Effects of saturated and unsaturated fatty acids on estimated desaturase activities during a controlled dietary intervention

Background and aimsDirect measurement of desaturase activities are difficult to obtain in humans. Consequently, surrogate measures of desaturase activity (estimated desaturase activities) have been frequently used in observational studies, and estimated Δ⁹- (or stearoyl-CoA-desaturase (SCD)), Δ⁶- and Δ⁵-desaturase activities have been associated with cardiometabolic disease. Data on how the markers of desaturase activities are modified by changes in dietary fat quality are lacking and therefore warrant examination.Methods and resultsIn a two-period (three weeks) strictly controlled cross-over study, 20 subjects (six women and 14 men) consumed a diet high in saturated fat (SAT-diet) and a rapeseed oil diet (RO-diet), rich in oleic acid (OA), linoleic acid (LA) and α-linolenic acid (ALA). Estimated desaturase activities were calculated as precursor to product FA ratios in serum cholesteryl esters and phospholipids. The estimated SCD [16:1 n-7/16:0] and Δ⁶-desaturase [20:3 n-6/18:2 n-6] was significantly higher while Δ⁵-desaturase [20:4 n-6/20:3 n-6] was significantly lower in the SAT-diet (P < 0.001 for all), compared to the RO-diet. The serum proportions of palmitic, stearic, palmitoleic and dihomo-γ-linolenic acids were significantly higher in the SAT-diet while the proportions of LA and ALA were significantly higher in the RO-diet.ConclusionThis is the first study to demonstrate that surrogate measures of desaturase activities change as a consequence of an alteration in dietary fat quality. Both the [16:1/16:0]-ratio and 16:1 seem to reflect changes in saturated fat intake and may be useful markers of saturated fat intake in Western countries.     

Improvements in glucose tolerance and insulin sensitivity after lifestyle intervention are related to changes in serum fatty acid profile and desaturase activities: the SLIM study

Aims/hypothesis The aim of this study was to investigate whether lifestyle intervention-induced changes in serum fatty acid profile of cholesteryl esters and estimated desaturase activities are related to improvements in insulin sensitivity in subjects at risk of type 2 diabetes. Materials and methods In the Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM), 97 men and women with IGT were randomised to a combined diet and exercise programme (47 intervention) or a control group (50 control subjects). At baseline and after 1 year the following assessments were made: an OGTT, an exercise test to determine maximal aerobic capacity, anthropometry, and analysis of the serum fatty acid profile of cholesteryl esters. Results The lifestyle programme was effective in reducing the intake of total and saturated fat, increasing physical activity, reducing obesity and improving insulin sensitivity and glucose tolerance. Regression analysis of the total population showed that an increase in the C20:4 n-6/C20:3 n-6 ratio (estimated Δ5-desaturase activity) and reductions in the C18:3 n-6/C18:2 n-6 ratio (estimated Δ6-desaturase activity) and the C16:1 n-7/C16:0 ratio (estimated Δ9-desaturase activity or stearoyl-CoA desaturase-1) were significantly associated with a decrease in homeostasis model assessment for insulin resistance. After adjustment for lifestyle changes (change in percentage body fat, aerobic capacity and saturated fat intake), these associations were partly reduced, but remained statistically significant. Conclusions/interpretation Lifestyle-induced changes in fatty acid profile of cholesteryl esters and desaturase activities were independently related to changes in insulin sensitivity in subjects at risk of type 2 diabetes.     

