It has been shown using proton magnetic resonance spectroscopy (1H MRS) that, in a group of females, whole-body insulin resistance was more closely related to accumulation of saturated intramyocellular lipid (IMCL) than to IMCL concentration alone. This has not been investigated in males. We investigated whether age- and body mass index-matched healthy males differ from the previously reported females in IMCL composition (measured as CH2:CH3) and IMCL concentration (measured as CH3), and in their associations with insulin resistance. We ask whether saturated IMCL accumulation is more strongly associated with insulin resistance than other ectopic and adipose tissue lipid pools and remains a significant predictor when these other pools are taken into account. In this group of males, who had similar overall insulin sensitivity to the females, IMCL was similar between sexes. The males demonstrated similar and even stronger associations of IMCL with insulin resistance, supporting the idea that a marker reflecting the accumulation of saturated IMCL is more strongly associated with whole-body insulin resistance than IMCL concentration alone. However, this marker ceased to be a significant predictor of whole-body insulin resistance after consideration of other lipid pools, which implies that this measure carries no more information in practice than the other predictors we found, such as intrahepatic lipid and visceral adipose tissue. As the marker of saturated IMCL accumulation appears to be related to these two predictors and has a much smaller dynamic range, this finding does not rule out a role for it in the pathogenesis of insulin resistance.

To explore the relationship between the fatty acid lipophilic index (LI) of the erythrocyte membrane and oral cancer risk, as well as to evaluate the possibility of LI acting as a mediator of the association between body mass index (BMI) and oral cancer.

Twenty-three fatty acids (FAs) of the erythrocyte membrane were measured using gas chromatography in 380 patients with oral cancer and 387 control subjects. The LI was calculated based on the FA proportion and FA melting points. The association of BMI and erythrocyte LI with oral cancer risk was analysed using logistic regression. The mediation effect of LI on the association between BMI and oral cancer risk was evaluated using mediation analysis.

Among the control group, 46.0% were overweight or obese, which was significantly higher than that of oral cancer patients (29.5%). Significant differences in erythrocyte membrane saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) were observed between the patient and control groups. The proportion of C18:1 n-9 from the MUFA family increased in oral cancer patients (12.67%) compared with controls (12.21%). While the total proportion of n-3 PUFAs decreased in oral cancer patients compared with controls, with C20:5 n-3 decreasing from 0.66 to 0.47%, and C22:6 n-3 decreasing from 5.82 to 4.86%. The LI was lower in the control participants (M = 27.6, IQR: 27.3-27.9) than in the oral cancer patients (M = 28.2, IQR: 27.9-28.5). BMI was inversely associated with oral cancer risk with a fully adjusted OR of 0.59 (95% CI: 0.43-0.83), while LI was positively associated with oral cancer risk with a fully adjusted OR of 1.99 (95% CI:1.36-2.94). LI explained 7% of the variance in the relationship between BMI and oral cancer risk.

The distribution of the FA profile in erythrocyte membranes differed between the oral cancer patients and the control group. The LI derived from the profile of FAs was positively associated with the risk of oral cancer, and the associations between BMI and oral cancer risk can be explained, at least in part, by LI.

The metabolic syndrome unites three pathologies of the person - obesity, arterial hypertension and diabetes. In recent years the progressing of such distribution covering from 2.5% to 3.8% of the population with increase twice each 10-15 years is noted. Even at maintenance of level of sugar at diabetes accumulation of the secondary metabolites breaking small vessels isn't excluded. At the same time many life-endangering complications develop.

To identify the possibilities of plasmapheresis in the prevention and treatment of complications of metabolic syndrome.

Analysis of the world literature data on complications of metabolic syndrome and methods of their treatment.

At metabolic syndrome the frequency of strokes and myocardial infarctions there is twice more often than in population. For 5-9 years the general life expectancy decreases. Disorders of microcirculation at diabetes lead to a retinopathy with total loss of sight, a nephropathy from the outcome in a renal failure, to polyneuropathy and diabetic foot syndrome with high risk of high level amputations of the lower extremities. At the same time medicamentous therapy is not able to prevent such complications and almost only way of removal of these pathological metabolites is therapeutic apheresis, mainly the plasmapheresis. Data from our own studies confirm the effectiveness of such tactics.

Plasmapheresis has to be applied not only to the correction of already critical conditions, but also to their prevention.

