The Effect of Tianmai Xiaoke Pian on Insulin Resistance through PI3-K/AKT Signal Pathway

In the clinical setting, given the potential adverse effects of thiazolidinediones and biguanides, we often have difficulty in treatment that no other insulin sensitizers are available for use in type 2 diabetic mellitus (T2DM) patients. Tianmai Xiaoke Pian (TMXKP) is a traditional Chinese medicine tablet, which is comprised of chromium picolinate, Tianhuafen, Maidong, and Wuweizi. To understand its mechanism of action on insulin resistance, TMXKP (50 mg/kg orally) was tested in T2DM rats (induced by a high-fat diet and streptozotocin). Eight weeks later, fasting blood glucose (FBG) and oral glucose tolerance tests (OGTT) were performed. Area under the curve (AUC) and homeostatic model assessment of insulin resistance (HOMA-IR) were calculated, and PI3-K/AKT signal pathway-related genes and proteins were tested by reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis in muscle, adipose, and liver tissues, respectively. TMXKP significantly reduced FBG, OGTT, AUC, and HOMA-IR in diabetic ratsP<0.05. Furthermore, we also observed that TMXKP could significantly decreaseIRS-1,IRS-2,PI3-K p85α, andAKT2gene expression and also IRS-1, IRS-2, PI3-K, AKT2, and p-AKT2 protein expression levelsP<0.05in diabetic rats. These findings confirm that TMXKP can alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Thus TMXKP appears to be a promising insulin sensitizer.

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The Effect of Chrysin-Loaded Phytosomes on Insulin Resistance and Blood Sugar Control in Type 2 Diabetic db/db Mice

Molecules ◽

10.3390/molecules25235503 ◽

2020 ◽

Vol 25 (23) ◽

pp. 5503

Author(s):

Seong-min Kim ◽

Jee-Young Imm

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Phosphoenolpyruvate Carboxykinase ◽

Glucose Transporter ◽

Fasting Blood Glucose ◽

Normal Diet ◽

Molar Ratio ◽

Oral Glucose ◽

Peroxisome Proliferator ◽

Model Assessment

Although a variety of beneficial health effects of natural flavonoids, including chrysin, has been suggested, poor solubility and bioavailability limit their practical use. As a promising delivery system, chrysin-loaded phytosomes (CPs) were prepared using egg phospholipid (EPL) at a 1:3 molar ratio and its antidiabetic effects were assessed in db/db diabetic mice. Male C57BLKS/J-db/db mice were fed a normal diet (control), chrysin diet (100 mg chrysin/kg), CP diet (100 mg chrysin equivalent/kg), metformin diet (200 mg/kg) or EPL diet (vehicle, the same amount of EPL used for CP preparation) for 9 weeks. Administration of CP significantly decreased fasting blood glucose and insulin levels in db/db mice compared with the control. An oral glucose tolerance test and homeostatic model assessment for insulin resistance were significantly improved in the CP group (p < 0.05). CP treatment suppressed gluconeogenesis via downregulation of phosphoenolpyruvate carboxykinase while it promoted glucose uptake in the skeletal muscle and liver of db/db mice (p < 0.05). The CP-mediated improved glucose utilization in the muscle was confirmed by upregulation of glucose transporter type 4, hexokinase2 and peroxisome proliferator-activated receptor γ during treatment (p < 0.05). The CP-induced promotion of GLUT4 plasma translocation was confirmed in the skeletal muscle of db/db mice (p < 0.05). Based on the results, CP showed greater antidiabetic performance compared to the control by ameliorating insulin resistance in db/db mice and phytosome can be used as an effective antidiabetic agent.

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Sex differences in glucose metabolism of streptozotocin-induced diabetes inbred mice (C57BL/6J)

Applied Biological Chemistry ◽

10.1186/s13765-020-00547-5 ◽

2020 ◽

Vol 63 (1) ◽

Author(s):

Boyoung Kim ◽

Yoo Yeon Kim ◽

Phuong Thi-Thanh Nguyen ◽

Hajin Nam ◽

Jun Gyo Suh

Keyword(s):

