HBO IN THE METABOLIC CONTROL OF INSULIN-DEPENDENT

DIABETES MELLITUS : A CONTROLLED STUDY

S.E. Efuni, I.M. Kakhnovsy, V.V. Rodionov . All Union Institute of Surgery, Moscow, USSR

SUMMARY

We have treated 289 patients -with insulin-dependent diabetes mellitus (IDDM). 137 patients were
treated with metabolic control (control) and 152 patients received in addition adjunctive hyperbaric
oxygen (HBO) therapy. Glycaemia was lowered on an average of 7.32 mmol/L in the HBO group and
on an average of 4.9 mmol/L in the control group. To achieve these results we had to increase the
insulin requirements on an average of 22.1 units in the control group, whereas it was possible to
reduce these requirements by 8 to 38 units in the HBO group. HBO similarly allowed an increase in
S-peptid, STH, glucagon whereas these factors were diminished in the control group. HbAl c was
better controlled in the HBO group. We suggest that HBO is a valuable adjunct in the treatment of
decompensated IDDM except for cases with a labile course and freqUent hypoglycaemic fits,
proliferative diabetic retinopathy and Kimmelstiel Wilson's disease.

KEY WORDS
Metabolic control, insulin-dependent diabetes mellitus, IDDM, hyperbaric oxygen
therapy.
INTRODUCTION
Hormonal imbalance in decompensated diabetes mellitus causes changes in
metabolism, hormone reception and microcirculation. Lowered glucose utilization
heightens the use of lipids and amino acids as the major sources of energy whose
complete catabolism is realized once O2 supply is increased by an average of 20%
(13). Disturbed glycolysis in the erythrocytes results in elevated HbA Ic and
lowered 2,3 DPG concentrations as well as acid shifts in pH values followed by
hampered oxygen transporting functions of the erythrocytes (1,4,9,14,15).
Disturbed circulation is due to disturbed endo-, exo- and vascular parameters (5).
These events depend of the dissolution of oxygen in the protein-lipid film
surrounding the surface of the capillaries and the erythrocytes, the formation of
plasmic thrombi and intravascular stasis as well as still more drastic changes in the
transport and utilisation of oxygen by the tissues (2,3,6,7,12). Disturbed metabolism
and microcirculation in diabetes change the sensitivity of receptors through inhibiting
or hindering their bonding with insulin by 30-50% (8,10,11). This is why diabetic
patients need more exogenous insulin. Under such conditions, the conventional
therapy of decompensated diabetes might prove insufficiently effective since it is
impossible to completely correct carbohydrate, lipid and protein metabolism in
disturbed tissue respiration and energy deficit. Hyperbaric oxygenation offers such
possibilities.

MATERIAL AND METHODS

We have studied 289 patients with decompensated insulin-dependent diabetes
mellitus (IDDM). 158 were males, 131 females, 80% of the patients were less than
40 years old, 52% of them had a disease history of more than 5 years. Diabetic
microangiopathies were present in 80% of the cases. 24% of the patients had no
acid-base disturbances. 29% had an arterial hypoxemia with a PO, Index of
9.23-0.1 kPa, 26% had a partially compensated metabolic acidosis, 15% an
arterial hypoxemia with metabolic acidosis and 6% a partially compensated
respiratory alkalosis. The patients were divided in 2 groups. Group 1 (152 patients)
received 10-15 hyperbaric oxygen (HBO) treatments of 60 minutes each in
addition to conventional metabolic control. The chamber pressure was raised to
1.7-2.0 ATA. Group 2 (137 patients) received only metabolic control and served
as control group. Patients with severe IDDM were preferentially allocated to the
HBO treatment.

