Relationship of dietary fat and serum cholesterol ester and phospholipid fatty acids to markers of insulin resistance in men and women with a range of glucose tolerance

High-fat diets are associated with insulin resistance, however, this effect may vary depending on the type of fat consumed. The purpose of this study was to determine the relationship between intakes of specific dietary fatty acids (assessed by 3-day diet records and fatty acid composition of serum cholesterol esters [CEs] and phospholipids [PLs]) and glucose and insulin concentrations during an oral glucose tolerance test (OGTT). Nineteen men and 19 women completed the study. Nine subjects had type 2 diabetes or impaired glucose tolerance. Fasting insulin correlated with reported intakes of total fat (r = .50, P < .01), monounsaturated fat (r = .44, P < .01), and saturated fat (r = .49, P < .01), but not with trans fatty acid intake (r = .11, not significant [NS]). Fasting glucose also correlated with total (r = .39, P < .05) and monounsaturated fat intakes (r = .37, P < .05). In multivariate analysis, both total and saturated fat intake were strong single predictors of fasting insulin (R2 approximately .25), and a model combining dietary and anthropometric measures accounted for 47% of the variance in fasting insulin. Significant relationships were observed between fasting insulin and the serum CE enrichments of myristic (C14:0), palmitoleic (C16:1), and dihomo-gamma-linolenic (C20:3n-6) acids. In multivariate analysis, a model containing CE 14:0 and percent body fat explained 45% of the variance in fasting insulin, and C14:0 and age explained 30% of the variance in fasting glucose. PL C20:3n-6 explained 30% of the variance in fasting insulin, and a model including PL C18:1n-11 cis, C20:3n-6, age and body fat had an R2 of .58. In conclusion, self-reported intake of saturated and monounsaturated fats, but not trans fatty acids, are associated with markers of insulin resistance. Furthermore, enhancement of dihomo-gamma-linolenic and myristic acids in serum CE and PL, presumably markers for dietary intake, predicted insulin resistance.     

Effect of increased plasma non-esterified fatty acids (NEFAs) on arginine-stimulated insulin secretion in obese humans

Aims/hypothesis: We have shown previously that the increase of plasma non-esterified fatty acids for 48 h results in decreased glucose-stimulated insulin secretion in lean and non-diabetic obese subjects. It is currently not known if a prolonged increase in non-esterified fatty acids also impairs the insulin secretory response to non-glucose secretagogues. Methods: Heparin and intralipid (to increase plasma non-esterified fatty acid concentrations by about two- to fourfold) or normal saline was infused intravenously for 48 h in 14 non-diabetic obese subjects. On the third day in both studies, insulin, C-peptide, proinsulin, and insulin secretion rate were assessed in response to an intravenous arginine infusion at fasting glucose concentration and a second arginine infusion after a 60-min 11 mmol/l hyperglycaemic clamp. Results: There were no significant differences detected in acute (5 min) or total (90 min) arginine-stimulated C-peptide or insulin secretion response in the heparin-intralipid study compared with the control group at fasting glucose or during hyperglycaemia. Conclusion/interpretation: We have shown that a prolonged increase in plasma NEFA does not blunt arginine-stimulated insulin secretion or plasma insulin concentrations in non-diabetic obese subjects. These findings suggest that the previously demonstrated NEFA-induced impairment in insulin secretory response to glucose cannot be generalized for non-glucose secretagogues. [Diabetologia (2001) 44: 1989–1997] Received: 27 November 2001 and in revised form: 2 August 2001     

Polyunsaturated fatty acids may impair blood glucose control in type 2 diabetic patients.

