DIABETES
Diabetes mellitus or ‘sugar diabetes’ is the most common glandular condition in North America. It affects 10 to 25 million people, most of whom have yet to be diagnosed. Diabetics run an above-average risk of developing heart disease and stroke, the leading causes of death in the USA and Canada. Given that most types of diabetes and its complications are related to life-style and environment, this is for the most part a preventable problem.
Diabetes mellitus is an insulin disorder that impairs the body’s ability to metabolize sugar. The important hormone insulin is responsible for the absorption of sugar into cells for on-demand energy and into the liver and fat cells for energy storage. There are two principal types of diabetes mellitus.
In type 1 diabetes mellitus, insulin-producing cells in the pancreas are destroyed. With regular injections of insulin, the patient may lead a normal life. Without it, he or she may lapse into coma and die.
In type 2 diabetes mellitus, pancreatic production of insulin is diminished or the body gradually loses its ability to utilize it. This is by far the most common form of diabetes and is usually linked to bad eating habits, obesity and poor life-style.
Both type 1 and type 2 diabetes are generally characterized by high blood sugar (hyperglycemia) but in cases of overmedication or illness/stress during medication blood sugar levels can plummet (hypoglycemia). Both events are potentially serious.
Hyperglycemia produces excessive thirst and urination, fatigue, weight loss, and dehydration. Occasionally, life-threatening illnesses (hyper-os-molar coma or ketoacidosis) may result from excessive sugar levels. These are medical emergencies requiring immediate hospitalization.
Some diabetics take insulin injections or pills to lower sugar levels and are susceptible to the complications of low blood sugar levels. This may happen because they take too much medication, miss a meal, increase their energy expenditures, become sick or febrile, or suffer any sort of stress. This condition too must be treated immediately. Usually, a sweet drink or food is enough and produces rapid results.
Apart from the emergencies resulting from such blood sugar imbalances, most diabetics fall ill from complications of diabetes itself, of which there are two types: reduced ability to fight infection and damage to the circulatory system, including both small and large blood vessels. These complications can cause symptomatic problems with the eyes, muscle, kidneys and bladder. They can also reduce energy levels, promote thirst, and cause tingling in the extremities. Cardiovascular plaque buildup is another result of diabetic complications.
DIABETES AND THE IMMUNE SYSTEM
Diabetics should be considered immune-compromised because they are prone to many more infections than they can normally resist. Their immune systems may be overwhelmed by thrush and other fungal infections of the skin and even of the bloodstream. Bacterial infections are more common and their consequences are serious – gangrene (especially of the toes and foot) and sepsis. Diabetics with any sort of infection must always be treated immediately and aggressively.
Most illness and death in diabetics is caused by circulatory damage. This can include heart disease, myocardial infarction, high blood pressure, atherosclerosis, stroke, renal failure, neuropathy, blindness and other effects of impaired blood circulation. In fact, diabetic complications are the major cause of blindness in the USA. Diabetics are also more prone to cataracts and glaucoma.
GLUTATHIONE’S ROLE IN DIABETES
GSH plays an important role in the fight against diabetes. We have seen that it can prevent circulatory problems such as arteriosclerosis and stroke – the main causes of diabetic death. GSH also enhances the immune system. Many visits to the doctor or hospital could be avoided if diabetics were less prone to infection. Elevated GSH levels may help by providing:
? Immune system support against infection
? Decrease of oxidative stress from hyperglycemia
? Decrease of platelet aggregation
? Prevention of vascular complications including:
? Atherosclerosis (including heart disease, stroke)
? Nephropathy (kidney damage)
? Retinopathy (retinal damage)
? Neuropathy (nerve damage)
In this way, GSH can help weakened immune system combat bacterial infection and fungal infection, support compromised circulation against hardening of the arteries (arteriosclerosis), kidney failure (nephropathy), visual loss (retinopathy) and neurological problems (neuropathy). It also retards oxidative stress and anemia in dialysis patients.
It is clear that the small blood vessels of diabetics are subject to accelerated degeneration, but the causes of this particular illness are still being identified. Recent studies demonstrate that diabetics are more prone than others to oxidative stress and free radical formation. In fact, the blood and tissues of diabetics are marked by critically low GSH levels.
R.K. Sundaram’s studies suggest that this antioxidant deficiency precedes the subsequent complications of diabetes. K. Yoshida and his research group have shown that low or weak GSH synthesis leads to increased cellular damage and other complications. Going one step further, Thornalley’s trials revealed a correspondence between low GSH levels
and higher diabetic complications. S.K. Jain & R. McVie suggest that the low GSH levels characteristic of diabetes play a role in impaired insulin secretion in uncontrolled diabetic patients.
Many researchers have established a link between low GSH levels and a higher likelihood of endothelial damage, with increased platelet aggregation.
Other researchers have looked more specifically at the relationship of GSH to isolated complications such as hypertension, diabetic neuropathy and nephropathy, with favorable results. The role of GSH in protecting red blood cells from oxidative damage in the case of renal dialysis is also very promising.
CASE STUDY
Deana was a motivated, positive entrepreneur who developed a wellness health center even though she suffered from a serious case of diabetes. Increasingly fatigued, this 32 year-old Texan continued to run her center even after receiving and rejecting a kidney transplant, failing eyesight and dialysis treatments. Eventually she developed a chronic foot infection that required weekly debriding of dead tissue. Her doctor feared that amputation might prove necessary. She began taking high doses of the whey protein isolate Immunocal and found her energy levels increased over several weeks. Kidney function tests and hemoglobin levels improved. Medication doses for her anemia and hypertension were decreased or eliminated. Peripheral circulation was better. Five months later the foot was healed. Deana has since married and continues to run her clinic.
