promega and Diabetes-Mellitus--Type-2

The effects of dietary supplementation with n-3 fatty acids on lipid and glucose metabolism and on fibrinolysis were evaluated in 14 non-insulin-dependent diabetic patients who were given 10 g of MaxEPA (3 g n-3 fatty acids) or placebo (olive oil) per day in a randomized double-blind cross-over study during two consecutive 8-week periods. The serum triglyceride (TG) concentrations decreased by 27% (P < 0.01) after addition of MaxEPA with a reduction of VLDL TG by 36% (P < 0.05) while LDL cholesterol increased by 6% (P = 0.05). The fasting blood sugar and HbA1c concentrations increased significantly after addition of MaxEPA but the changes were not significantly different from those during the placebo period. The highest glucose concentrations at fasting and after an i.v. glucose injection were seen after MaxEPA while the serum insulin concentrations were unchanged. The peripheral insulin sensitivity, as measured by a euglycaemic, hyperinsulinaemic clamp technique, did not change during the study. The mean plasminogen inhibitor-1 (PAI-1) activity of the patients was elevated compared with healthy controls. In spite of the reduction of the triglyceride concentrations and unchanged insulin levels, there was a significant increase of the activity of PAI-1 (+21%, P < 0.01) after MaxEPA suggesting a possible impairment of the fibrinolytic capacity. In many situations there seems to be a reduction of PAI-1 when the triglycerides are lowered. In the diabetic patients given n-3 fatty acids this was not the case.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids; Fatty Acids, Omega-3; Female; Fibrinolysis; Fish Oils; Humans; Lipoproteins; Male; Middle Aged; Plasminogen Activator Inhibitor 1; Triglycerides

Eight male non-insulin-dependent diabetic patients participated in a double-blind randomized cross-over study (2 weeks for each period) evaluating the effects of 10 g/day fish oil dietary supplementation on glucose and lipid metabolism. Fasting serum triglyceride concentrations were decreased by fish oil because of a reduction in VLDL (1.4 +/- 0.2 vs. 1.9 +/- 0.2 mmol/l, P less than 0.025). LDL cholesterol concentration was instead increased (3.4 +/- 0.3 vs. 2.8 +/- 0.3 mmol/l, P less than 0.025) and net changes in VLDL triglyceride and in LDL cholesterol were inversely correlated (r = -0.86, P less than 0.01). Plasma free fatty acids concentrations and turnover rate [( 3H]palmitate method) were similar after fish oil and placebo. Fish oil supplement did not induce significant changes in fasting blood glucose (8.1 +/- 1.1 vs. 8.5 +/- 1.2 mmol/l) and average daily blood glucose (BG) (9.4 +/- 3.2 vs. 9.3 +/- 3.5 mmol/l). Glucose stimulated plasma insulin response during a hyperglycemic clamp was not significantly influenced by fish oil both in the early phase and during steady state. Insulin sensitivity (M/I index) was also unchanged. In conclusion, this study shows that a dietary supplement of fish oil decreases plasma triglyceride levels in non-insulin-dependent diabetic patients, an increased conversion rate of VLDL to LDL playing a role in this change. With this dosage of fish oil no relevant variations in glycemic control, insulin secretion and insulin sensitivity occurred.

Topics: Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Double-Blind Method; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Nonesterified; Fatty Acids, Omega-3; Fish Oils; Humans; Insulin; Lipids; Male; Middle Aged; Triglycerides

The aim of this study was to evaluate the effects of a fish oil preparation (MaxEPA) on hemostatic function and fasting lipid and glucose levels in non-insulin-dependent diabetic (NIDDM) subjects. Eighty NIDDM outpatients aged 55.9 yr (mean SD 11.5 yr) participated in a prospective double-blind placebo-controlled study of MaxEPA capsules (10 g/day) or olive oil (control) treatment over 6 wk. Patients received either MaxEPA or olive oil in addition to preexisting therapy. Metabolic and hemostatic variables were measured before treatment and after 3 and 6 wk. Platelet membrane eicosapentaenoic acid (EPA) content increased in the treatment group (P less than 0.001). MaxEPA supplementation was associated with a significant fall in total triglycerides (P less than 0.001) but did not affect total cholesterol (P = 0.7) compared with control treatment. Fasting plasma glucose increased after 3 wk (P = 0.01) but not after 6 wk (P = 0.17) treatment with MaxEPA. Spontaneous platelet aggregation in whole blood fell in the MaxEPA group (P less than 0.02) after 6 wk, but there were no changes in agonist-induced platelet aggregation, thromboxane generation in platelet-rich plasma, or plasma beta-thromboglobulin and platelet factor IV levels. An increase in clotting factor VII (P = 0.02), without changes in fibrinogen or factor X levels, occurred in the MaxEPA group. Similar reductions in blood pressure were observed in both groups. Dietary supplementation with MaxEPA capsules (10 g/day) in NIDDM subjects is associated with improvement in hypertriglyceridemia but with deleterious effects in factor VII and blood glucose levels. Most indices of platelet function are unaffected by this therapy.