Fifteen patients with Type 2 diabetes were given two diets rich in either saturated fat or polyunsaturated fat in alternate order over two consecutive 3-week periods on a metabolic ward. Both diets contained the same amount of fat, protein, carbohydrates, dietary fibre, and cholesterol. The proportions of saturated, monounsaturated and polyunsaturated fatty acids in the saturated fat diet were 16, 10, and 5%-energy and in the polyunsaturated fat diet (PUFA) 9, 10, and 12%-energy. The PUFA diet contained a high proportion of n-3 fatty acids. Metabolic control improved significantly in both dietary periods, due to both qualitative dietary changes and a negative energy balance. The serum lipoprotein concentrations decreased on both diets but the serum lipids were significantly lower after the PUFA diet (serum triglycerides -20%, p = 0.001; serum cholesterol -5%, p = 0.03; VLDL-triglycerides -29%, p less than 0.001; and VLDL-cholesterol -31%, p = 0.001) than after the saturated fat diet. Average blood glucose concentrations during the third week were significantly higher fasting (+15%, p less than 0.01), and during the day at 1100 h (+18%, p less than 0.001) and 1500 h (+17%, p = 0.002) on PUFA than on the saturated fat diet. Significantly higher blood glucose levels were also recorded with a standard breakfast, while the sum of the insulin values was lower (-19%, p = 0.01). HbA1c did not differ significantly between the two dietary periods.(ABSTRACT TRUNCATED AT 250 WORDS)     

Fatty acid composition of serum cholesterol esters in different degrees of glucose intolerance: a population-based study

The fatty acid composition of serum cholesterol esters was investigated in 325 subjects with normal glucose tolerance, 97 subjects with impaired glucose tolerance (IGT), and 98 subjects with non-insulin-dependent diabetes mellitus (NIDDM) identified by population-based screening. The proportions of palmitic acid (16:0) and palmitoleic acid (16:1) in serum cholesterol esters increased from the normal glucose tolerance group to the IGT and diabetic groups. On the other hand, the proportion of linoleic acid (18:2) was lower in diabetic subjects than in the subjects with IGT or normal glucose tolerance. The proportions of gamma-linolenic (18:3), dihomo-gamma-linoleic (20:3), and arachidonic (20:4) acids were highest in diabetic subjects and lowest in subjects with normal glucose tolerance. Our findings suggest that subjects with NIDDM or IGT have had higher dietary intake of saturated fatty acids. Both serum insulin and blood glucose concentrations probably have an effect on the elongation and desaturation of fatty acids, but the metabolism of linoleic acid to prostaglandin precursors seems to be different in different types of diabetes, NIDDM patients showing no abnormalities. The possibility that the fatty acid composition of plasma and membrane lipids has a role in insulin resistance and blood glucose regulation deserves further investigation.     

A higher-carbohydrate, lower-fat diet reduces fasting glucose concentration and improves β-cell function in individuals with impaired fasting glucose

The objective was to examine the effects of diet macronutrient composition on insulin sensitivity, fasting glucose, and β-cell response to glucose. Participants were 42 normal glucose-tolerant (NGT; fasting glucose <100 mg/dL) and 27 impaired fasting glucose (IFG), healthy, overweight/obese (body mass index, 32.5 ± 4.2 kg/m(2)) men and women. For 8 weeks, participants were provided with eucaloric diets, either higher carbohydrate/lower fat (55% carbohydrate, 18% protein, 27% fat) or lower carbohydrate/higher fat (43:18:39). Insulin sensitivity and β-cell response to glucose (basal, dynamic [PhiD], and static) were calculated by mathematical modeling using glucose, insulin, and C-peptide data obtained during a liquid meal tolerance test. After 8 weeks, NGT on the higher-carbohydrate/lower-fat diet had higher insulin sensitivity than NGT on the lower-carbohydrate/higher fat diet; this pattern was not observed among IFG. After 8 weeks, IFG on the higher-carbohydrate/lower-fat diet had lower fasting glucose and higher PhiD than IFG on the lower-carbohydrate/higher-fat diet; this pattern was not observed among NGT. Within IFG, fasting glucose at baseline and the change in fasting glucose over the intervention were inversely associated with baseline PhiD (-0.40, P < .05) and the change in PhiD (-0.42, P < .05), respectively. Eight weeks of a higher-carbohydrate/lower-fat diet resulted in higher insulin sensitivity in healthy, NGT, overweight/obese individuals, and lower fasting glucose and greater glucose-stimulated insulin secretion in individuals with IFG. If confirmed, these results may have an impact on dietary recommendations for overweight individuals with and without IFG.     