Free fatty acids released from human adipose tissue contain a limited amount of non-esterified poly-cis-unsaturated fatty acids. In cases of elevated plasma free fatty acids, this condition ultimately leads to a shift from unsaturated to saturated fatty-acyl chains in membrane phospholipids. Because this shift promotes the physical attractive van der Waals interactions between phospholipid acyl chains, it increases stiffness of both erythrocyte and endothelial membranes, which causes a reduction in both insulin-independent and insulin-dependent Class 1 glucose transporters, a reduction in cell membrane functionality, and a decreased microcirculatory blood flow which results in tissue hypoxia. Against the background of these processes, we review recently published experimental phospholipid data obtained from Drosophila melanogaster and from human erythrocytes of controls and patients with type 2 diabetes, with and without retinopathy, along the way free fatty acids interfere with eye and kidney function in patients with type 2 diabetes and give rise to endoplasmic reticulum stress, reduced insulin sensitivity, and ischemia.

Maternal diet during pregnancy can modulate skeletal muscle development of the offspring. Previous studies in pigs have indicated that a fat supplemented diet during pregnancy can improve piglet outcome, however, this is in contrast to human studies suggesting adverse effects of saturated fats during pregnancy. This study aimed to investigate the impact of a fat supplemented (palm oil) "high fat" diet on skeletal muscle development in a porcine model. Histological and metabolic features of the biceps femoris muscle obtained from 7-day-old piglets born to sows assigned to either a commercial (C, n = 7) or to an isocaloric fat supplementation diet ("high fat" HF, n = 7) during pregnancy were assessed.

Offspring exposed to a maternal HF diet demonstrated enhanced muscular development, reflected by an increase in fractional growth rate, rise in myofibre cross-sectional area, increased storage of glycogen and reduction in lipid staining of myofibres. Although both groups had similar intramuscular protein and triglyceride concentrations, the offspring born to HF mothers had a higher proportion of arachidonic acid (C20:4n6) and a reduction in α-linolenic acid (C18:3n3) compared to C group offspring. The HF group muscle also exhibited a higher ratio of C20:3n6 to C20:4n6 and total n-6 to n-3 in conjunction with up-regulation of genes associated with free fatty acid uptake and biogenesis.

In conclusion, a HF gestational diet accelerates the maturation of offspring biceps femoris muscle, reflected in increased glycolytic metabolism and fibre cross sectional area, differences accompanied with a potential resetting of myofibre nutrient uptake.

Biochemical predictors of infants' growth changes are not available.

We tested whether retinol-binding protein (RBP), docosahexaenoic acid and insulin (I) measured within 72 h from birth are associated with growth changes in infants born to mothers with gestational diabetes mellitus (GDM).

Fifty-six children, 32 born to diabetic mothers treated with insulin (GDM-I) and 24 born to diabetic mothers treated with diet (GDM-D), were evaluated at 0, 1, 3, 6 and 12 months of life.

At multivariable regression performed using generalized estimating equations, early RBP levels and maternal body mass index were associated to average weight changes and early RBP and insulin levels to average length changes, respectively. There was no difference between GDM-I and GDM-D infants.

This exploratory study suggests that early RBP levels may be a predictor of growth changes.

Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic (16:1n-7), myristoleic (14:1n-5) and trans-palmitoleic acid (16:1n-7t). Negative correlation was found with baseline oleic acid (18:1n-9). Lower baseline monounsaturated fatty acids (14:1n-5, 16:1n-7 and trans 16:1n-7) in adipose tissue triglycerides predict better weight maintenance. Lower oleic acid predicts lower weight decrease. These findings suggest a specific role of monounsaturated fatty acids in weight management and as weight change predictors.

The popular short echo time (1)H MR spectroscopy acquisition method for detection of intramyocellular lipids suffers from spectral overlap due to the large, broad, and asymmetric extramyocellular lipid signals, the time-consuming practice of selecting "lean" voxels for spectroscopy, and the overlap of the extramyocellular lipid signal with the creatine methyl (1)H signal at approximately 3 parts per million (ppm), commonly used as an internal standard. Using an alternative acquisition strategy, spectra with well-resolved intramyocellular lipids resonances were acquired from large volumes (10 to 15 mL) of human soleus muscle in less than 5 min by single-voxel 7-T (1)H MR spectroscopy, using an echo time of 280 ms. From the high-resolution spectra, an average intramyocellular lipid concentration of 7.7 +/- 3.5 mmol/kg muscle was found for 25 healthy subjects (male/female 17/8; age 29.4 +/- 6.6 years). Since water suppression was not required, the (1)H signals from unsaturated intracellular triglycerides at about 5.3 ppm were easily detected, which, in combination with the well-determined -(CH(2))(n)-/CH(3) intensity ratio at long echo time, enabled assessment of the composition of triglycerides in the intramyocellular lipids compartment. Long-echo single-voxel spectroscopy at 7 T offers rapid and convenient acquisition of high-resolution spectra from human soleus muscle.