Topics: Blood Glucose; Cardiovascular Diseases; Cholesterol; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diet, Diabetic; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Food, Fortified; Hemostasis; Humans; Lipids; Male; Thromboxane B2; Triglycerides

Serum triacylglycerols (TG), VLDL, HDL, fatty acid and eicosanoid spectrum are among the factors determining the risk of cardiovascular complications in NIDDM. N-3 polyunsaturated fatty acids (PUFA) are expected to have beneficial effects on these factors. In NIDDM patients there have however been previously reported (late 1980s) some adverse effects.. Our aim was to verify the effects of n-3 PUFA in NIDDM patients using relatively low dosage.. The investigated group included 21 NIDDM patients with dyslipoproteinemia type IV. The patients were treated for 28 days with 1.7 g EPA (eicosapentaenoic acid) + 1.15 g DHA (docosahexaenoic acid)/day (10 capsules/day of MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the BIO-LACHEMA kits, the fatty acid spectrum in phospholipids was determined by gas chromatography and prostanoids (after their separation) were measured by RIA methods.. After the MAXEPA treatment there has been a strong decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels, accompanied by a significant increase in HDL (p < 0.02). The final-to-baseline TG ratio in individual patients negatively correlated with the relative percentage of EPA in phospholipids after the treatment (p < 0.03; r = -0.474). There was no significant change in serum total cholesterol, fasting glycaemia and glycosylated hemoglobin. There was a slight, but statistically already significant (p < 0.05), rise in LDL. The relative percentage of EPA, docosapentaenoic acid and DHA in serum phospholipids increased sharply (p < 0.001, p < 0.001, p < 0.001). The increase of n-3 PUFA in individual patients was linked with the decrease in n-6 PUFA (p < 0.001; r = -0.686). The spectrum of the latter has changed also very markedly. The prostacyclin PGI2-to-thromboxane TxA2 ratio increased significantly (p < 0.001). Beneficial effects of n-3 fatty acids have prevailed and this kind of treatment seems very encouraging also in NIDDM patients. The results are logically compatible with other authors' results pattern formed in 1990s. A slight rise in serum LDL needs a more detailed discussion since only its phenotype B ("small dense LDL particles") has been recently found to be atherogenic. (Tab. 2, Fig. 5, Ref. 15.)

Topics: Cardiovascular Diseases; Cholesterol, HDL; Cholesterol, VLDL; Diabetes Mellitus, Type 2; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Omega-3; Female; Fish Oils; Humans; Hyperlipoproteinemia Type IV; Male; Middle Aged; Risk Factors; Triglycerides

Increased interest in using omega-3 fatty acids led us to examine their metabolic effects in six men with type II (non-insulin-dependent) diabetes mellitus. After 1 month of a diet supplemented with these fatty acids, the patients' fasting glucose rose from 13.1 +/- 1.3 to 15.3 +/- 1.3 mmol/L (P = 0.03) and glucose area during a mixed meal profile rose by 22% (P = 0.04). Basal hepatic glucose output rose from 97 +/- 9 to 122 +/- 8 mg/m2 . min (P = 0.004) but glucose disposal rates measured by euglycemic glucose clamp were unchanged. Fasting insulin levels were similar; peak insulin levels stimulated by meals or intravenous glucagon fell by 30% and 39%, respectively. Plasma and erythrocyte content of omega-3 fatty acid rose significantly. After omega-3 fatty acid withdrawal, fasting glucose returned to baseline. Omega-3 fatty acid treatment in type II diabetes leads to rapid but reversible metabolic deterioration, with elevated basal hepatic glucose output and impaired insulin secretion but unchanged glucose disposal rates. Caution should be used when recommending omega-3 fatty acids in type II diabetic persons.

Topics: Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Dietary Fats, Unsaturated; Docosahexaenoic Acids; Drug Combinations; Eicosapentaenoic Acid; Fatty Acids, Unsaturated; Fish Oils; Glucose; Glucose Tolerance Test; Humans; Insulin; Lipids; Liver; Male; Middle Aged