Essential fatty acids and the complications of diabetes mellitus

In animals and humans with diabetes mellitus there is evidence that normal metabolism of essential fatty acids is impaired. The main dietary essential fatty acids, linoleic acid of the n-6 series and alpha-linolenic acid of the n-3 series, must both be 6-desaturated and converted to further metabolites if they are to exert all their desirable effects on the body. 6-desaturation is impaired in diabetes and a lack of adequate rates of formation of the 6-desaturated metabolites may be involved in the abnormalities in membrane function, in lipid metabolism and in haemostasis and the microcirculatory system which are seen in diabetes. Attempts to overcome the block by giving very large amounts of dietary linoleic acid, or to by-pass the block by giving 6-desaturated metabolites such as gamma-linolenic acid and eicosapentaenoic acid, have both given promising results.     

Placental metabolic profiling in gestational diabetes mellitus: An important role of fatty acids

AimGestational diabetes mellitus (GDM) is the most common metabolic disorder during pregnancy. Accumulating studies have reported metabolites that are significantly associated with the development of GDM. However, studies on the metabolism of placenta, the most important organ of maternal‐fetal energy and material transport, are extremely rare. This study aimed to identify and discuss the relationship between differentially expressed metabolites (DEM) and clinical parameters of the mothers and newborns.MethodsIn this study, metabolites from 63 placenta tissues (32 GDM and 31 normal controls) were assayed by ultra‐performance liquid chromatography‐high resolution mass spectrometry (UPLC‐HRMS).ResultsA total of 1297 annotated metabolites were detected, of which 87 significantly different in GDM placenta. Lipids and lipid‐like molecules accounted for 62.1% of DEM as they were significantly enriched via the “biosynthesis of unsaturated fatty acids” and “fatty acid biosynthesis” pathways. Linoleic acid and α‐linolenic acid appeared to be good biomarkers for the prediction and diagnosis of GDM. In addition, the level of PC(14:0/18:0) was negatively correlated with neonatal weight. 14 metabolites significantly different in male and female offspring, with the most increase in female newborns.ConclusionEven if maternal blood glucose level is well controlled, there are still metabolic abnormalities in GDM. Lipids and lipid‐like molecules were the main differential metabolites, especially unsaturated fatty acids.     

Biological effects of omega-3 fatty acids in diabetes mellitus.

Fish oils exert important biological effects on several pathways predisposing to atherosclerosis. Epidemiological studies provided the initial evidence that omega-3 fatty acids may be the principal factor in fish oils responsible for these effects and have led to several short-term clinical trials in which fish-oil concentrates have been administered to various populations at risk for coronary heart disease, including patients with diabetes mellitus. omega-3 Fatty acids reduce serum lipids and lipoproteins, impair platelet aggregation, increase cell membrane fluidity, and lower blood pressure in humans. In this review, we highlight these and other potentially antiatherogenic properties of marine lipids in diabetic subjects.     

罗格列酮对2型糖尿病游离脂肪酸的影响

目的观察罗格列酮对2型糖尿病游离脂肪酸（FFA）的影响。方法60例2型糖尿病患者,随机分为罗格列酮组与二甲双胍组。治疗前和治疗3个月后,测量身高和体质量,计算体质量指数（BMI）,观察空腹血糖（FBS）、甘油三酯（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、FFA、糖化血红蛋白（HbA1c）的变化。结果治疗后两组FBS、HbA1c均下降。罗格列酮组FBS治疗前后（10．34±3．08）mmol／L vs（7．75±1．46）mmol／L（P〈0．01）,HbA1c（8．85±2．28）％vs（7．28±1．33）％（P〈0．01）;二甲双胍组FBS（9．51±2．89）mmol／Lvs（7．36±1．40）mmol／L（P〈0．01）,HbA1c（9．26±2．45）％vs（7．61±1．23）％（P〈0．01）。但两组之间比较无统计学意义（P〉0．05）。罗格列酮组治疗前后FFA（0．65±0．24）mmol／Lvs（0．54±0．19）mmol／L（P〈0．05）。而二甲双胍组治疗前后FFA无明显下降。结论罗格列酮治疗降低FFA的水平,有助于减少2型糖尿病大血管并发症的发生。     