The association of desaturase 9 and plasma fatty acid composition with insulin resistance-associated factors in female adolescents

Desaturase 9 (Δ9), which converts saturated fatty acids (SFAs) into monounsaturated fatty acids, is an important component in leptin-mediated energy homeostasis in rodent models. Few human studies, however, have been performed regarding the clinical relevance of Δ9, particularly whether Δ9 is involved in the relationship between blood fatty acid profiles and insulin resistance-associated factors. The aim of the present study was to examine fatty acid data from 178 apparently healthy female adolescents and determine whether (a) Δ9 has independent associations with adiposity, insulin resistance level, and fasting plasma polyunsaturated fatty acids (PUFAs); (b) Δ9 is a predictor of fasting blood lipid profile; and (c) the associations between fasting plasma fatty acid component and insulin resistance level are independent of abdominal obesity level. Desaturase 9-16 (surrogate of Δ9 as calculated by plasma ratio C16:1 n-7/C16:0) correlated with waist girth (r = .160, P < .05), homeostasis model assessment of insulin resistance (HOMA-IR) (r = .201, P < .01), plasma PUFAs (eg, C20:4 n-6 [r = −.269, P < .001], C22:6 n-3 [r = −.274, P < .001]). After adjustment for dietary SFAs, Δ9-16 had stronger correlation with waist (r = .227, P < .01) and significant correlation with PUFAs, whereas it had a nonsignificant correlation with HOMA-IR. The same pattern was observed with Δ9-18 (surrogate of Δ9 as calculated by plasma ratio C18:1 n-9/C18:0). After adjustment for dietary SFAs, waist, and HOMA-IR, Δ9-16 and Δ9-18 were still positive predictors of triglyceride (both P < .001) and apolipoprotein B (Δ9-18, P < .001; Δ9-16, P = .052). After adjustment for waist, HOMA-IR only remained a positive determinant of medium-chain SFAs (C14:0, P < .001; C16:0, P < .05); but it emerged to be inversely related to C20:4 n-6 (P < 0.1). The positive and independent associations of medium-chain SFAs with insulin resistance level suggest their vital roles in diabetes pathogenesis, whereas certain PUFAs such as C20:4 n-6 appear to be protective. The observed associations of Δ9 with adiposity and plasma lipid profile in these apparently healthy female adolescents support the concept derived from rodent models that Δ9 activity is independently reflective of higher body mass index and higher circulatory triglyceride levels.     

Fatty acid profile of the erythrocyte membrane preceding development of Type 2 diabetes mellitus

Background and aimsThe respective roles of dietary fatty acids in the pathogenesis of diabetes are as yet unclear. Erythrocyte membrane fatty acid (EMFA) composition may provide an estimate of dietary fatty acid intake. This study investigates the relation between EMFA composition and development of Type 2 diabetes mellitus.Methods and resultsIn a nested case-referent design we studied 159 individuals tested as non-diabetic at baseline who after a mean observation time of 5.4 ± 2.6 years were diagnosed with Type 2 diabetes mellitus and 291 sex- and age-matched referents. Higher proportions of pentadecanoic acid (15:0) and heptadecanoic acid (17:0) were associated with a lower risk of diabetes. In accordance with earlier findings, higher proportions of palmitoleic (16:1 n-7), dihomo-γ-linolenic (20:3 n-6) and adrenic (22:4 n-6) acids were associated with increased risk, whereas linoleic (18:2 n-6) and clupanodonic (22:5 n-3) acids were inversely associated with diabetes. After adjustment for BMI, HbA1c, alcohol intake, smoking and physical activity the only significant predictors were 15:0 and 17:0 as protective factors and 22:4 n6 as risk factor.ConclusionIn accordance with previous studies, our results indicate that EMFA-patterns predict development of Type 2 diabetes mellitus. The inverse association with two saturated fatty acids, previously shown to reflect consumption of dairy products, is a new finding.     