RESULTS
All the patients of group 1 reported a marked subjective improvement; pain in the
extremities disappeared and visual acuity improved. In 72.5% of the patients, the
improvement was present after 3-5 treatments and in 22.8% after 5-7 treatments.
Patients also reported slight hypoglycaemic sensations so that we started to reduce the
dose of insulin according to the glycaemia. At the end of the HBO treatment (at day 12-
19) the glycaemia was reduced to 7.24 -0.13 mmol/l in 95% of the patients. There was
a normoglycaemia in 37% and an aglucosuria in 41 % of the cases. The major
dynamic changes achieved by treatment are summarized in Tables 1, 2 and 3. Eight
patients of group 1, with severe IDDM and a disease history of more than 20 years
(5 with Kimmelstiel-Wilson's disease and proliferative retinopathy and 3 who ate
readily assimilated carbohydrates (for fear of hypoglycaemic sensations) did not
respond to metabolic control with adjunctive HBO therapy.
The metabolic improvement described in Table 2 occurred between day 12-19 in
group 1 and between day 25-27 in group 2. It was paralleled by an improvement in
blood gas analysis and in ABE values in 95% of the patients of group1. Hypoxia was
stopped and metabolic imbalances partially compensated after the 1st HBO
treatment. Ketonuria was abolished after the 2nd HBO treatment. Only 68.3% of
the patients of group 2 improved their blood gas analysis and ABE values. The
remaining patients of group 2 (31.7%) showed either the same metabolic imbalance or
changes from one type of disturbance to another, for example partially
compensated metabolic acidosis to compensated respiratory alkalosis.
Blood lactate normalised in 66.5% of the patients of group 1 and only in 34.4% of
the patients of group 2. Certain enzymatic activity like the alpha-GPDG granule
index increased by 18% (p<0.001) in group 1 and 11.1 % in group 2, and the SDG
activity index increased by 15% (p<0.001) in group 1 and 9% in group 2.
In our study, HBO enhanced the activity of NAD-dependent cytoplasmic and
mitochondria! enzymes, thus improving the transport and utilization of oxygen to
the tissues. Erythrocytes seem also to be reinvigorated by the HBO treatment. The
HbA 1 c content decreased by 31 % (p<0.001) at day 12-19 while the 2,3-DPG
concentration rose by an average of 13.2% (p<0.05) in 75.3% of the patients of group
1. In group 2, at day 2527, the decrease in HbA Ic was only 12.8% in 92% of the
cases and the increase in 2,3DPG concentration only 2.6% in 43.3% of the patients.
Thus the metabolic control of IDDM with adjunctive HBO promotes an earlier and
more profound activation of the aerobic glycolysis and of the oxygen transport
function of the erythrocyte. 75.6% of the patients of group 1 showed an
improvement in blood viscosity as well as in adhesiveness and aggregability of
platelets and erythrocytes. In 73.8% of the patients, the previously poor muscular
blood circulation improved by 20%.
Repeated fluorescent angiography of the retinal vessels 10-12 weeks after the
completion of the treatment revealed a reversion of the ischamic edema with
complete resorption of the microinfarctions in 50% of the patients. The number of
microaneurysms decreased in 25% of the patients; in another 33% the pathological
hyperpermeability of the microvessels lessened and the circulation of the contrast
substance was accelerated. There were no changes in the control group, the
ischaemic edema having become a source of neovascularization.

DISCUSSION
Hyperbaric oxygen therapy speeds the normalization of the glyco-dependent
metabolism. The blood gas composition, the acid-base equilibrium can be normalised
without angioprotectors, anticoagulants or lipolytic drugs. HBO possibly leads to an
enhancement of the residual function of the pancreatic beta cells. Exogenous insulin
requirements can rapidly be lowered without danger if the glycaemia is carefully
monitored.

CONCLUSIONS
Our results suggest that the adjunctive use of HBO is a valuable tool in the
management of decompensated IDDM. In our experience, HBO is not effective in
IDDM with a labile course and frequent hypoglycaemic fits, proliferative diabetic
retinopathy and Kimmelstiel-Wilson's disease.

REFERENCES

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415. 1980.
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Table 1 Comparison of the major dynamic changes in the hormonal status and doses of
exogenous insulin with type 1 diabetes mellitus receiving complex and conventional therapy

Index Group 1 p Group 2 p p1

with HBO no HBO

Plasma STG level

nmole/l (0.2 ± 0.02)
before treatment 1.48 ± 0.12 xx 1.35 ± 0.19 x
after treatment 0.16 ± 0.01 0.67 ± 0.11

Plasma glycogen level

nmole/l (0.02 ± 0.001)
before treatment 0.16 ± 0.006 xxx 0.14 ± 0.01 x
after treatment 0.04 ± 0.003 0.07 ± 0.02

