemia10. Studies have shown that hyperglycemia alone and not insulin or epinephrine or glucagon is a direct determinant of plasma potassium. The hyperkalemia may be intermittent or persistent.11,12

Physicians treating patients with diabetes should be aware of the dangers of precipitating life threatening hyperkalemia whenever prescribing for their patients. Dangerous hyperkalemia during use of ACE inhibitors and potassium-sparing diuretics have been reported in diabetic patients.13-16

Hyperkalemia is a common and potentially lethal clinical problem. The efficacy of intravenous insulin in cases of hyperkalemia in end stage kidney disease is reported 17.

Our objective is to draw attention to the fact that hyperglycemia induces severe hyperkalemia especially in the setting of insulin absence or reduced insulin responsiveness. The risk factors for hyperkalemia include advanced age, significant prematurity, and the presence of renal failure, diabetes mellitus, and heart failure. Polypharmacy, particularly the use of potassium supplements and potassium-sparing diuretics, in patients underlying renal insufficiency contributed to hyperkalemia in almost one half of the cases.13,17 The data are not available about the incidence of hyperkalemia in diabetics in Saudi Arabia. Our study is the first of its kind in this region.

METHODS

In this study 362 diabetic patients and 158 control non-diabetics were studied from September 2003 to August 2005 at Al Iman general hospital and prince Salman hospitals of Riyadh, Saudi Arabia.

The average age of the male and female control subjects was 19.5 (6-25) years and 18 (5 - 24) years while the mean age of Type 1 male diabetics was 17 ( 4-25) years and female was 18 (5- 23) years of age. Similarly the male and female control subjects included in the study of Type 2 diabetes were 45 ( 26-75) and 46 ( 26- 79) years of age. The average age of the diabetic Type 2 male and female patients was 47 (32 - 80) and 45 ( 35 -72) years respectively.

 

The patients were classified in Type 1 and Type 2 diabetes mellitus on the basis of classification of diabetes of 1997 given by the "International expert committee on the diagnosis and classification of diabetes mellitus".18 We found 119 patients were diagnosed as Type 1 and 243 as Type 2 diabetes mellitus .

The Type 1 and Type 2 diabetics were subdivided into three study groups based on their fasting plasma glucose (FPG) levels as Group -1 (7.1- 10 mmol/L ), group-2 ( 10.1- 20 mmol/L ) and Group -3 ( > 20 mmol/ L) .The non diabetic control group having a FPG level of < 7.0 mmol /L and corresponding to the age group of less than 25 years and more than 25 years for Type 1 and Type 2 diabetes mellitus were selected randomly from the out-patients of the hospitals under study .

The serum potassium levels of >5.0 mmol/ L was considered as hyperkalemia.11
In each group of normal control subjects and diabetic patients, a blood sample of 10 ml was withdrawn after twelve hours of fasting in fluoride and plain vials, and subjected to measurement of plasma glucose level and serum potassium ion. Samples were stored at 4°C for not more than 2 hours. The plasma was carefully separated by centrifugation at 3000 rpm for 10 minutes. Fasting plasma glucose was measured by glucoxidase peroxidase (God Pod) method on Dade-Behring, Dimension AR analyzer. The estimation of serum potassium was carried out by spectrophotometry.

All the subjects under study had undergone a thorough examination and tests for renal functions and significantly none of our diabetic patients had shown signs of renal failure.

STATISTICAL ANALYSIS

Comparison of continuous variables was carried out by student t test. The value of p < 0.05 for different variables was considered significant. Analysis of variance was used to test differences between the potassium ion concentration and the duration of hyperkalemia. Pearson's correlation coefficient was applied to correlate the levels of FPG with serum potassium.

RESULTS

It was observed that mostly older patients with a mean age of 60 had FPG level of > 20 mmol/L and fell in the group 3 .The females with Type 2 diabetes in group 2 with FPG level between 10.1 and 20.0 mmol/L were the oldest with an average age of 58 years.
There was no significant difference in the mean FPG levels of male and female control subjects studied with Type 1 and Type 2 diabetes mellitus patients. The FPG level ranged between 4.05 to 5.03 mmol/L.

The mean serum potassium level in the controls of Type 2 diabetes was a little higher (4.1+ 0.6 vs 3.9 + 0.11 mmol /L ) than Type 1 controls (p< 0.05).

Table1: shows the mean and SD of the levels of serum potassium in three study groups of Type 1 diabetes mellitus patients.

Table 2: shows the mean and SD of the levels of serum potassium in the patients of three study groups of diabetes mellitus Type 2.

No significant sex bias was noticed in the serum potassium levels in the Type 1 diabetes mellitus patients, while in Type 2 diabetes the male patients in group 2 and 3 had higher levels of serum potassium.