Increased tissue n-3 polyunsaturated fatty acid (PUFA) is associated with improved insulin sensitivity in type 2 diabetes. However, this relationship among Chinese is not clear. To investigate the relationship between plasma phospholipids (PL) fatty acid composition and insulin resistance (IR) in type 2 diabetes mellitus, 186 type 2 diabetes and 180 healthy subjects were studied in this case-control study. In the sex, age and BMI controlled partial correlation, homeostasis model assessment (HOMA)-IR and blood glucose was significantly negatively correlated with plasma PL n-3 PUFA, 20:5n-3 and ratio of n-3:n-6 (p<0.01), and positively correlated with n-6 PUFA (p<0.001) and saturated fatty acid (p<0.05) in the diabetes patients. PL 22:6n-3 was also significantly negatively correlated with HOMA-IR (p<0.01), but not with blood glucose. Fasting insulin was significantly negatively correlated with plasma PL n-3 PUFA, 20:5n-3, 22:6n-3 and ratio of n-3:n-6 (p<0.01). The 18:3n-3 was not associated with HOMA-IR and fasting insulin. The results suggested that increased plasma PL n-3 PUFA, 20:5n-3, 22:6n-3 and ratio of n-3:n-6 PUFA was associated with decreased HOMA-IR in type 2 diabetes. Increased plasma PL n-3 PUFA improves insulin sensitivity in type 2 diabetes.

The objective was to investigate in a group of obese subjects the course in skeletal muscle phospholipid (SMPL) fatty acids (FA) during a 24-weeks weight maintenance program, which was preceded by a successful very low calorie dietary intervention (VLCD). Special focus was addressed to SMPL omega-3 FA, which is a lipid entity that influences insulin action.

Nine obese subjects (BMI = 35.7 +/- 1.0 kg/m(2)), who had completed an 8 weeks VLCD (weight-loss = -9.7 +/- 1.6 kg, P < 0.001), had obtained skeletal muscle biopsies (vastus lateralis) before and after a dietician-guided 24-weeks weight-maintenance program (-1.2 +/- 1.5 kg, P = ns). SMPL FA composition was determined by gas liquid chromatography. During the preceding VLCD, insulin sensitivity (HOMA-IR) and glycemic control (HbA1c) improved but no change in SMPL omega-3 FA was observed. During the weight-maintenance program five subjects received the pancreas lipase inhibitor Orlistat 120 mg t.i.d. versus placebo.

HOMA-IR and HbA1c stabilized and SMPL total omega-3 FA, docosahexaenoic acid and ratio of n-3/n-6 polyunsaturated FA increased by 24% (P < 0.01), 35% (P < 0.02) and 26% (P < 0.01), respectively, whereas saturated and monounsaturated FA did not change. Plasma total-cholesterol and LDL-cholesterol, which decreased during the VLCD, reverted to pre-VLCD levels (P < 0.01). Orlistat therapy was associated with weight-loss (P < 0.05), trends for better glycemic control (P = 0.15) and greater increase in SMPL docosahexaenoic acid (P = 0.12) but similar reversal of plasma cholesterols compared to placebo.

The data are consistent with the notion that greater SMPL omega-3 FA obtained during a weight-maintenance program may play a role for preserving insulin sensitivity and glycemic control being generated during a preceding VLCD.

The incidence rate of obesity in youth has continued to increase worldwide and about 30% of obese children display insulin resistance (IR) and other metabolic abnormalities. The present study reviews the mechanisms for development of IR in the obese child and possible links between IR and dietary factors in childhood and adolescence. Although increased concentrations of plasma free fatty acids (FFA) and their counter part at intracellular level, long-chain acyl-coenzyme A (LC acyl-CoA), have been related to the early onset of IR in childhood obesity, a new endocrine paradigm states that adipose tissue secretes a wide variety of hormones and cytokines that regulate lipid energy metabolism. These hormonal changes precede any changes in metabolites such as FFA and glucose and appear to be associated with early IR in childhood. Excessive caloric intake increases IR in children; opposite, substantial reduction of overweight achieved by a hypocaloric diet decreases it. Elevated consumption of animal protein, particularly in early life, as well as diets rich in saturated, trans, and n-6 polyunsaturated fatty acids, and diets with a high carbohydrate to fat ratio, besides a high glycaemic and low-fiber diet also appear to exacerbate adiposity and IR.

