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Exchangeable potassium in diabetics
Exchangeable Potassium in Diabetics ByNANCY TELFER Exchangeable potassium was determined in a nondiabetic group and in 2 groups of diabetics-uncontrolled and glycosuric and controlled or uncontrolled but aglycosuric- in order to see whether sustained glycosuria had any effect upon exchangeable potassium. The measured exchangeable potassium was compared with the predicted exchangeable potassium as determined by (a) age and sex, (b) age, sex and weight, and (c) age, sex and corrected weight. The results were expressed as per cent of the predicted values. There was no significant difference in the results between (1) the
uncontrolled and glycosuric group, and (2) the controlled or uncontrolled but aglycosuric group. There was a surprising and highly significant difference between the exchangeable potassium values of the nondiabetic group and the diabetic patients, both controlled and uncontrolled. Whereas results for the nondiabetic group averaged 95 per cent of the predicted values, those for both groups of diabetic were only 73 per cent. Several possible reasons for this lowered exchangeable potassium are discussed. (Metabolism 15: No. 6, June, 502-509, 1966)
S
INCE THE initial successes with insulin, there has been an increasing number of diabetics who are difficult to control. In addition, abnormal glucose tolerance tests have been observed in potassium deficient nondiabetics and in subjects given thiazide diuretics. In these patients, the abnormal glucose tolerance may be corrected with potassium repletion.1-3 Thus the possibility that potassium deficiency resulting from the osmotic effect of consistent glycosuria in a poorly controlled diabetic could contribute to difficulty in control was studied. Aikawa’ determined the exchangeable potassium values in a heterogeneous group of diabetics, ranging from aglycosuric to frankly acidotic subjects. Weekly determinations of the exchangeable potassium showed increases during the first week of hospitalization in the uncontrolled diabetics, whether or not potassium supplements were given. The exchangeable potassium reached a plateau between the second and third weeks. He concluded that the better controlled diabetics had higher exchangeable potassium values. This study was designed to determine the exchangeable potassium in glycosuric and aglycosuric diabetics to evaluate the relationship between glycosuria and potassium, and the effect of potassium loss on diabetic control. _.__~~___
---
_
~_._ ._._ ~_~_.
From the Department of Medicine, Harbor General Hospital, Torrance, California, and University of California Center for the Health Sciences, Los Angeles, California. Presented in part at the Annual Meeting of the Western Section of the Amekan Federation for Clinical Research, Carmel, Calif., January 27-30, 1965. This study was supported in part by a grant from the Diabetes Association of Southern California and in part by U. S. Public Health Service Grant No. HE - 0894-01. Received for publication Feb. 18, 1966. Harbor General Hospital, Assistant NANCY TELFER, M.D.: Chief, Outpatient Clinics, Professor of Medicine, University of California Center for the Health Sciences. 502
CXCHANGEABLE
I'OTASSIUM
503
IN DIABETES
MATERIALS
AND METHODS
The subjects were selected from the wards nnd clinics of Harbor General Hospital. Two determinations for exchangeable potassium were obtained in the nondiabetic group. which wirs coml~osed of 6 healthy hospital emplovees and 11 patients with ii variety of disorders. including lams. tluoclenal deer. recovering mvocarclial infarction. recent cerebral concussion. recent fracture and thromhophlebitis. The di;rbetics were divided into 2 groups on the basis of glycosurio (a) 23 uncontrolled and glyrosuric ( lJC; ) ; (11) 14 either controlled or uncontrolled. but aglycosuric ( C-UA ). Di;ibetics with foisting true blood sugzus ( FBS) consistently over 170 mg./lOO ml. were “iineontrolled”: those with FBS consistently less than 130 mg./lOO ml. were “controlled.” Uncontrolled glycosuric di&etics (UC) 12x 1 recorded stronglv positive urine reactions foi scver:tl weeks; hut were not in ncidosis (hod negative urine acetone reactions) nt the time of the stud!;. Several “uncontrolled” tlialietics who had high renal thresholds were therefore ~iglycosiuic ;mtl were studied with the “controlled’ aglycosuric diabetics. Patients with congestive heurt failure or cirrhosis.’ 1 musci~lar dystrophy.‘~ renal disease or chronic di;rrrheai--or who were on medicntions that might aff'ect potassium balance. such IIS thizizitle tlilrretics” were omitted. The 24 hour exchangeable potassium w;is measured either with 400 uc. of radioactive potassiiim (KJ”) or rubidium (Rh*“). using urine for the hY42 determinations and s;iliva for the RIP determinations. The tracer doses were given orally. and urine was collected during the ne\t 24 hours so thnt the excreted K’” or Rbs” could be subtracted from the administered dose. Three specimens of urine or saliva were collected at 24%. 25 and 25 % hours and the r:\tio of radioactive potassium4” or rubidiinn ‘I’; to nonfiidioactive potassium was determined. Esch;mgeal~le l~ol;issium wiis calculated using the formula: Administered KC%zz ~___.___~
K42 (mE(t.) Ka2 nc./L./K;“!’
