Efuni Diabetes

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 1219) 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 1. Galenok V.G., Dicker V.E. In: Hypoxia and carbohydrate metabolism. Novosibirsk. 1986 (in Russian). 2. Galenok V.G., Gostsinkaya E. V., Khodas M.Ya., et al. In: Hemorheology in disturbed carbohydrate metabolism. Novosibirsk. 1987 (in Russian). 3. Kakhnovsy I.M., Efuny S.N., Khodas MLYa., et al. Clinical Medicine. 9. 83-88. 1981 (in Russian). 333 4. Kakhnosvky I.M., Kutznekov D.A., Mosolova LA., et al. Terapevti chesky arkhiv. 8. 79-84. 1983 (in Russian). 5. Kakhnosvky I.M., Pogosbekyan L.M., Bokaneva I.A., et al. Soviet Medicine. 10. 33-37. 1980 (in Russian). 6. Kodolova I.M., Lysenki L.V., Saltykov B.B. Arkiv. Patologii. 64. (7). 35-40 (in Russian). 7. Losev N.I., Khisrov N.K., Grachev S.V. In: Pathophysiology of hypoxemic states and the body's adaptation to hypoxia. Moscow. 1982. (in Russian). 8. Blecher M. Clin. Chem. 25. (1). 11-19. 1979. 9. Ditzel J., Dyeborg N.K. Metabolism 26. 141-150. 1977. 10. Forgne M.E., Freichet P. Diabetes. 24. 715-723. 1975. 11. Grabnir K.K., Neruzkar S.G., Cruz J.A. Hormone M eta bo I. Res. 12. (8). 414415. 1980. 12. Moscowwitz P., Meite S., Moscowwitz A. Science. 149. 72-79. 1965. 13. Opie L.H. Lancet. I 7796. 192-195. 1973. 14. Stande E. Fortschr. Med. B94. (10). 573-575. 1976. 15. Tegos C, Bender E. J. Lab. Clin. Med. 96. (2) 85-89. 1980.

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 with HBO

p

Group 2 no HBO

p

Plasma STG level nmole/l (0.2 ± 0.02) before treatment after treatment

1.48 ± 0.12 0.16 ± 0.01

xx

1.35 ± 0.19 0.67 ± 0.11

x

Plasma glycogen level nmole/l (0.02 ± 0.001) before treatment after treatment

0.16 ± 0.006 0.04 ± 0.003

xxx

0.14 ± 0.01 0.07 ± 0.02

x

Plasma daily catecholamines nmole/l (30.8 ± 4.5) before treatment after treatment

59.2 ± 3.05 42.7 ± 4.2

x

58.8 ± 3.1 50.3 ± 3.03

Plasma 6-peptide level nmole/l (0.74 ± 0.12) before treatment after treatment

0.14 ± 0.02 0.36 ± 0.04

xxx

0.16 ± 0.03 0.12 ± 0.08

Total dose of exogenous insulin (units) before treatment after treatment

67.7 ± 1.8 56.1 ± 1.6

xxx

53.3 ± 2.0 73.4 ± 2.3

p1

xx

xxx

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

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 with HBO

p

Group 2 no HBO

p

Plasma lactate level nmole/l (1.44 ± 0.44) before treatment after treatment

2.40 ± 0.06 2.00 ± 0.05

xxx

2.45 ± 0.12 2.10 ± 0.15

Number of alphaGPDG granules units (10.2 ± 0.6) before treatment after treatment

3.7 ± 0.2 8.1 ± 0.3

xx

4.1 ± 1.6 5.8 ± 0.6

x

Alpha-GPDG granules activity units (149.6 ± 2.56) before treatment after treatment

117.7 ± 2.5 139.3 ± 2.4

xxx

113.7 ± 6.2 126.4 ± 5.4

x

Number of SDG granules units (17.2 ± 1.3) before treatment after treatment

13.8 ± 0.3 17.7 ± 0.2

xx

14.3 ± 0.9 16.3 ± 0.8

SDG activity units (221 ± 10.2) before treatment after treatment

192.8 ± 3.9 237.3 ± 3.5

xxx

199.7 ± 6.9 319.3 ± 6.8

True intra-erythrocytic pH value (7.19 ± 0.01) before treatment after treatment

7.10 ± 0.01 7.15 ± 0.01

x

7.11 ± 0.01 7.13 ± 0.02

Metabolic intraerythrocytic pH value (7.18 ± 0.02) before treatment after treatment

7.13 ± 0.01 7.18 ± 0.01

x

7.13 ± 0.01 7.15 ± 0.01

x

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

p1

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 With HBO

p

Group 2 no HBO

p

p1

HbA1c level % (6.40 ± 0.34) before treatment after treatment

17.18 ± 0.14 11.9 ± 0.26

xxx

17.15 ± 0.48 15.01 ± 0.47

xx

xxx

2,3-DPG content mmole/l (4.32 ± 0.18) before treatment after treatment

3.85 ± 0.13 4.31 ± 0.06

x

3.19 ± 0.19 4.08 ± 0.12

x

Oxyhemoglobin dissociation curve at pH 7.40 (26.4 ± 0.54) before treatment after treatment

26.5 ± 0.4 27.6 ± 0.5

xx

25.7 ± 0.3 26.9 ± 0.6

25.2 ± 0.5 0.36 ± 0.04

xx

25.3 ± 0.4 26.4 ± 0.6

95.17 ± 0.16 96.16 ± 0.14

xxx

94.90 ± 0.14 95.00 ± 0.21

Oxyhemoglobin dissociation curve at pH 7.20 (26.4 ± 0.5) before treatment after treatment Hb saturation with oxygen (HbO2) in % (95.0 ± 3.0) before treatment after treatment

xxx

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