scholarly journals Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle

2000 ◽  
Vol 279 (1) ◽  
pp. E146-E154 ◽  
Author(s):  
Ellen E. Blaak ◽  
Anton J. M. Wagenmakers ◽  
Jan F. C. Glatz ◽  
Bruce H. R. Wolffenbuttel ◽  
Gerrit J. Kemerink ◽  
...  

In this study, we investigated the hypothesis that impairments in forearm skeletal muscle free fatty acid (FFA) metabolism are present in patients with type 2 diabetes both in the overnight fasted state and during β-adrenergic stimulation. Eight obese subjects with type 2 diabetes and eight nonobese controls (Con) were studied using the forearm balance technique and indirect calorimetry during infusion of the stable isotope tracer [U-13C]palmitate after an overnight fast and during infusion of the nonselective β-agonist isoprenaline (Iso, 20 ng · kg lean body mass−1 · min−1). Additionally, activities of mitochondrial enzymes and of cytoplasmatic fatty acid-binding protein (FABP) were determined in biopsies from the vastus lateralis muscle. Both during fasting and Iso infusion, the tracer balance data showed that forearm muscle FFA uptake (Con vs. type 2: fast 449 ± 69 vs. 258 ± 42 and Iso 715 ± 129 vs. 398 ± 70 nmol · 100 ml tissue−1 · min−1, P < 0.05) and FFA release were lower in type 2 diabetes compared with Con. Also, the oxidation of plasma FFA by skeletal muscle was blunted during Iso infusion in type 2 diabetes (Con vs. type 2: Iso 446 ± 274 vs. 16 ± 70 nmol · 100 ml tissue−1 · min−1, P < 0.05). The net forearm glycerol release was increased in type 2 diabetic subjects ( P < 0.05), which points to an increased forearm lipolysis. Additionally, skeletal muscle cytoplasmatic FABP content and the activity of muscle oxidative enzymes were lowered in type 2 diabetes. We conclude that the uptake and oxidation of plasma FFA are impaired in the forearm muscles of type 2 diabetic subjects in the overnight fasted state with and without Iso stimulation.

2008 ◽  
Vol 54 (1) ◽  
pp. 181-187 ◽  
Author(s):  
Anna Cabré ◽  
Iolanda Lázaro ◽  
Josefa Girona ◽  
Josep M Manzanares ◽  
Francesc Marimón ◽  
...  

Abstract Background: Fatty acid–binding protein 4 (FABP4) has been linked to metabolic syndrome development, diabetes, and arteriosclerosis, but the role of FABP4 in target organ damage has not been assessed. We evaluated whether plasma FABP4 is associated with renal dysfunction in type 2 diabetic patients. Methods: In 263 individuals (161 type 2 diabetic patients and 102 healthy nondiabetic controls), we analyzed the correlation between FABP4 and creatinine or glomerular filtration index (MDRD-GFR) regarding the presence or absence of microalbuminuria. Patients with severe chronic kidney disease (MDRD-GFR &lt;30 mL/min/1.73 m2) or albuminuria were not included. Results: FABP4 concentrations were higher in diabetic patients with MDRD-GFR &lt;60 mL/min/1.73 m2 (P &lt;0.001). We observed a significant, direct correlation between FABP4 and creatinine (r = 0.446, P &lt;0.001) and an inverse correlation between FABP4 and MDRD-GFR (r = −0.511, P &lt;0.001) in type 2 diabetic patients, but not in nondiabetic individuals. These correlations were sustained when only those patients without microalbuminuria were analyzed (r = 0.414, P &lt;0.001 and r = −0.510, P &lt;0.001, respectively). Type 2 diabetic patients with FABP4 in the highest tertile compared with those in the lower tertiles had increased adjusted odds ratios for moderate renal dysfunction [7.5 (95%CI 1.8–30.7), P = 0.005 and 15.3 (3.1–76.4), P = 0.001; respectively], independent of microalbuminuria. Conclusions: High FABP4 plasma concentrations are associated with high plasma creatinine and low MDRD-GFR in patients with type 2 diabetes even in the absence of microalbuminuria or clinically relevant alterations of creatinine and MDRD-GFR values. FABP4 concentrations should be taken into consideration as an early marker of kidney damage in patients with type 2 diabetes.


2018 ◽  
Vol 64 (10) ◽  
pp. 1496-1504 ◽  
Author(s):  
Chi Ho Lee ◽  
Chloe Y Y Cheung ◽  
Yu Cho Woo ◽  
David T W Lui ◽  
Michele M A Yuen ◽  
...  