- Excreted
K”” (mEq.
)
mEq,/L.
Serum sodium. potassium. carbon dioxide. chloride. blood sugar. BUIi or creatinine ;md osmolalit~~ were nrensured at the time of the 24 hour urine collection. ;IS were 24 hour urin;u\volrnne. sugar. sodium. chloride. potassium and osmolality. .Veasured Ii_ valnes were expressed as per cent of predicted K,. values. The predicted values were determined on 3 bases ( 1) age and sex.‘“~‘” (2) age. sex and weight.‘” and (3) age, ses and corrected weight. An :ubitrarv correction for possible ohesitv was made in subjects in whom the measured Ii* W~IS less than 90 per cent of the predicted K,,. In such C’XPS. if ii m;m weighed more than 70 Kg.. or :i womzm more than 60 Kg.. their predietetl Wlues were recirlcul~ited using 70 and 60 Kg.. respectively. RESULTS
Twenty Table
determinations
were
1). Using predicted
nondiabetics
was 94.0 per cent
sex and weight, were overweight.
the results
t
were
of the diabetic
1. Of the 23 UG subjects,
on nondiabetic
17.4. Using
predicted
correction
15.4 of the predicted subjects
subjects
(Fig.
1 and 2,
on age and sex, the mean vaIue for the
92.4 per cent
Using the arbitrary
the results were 95 per cent * The results
made
values based
values
-+ 14.6.
Four
for the 4 overweight
on age, subjects.
value,
are shown in Figures
10 had determinations
based
of the subjects
3 and 4 and Table
with Rb”” and 13 with
I(-‘“.
Nine were considered overweight on the arbitrary scale. The mean Ii, values were : 71.4 per cent t 16.8 of the predicted value based on age and sex; 70.6 per cent f 12.5 of the predicted value based on age, sex and weight; and 73.8 per cent + 14.1 of the predicted The results by all 3 methods
value based
of calculation
on age, sex and corrected
were highly
significant
weight.
(p < 0.001)
504
Fig.
NANCY
I.-Nondiabetics:
Measured
K, compared
with predicted
TELFER
K, based on age,
sex and weight.
lml
2500
3m
3500
4axl
Ke predicted
Fig.
2.-Nondiabetics:
age, sex and corrected
Measured
weight.
K,, compared
with
predicted
K,. hnsed
on
EXCHANGEABLE
POTASSIUM
Table
l.-Per
Cent of Predicted
Age
Subjects
NO.
(mean)
Nondiabetic UG
20. 24
445 47.5
C-WA
16
“Dixon I-1. 121.
and hlassay:
505
IN DIABETES
K, (and S.D.)
Age-Sex _______.
.-
94.0% & 17.4 f71.4% x!z 16.8
f70.5% F 25.7 60.9 __ ~~~__ Introduction to Statistical s = \:/(.y
Based On:*
~
Age-Sex-Weight
Age-&XCorrected Weight
92.4% ___-.-k 14.6 f70.61 I 12.5
95.0% + 15.4 f73.88 -c 14.1
f67.8% 2
f73.48
Analysis.
19.4
McGraw-Hill,
-
I 22.4 --2nd rd.. 1957.