Substituting dietary saturated for monounsaturated fat impairs insulin sensitivity in healthy men and women: The KANWU study

Aims/hypothesis. The amount and quality of fat in the diet could be of importance for development of insulin resistance and related metabolic disorders. Our aim was to determine whether a change in dietary fat quality alone could alter insulin action in humans. Methods. The KANWU study included 162 healthy subjects chosen at random to receive a controlled, isoenergetic diet for 3 months containing either a high proportion of saturated (SAFA diet) or monounsaturated (MUFA diet) fatty acids. Within each group there was a second assignment at random to supplements with fish oil (3.6 g n-3 fatty acids/d) or placebo. Results. Insulin sensitivity was significantly impaired on the saturated fatty acid diet (-10 %, p = 0.03) but did not change on the monounsaturated fatty acid diet ( + 2 %, NS) (p = 0.05 for difference between diets). Insulin secretion was not affected. The addition of n-3 fatty acids influenced neither insulin sensitivity nor insulin secretion. The favourable effects of substituting a monounsaturated fatty acid diet for a saturated fatty acid diet on insulin sensitivity were only seen at a total fat intake below median (37E %). Here, insulin sensitivity was 12.5 % lower and 8.8 % higher on the saturated fatty acid diet and monounsaturated fatty acid diet respectively (p = 0.03). Low density lipoprotein cholesterol (LDL) increased on the saturated fatty acid diet ( + 4.1 %, p < 0.01) but decreased on the monounsaturated fatty acid diet (MUFA) (–5.2, p < 0.001), whereas lipoprotein (a) [Lp(a)] increased on a monounsaturated fatty acid diet by 12 % (p < 0.001). Conclusions/interpretation. A change of the proportions of dietary fatty acids, decreasing saturated fatty acid and increasing monounsaturated fatty acid, improves insulin sensitivity but has no effect on insulin secretion. A beneficial impact of the fat quality on insulin sensitivity is not seen in individuals with a high fat intake ( > 37E %). [Diabetologia (2001) 44: 312–319] Received: 21 August 2000 and in revised form: 8 November 2000     

2型糖尿病患者游离脂肪酸水平与认知功能障碍的关系

目的探讨2型糖尿病(T2DM)患者游离脂肪酸(FFA)水平与认知功能障碍的关系。方法选择183例患者,根据口服葡萄糖耐量试验结果分为T2DM组80例、葡萄糖耐量异常(IGT)组45例和葡萄糖耐量正常(NGT)组58例,行空腹游离脂肪酸(fFFA)、2h游离脂肪酸(2hFFA)和蒙特利尔认知评估量表(MoCA)测定。结果T2DM组患者fFFA、2hFFA高于NGT组和IGT组[(0.65±0.30)mmol/L vs(0.55±0.27)mmol/L和(0.43±0.19)mmol/L,P=0.001,(0.31±0.15)mmol/L vs(0.22±0.14)mmol/L和(0.11±0.13)mmol/L,P=0.000],MoCA评分低于NGT组和IGT组[(16.01±11.62)分vs(22.34±6.42)分和(27.21±2.83)分,P=0.000];fFFA、2hFFA与MoCA评分呈负相关(r=-0.891,-0.469,P<0.05)。结论 fFFA、2hFFA与胰岛素抵抗及糖尿病患者认知功能障碍存在一定的相关性。     

Lower-body fat mass as an independent marker of insulin sensitivity--the role of adiponectin

AIMS: To study the association between lower-body fat and estimates of whole-body insulin sensitivity in middle-aged men with and without a history of juvenile onset obesity, and to determine the possible mediating role of fasting serum adiponectin level as an insulin-sensitizing peptide. METHODS: A total of 401 men aged 39-65 y, body mass index 18-54 kg/m2, participated in the study. The following variables were measured on the study participants: regional body fat distribution as assessed by dual energy X-ray absorptiometry, abdominal sagittal diameter, maximal oxygen uptake (VO2max), physical activity, fasting and post-glucose load levels of plasma glucose, serum insulin, and blood non-esterified fatty acid plus fasting levels of serum adiponectin and HbA1c. RESULTS: Lower-body fat mass was positively associated with insulin sensitivity as estimated by Matsudas index also after adjusting for age, lean tissue mass, trunkal fat mass, weight changes since draft board examination, VO2max and the level of physical activity. In a subgroup of men selected for a large lower-body fat mass, fasting serum insulin concentration was 24% lower (P<0.01) and fasting serum adiponectin 33% higher (P<0.005) compared to a subgroup of men with a small lower-body fat mass but with similar trunkal fat mass. CONCLUSION: Lower-body fat mass is positively associated with an estimate of insulin sensitivity independently of trunkal fat mass in both lean and obese middle-aged men and this effect could partly be statistically explained by variations in serum adiponectin levels.     

