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Incidence of hyperkalemia
in patients of type 1 and type 2 diabetes mellitus
in Saudi Arabia
..........................................................................................................................
Abdul Rahman Al-ajlan
PhD
Associate Professor of Clinical Biochemistry
Dean, Riyadh College of Health Sciences,(Men)
Address correspondence to:
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
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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.
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Key words: Diabetes
Mellitus, Hyperkalemia, Saudi Arabia
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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.
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.
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.
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.
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
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Table
1. Mean
and SD of serum potassium levels in different
study groups of type 1 diabetes mellitus
patients
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Study groups
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FPG level
mmol / L
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S. potassium
level ( Mean & SD)
mmol / L
|
|
M
(n=94)
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F
(n=61)
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Control (n= 36)
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< 7.0-7.0
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4.0 + 0.52
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3.9 + 0.11
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Group 1 (n=27)
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7.1 – 10.
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4.7 + 1.01
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4.5 + 0.98
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Group 2 (n= 74)
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10-20
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5.9 + 1.1
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5.8 + 1.3
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Group 3 (n=13)
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> 20
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6.8 + 1.2
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6.3 + 1.1
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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
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Study groups
|
FPG level
mmol/ L
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S. potassium
level (Mean & SD)
mmol /
L
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M
(n=215)
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F
(n=150)
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Control (n=122)
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< 7.0-7.0
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4.3 +
0.8
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4.1 +
0.6
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Group 1 (n=78)
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7.1 – 10.
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5.5 +
1.4
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4.9 +
1.2
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Group 2 (n=130)
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10 - 20
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7.2 +
1.4
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6.6 +
1.05
|
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Group 3 (n=35)
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> 20
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8.1 +
1.7
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8.0 + 1.09 |
n= number , FPG = Fasting Plasma Glucose,
SD = Standard deviation, M= Male, F=
Femal
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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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