游离脂肪酸与子痫前期和妊娠期糖尿病发生的相关性

目的:探讨孕晚期游离脂肪酸对子痫前期和(或)妊娠期糖尿病(GDM)发病率的影响。方法:选择417例孕晚期子痫前期和(或)GDM为观察组,另选2 018例正常妊娠孕妇为对照组。检测并比较2组血清总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和游离脂肪酸(FFA)。采用logistic回归模型分析血脂子痫前期和(或)GDM的关系。结果:校正混杂因素[孕妇年龄、孕前体质指数(BMI)和采血时的孕周]后,孕晚期FFA浓度升高会增加子痫前期、GDM和子痫前期合并GDM的风险(P0.01)。孕晚期TG水平升高会增加子痫前期、GDM发生的风险(P0.001)。结论:孕晚期FFA水平升高可使子痫前期和(或)GDM发生风险增加。     

老年2型糖尿病患者血清抵抗素、游离脂肪酸水平研究

目的探讨血清抵抗素、游离脂肪酸与老年糖尿病及胰岛素抵抗的关系。方法测量老年(年龄>60岁)2型糖尿病患者82例(老年糖尿病组),成年(年龄<60岁)2型糖尿病患者70例(成年糖尿病组),老年健康体检者50例(对照组)空腹血清抵抗素、游离脂肪酸、空腹血糖及胰岛素水平,计算胰岛素抵抗指数。结果老年糖尿病组血清抵抗素、游离脂肪酸水平高于对照组与成年糖尿病组(P<0.05或P<0.01)。老年糖尿病组胰岛素抵抗程度较成年糖尿病组明显,并伴有脂代谢紊乱。结论血清抵抗素、游离脂肪酸与老年糖尿病尤其是老年胰岛素抵抗密切相关。     

Gestational diabetes mellitus upsets the proportion of fatty acids in umbilical arterial but not venous plasma

OBJECTIVE—Neonates of women with gestational diabetes mellitus (GDM) have reduced levels of arachidonic acid (AA) (20:4 n-6) and docosahexaenoic acid (DHA) (22:6 n-3). To assess whether this is the result of impaired placental transfer or endogenous fetal metabolism, fatty acids in umbilical venous and arterial plasma were analyzed in neonates of GDM women.RESEARCH DESIGN AND METHODS—Fatty acids were analyzed by gas chromatography in the plasma of 15 subjects with GDM and 30 healthy control subjects undergoing elective cesarean section and in vein and artery cord blood collected separately.RESULTS—The percentages of AA (20:4 n-6), DHA (22:6 n-3), and total n-6 or n-3 polyunsaturated fatty acids (PUFAs) as well as total PUFAs were lower in umbilical arterial but not in venous plasma of neonates of the GDM versus the control group.CONCLUSIONS—An altered handling or metabolism of long-chain PUFAs by the fetus rather than impaired placental transfer seems to be responsible for the lower proportion of those fatty acids in the plasma of neonates of GDM mothers.Whereas plasma levels of arachidonic acid (AA) and docosahexaenoic acid (DHA) in neonates of women with type 1 diabetes (1), type 2 diabetes (2), or gestational diabetes mellitus (GDM) (3) are low, the levels of AA and DHA in GDM women are normal or even enhanced (4) compared with those of healthy control subjects. Because it is unknown whether this decline in neonates is due to impaired transfer or altered intrauterine fetal metabolism, we analyzed fatty-acid profiles in umbilical venous and arterial plasma and in control and GDM mothers at the time of cesarean delivery.     