Fatty acid composition of serum lipids: is this marker of fat intake still relevant for identifying metabolic and cardiovascular disorders?

Analysis of the fatty acid composition of serum lipid fractions is an old but still useful method for several purposes. The proportions of essential polyunsaturated and trans fatty acids are biomarkers of dietary intake that can be used to improve estimates of fatty acid intake in dietary trials and population studies. Furthermore, the metabolism of essential n-6 and n-3 fatty acids is reflected in the serum fatty acid composition. Changes in the activity of the delta-6 and delta-5 desaturases, which affect the proportions of dihomogamma-linolenic acid and arachidonic acid in serum lipids, are associated with insulin resistance and may explain differences in coronary heart disease risk.     

Rosiglitazone short-term monotherapy lowers fasting and post-prandial glucose in patients with Type II diabetes

Abstract Aims/hypothesis. The short-term efficacy, safety and tolerability of rosiglitazone were compared with placebo in patients with Type II (non-insulin-dependent) diabetes mellitus in a dose-ranging study.?Methods. After a 2-week placebo run-in phase, 303 patients were randomly assigned to 8 weeks of treatment with twice-daily placebo or 2, 4 or 6 mg of rosiglitazone.?Results. All rosiglitazone doses significantly reduced fasting plasma glucose compared with baseline. All rosiglitazone treatment groups showed significantly reduced peak postprandial glucose concentrations compared with baseline (p < 0.001) and with placebo (p < 0.0001) and reduced postprandial glucose excursion, without an increase in the area under the postprandial insulin concentration-time curve. Rosiglitazone at 4 and 6 mg twice daily prevented the increase in HbA_{1 c} observed in the placebo group. C peptide and serum insulin concentrations were significantly reduced from baseline in all rosiglitazone treatment groups. In all rosiglitazone treatment groups, non-esterified fatty acids decreased significantly (p < 0.0001) and triglycerides did not change. Although total LDL and HDL cholesterol increased significantly in the rosiglitazone treatment groups, total cholesterol/HDL ratios did not change significantly. The proportion of patients with one or more adverse event was similar in all four treatment groups. No patient showed evidence of hepatotoxicity.?Conclusion/interpretation. Rosiglitazone given twice daily significantly reduced fasting and postprandial glucose concentrations, C peptide, insulin and non-esterified fatty acids in Type II diabetic patients. The glucose-lowering effect of the 4-mg twice-daily dose of rosiglitazone was similar to that of 6-mg twice daily, suggesting that 4 mg twice daily should be the maximum clinical dose. [Diabetologia (2000) 43: 278–284] Received: 15 July 1999 and in revised form: 30 September 1999     

Dietary fatty acids modify insulin secretion of rat pancreatic islet cells in vitro

The type of dietary fat affects the action of insulin by changes induced in the fatty acid composition of cell membranes. Little is known, however, about the effects of dietary fatty acids on insulin secretion or the possible relation between the fatty acid composition of the membrane phospholipids and insulin secretion. We therefore studied the effects of dietary fatty acids on insulin secretion stimulated by glucose, forskolin and arginine, and on the insulin content of isolated pancreatic islets, as well as on the fatty acid composition of muscle phospholipids, which were used as markers of the diet-induced modifications in the cell membranes. Five groups of rats were fed for one month with diets varying only in their fat composition: olive oil, sunflower oil, soybean oil, fish oil and palmitic acid (16:0) + soybean oil (SAT). The SAT group had higher insulin secretion, independently of the secretagogue used. No significant differences were found in insulin content between the groups. The dietary fatty acids modified the fatty acid composition of the muscle phospholipids, both in endogenously synthesized fatty acids and in those which were unable to be synthesized by the organism. No statistically significant relation was found between insulin secretion and the content of certain fatty acids in the muscle phospholipids.     