Relationship of serum fatty acid composition and desaturase activity to C-reactive protein in Japanese men and women

BackgroundAlthough fatty acid composition in serum and desaturase activity, which alters serum fatty acid composition, has been associated with C-reactive protein (CRP) concentration in Western populations, no study has been carried out in non-Western populations. We examined the association of serum fatty acids and estimated desaturase activity with CRP concentrations in Japanese men and women.MethodsSubjects were 489 Japanese municipal employees aged 21–67 years who participated in a survey at the time of a periodic health check-up. Serum high-sensitivity CRP concentrations were measured using the latex agglutination nephelometry method. Fatty acid composition was measured in serum cholesteryl esters and desaturase activities by fatty acid product-to-precursor ratios. Relationships were assessed using multiple regression.ResultsSerum CRP concentration was positively associated with palmitic acid (P for trend = 0.002) and inversely with alpha-linolenic acid (P for trend = 0.01) in men, and positively with dihomo-gamma-linolenic acid (P for trend in men or women = 0.01) and inversely with delta-5-desaturase (20:4n-6/20:3n-6) (P for trend in men and women = 0.05 and 0.002, respectively) in men and women.ConclusionsLow-grade inflammation may be associated with a serum fatty acid pattern of high palmitic acid or low alpha-linolenic acid in men, and of high dihomo-gamma-linolenic acid or low delta-5-desaturase in both sexes.     

Comparison of A1C, fasting and 2-h post-load plasma glucose criteria to diagnose diabetes in Italian Caucasians

Background and aimsThe American Diabetes Association (ADA) has revised criteria for diagnosis of type 2 diabetes recommending an A1C cut point of ≥6.5% in addition to criteria based on glucose levels. We compared A1C, fasting plasma glucose (FPG) or 2-h post-challenge glucose (2-hPG) criteria for the diagnosis of diabetes in a cohort of Italian Caucasians.Methods and resultsA total of 1019 individuals without known diabetes completed an oral glucose tolerance test (OGTT) and had A1C measured. Moderate agreement existed for A1C and FPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.522), with 85.5% of individuals classified as not having diabetes by both A1C and FPG criteria, and 5.8% classified as having diabetes by both A1C and FPG criteria. Discordant classifications occurred for 5.5% of individuals who had an A1C ≥ 6.5% and FPG <126 mg dl^?1, and for 3.2% who had an A1C <6.5% and FPG ≥126 mg dl^?1. Modest agreement existed for A1C and 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.427), with 81.8% of individuals classified as not having diabetes by both A1C and 2-hPG criteria, and 6.0% classified as having diabetes by both A1C and 2-hPG criteria. The area under the receiver operating characteristic curve of A1C for identifying subjects with diabetes according to FPG or 2-hPG criteria was 0.856 and 0.794, respectively. Modest agreement existed for A1C and FPG and/or 2-hPG criteria for diagnosis of type 2 diabetes (κ coefficient = 0.446).ConclusionsA1C ≥ 6.5% demonstrates a moderate agreement with fasting glucose and 2-hPG for diagnosing diabetes among adult Italian Caucasians subjects.     

Health insurance status and type associated with varying levels of glycemic control in the US: The multi-ethnic study of atherosclerosis (MESA)

AimsTo investigate associations of health insurance with measures of glucose metabolism, and whether associations vary by diabetes status or insurance type.MethodsCross-sectional analysis of baseline data from the Multi-Ethnic Study of Atherosclerosis. Cohort a priori stratified by age <65 (N = 3,665) and ≥65 years (N = 2,924). Multivariable linear and logistic regression assessed associations between insurance and fasting glucose, HOMA-IR, and prevalent diabetes, controlling for relevant confounders, including age, sex, race/ethnicity, income, and education.ResultsIn participants <65, compared to uninsured, having any insurance was associated with lower fasting glucose in participants with diabetes (Mean Difference = ?20.4 mg/dL, P = 0.01), but not in participants without diabetes. Compared to Private insurance, uninsured participants had higher fasting glucose (Mean Difference = 3.8 mg/dL, P = 0.03), while participants with Medicaid had higher HOMA-IR (Mean Difference = 3.5 mg/dL, P < 0.01). In participants ≥65, compared to Private insurance, uninsured participants (Mean Difference = 7.5 mg/dL, P = 0.02), and participants with Medicaid only (Mean Difference = 19.9 mg/dL, P < 0.01) or Medicare + Medicaid (Mean Difference = 5.2 mg/dL, P = 0.03) had higher fasting glucose.ConclusionsIn this large multiethnic cohort, having any insurance was associated with significantly lower fasting glucose for individuals with diabetes. Levels of fasting glucose and insulin resistance varied across different insurance types.     