The state of erythrocyte membranes in diabetes mellitus]

Study of red cell membranes in diabetics has shown that physicochemical shifts in the red cell membrane lipid bilayer, elevated lipid peroxidation, and disordered thiol compound metabolism are among the crucial aspects in the pathogenesis of diabetes mellitus. EPR spectroscopy in complex with other biochemical methods will help monitor the adequacy of therapy.     

Effect of insulin treatment on fatty acids of plasma and erythrocyte membrane lipids in type 2 diabetes

Serum lipoproteins and fatty acid compositions of serum and erythrocyte membrane lipids were analyzed from sixteen Type 2 diabetic subjects with secondary drug failure before and after four weeks' insulin therapy. The insulin treatment clearly improved diabetic control (p less than 0.01), decreased serum total cholesterol (-14%, p less than 0.01), triglycerides (-50%, p less than 0.001), plasma free fatty acids (-28%, p less than 0.01), and especially serum VLDL-triglyceride levels (-62%, p less than 0.001) and resulted in a significant weight gain of patients (1.4 kg, p less than 0.05). Of the individual plasma fatty acids saturated (-32%) and monoenoic (-36%) fatty acids fell more than the polyunsaturated fatty acids of exogenous origin, eg linoleic acid (-11%), other n-6 polyunsaturated fatty acids (PUFA) (-11%), and n-3 PUFA (-13%) suggesting that the decrease in serum VLDL-triglycerides is mainly associated with the suppression of endogenous fatty acids. Before the insulin treatment but less strongly during it, the contents of linoleic acid were positively and those of dihomogammalinolenic acid, arachidonic acid, and arachidonic acid/linoleic acid ratios of plasma and erythrocyte membrane lipids inversely correlated with glycosylated HbA1 levels, suggesting that the conversion of linoleic acid to prostanoid precursor fatty acids is affected by the poor glycemic control in Type 2 diabetic patients.     

Non-insulin-dependent diabetes mellitus: dietary monounsaturated fatty acids and low-density lipoprotein composition and function

Alterations in low-density lipoprotein (LDL) composition in diabetes affect its function with respect to control of de novo cholesterol synthesis. We examined the effect of 4 weeks of an oleic-acid-rich diet on LDL composition and function in eight Type 2 diabetic and eight non- diabetic control subjects. LDL (density 1.019-1.063 g/l) was isolated by sequential ultracentrifugation. LDL composition was measured and LDL fatty acids were determined by gas liquid chromatography. Cholesterol synthesis was measured by [14C]-acetate incorporation into the freshly isolated mononuclear leucocytes. Fasting blood glucose fell from 9.3 +/- 2.0 to 8.2 +/- 1.2 mmol/l (p < 0.05) and fasting serum insulin increased from 8.3 +/- 2.8 to 10.4 +/- 5.0 mIU/l (p > 0.05) in the diabetic patients. LDL oleic acid increased in the diabetic patients from 18.8 +/- 1.8% to 22.5 +/- 1.9% (p < 0.01) and in the non-diabetic subjects from 19.9 +/- 1.8% to 23.3 +/- 2.8% (p < 0.01). The LDL- esterified to free cholesterol ratios of 3.0 +/- 0.6 and 2.7 +/- 0.2 for the diabetic and non-diabetic patients were similar, and decreased significantly (p < 0.01) to 2.4 +/- 0.5 and 2.2 +/- 0.4, respectively. Baseline [14C]-acetate incorporation was similar in the two groups, and decreased after diet from 437 +/- 239 to 249 +/- 144 ng/g cell protein (p < 0.05) in the diabetic patients. There was a negative correlation between the LDL-esterified to free cholesterol ratio and the ratio of oleic to linoleic acid in the LDL (r = -0.39, p < 0.05) and a negative correlation between fasting blood glucose and LDL oleic acid in the diabetic patients (r = -0.51, p < 0.05). Enrichment of LDL with oleic acid appears to improve its ability to regulate endogenous cholesterol synthesis in both control and diabetic subjects. In the diabetic population, the diet had a favourable effect on glycaemic control.      