The effects of a low-dose intravenous insulin infusion upon plasma glucose and non-esterified fatty acid levels in very obese and non-obese human subjects

Summary After an overnight fast, the effects of a 30-min low-dose intravenous insulin infusion (2.6 units/h) upon plasma glucose and non-esterified fatty acids were compared in 29 very obese patients and 17 nonobese controls. The dose of insulin was chosen so as to have its sole or predominant hypoglycaemic effect upon hepatic glucose release. The proportional fall from basal values at 30 min of both plasma glucose and non-esterified fatty acids was significantly greater in the controls and there was no difference between males and females. In the controls the fall in plasma glucose and non-esterified fatty acids was significantly and inversely correlated with the basal plasma insulin level. Neither index of insulin sensitivity was significantly related with the basal plasma insulin in the obese subjects. Weight loss in the obese subjects led to increased insulin sensitivity; in particular, the degree of change in insulin-induced nonesterified fatty acids was significantly related to the percentage change in weight. Despite their extreme degree of obesity, the distributions of basal plasma insulin levels and the indices of insulin sensitivity in the obese subjects overlapped with those of the nonobese controls.     

Fetal Growth and Insulin Resistance in Adult Life: Role of Plasma Triglyceride and Non-esterified Fatty Acids

Reduced fetal growth is associated with insulin resistance and a high prevalence of glucose intolerance in adult life. Because babies who are growth retarded have elevated levels of triglyceride and non-esterified fatty acids (NEFA), and because similar abnormalities are observed in subjects with the insulin resistance syndrome, impaired regulation of lipid metabolism could be one of the mechanisms explaining the link between reduced fetal growth and insulin resistance. We have, therefore, measured fasting plasma triglyceride and NEFA, and the insulin-mediated suppression of NEFA during an oral glucose tolerance test in 93 men and women aged 50, born in Preston, whose birthweight and body size at birth had been recorded. Elevated fasting plasma triglycerides and reduced NEFA suppression during the oral glucose tolerance test were associated with the male sex, glucose intolerance, central obesity as indicated by a high waist to hip ratio and insulin resistance as measured by a short insulin tolerance test. However there were no statistically significant relationships between the birth measurements and the circulating lipid levels. Moreover in regression analyses the relationships between thinness at birth and insulin resistance or glucose intolerance in adult life were unaffectived by the addition of triglyceride or NEFA in the models. These results suggest that the link between reduced fetal growth and insulin resistance in the adult is not mediated by an abnormal regulation of lipid metabolism.     

n-3多不饱和脂肪酸对高脂诱导胰岛素抵抗大鼠肝脏和骨骼肌胰岛素受体及葡萄糖转运蛋白4的作用

目的探讨n-3脂肪酸对饱和脂肪酸诱导的大鼠胰岛素抵抗(IR)肝脏和骨骼肌胰岛素受体(InsR)及葡萄糖转运蛋白4(GluT-4)的作用。方法45只雄性Wistar大鼠分为对照组、高脂组和n-3脂肪酸组。各组饲养11周后测定有关指标。结果(1)与对照组比较，高脂组大鼠体内脂肪相对含量、空腹血糖(FBG)、血清胰岛素(Ins)、甘油三酯(TG)、胆固醇(TC)、胰岛素抵抗指数(IRI)、肝脏TC和TG含量、肌肉中TG含量均显著升高；而肌肉组织中TC含量无显著改变，高脂组肝脏和肌肉InsR含量、肌肉Glut-4蛋白的相对含量均明显下降。(2)n-3脂肪酸组体内脂肪相对含量、FBG、Ins、TG、TC、IRI、肝脏TC和TG含量、肌肉组织中TG含量较高脂组均明显降低，肝脏InsR含量和肌肉GluT-4较高脂组明显升高。结论适量n-3脂肪酸代替饱和脂肪酸的一部分热量后，可增加IR大鼠肝脏InsR含量和肌肉GluT-4蛋白表达。     

Beneficial effects of long-chain n-3 fatty acids included in an energy-restricted diet on insulin resistance in overweight and obese European young adults