-x)? n-l
/
_____
s2 = \!__-_
(n, -
1 )S,“(n, - l)S, ._ ..~ ..___ ~~ ~~~ n1 + nz -2
-
t= sp tc.01
-
x1 - x2 -____
_____
.,I’ 1
+ _’
N,
N,
> p > 0.001).
as compared to the nondiabetics (Table 1). Of the C-VA patients, 4 had determinations with RbRK, the remainder with K42. Ten were considered overweight. The mean K, values were: 70.5 per cent rfr 25.7 of the predicted value based on age and sex, 67.8 percent f 19.4 of the predicted value based on age, sex and weight, and 73.4 per cent f 22.4 of the predicted value based on age. sex and corrected weight. Again, results for the C-UA patients compared to the nondiabetics were highly significant (p < 0.001) by all 3 methods of calculation (Table 1). There was no significant difference betweerl the UG and C-UA groups. Figure 5 shows the effect of the correction for overweight. Although the CUA diabetics appear to be more obese than the UG diabetics, these differences are not significant. The C-UA group was significantly older than the other two. There was no significant difference between the sexes; the mean value for the UG females WFS 72.7 per cent + 14.9 of the predicted value based on age, sex and corrected weight; it was 69.5 per cent * 19.7 for the UG males (7 > p > 6). There was no apparent difference between the controlled and uncontrolled diabetics. The mean value for the C diabetics (6 females, 3 males) was 66.5 per cent, for the UA diabetics 76.4 per cent and for the UC diabetics 73.8 per cent of the predicted values based on age, sex and corrected weight. Serum potassium values were greater than 3.9 mEq. in all subjects of the UG group and in all but one of the C-UA group. Serum osmolarities above 295 mOsm./L. were found in one of 14 C-UA and 7 of 22 UC subjects. Twentyfour hour potassium excretions varied from 10 to 79 mEq., and were higher than the estimated intake of 60 mEq. in one of 16 C-UA spbjects; they varied from 10 to 226 mEq. and were over 60 mEq. in 6 of 22 UG subjects. Some patients had unexpectedly high values for the measured K,; values
506
NANCY
TELFER
woo
2.5al
moo
1.500
mo
mes
loo0
zcm
lsal
K,
Fig. S.-Diabetics: sex aid weight.
Measured
Fig. 4.-Diabetics: Measured sex and corrected weight.
2xlo
3om
3500
4&m
predicted
K,
compared
with predicted
K,
compared
with predicted
K, based
K, based
on age,
on age,
EXCHANGEABLE
POTASSIUM
::::: II 507
IN DIABETES
n q q
K,
Predmed
(Age-Sex-WaghO
K,
Predicred
(Age-Sex-Corrected
K,
Measured
Weigh,
;:I:;: ::::: .::::: ::;:I :i:i: ::::: ::::: ::::: ::::: ::::: :::::
>_i$ ::::: :::.: ::::: ::::: i# ;:i:; :‘:i$‘: ::::: ::::: ::::: ::::: :;:I: :::::
lrncmltrolled ClyCOSWlC
(9)
Controlled and llncontrolled Aglycosuric (7)
subjects compared with Fig. 5.-LMeasured Ii, in “overweight” based on age. sex and weight and age, SPS and corrected weight.
predicted
K,.
were 90 per cent or more of the predicted K,. were found in 2 UG and 4 C-UA diabetics; 3 were overweight. One man was a weight lifter, which not only contributed to his size. but also raises the question as to the normal K,. in weight lifters; his K, might be relatively low considering his muscIe mass. Two of the (: patients were well controlled on diet alone, having had their diabetes discovered during a stressful situation. At the time that the K, was measured their weights were normal and they had normal fasting and 2 hour postprandial blood sugars. Four required only dietary management and 5 were on oral hypoglycemic agents. Of the 7 UA patients, 2 were managed on diet. 4 v\rithoral hvpoglvcemic agents, and one with insulin. that
DISCUSSION
The condition of the diabetics in this series probably approximates that of the more stable subjects of Aikawa’s series. He demonstrated that some potassium was retained during the first week of hospitalization in many diabetics with or without potassium supplements, that exchangeable potassium rc’mained stable thereafter. The K, values are similar in the two series. However, there was no difference between the sexes in this series, and the controlled diabetics had lower values than either of the uncontrolled groups, although the groups were too small for statistica analysis. Of interest is the unexpected finding that diabetics, whether or not their diabetes is controlled, have lower K, values than nondiabetics. The cause of
508
NANCY
POSSIBLE INCREASE IN K
TELFER
NQT AVAILABLE FOR K
1 P qB I
K
I
KO
NORMAL
PSEUDO DEPLETION (MUSCULAR WASTING)
K DEFICIENCY
DEPLETlDN (METABOLIC DISORDER 1
Fig. 6.-Open columns represent total body potassium capacity. Dark columns represent exchangeable potassium (K,) Normal: Potassium capacity equals K,. Deficiency: Potassium capacity normal, K, decreased. Pseudodepletion: Potassium capacity decreased. Depletion: Reduced potassium capacity and K, secondary to metabolic disorder; potential potasisum capacity is normal.
