Plasma Myokines and Objective Measures of Insulin Resistance in Latino Adults

Presentation Number: LB SAT 74
Date of Presentation: April 1st, 2017

Freddy JK Toloza1, Jose Oscar Mantilla-Rivas1, Maria Camila Perez-Matos1, Maria Laura Ricardo-Silgado2, Martha Catalina Morales-Alvarez1, Jairo Arturo Pinzon-Cortes1, Maritza Perez-Mayorga3, Martha Lilliana Arevalo-Garcia4, Giovanni Tolosa-Gonzalez4 and Carlos Olimpo Mendivil*1
1Universidad de los Andes, Bogota, Colombia, 2Universidad de los Andes, Bogota, 3Universidad Militar Nueva Granada, Bogota, 4Fundacion Santa Fe de Bogota

Abstract

Background:

Myokines are a group of small proteins released by skeletal muscle in response to contraction or cellular stress. Several studies have correlated myokines with the induction of specific cellular responses (ie. fat browning, fatty acid uptake), but little is known about their overall influence on insulin resistance (IR).

Aim

To explore the association between plasma myonectin, myostatin and Fibroblast Growth Factor-21 (FGF-21) and objective measures of IR in humans.

Methods:

We studied 81 Latino adults, aged 30-65 (33% normal BMI, 54% overweight, 13% obese), without known diabetes or muscle disease. After a 12-hour fast and rest period, they underwent a 5-point OGTT to derive IR indexes: HOMA-IR, QUICKI, Insulin Sensitivity Index (ISI), incremental area under the insulin curve (iAUCins) and Corrected Insulin Response at 30 minutes (CIR-30). Twenty-one participants additionally underwent a hyperinsulinemic-euglycemic clamp. We measured circulating levels of myonectin, myostatin and FGF-21 by immunometric assays. Since iAUCins showed the highest correlation with whole-body insulin-stimulated glucose disposal at steady state in the clamp (r= -0.49, p=0.02), IR was defined as belonging to the highest quartile of iAUCins, or to the lowest quartile of glucose disposal (M).

Results:

Plasma myonectin increased across quartiles of iAUCins (Q1: 154.6 ng/mL, Q4: 178.9 ng/mL, p-trend=0.021), and decreased across quartiles of the ISI (Q1: 178.1 ng/mL, Q4: 150.3 ng/mL, p-trend=0.012). In the euglycemic clamp, myonectin correlated positively albeit nonsignificantly with glucose disposal (r=0.420, p=0.08). Plasma myonectin was positively correlated with HbA1c (r=0.33, p=0.007), but not with BMI, percent body fat, percent abdominal fat or percent lean body mass.

Myostatin on the other hand increased across quartiles of the CIR-30, a marker of beta-cell function (Q1: 2354 pg/mL, Q4: 3474 pg/mL, p-trend=0.004), but did not associate with other insulin sensitivity indexes or with glucose disposal. Myostatin showed an unexpected positive association with percent lean body mass (r=0.36, p=0.001), and with HbA1c (r=0.35, p=0.004).

FGF-21 increased dramatically across quartiles of iAUCins (Q1: 169.3 pg/mL, Q4= 240.6 pg/mL), but the trend did not reach a significantly monotonic linear trend (p=0.14). FGF-21 was close to a significant association with glucose disposal (r=0.43, p=0.06). In accordance with its postulated role in adipocyte browning, FGF-21 showed a significant direct correlation with percent lean body mass (r=0.38, p=0.001) and an inverse relationship with percent body fat (r= -0.286, p=0.012).

 

Conclusions:

The positive association of some myokines with IR indexes in the OGTT while being positively correlated with glucose disposal in the clamp suggests that their secretion is an attempt at a compensatory adaptation to insulin resistance.

 

Nothing to Disclose: FJT, JOM, MCP, MLR, MCM, JAP, MP, MLA, GT, COM