CONCLUSION
Circulatory damage contributes substantially to diabetic complications and GSH helps fight the oxidative damage that contributes to this damage. In fact, the blood and tissues of diabetics are marked by critically low GSH levels. These complications could be avoided or minimized if diabetics were less prone to infection, and elevated GSH levels may help accomplish that.
REFERENCES TO DIABETES
BRAVENBOER B, KAPPELLE AC, HAMERS FPT, VAN BUREN T, ERKELENS DW, GISPEN WH. Potential use of glutathione for the prevention and treatment of diabetic neuropathy in the streptozotocin-induced diabetic rat. Diabetologia 35:813-817, 1992
CERIELLO A, CURCIO F, DELLO RUSSO P, PEGORARO I, STEL G, AMSTAD P, CERUTTI P. The defense against free radicals protects endothelial cells from hyperglycemia-induced plasminogen activator inhibitor 1 over-production. Blood Coagulation and Fibrinolysis 6:133-137, 1995
CERIELLO A, GIACOMELLO R, STEL G, MOTZ E, TABOGA C, TONUTTI L, PIRISI M, FALLETI E, BARTONI E. Hyperglycemia-induced thrombin formation in diabetes. The possible role of oxidative stress. Diabetes 44:924-928, 1995
CERIELLO A, MOTZ E, CAVARAPE A, LIZZIO S, RUSSO A, QUATRARO A, GIUGLIANO D. Hyperglycemia counterbalances the antihypertensive effect of glutathione in diabetic patients: evidence linking hypertension and glycemia through the oxidative stress in diabetes mellitus. Journal of Diabetes Complications 11:250-255, 1997
CIUCHI E, ODETTI P, PRANDO R. Relationship between glutathione and sorbitol concentrations in erythrocytes from diabetic patients. Metabolism 45:611-613, 1996
CIUCHI E, ODETTI P, PRANDO R. The effect of acute glutathione treatment on sorbitol level on erythrocytes from diabetic patients. Diabetes Metabolism 23:58-60, 1997
CURCIO F, CERIELLO A. Decreased cultured endothelial cell proliferation in high glucose medium is reversed by antioxidants: new insights on the pathophysiological mechanisms of diabetic vascular complications. In Vitro Cell Developmental Biology 28A: 787-790, 1992
CURCIO F, PEGORARO I, DELLO RUSSO P, FALLETI E, PERRELLA G, CERIELLO A. SOD and GSH inhibit the high glucose-induced oxidative damage and the PDGF increased secretion in cultured human endothelial cells. Thrombolysis and Hemostasis: 74:969-973, 1995
DI SIMPLICIO P, DE GIORGIO LA, CARDAIOLI E, LECIS R, MICELI M, ROSSI R, ANICHINI R, MIAN M, SEGHIERI G, FRANCONI F. Glutathione, glutathione utilizing enzymes and thioltransferase in platelets of insulin-dependent diabetic patients: relation with platelet aggregation and with microangiographic complications. European Journal of Clinical Investigation 25A: 665-669, 1995
DONNINI D, ZAMBITO AM, PERRELLA G, AMBESI-IMPIOMBATO FS, CURCIO F. Glucose may induce cell death through a free radical-mediated mechanism. Biochem Biophys Research Communications 219: 412-417, 1996
JAIN SK, MCVIE R. Effect of glycemic control, race and duration of diabetes on reduced glutathione content in erythrocytes of diabetic patients. Metabolism 43: 306-309, 1994
KAKKAR R, MANTHA SV, RADHI J, PRASAD K, KALRA J. Antioxidant defense system in diabetic kidney: a time course study. Life Science 60: 667-679, 1997
Kashiwagi A, Asahina T, Nishio Y, Ikebuchi M, Tanaka Y, Kikkawa R, Shigeta Y. Glycation, oxidative stress, and scavenger activity: glucose metabolism and radical scavenger dysfunction in endothelial cells. Diabetes 45: S84-S86, 1996
LOW PA, HICKANDER KK. TRITSCHLER HJ. The roles of oxidative stress and antioxidant treatment in experimental diabetic neuropathy. Diabetes 46: S38-S42, 1997
MURAKAMI K, KONDO T, OHTSUKA Y, FUJIWARA Y, SHIMANDA M, KAWAKAMI Y. Impairment of glutathione metabolism in erythrocytes from patients with diabetes mellitus. Metabolism 38:753-758, 1989
RUDICH A, KOZLOVSKY N, POTASHNIK R, BASHAN N. Oxidant stress reduces insulin responsiveness in 3T3-L1 adipocytes. American Journal of Physiology 272:E935-E940, 1997
SUNDARAM RK, BHASKAR A, VIJAYALINGAM S, VISWANATHAN M, MOHAN R, SHANMUGASUNDARAM KR. Antioxidant status and lipid peroxidation in type II diabetes mellitus with and without complications. Clinical Science 90:255-260, 1996
THORNALLEY PJ, MCLELLAN AC, LO TW, BENN J, SONKSEN PH. Negative association between erythrocyte reduced glutathione concentration and diabetic complications. Clinical Science 91:575-582, 1996
VIJAYALINGAM S, PARTHIBAN A, SHANMUGASUNDARAM KR, MOHAN V. Abnormal antioxidant status in impaired glucose tolerance and non-insulin-dependent diabetes mellitus. Diabetic Medicine 13:715-719, 1996
YOSHIDA K, HIROKAWA J, TAGAMI S, KAWAKAMI Y, URATA Y, KONDO T. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux. Diabetologia 38:201-210, 1995
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