This study investigated whether a very-lowcalorie dietary intervention (VLCD) may influence composition of skeletal muscle cell membrane phospholipid and composition and concentration of intramyocellular triglyceride (IMTG) in obese subjects. The working hypothesis proposed that a VLCD would decrease saturated fatty acids (FAs) and increase long-chain polyunsaturated FAs (LCPUFAs) in muscular structural lipids, as such changes have been associated with improved insulin sensitivity.

Skeletal muscle biopsies (vastus lateralis) were obtained from 13 obese subjects (nine women) before and after 8 weeks on VLCD (approximately 600 to 800 kcal/d). FA composition in muscle cell membrane phospholipid and concentration and FA composition of IMTG were determined by gas-liquid chromatography.

Baseline BMI was 36.0 +/- 3.4 kg/m2. Weight loss was 9.3 +/- 1.1 kg (8.8 +/- 1.1%; p < 0.0001); loss of adipose tissue was 5.9 +/- 0.9 kg (p < 0.0001). Insulin resistance (by homeostasis model assessment) decreased (-44 +/- 7%; p < 0.001). Muscle cell membrane phospholipid saturated FAs decreased (-3.2 +/- 1.3%; p < 0.05), whereas monounsaturated FAs (4.3 +/- 1.7%; p < 0.05), LCPUFAs (11 +/- 6%; p < 0.05), and the ratio of LCPUFAs to saturated FAs (12 +/- 5%; p < 0.05) increased. IMTG decreased, but not significantly (-5%). IMTG-saturated FAs decreased (-3.3 +/- 1.5%; p < 0.05), whereas LCPUFAn-3 (29 +/- 9%; p < 0.01), LCPUFAn-6 (33 +/- 9%; p < 0.01), and the ratio of LCPUFAs to saturated FAs (34 +/- 8%; p < 0.001) increased. Plasma total cholesterol (-15 +/- 6%; p < 0.05), low-density lipoprotein-cholesterol (-16 +/- 5%; p < 0.01), high-density lipoprotein-cholesterol (-8 +/- 2%; p < 0.01), and plasma triglyceride (-19 +/- 12%; p = 0.10) all decreased during the VLCD.

Desaturation of both muscle cell membrane phospholipid and IMTG was significant but modest during a VLCD in obese subjects. Further research must delineate whether such changes in skeletal muscle structural and depot lipid composition themselves are enough to promote the observed improvements in insulin action.

Pro12Ala variant of peroxisome-proliferator-activated receptor-gamma2 (PPAR-gamma2) may be linked to insulin sensitivity. This study examined whether an association of PPAR-gamma2 Pro12Ala with insulin resistance and plasma LCPUFAs may exist in obese children. One hundred and forty Italian normolipidemic obese children (58 girls and 82 boys, mean age [SD], 10.2 [2.7] y) entered the study. Obesity was defined according to International Obesity Task Force. BMI Z-scores were calculated. Fasting blood glucose, insulin, lipids and plasma fatty acids were measured. Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR). The frequency of Ala allele was 9%. Mean [SD] values of fasting insulin and HOMA-IR in Pro/Pro versus Pro12Ala groups were: 19.3 [10.6] versus 14.1 [10.4] microU/mL (p = 0.017) and 4.2 [2.3] versus 3.0 [2.3] (p = 0.022). Mean [SD] values of plasma C20:3n-9 and of C20:4n-6, C20:5n-3, C22:6n-3 and n-6/n-3 LCPUFA in phospholipds in Pro/Pro versus Pro12Ala groups were: 0.15 [0.07] versus 0.12 [0.08] % (p = 0.014), 8.9 [1.9] versus 10.2 [2.6] % (p = 0.023), 0.34 [0.15] versus 0.42 [0.11] % (p = 0.005), 2.1 [0.9] versus 2.6 [0.9] % (p = 0.032) and 4.8 [1.2] versus 4.2 [0.7] (p = 0.017). Pro12Ala may be associated with higher insulin sensitivity and higher LCPUFAs, particularly n-3, levels in plasma phosholipids of obese children.