the low 24 hour K, is obscure, but there are 3 possible explanations5 (Fig. 6): ( 1) there may be a simple potassium loss, with a normal body capacity for potassium, (2) a decrease in the body capacity for potassium as in muscle wasting, or (3) a metabolic defect which inhibits normal utilization of potassium, although the body capacity for potassium is potentially normal, i.e. acidosis. The present findings are not explained by a lack of insulin since adult onset diabetics may have an increased insulin secretion in response to a glucose load. There is no evidence which indicates whether diabetics have a decreased capacity for potassium, or: a metabolic defect which precludes normal cellular concentrations of potassium. Since it has been observed that diabetics manifest premature aging, at least in the cardiovascular system, and that the total body potassium decreases with age, 2~11-13it may be that the decrease in exchangeable potassium is evidence of an increased rate of cellular aging. ACKNOWLEDGMENT I wish to express my appreciation Miss Marcia Young.
for the technical
assistance
of Mrs. Brita Hetter
and
REFERENCES 1. Sagild, U., Anderson, V., and Andreasen, P. B.: Glucose tolerance and insulin responsiveness in experimental potassium depletion. Acta Med. Stand. 169:243, 1961. 2. -, and -: Further studies on glucose metabolism in experimental potassium depletion: effect of insulin, glucagon.
and muscular exercise. Acta Med. Stand. 175:681, 1964. 3. Rapoport, M. I., and Hurd, H. F.: Thiazide-induced glucose tolerance treated with potassium. Arch. Int. Med. 113:405, 1964. 4. Aikawa, J. K., Felts, J. H., Jr., and Harrell, G. T.. Jr.: Isotopic studies of po-
EXCHANGEABLE
5.
6.
7.
8.
9.
POTASSIUM
509
IN DIABETES
tassium metabolism in diabetes. J. Clin. Invest. 32:15, 1963. Nagent de Deuschaisnes, C.. Collet, R. A.. Busset. R.. and Mach. R. S.: Exchangeable potassium in wasting, amyotrophy. heart-disease and cirrhosis of the liver. Lancet 1:681. 1961. Blahd, W. N.. Cassen, B.. and Lederer. M.: Body potassium in patients with muscular dystrophy. Ann. N. Y. Acad. Med. 110:282, 1963. Maxwell, M. H., and Kleeman, C. R.: Clinical Disorders of Fluid and Electrolyte Metabolism. New York, Blackiston Divison. McGraw-Hill book Co., 1962. 1,. 264. Corsa. L.. Jr.. Olney. J. M., Jr., Steenburg. R. W’.. Ball. M. R., and Moore, F. D.: The measurement of exchangeable potassium in man by isotope dilution. J. Clin. Invest. 29: 1280. 1950. Bauer. F. K.. Telfer, N., Lestina, J., and Jenkins, M. A.: Total exchangeable potassium determination in saliva us-
ing
K””
1:199,
and
Rbsa.
J.
Nut.
Med.
1960.
10. Sagild, sium
U.: Total in normal
Special Stand.
exchangeable potassubjects with K”s.
reference
to changes
J. Clin. Lab.
11. Allen,
T.
H.,
Langham, sium
Anderson,
W.
and
relation
H.:
gross to
Invest.
E.
Total
body
age.
J.
with 8:44,
age. 1956.
C..
body
and potas-
composition
Gerontol.
in
15:348.
1960. 12. Edelman. H.,
I. S.. Olney,
Broocks,
Body man
by
115:447,
Moore,
studies the
dilution
A.
F.
D.:
in the
hu-
principle.
1952.