Plasma daily
catecholamines
nmole/l (30.8 ± 4.5)
before treatment 59.2 ± 3.05 x 58.8 ± 3.1
after treatment 42.7 ± 4.2 50.3 ± 3.03

Plasma 6-peptide level

nmole/l (0.74 ± 0.12)
before treatment 0.14 ± 0.02 xxx 0.16 ± 0.03
xx
after treatment 0.36 ± 0.04 0.12 ± 0.08

Total dose of
exogenous insulin
(units)
before treatment 67.7 ± 1.8 xxx 53.3 ± 2.0 xxx xxx
after treatment 56.1 ± 1.6 73.4 ± 2.3

Normal values are given in ( )

p gives the significance of results before and after treatment p1 gives the significance
between both treatment groups after treatment.
p<0.05 = x, p<0.01 = xx, p<0.001 = xxx
Table 2 Comparison of some dynamic changes in the indices characterizing cellular
metabolism in patients with type 1 diabetes mellitus receiving adjunctive HBO or not

Index Group 1 p Group 2 p p1

with HBO no HBO

Plasma lactate level

nmole/l (1.44 ± 0.44)
before treatment 2.40 ± 0.06 xxx 2.45 ± 0.12
after treatment 2.00 ± 0.05 2.10 ± 0.15

Number of alpha-
GPDG granules units
(10.2 ± 0.6)
before treatment 3.7 ± 0.2 xx 4.1 ± 1.6 x
after treatment 8.1 ± 0.3 5.8 ± 0.6

Alpha-GPDG granules
activity
units (149.6 ± 2.56)
before treatment 117.7 ± 2.5 xxx 113.7 ± 6.2 x
after treatment 139.3 ± 2.4 126.4 ± 5.4

Number of SDG
granules
units (17.2 ± 1.3)
before treatment 13.8 ± 0.3 xx 14.3 ± 0.9
after treatment 17.7 ± 0.2 16.3 ± 0.8

SDG activity
units (221 ± 10.2)
before treatment 192.8 ± 3.9 xxx 199.7 ± 6.9
after treatment 237.3 ± 3.5 319.3 ± 6.8
True intra-erythrocytic
pH value (7.19 ± 0.01)
before treatment 7.10 ± 0.01 x 7.11 ± 0.01
after treatment 7.15 ± 0.01 7.13 ± 0.02
Metabolic intra-
erythrocytic pH value
(7.18 ± 0.02)
before treatment 7.13 ± 0.01 x 7.13 ± 0.01 x
after treatment 7.18 ± 0.01 7.15 ± 0.01

Normal values are given in ( )

p gives the significance of results before and after therapy; p1 gives the significance
between both treatment groups after treatment.
p<0.05 = x, p<0.01 = xx, p<0.001 = xxx
Table 3 Comparison of dynamic changes in the oxygen transport function of the erythrocytes
in patients with type 1 diabetes mellitus receiving complex and conventional therapy

Index Group 1 p Group 2 p p1

With HBO no HBO

HbA1c level %
(6.40 ± 0.34)
before treatment 17.18 ± 0.14 xxx 17.15 ± 0.48 xx xxx
after treatment 11.9 ± 0.26 15.01 ± 0.47

2,3-DPG content
mmole/l (4.32 ± 0.18)
before treatment 3.85 ± 0.13 x 3.19 ± 0.19 x
after treatment 4.31 ± 0.06 4.08 ± 0.12

Oxyhemoglobin
dissociation curve at pH
7.40 (26.4 ± 0.54)
before treatment 26.5 ± 0.4 xx 25.7 ± 0.3
after treatment 27.6 ± 0.5 26.9 ± 0.6

Oxyhemoglobin
dissociation curve at pH
7.20 (26.4 ± 0.5) 25.2 ± 0.5 xx 25.3 ± 0.4
before treatment 0.36 ± 0.04 26.4 ± 0.6
after treatment

Hb saturation with
oxygen (HbO2) in %
(95.0 ± 3.0)
before treatment 95.17 ± 0.16 xxx 94.90 ± 0.14 xxx
after treatment 96.16 ± 0.14 95.00 ± 0.21

Normal values are given in ( )

p gives the significance of results before and after therapy; p1 gives the significance
between both treatment groups after treatment.
p<0.05 = x, p<0.01 = xx, p<0.001 = xxx