Gestational diabetes mellitus (GDM) is a transient metabolic disorder that is a strong predictor of type 2 diabetes and cardiovascular disease. Previously, GDM was associated with reduced red cell long-chain omega-6 and omega-3 fatty acids in population (British) with high intake of total and saturated fat. The aim of the study was to examine blood fatty acids status of GDM patients (n=12) and normoglycaemic women (control, n=12) from South Korea where typical diet retains high omega-3 fat with low total fat intake. Subjects were matched for BMI and gestation week. Blood obtained at delivery were analyzed for plasma triacylglycerols (TG), phosphatidylcholine (PC), sphingomyelin (SM), and red cell PC, phosphatidylethanolamine (PE) and SM fatty acids. GDM patients had lower total saturated fatty acids (SFA) in the plasma TG (p<0.05) and PC (p<0.0001), and higher omega-6 and omega-3 metabolites in the plasma PC (p<0.05) than the controls. Conversely, the red cell PC and PE of the GDM contained higher proportions of palmitic (p<0.05) and SFA (p<0.05) but lower arachidonic (p<0.05) and docosahexaenoic (p>0.05) acids compared with the controls. Interestingly, red cell PC arachidonic acid level was comparable between Korean and British women whereas docosahexaenoic acid level decreased in the order of Korean control (5.5+/-0.9)>Korean GDM (3.5+/-2.1)=British control (3.9+/-2.9)>British GDM (2.8+/-2.3) (p<0.05). The similarity in the plasma and red cell fatty acids profile between Korean and British cohort suggests that the reduced membrane arachidonic and docosahexaenoic acids in GDM might be attributed to the effect of the disease itself regardless of ethnicity, obesity, or diet.

Pregestational maternal diabetes increases obesity and diabetes risks in the offspring. Both conditions are characterized by insulin resistance, and diabetes is associated with low membrane arachidonic (AA) and docosahexaenoic (DHA) acids.

We investigated whether type 1 and type 2 diabetes in pregnancy compromise maternal and fetal membrane essential fatty acids (FAs).

We studied 39 nondiabetic (control subjects), 32 type 1 diabetic, and 17 type 2 diabetic pregnant women and the infants they delivered. Maternal and cord blood samples were obtained at midgestation and at delivery, respectively. Plasma triacylglycerols and choline phosphoglycerides and red blood cell (RBC) choline and ethanolamine phosphoglyceride FAs were assessed.

The difference in maternal plasma triacylglycerol FAs between groups was not significant. However, the type 1 diabetes group had lower plasma choline phosphoglyceride DHA (3.7 +/- 0.9%; P < 0.01) than did the control group (5.2 +/- 1.6%). Likewise, RBC DHA was lower in the type 1 [choline: 3.4 +/- 1.5% (P < 0.01); ethanolamine: 5.9 +/- 2.5% (P < 0.05)] and type 2 [choline: 3.5 +/- 1.6% (P < 0.05)] diabetes groups than in the control group (choline: 5.5 +/- 2.2%; ethanolamine: 7.5 +/- 2.5%). Cord AA and DHA were lower in the plasma (type 1: P < 0.01) and RBC (type 2: P < 0.05) choline phosphoglycerides of the diabetics than of the control subjects, and cord RBC ethanolamine phosphoglycerides were lower in DHA (P < 0.05) in both diabetes groups than in the control group.

Diabetes (either type) compromises maternal RBC DHA and cord plasma and RBC AA and DHA. The association of these 2 FAs with insulin sensitivity may mean that the current finding explains the higher incidence of insulin resistance and diabetes in the offspring of diabetic women.

Intrauterine exposure to diabetes is a significant determinant of the development of obesity and early onset of Type 2 diabetes mellitus in the offspring. Both conditions are characterized by insulin resistance and the latter is associated with reduced membrane arachidonic and docosahexaenoic acids. Hence, we investigated if the membrane arachidonic and docosahexaenoic acids are depressed in the cord blood of babies born to women with gestational diabetes.

Cord (fetal) and maternal blood were obtained at delivery from control subjects (n = 33) and women with gestational diabetes (n = 40) and analysed for plasma triglycerides and cholinephosphoglycerides, and erythrocyte choline- and ethanolaminephosphoglycerides fatty acids.

Babies of gestational diabetic mothers had reduced docosahexaenoic acid in the plasma (5.9 +/- 1.4 vs. 7.1 +/- 2.0, P < 0.01) and erythrocyte (4.0 +/- 2.2 vs. 5.4 +/- 2.9, P < 0.05) cholinephosphoglycerides. Moreover, the total omega-6 and omega-3 fatty acids of the erythrocyte cholinephosphoglycerides were significantly lower (P < 0.05) in these babies. A similar trend was observed in plasma triglycerides and erythrocyte ethanolaminephosphoglycerides. The maternal plasma triglycerides and erythrocyte ethanolaminephosphoglycerides fatty acids profile were not different between the two groups. However, there was a reduction in arachidonic acid and total omega-6 fatty acids in the erythrocyte cholinephosphoglycerides of the gestational diabetic women.

The altered plasma and erythrocyte fatty acids in the cord blood of babies born to women with gestational diabetes suggests a perturbation in the maternal-fetal nutrient transport and/or fetal lipid metabolism.

