gamma-linolenic-acid and Diabetes-Mellitus--Type-1

Impaired conversion of linoleic acid to gamma-linolenic acid (GLA) has been demonstrated in animal diabetes and inferred from blood fatty acid profiles in human diabetes. This impairment could theoretically lead to defective nerve function because metabolites of GLA are known to be important in nerve membrane structure, nerve blood flow, and nerve conduction. Administration of GLA corrects the impaired nerve function in animal models of diabetes. Two multicenter, randomized, placebo-controlled trials in humans with diabetic neuropathy have shown significant benefits of GLA as compared with placebo in neurophysiological parameters, thermal thresholds, and clinical sensory evaluations. Further work is needed to define the place of this therapeutic approach and its interactions with other treatment modalities.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Lipids; Rats

Topics: Alprostadil; beta-Thromboglobulin; Blood Glucose; Blood Platelets; Cholesterol; Diabetes Mellitus, Type 1; Diet; Fatty Acids; gamma-Linolenic Acid; Glycated Hemoglobin; Humans; Hypoglycemia; Insulin; Linolenic Acids; Lipids; Phospholipids; Platelet Aggregation; Prostaglandins E; Thromboxane B2; Triglycerides

Impaired conversion of linoleic acid to gamma-linolenic acid (GLA) has been demonstrated in animal diabetes and inferred from blood fatty acid profiles in human diabetes. This impairment could theoretically lead to defective nerve function because metabolites of GLA are known to be important in nerve membrane structure, nerve blood flow, and nerve conduction. Administration of GLA corrects the impaired nerve function in animal models of diabetes. Two multicenter, randomized, placebo-controlled trials in humans with diabetic neuropathy have shown significant benefits of GLA as compared with placebo in neurophysiological parameters, thermal thresholds, and clinical sensory evaluations. Further work is needed to define the place of this therapeutic approach and its interactions with other treatment modalities.

Topics: Animals; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Fatty Acids, Essential; gamma-Linolenic Acid; Humans; Lipids; Rats

To compare the effects of placebo and GLA on the course of mild diabetic neuropathy over 1 yr.. We entered 111 patients with mild diabetic neuropathy from seven centers into a randomized, double-blind, placebo-controlled parallel study of GLA at a dose of 480 mg/day. MNCV, SNAP, CMAP, hot and cold thresholds, sensation, tendon reflexes, and muscle strength were assessed by standard tests in upper and lower limbs.. For all 16 parameters, the change over 1 yr in response to GLA was more favorable than the change with placebo, and for 13 parameters, the difference was statistically significant. Sex, age, and type of diabetes did not influence the result, but treatment was more effective in relatively well-controlled than in poorly-controlled diabetic patients.. GLA had a beneficial effect on the course of diabetic neuropathy.

Topics: Analysis of Variance; Anti-Inflammatory Agents, Non-Steroidal; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Female; gamma-Linolenic Acid; Humans; Linolenic Acids; Male; Middle Aged; Motor Neurons; Neural Conduction; Neurologic Examination; Neurons, Afferent; Reflex

Our previous study demonstrated that levels of dihomo-gamma-linolenic acid (DGLA) and arachidonic acid in serum total lipids decreased in association with increased plasma levels of prostaglandins E2 (PGE2) and F2 alpha (PGF2 alpha) in patients with insulin-dependent diabetes mellitus. In this study, 11 children with insulin-dependent diabetes mellitus completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid (GLA) on serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. GLA was given as the seed oil from the evening primrose (EPO) and all patients received either EPO capsules (containing 45 mg of GLA and 360 mg of linoleic acid) or indistinguishable placebo capsules for 8 months. Initially patients took 2 capsules daily for 4 months then 4 capsules daily for a further 4 months. All patients were assessed at the start of the study, after 4 months and at the end of the study, by measuring serum essential fatty acid and plasma PGE2 and PGF2 alpha levels. After administration of 4 capsules daily the DGLA levels increased and PGE2 levels decreased significantly (p less than 0.01) in the EPO compared with the placebo group. Neither fatty acid nor PGE2 and PGF2 alpha levels were altered by administration of 2 EPO capsules daily. This suggests that the altered essential fatty acid and PG metabolism in diabetes may be reversed by direct GLA supplementation.

Topics: Adolescent; Child; Diabetes Mellitus, Type 1; Dinoprost; Dinoprostone; Double-Blind Method; Fatty Acids; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Linoleic Acids; Male; Oenothera biennis; Plant Oils; Prostaglandins

Twenty-two patients with distal diabetic polyneuropathy confirmed both clinically and by objective nerve function studies, completed a double-blind, placebo-controlled study to assess the effect of dietary supplementation with gamma-linolenic acid on their neuropathy. Patients received either 360 mg gamma-linolenic acid (12 patients) or indistinguishable placebo capsules (10 patients) for 6 months. All patients were assessed at the beginning and end of the study period by neuropathy symptom and sign scoring, motor and sensory nerve conduction studies, and thermal threshold measurements. When compared with the placebo group, patients on gamma-linolenic acid showed statistically significant improvement in neuropathy symptom scores (p less than 0.001), median nerve motor conduction velocity (p less than 0.01) and compound muscle action potential amplitude (p less than 0.01), peroneal nerve motor conduction velocity (p less than 0.05) and compound muscle action potential amplitude (p less than 0.05), median (p less than 0.01) and sural (p less than 0.001) sensory nerve action potential amplitude and ankle heat threshold (p less than 0.001) and cold threshold (p less than 0.01) values. gamma-Linolenic acid therapy might have a useful role in the prevention and treatment of distal diabetic polyneuropathy.