Lean body mass is not beneficial,but may be detrimental for glucose tolerance – Splitting body mass index according to body composition

AimsTo study the combined effect of lean mass index (LMI) and fat mass index (FMI) on glucose regulation based upon findings in an oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR).MethodsWe conducted a population-based, cross-sectional study including 1617 participants without diabetes born in Helsinki from 1934 through 1944. LMI and FMI were calculated as lean and fat mass (kg)/height (m²). For analysis of the association between interaction of LMI and FMI and glucose regulation the participants were divided into tertiles of FMI and LMI.ResultsIn men LMI correlated positively with (fasting plasma glucose) FPG and HOMA-IR in the middle and high FMI level with a significant interaction between FMI and LMI on HOMA-IR. In women LMI was not associated with glucose regulation.In both men and women increased FMI was associated with increased FPG and 2-h plasma glucose concentrations and HOMA-IR.ConclusionsIn men high lean mass accompanied with fatness may be detrimental for glucose tolerance, whereas in women lean mass seemed to have little effect on glucose regulation. Fatness is the major determinant of glucose intolerance.     

Impaired glucose metabolism in colorectal cancer

Objective. Some studies have found that people with type 2 diabetes mellitus are at increased risk of neoplasms, especially colorectal cancer (CRC). In other studies it is also suggested that there is a higher incidence of diabetes mellitus in patients with CRC. The aims of this study were to assess whether the incidence of type 2 diabetes mellitus and impaired glucose tolerance (IGT) are higher in subjects with CRC and to determine the difference between diabetic subjects and healthy controls regarding glucose metabolism (glycaemia, insulinaemia, serum levels of C-peptide) as well as insulin resistance and sensitivity. Material and methods. The study included a total of 80 subjects: 40 enrolled patients (20 M, 20 F) with newly diagnosed sporadic colorectal cancer and 40 subjects with endoscopically excluded CRC or adenomas serving as controls. Subjects were matched for gender, age and body mass index (BMI) (age±5 years BMI±1 kg/m²). A 75-g oral glucose tolerance test was performed after an overnight fast. Samples for glycaemia, serum levels of C-peptide and insulin were taken at 0, 30, 60, 90, 120 and 150 min of the study. HOMA-IR, EIR, EIR/HOMA-IR indexes were calculated. Results. There was a significantly higher incidence of impaired glucose metabolism (IGM–diabetes mellitus or IGT) in CRC subjects. No differences were found in levels of glucose, insulin or C-peptide. Insulinaemia and C-peptide curves showed a shift typical of diabetes, in the form of a delayed insulin release peak. The HOMA-IR, EIR as well as the EIR/HOMA-IR indexes showed no differences between groups. Conclusions. A significantly higher incidence of IGM appears to occur in CRC patients than in the healthy population. This phenomenon is not dependent on age and body-weight, which may suggest that it is cancer that predisposes to diabetes rather than the other way round. The neoplastic process in the colon is not associated with hyperinsulinaemia or insulin resistance, but in CRC patients, pancreatic B-cell dysfunction typical of the early stages of diabetes is seen.     