Dietary polyunsaturated fatty acids (PUFA) have effects on diverse physiological processes impacting normal health and chronic diseases, such as the regulation of plasma lipid levels, cardiovascular and immune function, insulin action and neuronal development and visual function. Ingestion of PUFA will lead to their distribution to virtually every cell in the body with effects on membrane composition and function, eicosanoid synthesis, cellular signaling and regulation of gene expression. Cell specific lipid metabolism, as well as the expression of fatty acid-regulated transcription factors, likely play an important role in determining how cells respond to changes in PUFA composition. This review will focus on recent advances on the essentiality of these molecules and on their interplay in cell physiology, leading to new perspective in different therapeutic fields.

Epidemiological studies linking low birth weight and subsequent cardiometabolic disease have given rise to the hypothesis that events in fetal life permanently program subsequent cardiovascular risk. The effects of fetal programming may not be limited to the first-generation offspring. We have explored intergenerational effects in the dexamethasone-programmed rat, a model in which fetal exposure to excess glucocorticoid results in low birth weight with subsequent adult hyperinsulinemia and hyperglycemia underpinned by increased activity of the key hepatic gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK). We found that the male offspring of female rats that had been exposed prenatally to dexamethasone, but were not manipulated in their own pregnancy, also had reduced birth weight (5.66 +/- 0.06 vs. 6.12 +/- 0.06 g, P < 0.001), glucose intolerance, and elevated hepatic PEPCK activity (5.7 +/- 0.6 vs. 3.3 +/- 0.2 nmol.min(-1).mg protein(-1), P < 0.001). These effects resolved in a third generation. Similar intergenerational programming was observed in offspring of male rats exposed prenatally to dexamethasone mated with control females. The persistence of such programming effects through several generations, transmitted by either maternal or paternal lines, indicates the potential importance of epigenetic factors in the intergenerational inheritance of the "programming phenotype" and provides a basis for the inherited association between low birth weight and cardiovascular risk factors.

Gestational diabetes is a metabolic disorder affecting 2-5% of women and is a predictor of obesity, Type 2 diabetes mellitus and cardiovascular disease. Insulin resistance, a characteristic of gestational diabetes and obesity, is correlated with the fatty acids profile of the red cell and skeletal muscle membranes. We investigated the plasma and red cell fatty acid status of gestational diabetes. The effect of obesity on membrane fatty acids was also examined.

Fasting blood obtained at diagnosis was analysed for the fatty acids in plasma choline phosphoglycerides and red cell choline and ethanolamine phosphoglycerides.

There were reductions in arachidonic acid (controls 10.74+/-2.35 vs gestational diabetes 8.35+/-3.49, p<0.01) and docosahexaenoic acid (controls 6.31+/-2.67 vs gestational diabetes 3.25+/-2.00, p<0.0001) in the red cell choline phosphoglycerides in gestational diabetes. A similar pattern was found in the ethanolamine phosphoglycerides. Moreover, the arachidonic and docosahexaenoic acids depletion in the red cell choline phosphoglycerides was much greater in overweight/obese gestational diabetes (arachidonic acid=7.49+/-3.37, docosahexaenoic acid=2.98+/-2.18, p<0.01) compared with lean gestational diabetes (arachidonic acid=10.03+/-2.74, docosahexaenoic acid=4.18+/-1.42).

Apparently normal plasma choline phosphoglycerides fatty acids profile in the gestational diabetic women suggested that membrane lipid abnormality is associated specifically with perturbation in the membrane. The fact that the lipid abnormality is more pronounced in the outer leaflet of the membrane where most of receptor binding and enzyme activities take place might provide an explanation for the increased insulin resistance in gestational diabetes and obesity.

The data from the present investigation differ from those of the previous study. The new version of hydrolysed protein formula did not induce changes in insulinaemia or in the insulinaemia/glycaemia ratio in pre- and postprandial samples when compared with the intact protein formula. The investigation also confirmed that branch chain aminoacids regulate insulin secretion and that the length of chain is insulinotropic for fatty acids, while the degree of unsaturation is not able to reduce insulin secretion in the newborn baby. This could be caused by stimulation of insulin output activated by the C20:5 n 3; the effects of fatty acids are probably related more to the variable composition of cell membrane than to the fatty acids circulating levels.

It is still unknown whether the fatty acid composition of human skeletal muscle lipids is directly influenced by the fat composition of the diet.

We investigated whether the fatty acid composition of the diet is reflected in the fatty acid profile of skeletal muscle phospholipids and triacylglycerols.

