NOTE ON THE DISTRIBUTION OF BLOOD SUGAR

BY MICHAEL SOMOGYI
(From the Laboratory of the Jewish Hospital of St. Louis, St. Louis)

(Received for publication, December 22, 1930)

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A recent paper by Folin and Svedberg (1) introduces new per-
plexit,ies in the problem of the distribution of blood sugar between
corpuscles and plasma. Until recently the view that the concen-
tration of sugar in corpuscles and in plasma is nearly the same
found general acceptance. Expressed in a convenient term this
means that the ratio of distribution, corpuscle sugar: plasma sugar,
is about unity. In 1928 the writer, prompted by his observation
that the amount of non-sugar substances which reduce alkaline
copper solutions is about 5 times as much in corpuscles as in
plasma (2), studied the problem with the determination of true
sugar values, and reported that the corpuscles contain relatively
less sugar than the plasma. The distribution ratios, observed on
thirty-six healthy subjects, gave the average of 77: 100 (3). Ege
and Roche in 1930 fully corroborated these results, finding an
average ratio of 80: 100 (4). Folin and Svedberg now report the
substantially lower ratio of 6O:lOO for healthy persons.
The divergencies are even more striking in regard to the blood
of diabetic subjects. Investigators prior to 1928 contended that
the distribution ratio is distinctly lower in diabetic than non-
diabetic cases. (This was then accepted as “the fundamental
fact” in the structure of various theories advanced by Loewi and
his collaborators, by Falta and others in attempts to throw light
upon the nature of diabetes mellitus.) Diametrically opposed to
this stands the report of Folin and Svedberg (1) to the effect that
the corpuscles in the blood of diabetics contain relatively more
sugar than in the blood of non-diabetic subjects. Both of these
views are in sharp contrast to our own experimental evidence
reported in 1928, showing that the relative sugar content of cor-
puscles in diabetic and non-diabetic casesis the same. The aver-
731
732 Distribution of Blood Sugar

age corpuscle sugar: plasma sugar ratio for seventeen diabetic

cases was 77:100, identical with the figure we reported for the
non-diabetic cases.
As regards the earlier investigators, we have shown, that since
they determined total reduction values instead of the true sugar
content of corpuscles and plasma, their results do not express the
actual distribution of blood sugar. If this error is corrected by
deducting the amount of non-sugar reducing substances from the
apparent sugar values of both corpuscles and plasma, the entire

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picture is changed. First, the distribution ratio drops below
unity in non-diabetic as well as in diabetic cases, and, second, the
difference between diabetic and non-diabetic cases is wiped out
(3, 5), so that the older results fall in line with our findings which
are based upon true sugar values.
Comparison of Folin and Svedberg’s results with ours, however,
present.s a more difficult situation, since these authors also claim
that their figures represent the true relation between the sugar
contents of corpuscles and plasma. In order to scrutinize the
validity of our previous findings, we undertook an experimental
reexamination of the problem. Such revision seemed the more
desirable as we now possess, in the method of deproteinization
with zinc or copper, a simple and more direct approach to the
determination of true sugar than in our past work, where true
sugar was obtained as the difference of two separately determined
reduction values.
In the present work sugar was determined in whole blood after
deproteinization with zinc (6), and in plasma after deproteiniza-
tion with copper (7). In addition the cell volume was obtained
for the calculation of corpuscle sugar. (As pointed out in our
older work, corpuscle sugar values obtained by direct determina-
tion are worthless, since they are always too low because of loss
by glycolysis during centrifugation.) In Table I are present,ed
the results of fifteen experiments, the first nine samples obtained
from healthy individuals, the remaining six from diabetic patients.
The average of the distribution ratio for the fifteen cases is 0.79,
with variations from 0.70 to 0.86 in the non-diabetic, and from
0.75 to 0.84 for the diabetic cases, figures that fully confirm our
previous results. We believe it to be a fair proof of accuracy and
correctness that two substantially different analytical procedures
 M. Somogyi 733

(both carefully checked with all available criteria for adequacy)

led to practically identical results.
Inspection of Folin and Svedberg’s analytical data, on the other
hand, reveals that these authors determined total reduction values
and not the true sugar in plasma. Granting that their figures for
whole blood represent true sugar values (this is possible if loss of

TABLE I
Distribution of Sugar between Corpuscles and Plasma in Human Blood

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The figures represent true sugar values determined in zinc filtrates.