Fatty acid composition and estimated desaturase activities are associated with obesity and lifestyle variables in men and women

It is known that the fatty acid (FA) composition in serum cholesteryl esters to a certain extent mirrors not only the FA composition of dietary fat, but also the endogenous FA synthesis, where desaturases play an important part. A surrogate measure of delta9-, delta6- and delta5-desaturase activity can be calculated as a [product:precursor] fatty acid ratio. Delta9-desaturase activity is known to be high in conditions like diabetes, atherosclerosis and obesity. The aim of the present study was to relate the proportions of individual fatty acids in serum cholesteryl esters, as well as estimated desaturase ratios to markers of obesity and lifestyle variables (smoking, physical activity and dietary fat). We also studied gender differences. These relationships were studied in a reference population consisting of men (n=554) and women (n=295) who took part in a health survey concerning coronary heart disease in Sweden. We found positive and significant correlations between markers of obesity and the proportions of 16:0, 16:1 (n-7), 18:0, 18:3 (n-6), 20:3 (n-6), 20:4 (n-6), 20:5 (n-3), delta9 and delta6 activities, and an inverse correlation to delta5 activity and 18:2 (n-6). These relationships were independent of age and physical activity and in some cases of body mass index (BMI). For each standard deviation (SD) increase of delta9 and delta6 activities, the risk of being overweight was increased by about 60%, whereas the risk was reduced to about 30% for every SD increase of delta5 activity. Women were found to have significantly higher levels of delta9 and lower levels of delta6 desaturase activities than men. In conclusion, this study shows that a changed FA profile in serum cholesteryl esters and estimated desaturase activities are associated with obesity and lifestyle factors in men and women.     

Comparison of metabolic syndrome with glucose measurement for prediction of type 2 diabetes: The Isfahan Diabetes Prevention Study

AimsThe aim of this study was to compare the ability of the metabolic syndrome (MetS) and fasting and 2-h glucose to predict progression to diabetes in non-diabetic first-degree relatives (FDRs) of patients with type 2 diabetes.MethodsA total of 706 non-diabetics FDR 20–70 years old in 2003–2005 were followed through 2008 for the occurrence of type 2 diabetes mellitus. At baseline and through follow-ups, participants undergo a standard 75 g 2-h oral glucose tolerance test. MetS was defined by NCEP-ATP III.ResultsThe fasting and 2-h glucose values were better predictors of progression to diabetes than MetS. Compared to participants without MetS, the age-adjusted relative risk (RRs) of diabetes was similar for participants with MetS (1.09 (95% CI 0.92, 1.29)). The age-adjusted relative risk of diabetes among those with impaired glucose tolerance (IGT) and MetS was 1.89 (95% CI 1.47, 2.42) and among those with IGT but without MetS was 1.59 (95% CI 1.32, 1.91). Areas under the receiver operating characteristic curves were 0.789 for fasting and 0.760 for 2-h glucose versus 0.595 for number of metabolic abnormalities (P < 0.001).ConclusionsThese data indicate that fasting or 2-h glucose during the OGTT may be more effective and efficient than MetS in predicting progression to diabetes.     

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.     

Glucose tolerance and free fatty acid metabolism in adults with variations in TCF7L2 rs7903146

ObjectiveTCF7L2 variant rs7903146 is associated with increased risk for type 2 diabetes. We investigated the effect of TCF7L2 variant rs7903146 and glucose tolerance on free fatty acid (FFA) metabolism.Research Design and MethodsWe recruited 120 individuals, half homozygous for the major CC allele and half homozygous for the minor TT allele at rs7903146; each underwent a 2-h, 75 g oral glucose tolerance test (OGTT). Plasma glucose, insulin and free fatty acid concentrations were measured on blood collected before and during the OGTT.ResultsTotal FFA concentrations and percent FA species during OGTT were not different in CC and TT carriers when males and females were considered together. However, monounsaturated fatty acid (MUFA) concentrations and percentages were greater in TT than CC females during the OGTT. TT carriers with high HOMA-IR had significantly greater fasting FFA concentrations, lower disposition index (DI) and greater AUC of glucose than high HOMA-IR CC carriers, whereas no such differences were observed in the low HOMA-IR group. We found that fasting (826 ± 25 vs. 634 ± 22 μmol/L, P < 0.0001) and OGTT plasma FFA concentrations were greater in IGT than NGT subjects, and the difference remained after adjusting for sex, age, BMI, and genotype. Finally, IGT subjects had greater MUFA concentrations and percentages than NGT subjects during OGTT.ConclusionsDespite similar fasting insulin and glucose, fasting plasma FFA are greater in IGT than NGT adults. Insulin resistance and sex influence plasma FFA responses amongst carriers of the minor T allele of TCF7L2 rs7903146.     