Thirty-two healthy adults (25 men and 7 women) included in a larger controlled, multicenter dietary study were randomly assigned to diets containing a high proportion of either saturated fatty acids (SFAs) [total fat, 36% of energy; SFAs, 18% of energy; monounsaturated fatty acids (MUFAs), 10% of energy] or MUFAs (total fat, 35% of energy; SFAs, 9% of energy; MUFAs, 19% of energy) for 3 mo. Within each diet group, there was a second random assignment to supplementation with fish oil capsules [containing 3.6 g n-3 fatty acids/d; 2.4 g eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3)] or placebo. A muscle biopsy sample was taken from the vastus lateralis muscle after the diet period. Parallel analyses of diet and supplementation effects were performed.

The proportions of myristic (14:0), pentadecanoic (15:0), heptadecanoic (17:0), and palmitoleic (16:1n-7) acids in the skeletal muscle phospholipids were higher and the proportion of oleic acid (18:1n-9) was lower in the SFA group than in the MUFA group. The proportion of total n-3 fatty acids in the muscle phospholipids was approximately 2.5 times higher, with a 5 times higher proportion of eicosapentaenoic acid (20:5n-3), in subjects supplemented with n-3 fatty acids than in those given placebo. Similar differences were observed in the skeletal muscle triacylglycerols.

The fatty acid composition of skeletal muscle lipids reflects the fatty acid composition of the diet in healthy men and women.

The United Kingdom Prospective Diabetes Study (UKPDS) showed that tight glycemic control with any of several therapeutic regimens has the potential to significantly reduce the risk for long-term microvascular complications of type 2 diabetes. An important question that remains to be answered is what is the best approach to optimizing glycemic control in patients with this disease. This article reviews results of studies in which insulin was used alone or in combination with oral antidiabetic agents for treatment of patients with type 2 diabetes. Analysis of comparative studies (13 in insulin-naive and 26 in previously insulin-treated patients) showed that combination therapy involving one to two insulin injections per day plus oral therapy is usually more effective than insulin monotherapy for achieving and maintaining glycemic control. Combination treatment for type 2 diabetes can be significantly improved by newly developed preparations that lack the major limitations of older products. Once-daily administration of isophane insulin (NPH insulin) is limited by a 15-18-h duration of action and a peak effect that occurs about 6 h after injection. Insulin glargine, a new insulin analogue developed using recombinant DNA technology, has a flat pharmacodynamic profile and a 24-h duration of action. Results from a recent comparative study indicate that insulin glargine plus oral therapy may provide better post-dinner glucose control as well as less symptomatic and nocturnal hypoglycemia than oral therapy combined with NPH insulin. The studies reviewed in the present article support the conclusion that combination therapy with insulin glargine combined with one or more oral antidiabetic agents may be the treatment of choice for achieving glycemic control in patients with type 2 diabetes.

The cause of skeletal muscle insulin resistance is unclear, but high levels of intramyocellular lipids are often present in affected individuals. We aimed to establish the metabolic, familial, and anthropometric associations of intramyocellular lipid in a pediatric population. We studied 41 boys aged 6.9-9.9 y and 23 of their mothers by proton magnetic resonance spectroscopy. We related muscle lipid levels to important factors that define an increased risk of developing insulin resistance in adult life. There were significant associations between the boys' intramyocellular lipid and their waist circumference (r = 0.42, p = 0.007), body mass index SD score (r = 0.32, p = 0.04), weight SD score (r = 0.32, p = 0.04), glucose:insulin ratio (r= -0.59, p = 0.04), maternal log fasting insulin levels (r = 0.44, p = 0.04), maternal body mass index (r = 0.46, p = 0.03), and maternal intramyocellular lipid (r = 0.62, p = 0.003). In the 41 boys, waist circumference explained 19% of the variance in the boys' intramyocellular lipid. Maternal intramyocellular lipid explained 39% of the variance in the boys' intramyocellular lipid in the sub-group of 23 boys. Intramyocellular lipid levels have both metabolic and anthropometric associations in childhood. Before puberty, children develop or inherit muscle metabolic characteristics that are associated both with insulin resistance and risk factors for the development of insulin resistance syndrome in adult life.

