gamma-linolenic-acid and Diabetes-Mellitus

Hyperglycemia is one of the main metabolic disturbances in critically-ill patients and is associated with increased morbidity and mortality. Consequently, blood glucose levels must be safely and effectively controlled, that is, maintained within a normal range, avoiding hypoglycemia on the one hand and elevated glucose concentrations on the other. To accomplish this aim, insulin is often required, avoiding protocols designed to achieve tight glycemic control. To prevent hyperglycemia and its associated complications, energy intake should be adjusted to patients' requirements, avoiding overnutrition and excessive glucose intake. Protein intake should be adjusted to the degree of metabolic stress. Whenever patients require artificial feeding, the enteral route, if not contraindicated, should be used since parenteral nutrition is associated with a higher frequency of hyperglycemia and greater insulin requirements. Enteral nutrition should be administered early, preferably within the first 24 hours of admission to the intensive care unit, after hemodynamic stabilization. Specific diets for hyperglycemia, containing low glycemic index carbohydrates and fibre and enriched with monounsaturated fatty acids, can achieve good glycemic control with lower insulin requirements.

Topics: Blood Glucose; Consensus; Critical Illness; Diabetes Mellitus; Dietary Fiber; Dietary Proteins; Eicosapentaenoic Acid; Energy Intake; Enteral Nutrition; gamma-Linolenic Acid; Glutamine; Glycemic Index; Humans; Hyperglycemia; Hypoglycemic Agents; Insulin; Nutritional Support; Parenteral Nutrition; Trace Elements; Vitamins

A substantial disturbance of the metabolism of the n-6 essential fatty acids (EFAs) exists in both human and experimental diabetes mellitus. The process of conversion of dietary linoleic acid to gammalinolenic, dihomogammalinolenic and arachidonic acids, and other polyunsaturates is inadequate in diabetic patients. Disturbances of these EFAs and the 1- and 2-series prostaglandins derived from them cause a variety of microvascular, haemorheological, and other abnormalities leading to reduced blood flow and neural hypoxia. This will in turn produce an escalating cycle of further hypoxia through the generation of oxygen-free radicals and aggravation of neural capillary endothelial damage. Endoneurial hypoxia impairs axonal transport, produces demyelination, and reduces neural ATP-ase activity. Furthermore, depletion of polyunsaturated fatty acids derived from n-6 pathway may lead to abnormalities of myelin turnover, membrane-bound proteins (such as enzymes and receptors) and other axonal structural abnormalities. The disorders postulated here may synergistically interact with the metabolic changes described in both the glycosylation and the myoinositol hypotheses and may have important implications in the approach to treat diabetic neuropathy.

Topics: Diabetes Mellitus; Diabetic Neuropathies; Dietary Fats; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Models, Biological

Linoleic acid is the main dietary essential fatty acid (EFA). To be fully utilized by the body, it must be metabolized to a range of other substances. The first step in this pathway is delta-6-desaturation to gamma-linolenic acid (GLA). This step is slow and rate-limiting, particularly in humans. If delta-6-desaturation is impaired for any reason, the supply of further metabolites may be inadequate for normal function. If the consumption of further metabolites is excessive, then a normal rate of delta-6-desaturation may be inadequate. In these circumstances the direct supply of GLA or further metabolites may be of value. This concept is illustrated by atopic eczema and diabetes, which may represent inherited and acquired examples of inadequate delta-6-desaturation.

Topics: Dermatitis, Atopic; Diabetes Mellitus; Diabetic Neuropathies; Fatty Acid Desaturases; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linoleic Acid; Linoleic Acids; Linolenic Acids; Linoleoyl-CoA Desaturase

Topics: Aged; Autoimmune Diseases; Cardiovascular Diseases; Child; Dermatitis, Atopic; Diabetes Mellitus; gamma-Linolenic Acid; Humans; Linolenic Acids; Nutritional Physiological Phenomena

The cardioprotective properties of linoleic acid (LA), a major n-6 (ω-6) polyunsaturated fatty acid (PUFA), have been recognized, but less is known about its associations with other causes of death. Relatively little is also known about how the minor n-6 PUFAs-γ-linolenic acid (GLA), dihomo-γ-linolenic acid (DGLA), and arachidonic acid (AA)-relate to mortality risk.. We investigated the associations of serum n-6 PUFAs, an objective biomarker of exposure, with risk of death in middle-aged and older men and whether disease history modifies the associations.. We included 2480 men from the prospective Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42-60 y at baseline in 1984-1989. The stratified analyses by baseline disease status included 1019 men with a history of cardiovascular disease (CVD), cancer, or diabetes and 1461 men without a history of disease.. During the mean follow-up of 22.4 y, 1143 deaths due to disease occurred. Of these, 575 were CVD deaths, 317 were cancer deaths, and 251 were other-cause deaths. A higher serum LA concentration was associated with a lower risk of death from any cause (multivariable-adjusted HR for the highest compared with the lowest quintile: 0.57; 95% CI: 0.46, 0.71; P-trend < 0.001) and with deaths due to CVD (extreme-quintile HR: 0.54; 95% CI: 0.40, 0.74; P-trend < 0.001) and non-CVD or noncancer causes (HR: 0.48; 95% CI: 0.30, 0.76; P-trend = 0.001). Serum AA had similar, although weaker, inverse associations. Serum GLA and DGLA were not associated with risk of death, and none of the fatty acids were associated with cancer mortality. The results were generally similar among those with or without a history of major chronic disease (P-interaction > 0.13).. Our findings showed an inverse association of a higher biomarker of LA intake with total and CVD mortality and little concern for risk, thus supporting the current dietary recommendations to increase LA intake for CVD prevention. The finding of an inverse association of serum AA with the risk of death needs replication in other populations.