F. D.. Olesen.
J. D.. Parker,
J. M.. James,
and
composition: being
Science 13. Moore,
L.,
K. H.. McMurrey.
H. V., Ball,
M. R.. and
Boyden. C. M.: The body cell mass and its supporting environment. In: Body Composition in Health and Disease. Philadelphia, W. B. Saunders, 1963, p. 87.
uncontrolled and glycosuric group, and (2) the controlled or uncontrolled but aglycosuric group. There was a surprising and highly significant difference between the exchangeable potassium values of the nondiabetic group and the diabetic patients, both controlled and uncontrolled. Whereas results for the nondiabetic group averaged 95 per cent of the predicted values, those for both groups of diabetic were only 73 per cent. Several possible reasons for this lowered exchangeable potassium are discussed. (Metabolism 15: No. 6, June, 502-509, 1966)
S
INCE THE initial successes with insulin, there has been an increasing number of diabetics who are difficult to control. In addition, abnormal glucose tolerance tests have been observed in potassium deficient nondiabetics and in subjects given thiazide diuretics. In these patients, the abnormal glucose tolerance may be corrected with potassium repletion.1-3 Thus the possibility that potassium deficiency resulting from the osmotic effect of consistent glycosuria in a poorly controlled diabetic could contribute to difficulty in control was studied. Aikawa’ determined the exchangeable potassium values in a heterogeneous group of diabetics, ranging from aglycosuric to frankly acidotic subjects. Weekly determinations of the exchangeable potassium showed increases during the first week of hospitalization in the uncontrolled diabetics, whether or not potassium supplements were given. The exchangeable potassium reached a plateau between the second and third weeks. He concluded that the better controlled diabetics had higher exchangeable potassium values. This study was designed to determine the exchangeable potassium in glycosuric and aglycosuric diabetics to evaluate the relationship between glycosuria and potassium, and the effect of potassium loss on diabetic control. _.__~~___
---
_
~_._ ._._ ~_~_.
From the Department of Medicine, Harbor General Hospital, Torrance, California, and University of California Center for the Health Sciences, Los Angeles, California. Presented in part at the Annual Meeting of the Western Section of the Amekan Federation for Clinical Research, Carmel, Calif., January 27-30, 1965. This study was supported in part by a grant from the Diabetes Association of Southern California and in part by U. S. Public Health Service Grant No. HE - 0894-01. Received for publication Feb. 18, 1966. Harbor General Hospital, Assistant NANCY TELFER, M.D.: Chief, Outpatient Clinics, Professor of Medicine, University of California Center for the Health Sciences. 502
CXCHANGEABLE
I'OTASSIUM
503
IN DIABETES
MATERIALS
AND METHODS
The subjects were selected from the wards nnd clinics of Harbor General Hospital. Two determinations for exchangeable potassium were obtained in the nondiabetic group. which wirs coml~osed of 6 healthy hospital emplovees and 11 patients with ii variety of disorders. including lams. tluoclenal deer. recovering mvocarclial infarction. recent cerebral concussion. recent fracture and thromhophlebitis. The di;rbetics were divided into 2 groups on the basis of glycosurio (a) 23 uncontrolled and glyrosuric ( lJC; ) ; (11) 14 either controlled or uncontrolled. but aglycosuric ( C-UA ). Di;ibetics with foisting true blood sugzus ( FBS) consistently over 170 mg./lOO ml. were “iineontrolled”: those with FBS consistently less than 130 mg./lOO ml. were “controlled.” Uncontrolled glycosuric di&etics (UC) 12x 1 recorded stronglv positive urine reactions foi scver:tl weeks; hut were not in ncidosis (hod negative urine acetone reactions) nt the time of the stud!;. Several “uncontrolled” tlialietics who had high renal thresholds were therefore ~iglycosiuic ;mtl were studied with the “controlled’ aglycosuric diabetics. Patients with congestive heurt failure or cirrhosis.’ 1 musci~lar dystrophy.‘~ renal disease or chronic di;rrrheai--or who were on medicntions that might aff'ect potassium balance. such IIS thizizitle tlilrretics” were omitted. The 24 hour exchangeable potassium w;is measured either with 400 uc. of radioactive potassiiim (KJ”) or rubidium (Rh*“). using urine for the hY42 determinations and s;iliva for the RIP determinations. The tracer doses were given orally. and urine was collected during the ne\t 24 hours so thnt the excreted K’” or Rbs” could be subtracted from the administered dose. Three specimens of urine or saliva were collected at 24%. 25 and 25 % hours and the r:\tio of radioactive potassium4” or rubidiinn ‘I’; to nonfiidioactive potassium was determined. Esch;mgeal~le l~ol;issium wiis calculated using the formula: Administered KC%zz ~___.___~
K42 (mE(t.) Ka2 nc./L./K;“!’