Fourteen pairs of obese female monozygotic twins were recruited for a study of genetic influences on serum and adipose fatty acid (FA) composition. Following 1 wk of inpatient stabilization, fasting serum and adipose tissue obtained by surgical excision were analyzed by thin-layer and gas chromatography. Intrapair resemblances (IPR) for individual FA were assessed by Spearman rank correlation and by analysis of variance and were found in serum cholesteryl esters (CF), triglycerides (TG), and adipose TG. With two exceptions (CE linoleate and adipose eicosapentaenoate), these IPR were limited to the nonessential FA. Palmitate had significant IPR in four lipid fractions; in serum CE and adipose TG palmitate was strongly correlated with multiple measures of adiposity. In contrast to other lipid fractions, serum phosphatidylcholine (PC) FA had 12 [PR, of which 6 were essential FA including arachidonate (r = 0.76, P < 0.0005), eicosapentaenoate (r = 0.78, P < 0.0005), and docosahexaenoate (r = 0.86, P< 0.0001). The PC [PR could not be explained by analysis of preadmission 7-d food records. After dividing the pairs into two groups differing and nondiffering according to fat intake of individuals in the pair, there was no evidence of a gene-environment interaction between fat intake and FA composition. The IPR for nonessential FA indicate that there is active genetic control of either food choices or postabsorptive metabolic processing. The high level of IPR in the PC fraction in contrast to the other lipid fractions suggests strong genetic influence over selection of specific FA for this membrane fraction independent of diet.

To examine the pharmacology, therapeutics, pharmacokinetics, dosing guidelines, adverse effects, and drug interactions of insulin aspart, and summarize the clinical trials of efficacy and safety in patients with type or type 2 diabetes mellitus.

A MEDLINE database search (1985-May 2000) was performed to identify all applicable published articles and abstracts; in some cases, Novo Nordisk unpublished information was also obtained. Review articles on insulin analogs were also identified, as well as review chapters in medical textbooks.

The majority of the studies identified were in abstract form. These studies reported information on the pharmacokinetics of insulin aspart in healthy volunteers and in those with diabetes, as well as the therapeutic utility, safety, and clinical efficacy in patients with diabetes. A limited number of randomized studies were reported as artices in the medical literature

All published clinical studies were reviewed.

Insulin aspart, the second Food and Drug Administration-approved rapid-acting insulin analog, is produced by recombinant technology that replaces the proline at position 28 on the B chain of insulin with negatively charged aspartic acid. Insulin aspart exists as hexamers that rapidly dissociate into monomers and dimers on subcutaneous injection. When administered immediately prior to a meal, insulin aspart is at least as effective as regular human insulin in control of postprandial blood glucose concentrations. Insulin aspart achieves higher peak insulin concentrations in less time and with a shorter duration of action than regular human insulin.

Insulin aspart is a convenient premeal insulin for use by patients requiring mealtime insulin. Furthermore, due to favorable pharmacokinetics, insulin aspart controls postprandial blood glucose concentrations at least as well as regular human insulin and contributes to improved quality of life.

Endurance trained (n = 14) and untrained young men (n = 15) were compared regarding the fatty acid profile of the vastus lateralis muscle after 8 wk on diets with a similar fatty acid composition. The skeletal muscle phospholipids in the trained group contained lower proportions of palmitic acid (16:0) (-12.4%, P < 0.001) and di-homo-gamma-linolenic acid [20:3(n-6)] (-15.3%, P = 0.018), a lower n-6-to-n-3 ratio (-42.0%, P = 0.015), higher proportions of stearic acid (18:0) (+9.8%, P = 0.004) and sum of n-3 polyunsaturated fatty acids (+33.8%, P = 0.009), and a higher ratio between 20:4(n-6) to 20:3(n-6) (+18.4%, P = 0.006) compared with those in the untrained group. The group differences in 16:0, 20:3(n-6), 18:0/16:0, and 20:4(n-6)/20:3(n-6) were independent of fiber-type distribution. The trained group also showed a lower proportion of 16:0 (-7.9%, P < 0.001) in skeletal muscle triglycerides irrespective of fiber type. In conclusion, the fatty acid profile of the skeletal muscle differed between trained and untrained individuals, although the dietary fatty acid composition was similar. This difference was not explained by different fiber-type distribution alone but appears to be a direct consequence of changes in fatty acid metabolism due to the higher level of physical activity.

High-fat diets have been associated with insulin resistance, a risk factor for both Type II diabetes and heart disease. The effect of dietary fat on insulin varies depending on the type of fatty acid consumed. Saturated fatty acids have been consistently associated with insulin resistance. On the other hand, medium and long-chain fatty acid intakes are associated with insulin sensitivity, as are high intakes of w3 fatty acids. Trans fatty acids appear to potentiate insulin secretion, at least in the short-term, to a greater degree than cis fatty acids. This may reflect chronic alterations in insulin sensitivity, although this remains to be tested. In summary, although it must be emphasized that all diets high in fat cause insulin resistance relative to high-carbohydrate diets, it appears that dietary saturated, short-chain, and w6 fatty acids have the most deleterious effects on insulin action.