II-
-7

Sugar per 100 cc. of

Exper;xent Ratio corpuscle sugar
Ml volume
Vhole blood Plasma TCorpuscles plasma sugar
:cslculated )
-
per cent ml. mg. WJ.
1 42 99 106 89 0.84
2 45 98 108 86 0.80
3 45 111 125 94 0.75
4 44 92 106 75 0.71
5 48 114 122 105 0.86
6 48 117 132 101 0.77
7 47 129 147 109 0.74
8 36 103 111 89 0.80
9 50 137 160 114 0.70
10 43 182 196 163 0.83
11 44 233 253 207 0.82
12 44 228 246 205 0.83
13 48 262 285 239 0.84
14 47 367 408 321 0.79
15 36 405 445 334 0.75
-
Lowest................................... .. ... . 0.70
Highest .............. .......... 0.86
Average. ............ .......... ... .. . 0.79

sugar with the precipitated unlaked corpuscles approximately

cancels the amount of non-sugar reducing substances derived from
the plasma), the fact that for plasma total reduction values were
substituted for true sugar still remains an appreciable source of
error. We shall presently show that, slight and negligible as the
amount of non-sugar reducing substances in plasma may appear
(5 to 6 mg. per cent in equivalents of glucose as determined by the
734 Distribution of Blood Sugar

FolkWu method),’ it suffices grossly to distort the true picture of

the distribution of sugar. The relations involved can be best
demonstrated with Folin and Svedberg’s own figures, as given
in the accompanying tabular matter, by showing how the distribu-
tion ratio is affected when the plasma sugar values are corrected
by the deduction of 5 mg. per cent of reducing non-sugars.
Uncorrected Corrected
mg. per cent mg. per cent
First case of Table I (Adams)

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Sugar in unlaked whole blood.. . . . . . . . . . . . . . 72 72
Plasmasugar............................... 86 81
Corpuscle sugar, calculated on basis of cell
volume of 42 per cent.. . . . . . . . . . . . . . . . . . . . 53 60
Ratio of distribution, corpuscle sugar : plasma
sugar..................................... 0.61 0.74
Case 7 in Table III
Sugar in unlaked whole blood.. . . . . . . . . . . . . 73 73
Plasmasugar............................... 87 82
Cell volume 50 per cent, corpuscle sugar (cal-
culated)................................... 59 64
Ratio of distribution.. .. ... ... ... ... .. .. .. 0.68 0.78

It is evident from these examples that when the apparent plasma

sugar values, as recorded in Folin and Svedberg’s tables, are re-
placed by corrected values which are nearer true sugar values, the
distribution ratio proves to be considerably higher than calculated
by Folin and Svedberg. In fact, the results are well in accord
with our own.
The two examples above are representative of normal cases
with low blood sugar level. The following is the diabetic Case 1
in their Table III.
Uncorrected Corrected
nag. per cent“8. per cent
Sugar in unlaked whole blood.. . . . . . . . . . . . . . . . 230 230
Plasmasugar................................. 263 258
Corpuscle sugar, calculated on basis of cell
volume of 42 per cent.. . . . . . . . . . . . . . . . . . . . . . 184 191
Ratio of distribution.. .... .. ... ... .. ... ... ... . 0.69 0.74

‘In a previous paper (this Journal, 80, 738 (1928)), Somogyi and
Kramer reported a figure of 4 mg. of non-glucose reducing material per
100 cc. of plasma (four determinations). The average figure obtained
from over a dozen such determinations is about 5 mg. per cent.
 M. Somogyi 735

As can be seen, the correction of the plasma sugar entails in the

diabetic case, as in the non-diabetic, a rise in the distribution ratio
and at once removes the apparent difference between the distribu-
tion ratios of diabetic and nondiabetic cases. The difference is
actually nonexistent, and its origin is explained by a simple
arithmetical consideration. It can be seen in the above examples
that the inclusion of the reducing non-sugar substances in the
plasma sugar values lowers in both diabetic and non-diabetic cases
the quotient representing the distribution of blood sugar. This

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effect is the more marked the lower the blood sugar level is, while
at, very high hyperglycemic levels it becomes almost negligible.
As a result of this relation Folin and Svedberg obtain distribution
ratios for the blood of healthy, fasting subjects that are much too
low, and at the same time are led to the misconception that the
ratio in the diabetic (hyperglycemic) cases is higher than in the
non-diabetic.
BIBLIOGRAPHY

1. Folin, O., and Svedberg, A., J. Biol. Chem., 88, 715 (1930).
2. Somogyi, M., J. Biol. Chem., 76, 33 (1927).
3. Somogyi, M., J. Biol. Chem., 78, 117 (1928).
4. Ege, R., and Roche, J., Skand. Arch. Physiol., 69, 75 (1930).
5. Somogyi, M., Arch. Int. Med., 42, 931 (1928).
6. Somogyi, M., J. Biol. Chem., 86, 655 (1930).
7. Somogyi, M., J. Biol. Chem., 90,726 (1931).
 NOTE ON THE DISTRIBUTION OF
BLOOD SUGAR
Michael Somogyi
J. Biol. Chem. 1931, 90:731-735.

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