- Excreted
K”” (mEq.
)
mEq,/L.
Serum sodium. potassium. carbon dioxide. chloride. blood sugar. BUIi or creatinine ;md osmolalit~~ were nrensured at the time of the 24 hour urine collection. ;IS were 24 hour urin;u\volrnne. sugar. sodium. chloride. potassium and osmolality. .Veasured Ii_ valnes were expressed as per cent of predicted K,. values. The predicted values were determined on 3 bases ( 1) age and sex.‘“~‘” (2) age. sex and weight.‘” and (3) age, ses and corrected weight. An :ubitrarv correction for possible ohesitv was made in subjects in whom the measured Ii* W~IS less than 90 per cent of the predicted K,,. In such C’XPS. if ii m;m weighed more than 70 Kg.. or :i womzm more than 60 Kg.. their predietetl Wlues were recirlcul~ited using 70 and 60 Kg.. respectively. RESULTS
Twenty Table
determinations
were
1). Using predicted
nondiabetics
was 94.0 per cent
sex and weight, were overweight.
the results
t
were
of the diabetic
1. Of the 23 UG subjects,
on nondiabetic
17.4. Using
predicted
correction
15.4 of the predicted subjects
subjects
(Fig.
1 and 2,
on age and sex, the mean vaIue for the
92.4 per cent
Using the arbitrary
the results were 95 per cent * The results
made
values based
values
-+ 14.6.
Four
for the 4 overweight
on age, subjects.
value,
are shown in Figures
10 had determinations
based
of the subjects
3 and 4 and Table
with Rb”” and 13 with
I(-‘“.
Nine were considered overweight on the arbitrary scale. The mean Ii, values were : 71.4 per cent t 16.8 of the predicted value based on age and sex; 70.6 per cent f 12.5 of the predicted value based on age, sex and weight; and 73.8 per cent + 14.1 of the predicted The results by all 3 methods
value based
of calculation
on age, sex and corrected
were highly
significant
weight.
(p < 0.001)
504
Fig.
NANCY
I.-Nondiabetics:
Measured
K, compared
with predicted
TELFER
K, based on age,
sex and weight.
lml
2500
3m
3500
4axl
Ke predicted
Fig.
2.-Nondiabetics:
age, sex and corrected
Measured
weight.
K,, compared
with
predicted
K,. hnsed
on
EXCHANGEABLE
POTASSIUM
Table
l.-Per
Cent of Predicted
Age
Subjects
NO.
(mean)
Nondiabetic UG
20. 24
445 47.5
C-WA
16
“Dixon I-1. 121.
and hlassay:
505
IN DIABETES
K, (and S.D.)
Age-Sex _______.
.-
94.0% & 17.4 f71.4% x!z 16.8
f70.5% F 25.7 60.9 __ ~~~__ Introduction to Statistical s = \:/(.y
Based On:*
~
Age-Sex-Weight
Age-&XCorrected Weight
92.4% ___-.-k 14.6 f70.61 I 12.5
95.0% + 15.4 f73.88 -c 14.1
f67.8% 2
f73.48
Analysis.
19.4
McGraw-Hill,
-
I 22.4 --2nd rd.. 1957.
