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Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes.

ABSTRACT: The relationship between lipid metabolism with prediabetes (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus is poorly defined. We hypothesized that a lipidomic analysis of plasma lipids might improve the understanding of this relationship. We performed lipidomic analysis measuring 259 individual lipid species, including sphingolipids, phospholipids, glycerolipids and cholesterol esters, on fasting plasma from 117 type 2 diabetes, 64 prediabetes and 170 normal glucose tolerant participants in the Australian Diabetes, Obesity and Lifestyle Study (AusDiab) then validated our findings on 1076 individuals from the San Antonio Family Heart Study (SAFHS). Logistic regression analysis of identified associations with type 2 diabetes (135 lipids) and prediabetes (134 lipids), after adjusting for multiple covariates. In addition to the expected associations with diacylglycerol, triacylglycerol and cholesterol esters, type 2 diabetes and prediabetes were positively associated with ceramide, and its precursor dihydroceramide, along with phosphatidylethanolamine, phosphatidylglycerol and phosphatidylinositol. Significant negative associations were observed with the ether-linked phospholipids alkylphosphatidylcholine and alkenylphosphatidylcholine. Most of the significant associations in the AusDiab cohort (90%) were subsequently validated in the SAFHS cohort. The aberration of the plasma lipidome associated with type 2 diabetes is clearly present in prediabetes, prior to the onset of type 2 diabetes. Lipid classes and species associated with type 2 diabetes provide support for a number of existing paradigms of dyslipidemia and suggest new avenues of investigation.

SUBMITTER: Meikle PJ

PROVIDER: S-EPMC3785490 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes.

Meikle Peter J PJ Wong Gerard G Barlow Christopher K CK Weir Jacquelyn M JM Greeve Melissa A MA MacIntosh Gemma L GL Almasy Laura L Comuzzie Anthony G AG Mahaney Michael C MC Kowalczyk Adam A Haviv Izhac I Grantham Narelle N Magliano Dianna J DJ Jowett Jeremy B M JB Zimmet Paul P Curran Joanne E JE Blangero John J Shaw Jonathan J

PloS one 20130927 9

The relationship between lipid metabolism with prediabetes (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus is poorly defined. We hypothesized that a lipidomic analysis of plasma lipids might improve the understanding of this relationship. We performed lipidomic analysis measuring 259 individual lipid species, including sphingolipids, phospholipids, glycerolipids and cholesterol esters, on fasting plasma from 117 type 2 diabetes, 64 prediabetes and 170 norma ...[more]

PMID: 24086336

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Project description:Aims/hypothesisStudies investigating associations between kynurenines and cognitive function have generally been small, restricted to clinical samples or have found inconsistent results, and associations in the general adult population, and in individuals with type 2 diabetes in particular, are not clear. Therefore, the aim of the present study was to investigate cross-sectional associations between plasma kynurenines and cognitive function in a cohort of middle-aged participants with normal glucose metabolism, prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) and type 2 diabetes.MethodsPlasma kynurenines were quantified in 2358 participants aged 61 ± 8 years. Cross-sectional associations of kynurenines with cognitive impairment and cognitive domain scores were investigated using logistic, multiple linear and restricted cubic spline regression analyses adjusted for several confounders.ResultsEffect modification by glucose metabolism status was found for several associations with cognitive impairment, hence analyses were stratified. In individuals with prediabetes, 3-hydroxykynurenine (OR per SD 0.59 [95% CI 0.37, 0.94]) and 3-hydroxyanthranilic acid (0.67 [0.47, 0.96]) were associated with lower odds of cognitive impairment after full adjustment. In individuals with type 2 diabetes, kynurenine (0.80 [0.66, 0.98]), 3-hydroxykynurenine (0.82 [0.68, 0.99]), kynurenic acid (0.81 [0.68, 0.96]), xanthurenic acid (0.73 [0.61, 0.87]) and 3-hydroxyanthranilic acid (0.73 [0.60, 0.87]) were all associated with lower odds of cognitive impairment. Kynurenic acid (β per SD 0.07 [95% CI 0.02, 0.13]) and xanthurenic acid (0.06 [0.01, 0.11]) were also associated with better executive function/attention. No associations were observed in individuals with normal glucose metabolism.Conclusions/interpretationSeveral kynurenines were cross-sectionally associated with lower odds of cognitive impairment and better cognitive functioning in type 2 diabetes, while less widespread associations were seen in prediabetes. Low levels of kynurenines might be involved in the pathway of type 2 diabetes and cognitive decline but this needs further studies.