The most significant finding common to both Type 1 and Type 2 diabetes mellitus was a proportionate rise in the levels of serum potassium with the increasing levels of FPG. The highest levels of 8.1+ 1.7 ( r = 0.68 ) of serum potassium was found in the males of group 3 ( >20 FPG ) of Type 2 diabetics. In the Type 1 diabetes the marked rise in s.potassium level was observed in group 3 patients while in Type 2 patients there was a noticeable rise even in group 2.

DISCUSSION

In this study, which is first of its kind in Saudi Arabia, we had tried to find the incidence of hyperkalemia in Type 1 and 2 diabetes mellitus patients. 362 diabetes mellitus patients of which 119 were Type 1 and 243 Type 2 and 158 healthy control subjects were included in this study. For classification of diabetes mellitus we have followed the established criteria of the International expert committee18. The cut off upper limit for fasting plasma glucose (FPG) level in normal controls was taken as < 7.0 mmol/ L .Hyperkalemia was declared in patients having a serum potassium level of > 5.0 mmol / L 11.

As observed earlier by other authors we too did not find a significant difference in the levels of serum potassium in males and females.13,20

In accordance with most of the previous studies we observed that there was a rise in serum potassium levels with increasing FPG levels in Type1 and Type 2 diabetes mellitus patients 8 -13

Hyperkalemia is known to be relatively common in diabetic patients reflecting the role of insulin in potassium homeostasis. The unreported feature is the independent effect of diabetes in attenuating the early dip in serum potassium concentration and its later recovery. In these respects, patients with diabetes behaved remarkably like patients pretreated with ß Blockers, making sympathetic nerve dysfunction, the most plausible explanation for the effects on potassium.20

The higher levels of serum potassium in Type 2 diabetics having FPG level of > 20 mmol/L may be attributed to the fact that most of the patients in this group were elderly.5,6 Physiological and pathological events that occur in patients as they grow older may result in distal renal dysfunction, as well as decreased levels of plasma renin activity and plasma aldosterone. A syndrome termed hyporeninemic hypoaldosteronism, associated with hyperkalemia, has been frequently described in elderly patients. 5,6

The common occurrence of hyperkalemia in the elderly may be aggravated by the use of drugs that either further suppress renin and/or aldosteron or interfere with distal tubular potassium excretion.

Insulin resistance may also have had a role in preventing the early dip in serum potassium in diabetes by attenuating intracellular ionic flux early after the onset of symptoms, although the experimental finding of Brown and colleagues indicates that insulin does not contribute significantly to adrenergically driven changes in serum potassium.

We conclude that there appears a strong association between the hyperglycemia and hyperkalemia in both types of diabetes mellitus. 8-11,21 Specially in uncontrolled elderly Type 2 diabetics, having a FPG level of > 20 mmol /L, the hyperkalemia is marked and may lead to cardiac emergencies 4

Physicians while prescribing ACE inhibitors to their diabetic patients must be careful because a combination of uncontrolled hyperglycemia and use of ACE inhibitors may lead to severe hyperkalemia and may precipitate cardiac arrest.13-15

 

 

Table 1.  Mean and SD of serum potassium levels in different study groups of type 1 diabetes mellitus patients

Study groups

FPG level

mmol / L

S. potassium level ( Mean & SD)

mmol / L

M

(n=94)

F

(n=61)

Control (n= 36)

< 7.0-7.0

4.0 + 0.52

3.9 +  0.11

Group 1 (n=27)

7.1 – 10.

4.7 + 1.01

4.5 + 0.98

Group 2 (n= 74)

10-20

5.9 + 1.1

5.8 + 1.3

Group 3 (n=13)

> 20

6.8 + 1.2

6.3 + 1.1

n=  number , FPG = Fasting Plasma Glucose, SD = Standard deviation, M= Male, F= Female

back to text

Table 2. Mean and SD of serum potassium level in different study groups in type 2 diabetes mellitus patients

Study groups

FPG level

mmol/ L

S. potassium level (Mean & SD)

mmol / L

M

(n=215)

F

(n=150)

Control (n=122)

< 7.0-7.0

4.3 + 0.8

4.1 + 0.6

Group 1 (n=78)

7.1 – 10.

5.5 + 1.4

4.9 + 1.2

Group 2 (n=130)

10 - 20

7.2 + 1.4

6.6 + 1.05

Group 3 (n=35)

> 20

8.1 + 1.7

8.0 + 1.09


n=  number , FPG = Fasting Plasma Glucose, SD = Standard deviation, M= Male, F= Femal

 

ACKNOWLEDGEMENTS

Acknowledgement: The author would like to show his gratitude to Dr. S. Riaz Mehdi and
Dr. Sadre Alam for their technical and moral support in the course of study and preparation of this manuscript.

 

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