Topics: 8,11,14-Eicosatrienoic Acid; Adult; Arachidonic Acid; Biomarkers; Body Mass Index; Cardiovascular Diseases; Diabetes Mellitus; Diet; Fatty Acids, Omega-6; Follow-Up Studies; gamma-Linolenic Acid; Humans; Incidence; Linoleic Acid; Male; Middle Aged; Mortality; Neoplasms; Prospective Studies; Risk Factors; Socioeconomic Factors

Topics: Diabetes Mellitus; Expert Testimony; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Hypoglycemic Agents; Linoleic Acids; Oenothera biennis; Plant Oils; Professional Misconduct

Genetically diabetic mice (db/db) and their non-diabetic litter-mates were maintained for 15 weeks on diets supplemented with safflower oil or evening primrose (Oenothera bienis) oil, both essential fatty acid (EFA)-rich sources, or hydrogenated coconut oil (devoid of EFA). Plasma glucose was higher in the diabetic mice supplemented with the oils than in the unsupplemented diabetic mice. In the oil-supplemented non-diabetic mice, plasma glucose did not differ compared with the unsupplemented non-diabetic mice. The proportional content of arachidonic acid in the phospholipids of the pancreas was significantly decreased in diabetic mice, an effect which was completely prevented by supplementation with safflower or evening primrose oil but not hydrogenated coconut oil. In the liver phospholipids of the diabetic mice, dihomo-gamma-linolenic acid was proportionally increased, an effect reduced by supplementation with safflower oil but not evening primrose or hydrogenated coconut oils. In the liver triglycerides of the diabetic mice, gamma-linolenic acid, dihomo-gamma-linolenic acid and arachidonic acid were all proportionally decreased, effects which were also prevented by safflower or evening primrose oil but not hydrogenated coconut oil. Alopecia and dry scaly skin were prominent in the diabetic mice but less extensive in the diabetic mice supplemented with EFA.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus; Fatty Acids, Essential; gamma-Linolenic Acid; Linoleic Acid; Linoleic Acids; Linolenic Acids; Lipids; Liver; Mice; Mice, Inbred C57BL; Organ Size; Pancreas; Phospholipids; Skin; Triglycerides

Drugs which modify the conversion of essential fatty acids to prostaglandins and leukotrienes are the mainstays of treatment in rheumatology. Yet these drugs have little or no action in scleroderma or Sjogren's syndrome and under some circumstances may have adverse effects. Patients with scleroderma have been shown to have very high levels of circulating prostaglandins, coupled with depletion of the prostaglandin precursors, dihomogammalinolenic acid and arachidonic acid. Levels of the metabolites of arachidonic acid, 22:4n-6 and 22:5n-6, which have major roles in maintaining normal cell membrane characteristics were exceptionally low in both plasma and red cell membranes. Others have observed that various functions are highly resistant to normal actions of PGs in scleroderma. This raises the possibility that the high rate of PG formation in scleroderma may be beneficial, in compensation, and that clinical symptoms develop when PG precursors begin to be depleted. Red cell membrane fatty acids patterns in Sjogren's syndrome are almost identical to those in scleroderma. Placebo-controlled trials of supplementation with essential fatty acids have been found to be beneficial in both scleroderma and Sjogren's syndrome.

Topics: Animals; Ascorbic Acid Deficiency; Connective Tissue Diseases; Cyclic AMP; Diabetes Mellitus; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Linolenic Acids; Prostaglandins; Scleroderma, Systemic; Sjogren's Syndrome

Available evidence--some well-documented, some only preliminary--suggests that properly-designed nutritional insurance supplementation may have particular value in diabetes. Comprehensive micronutrient supplementation providing ample doses of antioxidants, yeast-chromium, magnesium, zinc, pyridoxine, gamma-linolenic acid, and carnitine, may aid glucose tolerance, stimulate immune defenses, and promote wound healing, while reducing the risk and severity of some of the secondary complications of diabetes.

Topics: Animals; Antioxidants; Ascorbic Acid; Calcium; Carnitine; Chromium; Diabetes Mellitus; gamma-Linolenic Acid; Humans; Linolenic Acids; Magnesium; Pyridoxine; Selenium; Thioctic Acid; Ubiquinone; Vitamin E; Zinc