-x)? n-l
/
_____
s2 = \!__-_
(n, -
1 )S,“(n, - l)S, ._ ..~ ..___ ~~ ~~~ n1 + nz -2
-
t= sp tc.01
-
x1 - x2 -____
_____
.,I’ 1
+ _’
N,
N,
> p > 0.001).
as compared to the nondiabetics (Table 1). Of the C-VA patients, 4 had determinations with RbRK, the remainder with K42. Ten were considered overweight. The mean K, values were: 70.5 per cent rfr 25.7 of the predicted value based on age and sex, 67.8 percent f 19.4 of the predicted value based on age, sex and weight, and 73.4 per cent f 22.4 of the predicted value based on age. sex and corrected weight. Again, results for the C-UA patients compared to the nondiabetics were highly significant (p < 0.001) by all 3 methods of calculation (Table 1). There was no significant difference betweerl the UG and C-UA groups. Figure 5 shows the effect of the correction for overweight. Although the CUA diabetics appear to be more obese than the UG diabetics, these differences are not significant. The C-UA group was significantly older than the other two. There was no significant difference between the sexes; the mean value for the UG females WFS 72.7 per cent + 14.9 of the predicted value based on age, sex and corrected weight; it was 69.5 per cent * 19.7 for the UG males (7 > p > 6). There was no apparent difference between the controlled and uncontrolled diabetics. The mean value for the C diabetics (6 females, 3 males) was 66.5 per cent, for the UA diabetics 76.4 per cent and for the UC diabetics 73.8 per cent of the predicted values based on age, sex and corrected weight. Serum potassium values were greater than 3.9 mEq. in all subjects of the UG group and in all but one of the C-UA group. Serum osmolarities above 295 mOsm./L. were found in one of 14 C-UA and 7 of 22 UC subjects. Twentyfour hour potassium excretions varied from 10 to 79 mEq., and were higher than the estimated intake of 60 mEq. in one of 16 C-UA spbjects; they varied from 10 to 226 mEq. and were over 60 mEq. in 6 of 22 UG subjects. Some patients had unexpectedly high values for the measured K,; values
506
NANCY
TELFER
woo
2.5al
moo
1.500
mo
mes
loo0
zcm
lsal
K,
Fig. S.-Diabetics: sex aid weight.
Measured
Fig. 4.-Diabetics: Measured sex and corrected weight.
2xlo
3om
3500
4&m
predicted
K,
compared
with predicted
K,
compared
with predicted
K, based
K, based
on age,
on age,
EXCHANGEABLE
POTASSIUM
::::: II 507
IN DIABETES
n q q
K,
Predmed
(Age-Sex-WaghO
K,
Predicred
(Age-Sex-Corrected
K,
Measured
Weigh,
;:I:;: ::::: .::::: ::;:I :i:i: ::::: ::::: ::::: ::::: ::::: :::::
>_i$ ::::: :::.: ::::: ::::: i# ;:i:; :‘:i$‘: ::::: ::::: ::::: ::::: :;:I: :::::
lrncmltrolled ClyCOSWlC
(9)
Controlled and llncontrolled Aglycosuric (7)
subjects compared with Fig. 5.-LMeasured Ii, in “overweight” based on age. sex and weight and age, SPS and corrected weight.
predicted
K,.
were 90 per cent or more of the predicted K,. were found in 2 UG and 4 C-UA diabetics; 3 were overweight. One man was a weight lifter, which not only contributed to his size. but also raises the question as to the normal K,. in weight lifters; his K, might be relatively low considering his muscIe mass. Two of the (: patients were well controlled on diet alone, having had their diabetes discovered during a stressful situation. At the time that the K, was measured their weights were normal and they had normal fasting and 2 hour postprandial blood sugars. Four required only dietary management and 5 were on oral hypoglycemic agents. Of the 7 UA patients, 2 were managed on diet. 4 v\rithoral hvpoglvcemic agents, and one with insulin. that
DISCUSSION
The condition of the diabetics in this series probably approximates that of the more stable subjects of Aikawa’s series. He demonstrated that some potassium was retained during the first week of hospitalization in many diabetics with or without potassium supplements, that exchangeable potassium rc’mained stable thereafter. The K, values are similar in the two series. However, there was no difference between the sexes in this series, and the controlled diabetics had lower values than either of the uncontrolled groups, although the groups were too small for statistica analysis. Of interest is the unexpected finding that diabetics, whether or not their diabetes is controlled, have lower K, values than nondiabetics. The cause of
508
NANCY
POSSIBLE INCREASE IN K
TELFER
NQT AVAILABLE FOR K
1 P qB I
K
I
KO
NORMAL
PSEUDO DEPLETION (MUSCULAR WASTING)
K DEFICIENCY
DEPLETlDN (METABOLIC DISORDER 1
Fig. 6.-Open columns represent total body potassium capacity. Dark columns represent exchangeable potassium (K,) Normal: Potassium capacity equals K,. Deficiency: Potassium capacity normal, K, decreased. Pseudodepletion: Potassium capacity decreased. Depletion: Reduced potassium capacity and K, secondary to metabolic disorder; potential potasisum capacity is normal.
