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