Associated factors of estimated desaturase activity in the EPIC-Potsdam study

Background and aimsAltered activity of desaturase enzymes may be involved in the development of metabolic diseases like type 2-diabetes. Desaturase activities might be modifiable by diet and lifestyle-related factors, but no study has systematically investigated such factors so far. We aimed to evaluate the association of demographic, anthropometric, dietary and lifestyle characteristics with estimated Δ5-, Δ6- and Δ9-desaturase activity.Methods and resultsA subsample (n = 1782) of the EPIC-Potsdam study was used for a cross-sectional analysis, involving men and women, mainly aged 35–65 years. Fatty acid (FA) product-to-precursor ratios, derived from the FA composition of erythrocyte membrane phospholipids, were used to estimate desaturase activities. Multiple linear regression models were used with estimated Δ5-, Δ6- and Δ9-desaturase activity as outcome and demographic (age, sex), anthropometric (BMI, WHR), dietary intake (FAs, carbohydrates) and lifestyle (physical activity, smoking, alcohol consumption) factors as exposure variables.Alcohol intake was positively associated with estimated Δ6- (explained variance in desaturase activity: 1.52%) and estimated Δ9-desaturase activity (explained variance: 5.53%). BMI and WHR showed a weak inverse association with estimated Δ5-desaturase activity (explained variance: BMI: 1.07%; WHR: 1.02%) and weak positive associations with estimated Δ6-(explained variance: BMI: 1.17%; WHR: 1.19%) and estimated Δ9-desaturase activities (explained variance: BMI: 0.70%; WHR: 0.96%). Age, sex, physical activity, smoking and dietary factors were only weakly associated with the estimated desaturase activities.ConclusionOur findings suggest that alcohol intake as well as obesity measures are associated with the FA ratios reflecting desaturase activity.     

不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗

目的　研究不同糖耐量人群血浆脂肪酸谱与胰岛素抵抗 (IR)之间的关系。方法　将受试者根据口服葡萄糖耐量试验 (OGTT)结果分为正常糖耐量组 (NGT) ,糖耐量受损组 (IGT )及 2型糖尿病组(DM )。采用毛细血管气相色谱法测定血浆脂肪酸谱 ,用胰岛素敏感指数 (IAI)评估IR。结果　DM组及IGT组血浆软脂酸 (C16:0 )、硬脂酸 (C18:0 )、二十二烷酸 (C2 2 :0 )、二十四烷酸 (C2 4:0 )和饱和脂肪酸浓度较NGT组明显升高 (P <0 .0 5～P <0 .0 1) ;花生四烯酸 (C2 0 :4)分别从NGT、IGT和DM组依次升高 ,差异有显著性 (P <0 .0 5～P <0 .0 1) ;血浆饱和脂肪酸 (SFA)从NGT、IGT、DM亚组依次升高 (P <0 .0 5～P <0 .0 1) ;NGT组的多不饱和脂肪酸 (PUFA)与饱和脂肪酸 (SFA)的比率高于IGT组和DM组 (均P <0 .0 5 ) ;血浆C16:0、C2 0 :4、C2 2 :0、SFA与IAI呈负相关 (P均 <0 .0 1)、PUFA/SFA与IAI呈正相关 (P <0 .0 1)。结论　不同糖耐量者血浆脂肪酸谱不同 ,糖耐量减低与 2型糖尿病患者SFA浓度升高 ,PUFA/SFA下降 ,且与胰岛素抵抗密切相关     

Relationships among acylation stimulating protein, adiponectin and complement C3 in lean vs obese type 2 diabetes