the low 24 hour K, is obscure, but there are 3 possible explanations5 (Fig. 6): ( 1) there may be a simple potassium loss, with a normal body capacity for potassium, (2) a decrease in the body capacity for potassium as in muscle wasting, or (3) a metabolic defect which inhibits normal utilization of potassium, although the body capacity for potassium is potentially normal, i.e. acidosis. The present findings are not explained by a lack of insulin since adult onset diabetics may have an increased insulin secretion in response to a glucose load. There is no evidence which indicates whether diabetics have a decreased capacity for potassium, or: a metabolic defect which precludes normal cellular concentrations of potassium. Since it has been observed that diabetics manifest premature aging, at least in the cardiovascular system, and that the total body potassium decreases with age, 2~11-13it may be that the decrease in exchangeable potassium is evidence of an increased rate of cellular aging. ACKNOWLEDGMENT I wish to express my appreciation Miss Marcia Young.
for the technical
assistance
of Mrs. Brita Hetter
and
REFERENCES 1. Sagild, U., Anderson, V., and Andreasen, P. B.: Glucose tolerance and insulin responsiveness in experimental potassium depletion. Acta Med. Stand. 169:243, 1961. 2. -, and -: Further studies on glucose metabolism in experimental potassium depletion: effect of insulin, glucagon.
and muscular exercise. Acta Med. Stand. 175:681, 1964. 3. Rapoport, M. I., and Hurd, H. F.: Thiazide-induced glucose tolerance treated with potassium. Arch. Int. Med. 113:405, 1964. 4. Aikawa, J. K., Felts, J. H., Jr., and Harrell, G. T.. Jr.: Isotopic studies of po-
EXCHANGEABLE
5.
6.
7.
8.
9.
POTASSIUM
509
IN DIABETES
tassium metabolism in diabetes. J. Clin. Invest. 32:15, 1963. Nagent de Deuschaisnes, C.. Collet, R. A.. Busset. R.. and Mach. R. S.: Exchangeable potassium in wasting, amyotrophy. heart-disease and cirrhosis of the liver. Lancet 1:681. 1961. Blahd, W. N.. Cassen, B.. and Lederer. M.: Body potassium in patients with muscular dystrophy. Ann. N. Y. Acad. Med. 110:282, 1963. Maxwell, M. H., and Kleeman, C. R.: Clinical Disorders of Fluid and Electrolyte Metabolism. New York, Blackiston Divison. McGraw-Hill book Co., 1962. 1,. 264. Corsa. L.. Jr.. Olney. J. M., Jr., Steenburg. R. W’.. Ball. M. R., and Moore, F. D.: The measurement of exchangeable potassium in man by isotope dilution. J. Clin. Invest. 29: 1280. 1950. Bauer. F. K.. Telfer, N., Lestina, J., and Jenkins, M. A.: Total exchangeable potassium determination in saliva us-
ing
K””
1:199,
and
Rbsa.
J.
Nut.
Med.
1960.
10. Sagild, sium
U.: Total in normal
Special Stand.
exchangeable potassubjects with K”s.
reference
to changes
J. Clin. Lab.
11. Allen,
T.
H.,
Langham, sium
Anderson,
W.
and
relation
H.:
gross to
Invest.
E.
Total
body
age.
J.
with 8:44,
age. 1956.
C..
body
and potas-
composition
Gerontol.
in
15:348.
1960. 12. Edelman. H.,
I. S.. Olney,
Broocks,
Body man
by
115:447,
Moore,
studies the
dilution
A.
F.
D.:
in the
hu-
principle.
1952.
F. D.. Olesen.
J. D.. Parker,
J. M.. James,
and
composition: being
Science 13. Moore,
L.,
K. H.. McMurrey.
H. V., Ball,
M. R.. and
Boyden. C. M.: The body cell mass and its supporting environment. In: Body Composition in Health and Disease. Philadelphia, W. B. Saunders, 1963, p. 87.