AIMS/HYPOTHESIS: Epidemiological research indicates that long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) improve insulin resistance. The aim of this study was to investigate the effects of seafood consumption on insulin resistance in overweight participants during energy restriction. METHODS: In this 8 week dietary intervention, 324 participants (20-40 years, BMI 27.5-32.5 kg/m(2), from Iceland, Spain and Ireland) were randomised by computer to one of four energy-restricted diets (-30E%) of identical macronutrient composition but different LC n-3 PUFA content: control (n = 80; no seafood; single-blinded); lean fish (n = 80; 150 g cod, three times/week); fatty fish (n = 84; 150 g salmon, three times/week); (4) fish oil (n = 80; daily docosahexaenoic/eicosapentaenoic acid capsules, no other seafood; single-blinded). Fasting glucose, insulin, adiponectin, plasma triacylglycerol and fatty acids in erythrocyte membrane were measured at baseline and endpoint. Insulin resistance was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Linear models with fixed effects and covariates were used to investigate the effects of seafood consumption on fasting insulin and HOMA-IR at endpoint in comparison with the control group. RESULTS: Of the participants, 278 (86%) completed the intervention. Fish oil intake was a significant predictor of fasting insulin and insulin resistance after 8 weeks, and this finding remained significant even after including weight loss, triacylglycerol reduction, increased LC n-3 PUFA in membranes or adiponectin changes as covariates in the statistical analysis. Weight loss was also a significant predictor of improvements. CONCLUSIONS/INTERPRETATION: LC n-3 PUFA consumption during energy reduction exerts positive effects on insulin resistance in young overweight individuals, independently from changes in body weight, triacylglycerol, erythrocyte membrane or adiponectin. Trial registration: ClinicalTrials.gov NCT00315770.     

Serum saturated fatty acids containing triacylglycerols are better markers of insulin resistance than total serum triacylglycerol concentrations

Aims/hypothesis

The weak relationship between insulin resistance and total serum triacylglycerols (TGs) could be in part due to heterogeneity of TG molecules and their distribution within different lipoproteins. We determined concentrations of individual TGs and the fatty acid composition of serum and major lipoprotein particles and analysed how changes in different TGs and fatty acid composition are related to features of insulin resistance and abdominal obesity.

Methods

We performed lipidomic analyses of all major lipoprotein fractions using two analytical platforms in 16 individuals, who exhibited a broad range of insulin sensitivity.

Results

We identified 45 different TGs in serum. Serum TGs containing saturated and monounsaturated fatty acids were positively, while TGs containing essential linoleic acid (18:2 n?6) were negatively correlated with HOMA-IR. Specific serum TGs that correlated positively with HOMA-IR were also significantly positively related to HOMA-IR when measured in very-low-density lipoproteins (VLDLs), intermediate-density lipoproteins (IDLs) and LDL, but not in HDL subfraction 2 (HDL₂) or 3 (HDL₃). Analyses of proportions of esterified fatty acids within lipoproteins revealed that palmitic acid (16:0) was positively related to HOMA-IR when measured in VLDL, IDL and LDL, but not in HDL₂ or HDL₃. Monounsaturated palmitoleic (16:1 n?7) and oleic (18:1 n?9) acids were positively related to HOMA-IR when measured in HDL₂ and HDL₃, but not in VLDL, IDL or LDL. Linoleic acid was negatively related to HOMA-IR in all lipoproteins.

Conclusions/interpretation

Serum concentrations of specific TGs, such as TG(16:0/16:0/18:1) or TG(16:0/18:1/18:0), may be more precise markers of insulin resistance than total serum TG concentrations.

     

Components of the insulin resistance syndrome in seven-year-old children: relations with birth weight and the polyunsaturated fatty acid content of umbilical cord plasma phospholipids

Aims/hypothesis: According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as indicated by the fatty acid composition of cord blood samples, relates to childhood body composition and glycaemic control. Methods: Fatty acid concentrations in umbilical cord blood were determined by gas-liquid chromatography in a birth-cohort of infants. When the children were seven years old, fasting glucose, insulin, proinsulin, and leptin levels were measured in 259 of these children, and relations with cord plasma fatty acid concentrations were studied. Results: Cord plasma phospholipid γ-linolenic acid and dihomo-γ-linolenic acid concentrations were negatively related to insulin concentrations and calculated insulin resistance (homeostasis model assessment) at seven years of age. The γ-linolenic acid concentrations were also negatively related to body fatness and proinsulin and leptin concentrations at seven years of age. No association was found for other polyunsaturated fatty acid concentrations at birth. Adjusted for age, sex, current weight, and gestational age, a lower birth weight related to higher values of insulin resistance variables. The highest insulin concentrations were found in children with a low birth weight and a low γ-linolenic acid concentration at birth. The relations between γ-linolenic acid concentration at birth and fasting insulin and calculated insulin resistance remained statistically significant when adjusted for birth weight. Conclusion/interpretation: These findings indicate that foetal availability or metabolism of γ-linolenic acid could be involved in the early origins of insulin resistance. [Diabetologia (2002) 45: 349–355] Received: 8 August 2001 and in revised form: 1 November 2001     