AbstractINTRODUCTIONRaised circulating adipocyte fatty acid–binding protein (AFABP) concentrations are associated with various adverse health conditions. However, their relationship with mortality remains to be defined, especially in view of the sexual dimorphism of circulating AFABP concentrations. Here we investigated prospectively whether serum AFABP concentrations predict multiple mortality outcomes in men and women alike, using a large clinic-based cohort of individuals with type 2 diabetes, a condition with raised AFABP concentrations.METHODSBaseline serum AFABP concentrations were measured in 5305 research participants with a monoclonal antibody-based sandwich immunoassay. The role of circulating AFABP concentrations in predicting mortality outcomes was evaluated by multivariable Cox regression analysis.RESULTSAmong the 5305 participants (59% men) in this study, over a median follow-up of 5 years, there were 512 deaths (19.3 deaths per 1000 person-years). Circulating AFABP concentrations, with higher levels in women at baseline, predicted all-cause mortality (P &lt; 0.001), cardiovascular mortality (P = 0.037), and infection-related deaths (P &lt; 0.002) among all participants. In sex-specific analyses, circulating AFABP concentration was an independent predictor of all-cause mortality in both men and women and a predictor of cancer-related deaths and infection-related deaths in men only. Furthermore, the addition of serum AFABP concentrations improved the time-dependent c statistics in predicting all-cause mortality in participants with type 2 diabetes (P = 0.008).CONCLUSIONSCirculating AFABP concentration was an independent predictor of various mortality outcomes in type 2 diabetes over and above known risk factors of reduced survival in men and women. The role of AFABP as a prognostic biomarker and therapeutic target warrants further investigation.


2017 ◽  
Vol 9 (4) ◽  
pp. 366-373 ◽  
Author(s):  
Hiroyuki Ito ◽  
Hitomi Yamashita ◽  
Mina Nakashima ◽  
Akifusa Takaki ◽  
Chiduko Yukawa ◽  
...  

2019 ◽  
Vol 13 (3) ◽  
pp. 283
Author(s):  
Lili Huang ◽  
Weizhuo Dominique Tan ◽  
Chengjian Wang ◽  
Zhengxiang Huang ◽  
Johannes D. Veldhuis ◽  
...  

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Mei-Zhen Wu ◽  
Chi-Ho Lee ◽  
Yan Chen ◽  
Shuk-Yin Yu ◽  
Yu-Juan Yu ◽  
...  

Abstract Background The relationship between adipocyte fatty acid-binding protein (AFABP) and cardiac remodelling has been reported in cross-sectional studies, although with conflicting results. Type 2 diabetes mellitus (T2DM) is associated with left ventricular (LV) hypertrophy and diastolic dysfunction, as well as elevated circulating AFABP levels. Here we investigated prospectively the association between AFABP with the longitudinal changes of cardiac remodelling and diastolic dysfunction in T2DM. Methods Circulating AFABP levels were measured in 176 T2DM patients without cardiovascular diseases (CVD) at baseline. All participants received detailed transthoracic echocardiography both at baseline and after 1 year. Multivariable linear and Cox regression analyses were used to evaluate the associations of circulating AFABP levels with changes in echocardiography parameters and incident major adverse cardiovascular events (MACE), respectively. Results The median duration between baseline and follow-up echocardiography assessments was 28 months. Higher sex-specific AFABP quartiles at baseline were associated with increase in LV mass and worsening of average E/e′ (all P < 0.01). Multivariable linear regression demonstrated that AFABP in the highest quartile was independently associated with both increase in LV mass (β = 0.89, P < 0.01) and worsening of average E/e′ (β = 0.57, P < 0.05). Moreover, multivariable Cox regression analysis showed that elevated baseline circulating AFABP level independently predicted incident MACE (HR 2.65, 95% CI 1.16–6.05, P < 0.05) after adjustments for age, sex, body mass index, glycated haemoglobin, hypertension, dyslipidemia and presence of chronic kidney disease. Conclusion Circulating AFABP level at baseline predicted the development of LV hypertrophy, diastolic dysfunction and MACE in T2DM patients without CVD.


Metabolism ◽  
2019 ◽  
Vol 96 ◽  
pp. 12-21 ◽  
Author(s):  
Ricardo Rodríguez-Calvo ◽  
Josefa Girona ◽  
Marina Rodríguez ◽  
Sara Samino ◽  
Emma Barroso ◽  
...  

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