Topics: Action Potentials; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Double-Blind Method; Fatty Acids, Essential; Female; Follow-Up Studies; gamma-Linolenic Acid; Humans; Linoleic Acids; Linolenic Acids; Male; Middle Aged; Neural Conduction; Neurons, Afferent; Oenothera biennis; Phospholipids; Placebos; Plant Oils; Random Allocation; Reference Values

The aim of this study was to observe whether polyunsaturated fatty acids (PUFAs) can protect rat insulinoma (RIN5 F) cells against streptozotocin (STZ)-induced apoptosis in vitro and type 1 diabetes mellitus (T1DM) and type 2 DM (T2DM) in vivo and if so, what would be the mechanism of this action.. RIN5 F cells were used for the in vitro study, whereas the in vivo study was performed in Wistar rats. STZ was used to induce apoptosis of RIN5 F cells in vitro and T1- and T2DM in vivo. The effect of PUFAs: γ-linolenic acid (GLA), arachidonic acid (AA) of ω-6 series, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) of ω-3 series; cyclooxygenase (COX) and lipoxygenase (LOX) inhibitors and antiinflammatory metabolite of AA and DHA, lipoxin A4 (LXA4), and resolvin D2 and protectin, respectively against STZ-induced cytotoxicity to RIN5 F cells in vitro and LXA4 against T1- and T2DM in vivo was studied. Changes in the antioxidant content, lipid peroxides, nitric oxide, and expression of PDX1, P65, nuclear factor-κb (NF-κb), and IKB genes in STZ-treated RIN5 F cells in vitro and Nrf2, GLUT2, COX2, iNOS protein levels in the pancreatic tissue of T1- and T2DM and LPCLN2 (lipocalin 2), NF-κb, IKB I in adipose tissue of T2DM after LXA4 treatment were studied. Plasma glucose, insulin, and tumor necrosis factor (TNF)-α levels also were measured in STZ-induced T1- and T2DM Wistar rats.. Among all PUFAs tested, AA and EPA are the most effective against STZ-induced cytotoxicity to RIN5 F cells in vitro. Neither COX nor LOX inhibitors blocked the cytoprotective action of AA in vitro and T1- and T2DM by STZ. LXA4 production by RIN5 F cells in vitro and plasma LXA4 levels in STZ-induced T1- and T2DM animals were decreased by STZ that reverted to normal after AA treatment. AA prevented both T1- and T2DM induced by STZ. Antiinflammatory metabolite of AA and LXA4 prevented both T1- and T2DM induced by STZ. The expression of Pdx1, NF-κb, IKB genes in the pancreas and plasma TNF-α levels in T1- and T2DM; Nrf2, Glut2, COX2, and iNOS proteins in pancreatic tissue of T1DM and LPCLN2, NF-κb, IKB I in adipose tissue of T2DM reverted to normal in LXA4-treated animals.. Both AA and LXA4 prevented STZ-induced cytotoxicity to RIN5 F cells in vitro and T1- and T2DM in vivo, suggesting that these two bioactive lipids may function as antidiabetic molecules. AA is beneficial against STZ-induced cytotoxicity and T1- and T2DM by enhancing the production of LXA4.

Topics: Animals; Apoptosis; Arachidonic Acid; Blood Glucose; Cell Line; Cyclooxygenase 2; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Eicosapentaenoic Acid; gamma-Linolenic Acid; Glucose Transporter Type 2; Homeodomain Proteins; Lipoxins; NF-E2-Related Factor 2; NF-kappa B; Nitric Oxide Synthase Type II; Pancreas; Rats; Rats, Wistar; Trans-Activators; Tumor Necrosis Factor-alpha

We studied hepatic microsomal gamma-linolenoyl-CoA elongation and fatty acid composition of liver microsomes in spontaneously diabetic Wistar BB rats. The liver microsomal gamma-linolenoyl-CoA elongation was decreased in diabetic Wistar BB rats during both normo- and hyperglycemic periods and restored during the hypoglycemic period following insulin treatment. These results are in agreement with our previously reported data on linoleic acid delta 6 and delta 5 desaturations and support the non-parallel relationship between the chain elongation system and the glycemia. The fatty acid composition of BB rat liver microsomes was only partially consistent with the gamma-linolenoyl-CoA elongation activity at the different periods of glycemia, probably because factors other than elongation impairments were involved in the evolution of fatty acid composition.