OBJECTIVE: The purpose of this study was to determine the relationships between adipocyte hormones acylation stimulating protein (ASP), adiponectin, complement C3 (C3) (ASP precursor) and insulin, C-reactive protein (CRP), lipid profiles and insulin resistance in lean vs obese type 2 diabetes subjects. SUBJECTS: Lean type 2 diabetes subjects (DL n = 27) vs obese type 2 diabetes subjects (DO n = 55) were compared to age-matched nondiabetic groups (Obese, OB n = 55 and control, CTL n = 50). RESULTS: The DO group demonstrated significant increases in plasma ASP and C3 with decreases in plasma adiponectin as compared to CTL. Interestingly, these increases in ASP and C3 were as high, or greater, in the DL group in spite of normal weight. By contrast adiponectin in the DL group was comparable to CTL, in spite of marked insulin resistance. C3 correlated with insulin, glucose and homeostasis model assessment of insulin resistance (HOMA-IR); ASP correlated with body mass index (BMI), glucose, insulin and plasma lipid parameters (non-esterified fatty acids (NEFA), triglyceride, cholesterol and apolipoprotein B). Adiponectin correlated with BMI, glucose, NEFA, triglyceride, high-density lipoprotein cholesterol and apolipoprotein A1 but not HOMA-IR, ASP or C3. CRP correlated only with HOMA-IR. CONCLUSION: Increased ASP and C3 are both associated with diabetes and related lipid factors but are not regulated coordinately. Adiponectin appears to be more closely related to body size (decreased in obese subjects) than insulin resistance in these subjects.     

Type 1 innate lymphoid cells are associated with type 2 diabetes

AimType 1 innate lymphoid cells (ILC1s) play a major role in regulating systemic inflammatory diseases. However, the relationship between ILC1s and type 2 diabetes (T2D) remains unclear. Thus, the present study investigated the relationship between ILC1s and glucose homoeostasis in humans.MethodsA total of 37 newly diagnosed T2D patients and 32 subjects with normal glucose tolerance (NGT), matched for age and body mass index (BMI), were enrolled in the study. Flow cytometric analysis of ILC1s derived from peripheral blood mononuclear cells (PBMCs) and omental adipose tissue was performed.ResultsT2D patients displayed greater numbers and frequencies of circulating and adipose tissue ILC1s (P < 0.05) compared with NGT subjects, and the two types of ILC1s correlated positively with each other. Circulating ILC1s were positively associated with glycated haemoglobin (HbA_1c), fasting plasma glucose (FPG), homoeostasis model assessment for insulin resistance (HOMA-IR), adipose tissue insulin resistance index (Adipo-IR) and serum free fatty acids (FFAs). A logistic regression model revealed that patients with higher ILC1 levels exhibited a 13.481-fold greater risk of developing T2D.ConclusionThis study is the first to provide evidence that ILC1 abnormalities are involved in the development of diabetes. The data also suggest a potential role of ILC1s as therapeutic indicators in the treatment of T2D.     

Human serum acylcarnitine profiles in different glucose tolerance states

Aims

To understand the relationship between serum acylcarnitine profiles and glucose tolerance status.

Methods

We analyzed 61 subjects who were divided into three groups based on their glucose tolerance status: normal glucose tolerance (NGT; n = 20, M/F = 9/11, mean age 48 years), pre-diabetes (Pre-DM; n = 20, M/F = 11/9, mean age 51 years), or newly diagnosed type 2 diabetes mellitus (T2DM; n = 21, M/F = 8/13, mean age 49 years). Fasting serum free carnitine and acylcarnitine concentrations were determined using isotope dilution electrospray ionization mass spectrometry coupled with high performance liquid chromatography.

Results

In comparison with NGT subjects, Pre-DM and type 2 diabetes subjects showed serum metabonomic changes highlighted by dysregulation of mitochondrial fatty acid combustion. Of the long-chain carnitine esters, significantly higher palmitoylcarnitine (C16), 3-OH-hexadecanoylcarnitine (C16-OH), carnitine C20, carnitine C22, and carnitine C24 concentrations (all P < 0.05) were noted in the newly diagnosed type 2 diabetes group, and even the pre-diabetes group.