Supplementation with n-3 fatty acids reduces triglycerides but increases PAI-1 in non-insulin-dependent diabetes mellitus

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.     

Splanchnic and leg exchange of glucose, amino acids, and free fatty acids during exercise in diabetes mellitus.

The influence of exercise on leg and splanchnic exchange of substrates was examined in eight insulin-dependent diabetics 24 h after withdrawal of insulin and in eight healthy controls studied at rest and after 40 min of bicycle ergometer exercise at 55-60% of maximal capacity. In four of the diabetic subjects, basal arterial ketone acid levels were 3-4 mmol/ liter (ketotic diabetics) and in the remainder, below 1 mmol/liter (nonketotic diabetics). ,ree fatty acid (FFA) turnover and regional exchange were evaluated with 14-C- labeled oleic acid. Leg uptake of blood glucose rose 13-18 fold during exercise in both the diabetics and controls and accounted for a similar proportion of the total oxygen uptake by leg muscles (25-28%) in the two groups. In contrast, leg uptake of FFA corresponded to 39% of leg oxygen consumption in the diabetic group but only 27% in controls. Systemic turnover of oleic acid was similar in the two groups. Splanchnic glucose output increased during exercise 3-4 fold above resting levels in both groups. In the diabetics, splanchnic uptake of lactate, pyruvate, glycerol, and glycogenic amino acids rose more than twofold above resting levels and was fourfold greater than in exercising controls. Total precursor uptake could account for 30% of the splanchnic glucose output in the diabetic group. In contrast, in the controls, total splanchnic uptake of glucose precursors was no greater during exercise than in the resting state and could account for no more than 11% of splanchnic glucose output. The augmented precursor uptake during exercise in the diabetics was a consequence of increased splanchnic fractional extraction as well as increased peripheral production of gluconeogenic substrates. The arterial glucagon concentration was unchanged by exercise in both groups, but was higher in the diabetics. In the diabetic subjects with ketosis in the resting state, exercise elicited a rise in arterial glucose and FFA, an augmented splanchnic uptake of FFA, and a 2-3 fold increase in splanchnic output of 3-hydroxybutyrate. Uptake of 3-hydroxybutyrate by the exercising leg rose more rapidly than splanchnic production, resulting in a fall in arterial levels of 3-hydroxybutyrate. It is concluded that (a) glucose uptake by exercising muscle in hyperglycemic diabetics is no different from that of controls; (b) splanchnic glucose output rises during exercise to a similar extent in diabetics and controls, while uptake of gluconeogenic substrates is markedly higher in diabetics and accounts for a greater proportion of total splanchnic glucose output; (c) exercise in diabetic patients with mild ketosis is associated with a rise in blood glucose and FFA levels as well as augmented splanchnic production and peripheral uptake of ketone bodies.     

胰岛素抗体阳性2型糖尿病患者血清尿酸水平变化研究

目的探讨胰岛素抗体(INS-Ab)阳性2型糖尿病患者血清尿酸(SUA)水平变化。方法收集应用重组人胰岛素治疗的住院2型糖尿病患者,共323例,按INS-Ab阳性或阴性分为INS-Ab阳性组和INS-Ab阴性组;在本院查体中心随机选择82例健康体检者作为正常对照组。采用单因素方差分析比较以上三组之间SUA水平的差异,应用秩和检验分析不同SUA水平2型糖尿病患者INS-Ab阳性率的变化。结果 (1)INS-Ab阳性组的SUA水平明显高于INS-Ab阴性组[(4.91±1.39)mg/dl vs.(4.31±1.25)mg/dl,t=10.46,P<0.05];(2)随着SUA水平升高,INS-Ab阳性率逐渐增加(Z=-3.194,P=0.001);(3)Logistic回归分析表明,高SUA是INS-Ab阳性的危险因素(OR=1.434,95%CI:1.154~1.780,P=0.001)。结论 INS-Ab阳性2型糖尿病患者SUA水平较高,高SUA水平是INS-Ab阳性的危险因素。