Topics: Acyl Coenzyme A; Animals; Anti-Inflammatory Agents, Non-Steroidal; Blood Glucose; Diabetes Mellitus, Type 1; Dietary Fats, Unsaturated; gamma-Linolenic Acid; Insulin; Linolenic Acids; Male; Mice; Microsomes, Liver; Rats; Rats, Inbred BB; Triglycerides

In an open study, the authors compared two groups of insulin-dependent diabetics matched for age and metabolic control, one of which was given a linoleic-gamma-linolenic acid mixture (3 g daily), the other served as control. The effect, attributed to gamma-linolenic acid only, was evaluated as explained in the text and is shown in the table. At the end of two months no change was found in the control group while favorable changes of HDL-cholesterol and platelet adhesiveness were observed in the experimental group.

Topics: Adult; Aged; Apolipoproteins; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 1; Fatty Acids, Essential; Female; gamma-Linolenic Acid; Humans; Hypolipidemic Agents; Linoleic Acids; Linolenic Acids; Male; Middle Aged; Oenothera biennis; Plant Oils; Risk Factors; Triglycerides

In addition to their usual diet, nine Type 1 (insulin-dependent) diabetic men and ten male control subjects took 20 g d, alpha-tocopheryl acetate enriched evening primrose oil (14.45 g 18:2c,omega 6, 1.73 g 18:3c,omega 6, 400 mg d,alpha-tocopheryl acetate) daily for one week. At start, diabetic patients had more 14:0, 15:0 and 18:2c,omega 6, and less 16:0, 16:1c,omega 7, 18:1c,omega 7, 18:3c,omega 6, 20:3c,omega 9, 20:3c,omega 6, 20:4c,omega 6 and 22:6c,omega 3 in plasma, erythrocytes and/or platelets. Furthermore, they had lower 16:1c,omega 7/16:0, 18:1c,omega 7/16:0, and 20:4c,omega 6/20:3c,omega 6 ratios and a higher 20:3c,omega 6/18:3c,omega 6 ratio. In diabetic patients, alpha-tocopherol levels in erythrocytes were lower, whereas those in plasma were normal. In both groups, oil intake changed fatty acid profiles. Most markedly, 20:3c,omega 6 increased, whereas the ratios 20:3c,omega 6/18:3c,omega 6 and 20:4c,omega 6/20:3c,omega 6 decreased. 20:4c,omega 6 increased in control subjects, but not in diabetic patients. Erythrocytes and platelets responded differently in their fatty acid profiles. alpha-tocopherol rose in plasma and, although less for diabetic patients, in erythrocytes. In diabetic patients as well as in control subjects, erythrocyte count, haemoglobin level, mean corpuscular haemoglobin content and concentration increased and glycosylated haemoglobin percentage decreased without an apparent decline in blood glucose levels. Plasma beta-thromboglobulin and platelet factor 4 decreased, especially in diabetic patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Blood Platelets; Body Height; Body Weight; Diabetes Mellitus, Type 1; Erythrocytes; Erythropoiesis; Fatty Acids, Essential; Fatty Acids, Nonesterified; Fatty Acids, Unsaturated; gamma-Linolenic Acid; Glycated Hemoglobin; Hemoglobins; Humans; Hypolipidemic Agents; Insulin; Linoleic Acids; Male; Oenothera biennis; Plant Oils; Reference Values

In order to gain insight into the mechanism of platelet dysfunction in insulin-dependent diabetics we studied in 17 patients the influence of a 6-week period with a dietary supplement of gamma-linolenate: 2 g/d (group I, n = 8) or 500 mg/d (group II, n = 9). Serum lipids, plasma beta-thromboglobulin (beta TG), platelet aggregation in vitro, and TxB2 and PGE1 released from platelets during the aggregation process were measured. In group I, serum triglycerides fell from 1.57 +/- 0.28 mmol/l to 0.99 +/- 0.17 mmol/l (P less than 0.01) and cholesterol fell from 5.85 +/- 0.55 mmol/l to 5.08 +/- 0.52 mmol/l (P less than 0.01). In group I plasma beta TG fell from 100.0 +/- 15.7 ng/ml to 73.7 +/- 12.1 ng/ml (P less than 0.025), while the sum of the percentages of the C18:3 omega 6 and its chain elongated (C20:3 omega 6) and desaturated (C20:4 omega 6) metabolites increased in serum triglycerides (P less than 0.05), cholesterol esters (P less than 0.02) and phospholipids (P less than 0.02). No changes were observed on the other parameters in either group. The results show that the lowering effects of gamma-linolenate on serum triglycerides, cholesterol and plasma beta TG occur only with daily intakes of 2 g. The changes in fatty acid composition of serum lipids suggest that the gamma-linolenate intake of 2 g may exert its beneficial effect through an increased incorporation of long-chain polyunsaturated fatty acids, but no firm conclusion can be drawn as membrane platelet fatty acid composition was not evaluated.

Topics: Adult; Aged; Blood Platelets; Diabetes Mellitus, Type 1; Dietary Fats; Female; gamma-Linolenic Acid; Hormones; Humans; Linolenic Acids; Lipids; Male; Middle Aged