Platelet aggregation in non-insulin-dependent diabetes is associated with platelet fatty acids

Platelet aggregation was measured in 15 patients having non-insulin-dependent diabetes mellitus (NIDDM) at the time of diagnosis and after three months of dietary treatment. Mean fasting plasma glucose fell from 13.0 to 8.8 mmol/l (p less than 0.0002), glycosylated haemoglobin fell from a mean of 11.3% to 9.0% (p less than 0.005) and insulin levels fell from a mean of 17.5 to 13.8 mU/l (p less than 0.005). Platelet aggregation showed a variable response and did not correlate with plasma glucose, glycosylated haemoglobin or plasma insulin. Multiple linear regression analysis was carried out on the aggregation values against the biochemical variables and platelet phospholipid fatty acid levels following logarithm transformation. Platelet linolenic acid and eicosapentaenoic acid levels were significantly inversely associated with aggregation but the difference between the relationship at diagnosis and after three months was not statistically significant. The association between platelet omega 3 fatty acids and platelet aggregation suggest that dietary change aimed at increasing the proportions of these fatty acids might favourably influence vascular disease in NIDDM via an effect on platelet function.     

The postprandial response of adiponectin to a high-fat meal in normal and insulin-resistant subjects

OBJECTIVE: Adiponectin is an adipose-specific protein with short-term effects in vivo on glucose and fatty acid levels. We studied the plasma concentration and the proteolytic activation status of adiponectin following the consumption of a high-fat, low-carbohydrate meal. DESIGN: Analysis of adiponectin concentration and polypeptide structure after consumption of a fat meal. SUBJECTS: Normal subjects (n=24) and first-degree relatives of patients with type II diabetes (n=20). MEASUREMENTS: All subjects had a normal fasting plasma glucose and glucose tolerance. Blood was collected for the determination of plasma insulin, adiponectin, triglyceride, and free fatty acids. Body composition was assessed with dual-energy X-ray absorptiometry and whole-body insulin sensitivity with a euglycaemic, hyperinsulinaemic clamp. Postprandial response over 6 h was determined for plasma adiponectin, glucose, insulin, triglyceride, and free fatty acids. Adiponectin was measured by commercial RIA and its polypeptide structure examined by Western blotting. RESULTS: The relatives were more insulin resistant and had increased adiposity compared with control subjects. There was no significant difference in postprandial response in fatty acids, triglyceride, or insulin between the groups. Postprandial levels of adiponectin measured by radioimmunoassay were not significantly different from fasting levels, and no breakdown products of adiponectin were detectable in postprandial samples by Western blotting. CONCLUSIONS: Levels of circulating adiponectin do not alter in response to a fat meal, despite evidence in mice that acute changes in adiponectin significantly affect postprandial fatty acid flux. Moreover, a fat meal challenge did not lead to significant activation of adiponectin by proteolytic conversion.     

Influence of dietary habits,age and gender on plasma fatty acids levels in a population of healthy Tunisian subjects

The fatty acids composition of circulating blood lipids is expected to be altered by many factors (ageing, dietary intake, lifestyle...). In addition to the ageing consequences on their lipid status, elderly subjects represent a population at risk of nutritional imbalance. The main objective of the present study was to investigate the associations between dietary habits and the plasma fatty acids patterns in a healthy Tunisian population with an emphasis on the gender and ageing differences for the ?6-desaturase activity and the EFA proportions. Nutritional habits and plasma fatty acids compositions have been therefore evaluated in 200 healthy volunteers (104 women and 96 men) aged between 40 and 82 years old. The findings revealed that the ?6-desaturase activity was reduced in elderly subjects (by 24% and 10% in women and men respectively). Moreover, DHA (C22:6n−3) and AA (C20:4n−6) were found to increase respectively in high fish and meat consumers. Plasma fatty acids composition could be sensitive to dietary habits according to particular food items and should then help for the establishment of optimal nutritional proportions.