Conclusions

This research provides further evidence of alterations in serum acylcarnitine profiles being associated with worse glucoseintolerance. The findings may suggest different degrees of involvement of dysregulated mitochondrial function and incomplete long-chain fatty acid oxidation pathways in the natural course of type 2 diabetes.     

Relationship between n-3 and n-6 plasma fatty acid levels and insulin resistance in coronary patients with and without metabolic syndrome

Background and aimsAnimal studies show that ecosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are effective for the prevention and treatment of insulin resistance (IR). Data from human studies are contradictory. We sought to determine whether the relationships between plasma n-3 and n-6 polyunsaturated fatty acid (FA) levels and IR differ according to the presence or absence of metabolic syndrome (MS) in a coronary heart disease sample.Method and resultsClinical, metabolic parameters, plasma phospholipid FA profiles and indirect measurement of IR (homeostatic model assessment-HOMA) were measured in 734 subjects, 8 weeks following acute coronary syndrome. FA levels and their correlations with IR were compared in subjects with and without MS. MS patients had higher saturated (16:0, 18:0) and n-6 (18:3n-6, 20:3n-6, 22:4n-6, 22:5n-6) FA levels, and lower EPA and DHA levels. HOMA-IR correlated positively with total saturated (r = 0.13, P = 0.017) and n-6 (r = 0.17, P = 0.001) FA levels and negatively with total n-3 FA levels (r = −0.13, P = 0.012), in MS subjects only. Total n-3 and n-6 FAs and n-6/n-3 ratio were associated with HOMA-IR levels in MS subjects independent of total saturated FA levels, age, sex, sedentary behaviour, smoking, waist circumference, triglycerides, HDL-cholesterol, and systolic blood pressure.ConclusionsRelationships between polyunsaturated FA type and IR vary according to the presence or absence of MS. N-3 FAs including EPA and DHA are associated with lower HOMA-IR, while the opposite is true for n-6 FAs. Prospective studies are required to address the potential effects of intermediate dose EPA and DHA on glucose handling in MS patients.     

Relationship between fatty liver and glucose metabolism: a cross-sectional study in 571 obese children

Background and aimsEarly onset type 2 diabetes mellitus (T2DM) is associated with obesity, insulin resistance and impaired beta-cell function. Non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for T2DM. We investigated the relationship between NAFLD and glucose metabolism in a large sample of obese children.Methods and ResultsA total of 571 obese children (57% males and 43% females) aged 8–18 years were consecutively studied at a tertiary care centre specialised in paediatric obesity. Liver ultrasonography was used to diagnose NAFLD after exclusion of hepatitis B and C and alcohol consumption. Oral-glucose tolerance testing (OGTT) was performed; insulin sensitivity was evaluated by using the insulin sensitivity index (ISI) and beta-cell function by using the ratio between the incremental areas under the curve (AUC) of insulin and glucose (incAUCins/incAUCglu). A total of 41% of the obese children had NAFLD. Impaired glucose tolerance or T2DM was present in 25% of the children with NAFLD versus 8% of those without it (p < 0.001). Children with NAFLD had higher body mass index (BMI), fasting glucose, 120-min OGTT glucose, incAUCins/incAUCglu and lower ISI as compared with children without NAFLD (p ≤ 0.002). At bootstrapped multivariable median regression analysis controlling for gender, age, pubertal status and BMI, NAFLD was an independent predictor of 120-min OGTT glucose and ISI, but not of incAUCins/incAUCglu. Similar findings were obtained using continuous liver steatosis as the predictor, instead of dichotomous NAFLD.ConclusionNAFLD was present in 41% of our obese children and was associated with higher insulin resistance, but not with impaired beta-cell function.