Project description:Background: Type 2 Diabetes (T2D) is a major concern among Asian Indians, not least because many develop T2D at despite having a normal BMI (body mass index), and with relatively low body fat. Asian Indians are also generally considered to have relatively low skeletal muscle mass and strength, this has not been explored in the context of T2D. Aim: The present study aimed to compare skeletal muscle mass, function and contractile quality (strength/mass) between healthy controls, those with prediabetes (PD) as well as T2D middle-aged non-obese Asian Indians. Methods: Adult males between the age of 20-50 years, consisting of healthy controls (n = 44), PD (n = 125) and T2D (n = 55) were studied. Skeletal muscle mass was measured using Dual X-ray Absorptiometry (DXA). Isometric and dynamic muscle function was measured using an isokinetic dynamometer (at 0, 60, 120, 180 degree/s). Muscle contractile quality was derived by dividing the peak muscle torque with the respective LMM (lower limb muscle mass). Fasting blood glucose (FBG) and insulin were used to derive insulin resistance (HOMA-IR). Results: The control group was on average 10 years younger than the other two groups (p < 0.01). The LMM was similar across the three study groups. However, the age-adjusted mean muscle torque was significantly lower in both absolute and normalized isometric and isokinetic strength in PD and T2D groups compared to controls (p ? 0.01), with the difference persisting even after adjusting for age and other covariates. However, there was no difference in muscle strength and contractile quality between the PD and T2D study groups. Conclusions: Muscle strength and contractile quality would appear to be sensitive and early indices of the trajectory toward diabetes in Asian Indians and more so than skeletal muscle mass. It is thus important to recognize the importance of functional measurements among this population when considering the role of muscle in diabetes. The data also would suggest that specific muscle conditioning (e.g., resistance training) might have efficacy in improving function as well as muscle mass, and thus aiding in the prevention of the trajectory toward the development of T2D.

Project description:BackgroundThe identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up.MethodsIn the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110-125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman's coefficients. Kaplan-Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models.ResultsDuring a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan-Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds.ConclusionsThe plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations. Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509.

Project description:ObjectiveDyslipidemia is a hallmark of diabetes mellitus (DM). However, specific lipid molecules closely associated with the initiation and progression of diabetes remain unclear. We used a pseudotargeted lipidomics approach to evaluate the complex lipid changes that occurred long before the diagnosis of type 2 diabetes mellitus (T2DM) and to identify novel lipid markers for screening prediabetes mellitus (PreDM) and T2DM in patients from multiple communities.MethodsFour hundred and eighty-one subjects consisting of T2DM, three subtypes of PreDM, and normal controls (NC) were enrolled as discovery cohort. Serum lipidomic profiles of 481 subjects were analyzed using an ultrahigh performance liquid chromatography-triple quadrupole mass spectrometry (UHPLC-QqQ-MS)-based pseudotargeted lipidomics method. The differential lipid molecules were further validated in an independent case-control study consisting of 150 PreDM, 234 T2DM and 94 NC.ResultsMultivariate discriminative analyses show that lipidomics data have considerable potential for identifying lipidome differences among T2DM, subtypes of PreDM and NC. Statistical associations of lipid (sub)species display significant variations in 11 lipid (sub)species levels for T2DM and distinctive differences in 8 lipid (sub)species levels between prediabetic and normoglycemic individuals, with further differences in 8 lipid (sub)species levels among subtypes of PreDM. Adjusted for sex, age and BMI, only two lipid (sub)species of fatty acid (FA) and phosphatidylcholine (PC) were associated at p< 0.05 for PreDM (all) and subtypes of PreDM. The defined lipid markers not only significantly improve the diagnostic accuracy of PreDM and T2DM but also effectively evaluating the risk of developing into each subtype of PreDM and T2DM when addition of age, sex, BMI, and FPG, respectively.ConclusionsOur findings improve insights into the lipid metabolic complexity and interindividual variations among subtypes of PreDM and T2DM, beyond the well-known differences in dyslipidemia in clinic.

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Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes.

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Plasma lipid profiling shows similar associations with prediabetes and type 2 diabetes.

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