Insulin Resistance ◽

Sex Differences ◽

Glucose Metabolism ◽

Glucose Tolerance ◽

Inbred Mice ◽

Glycosylated Hemoglobin ◽

Fasting Blood Glucose ◽

Oral Glucose ◽

Model Assessment ◽

Female Mice

Abstract Considering that sex differences in glucose metabolism are observed in mice, researchers unconsciously use male mice to reduce variations by an estrogen cycle in female mice. In this study, we investigated the sex differences in glucose homeostasis in streptozotocin (STZ)-induced diabetes inbred mice (C57BL/6J). The C57BL/6J male and female mice were injected with or without STZ (40 mg/kg) for 5 consecutive days. Levels of fasting blood glucose (FBG), glycosylated hemoglobin (HbA1C), lipid profiles, oral glucose tolerance, and insulin resistance were measured at 3 and 6 weeks after STZ treatment. The FBG level in the STZ-induced male (M-STZ) group was significantly higher than that in the STZ-induced female (F-STZ) group during the entire experimental period. Furthermore, HbA1C and glucose tolerance levels in the M-STZ group were significantly higher than those in the F-STZ group at 3 and 6 weeks after STZ treatment. The glucagon/insulin ratio in the M-STZ group was significantly higher than that in the F-STZ group. Values of the homeostatic model assessment-insulin resistance, an indicator of β-cell function and insulin resistance, significantly increased in both the M-STZ and F-STZ groups at 3 weeks after STZ treatment. However, insulin resistance was observed in the M-STZ group, but not in the F-STZ group, at 6 weeks after STZ treatment. Taken together, our results indicate that glucose metabolism in the M-STZ group was worse than that in the F-STZ group, indicating that estrogen may have an important role in glucose metabolism by STZ treatment.

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Studies of insulin resistance in patients with clinical and subclinical hyperthyroidism

Acta Endocrinologica ◽

10.1530/eje-10-0246 ◽

2010 ◽

Vol 163 (4) ◽

pp. 625-630 ◽

Cited By ~ 50

Author(s):

Eirini Maratou ◽

Dimitrios J Hadjidakis ◽

Melpomeni Peppa ◽

Maria Alevizaki ◽

Katerina Tsegka ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Transport ◽

Area Under The Curve ◽

Postprandial Glucose ◽

Tolerance Test ◽

Oral Glucose ◽

Model Assessment ◽

Subclinical Hyperthyroidism

ObjectiveAlthough clinical hyperthyroidism (HR) is associated with insulin resistance, the information on insulin action in subclinical hyperthyroidism (SHR) is limited.Design and methodsTo investigate this, we assessed the sensitivity of glucose metabolism to insulinin vivo(by an oral glucose tolerance test) andin vitro(by measuring insulin-stimulated rates of glucose transport in isolated monocytes) in 12 euthyroid subjects (EU), 16 patients with HR, and 10 patients with SHR.ResultsHR and SHR patients displayed higher postprandial glucose levels (area under the curve, AUC0–30032 190±1067 and 31 497±716 mg/dl min respectively) versus EU (27 119±1156 mg/dl min,P<0.05). HR but not SHR patients displayed higher postprandial insulin levels (AUC0–30011 020±985 and 9565±904 mU/l min respectively) compared with EU subjects (AUC0–3007588±743 mU/l min,P<0.05). Homeostasis model assessment index was increased in HR and SHR patients (2.81±0.3 and 2.43±0.38 respectively) compared with EU subjects (1.27±0.16,P<0.05), while Matsuda and Belfiore indices were decreased in HR (4.21±0.41 and 0.77±0.05 respectively,P<0.001) and SHR patients (4.47±0.33 and 0.85±0.05 respectively,P<0.05 versus EU (7.76±0.87 and 1 respectively). At 100 μU/ml insulin, i) GLUT3 levels on the monocyte plasma membrane were increased in HR (468.8±7 mean fluorescence intensity (MFI)) and SHR patients (522.2±25 MFI) compared with EU subjects (407±18 MFI,P<0.01 andP<0.05 respectively), ii) glucose transport rates in monocytes (increases from baseline) were decreased in HR patients (37.8±5%) versus EU subjects (61.26±10%,P<0.05).ConclusionsInsulin-stimulated glucose transport in isolated monocytes of patients with HR was decreased compared with EU subjects. Insulin resistance was comparable in patients with both HR and SHR.

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Rosiglitazone Elicits an Adiponectin-Mediated Insulin-Sensitizing Action at the Adipose Tissue-Liver Axis in Otsuka Long-Evans Tokushima Fatty Rats

Journal of Diabetes Research ◽

10.1155/2018/4627842 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Jia Li ◽

Yao-Ming Xue ◽

Bo Zhu ◽

Yong-Hua Pan ◽

Yan Zhang ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Protein Expression ◽

Inflammatory Responses ◽

Oral Glucose ◽

Model Assessment ◽

Insulin Sensitizer ◽

Nonesterified Fatty Acids ◽

Fasting Plasma ◽

Long Evans

Rosiglitazone is an agonist of peroxisome proliferator-activated receptor- (PPAR-) γ that is principally associated with insulin action. The exact mechanisms underlying its insulin-sensitizing action are still not fully elucidated. It is well known that adiponectin mostly secreted in adipose tissue is an insulin sensitizer. Here, we found that treatment of Otsuka Long-Evans Tokushima Fatty (OLETF) rats with rosiglitazone (3 mg/kg, once daily, by oral gavage for 33 weeks) attenuated the increase in fasting plasma insulin concentrations and the index of the homeostasis model assessment of insulin resistance along with the age growth and glucose concentrations during an oral glucose tolerance test. In addition, the increase in plasma alanine aminotransferase activity, concentrations of fasting plasma nonesterified fatty acids and triglyceride, and hepatic triglyceride content was also suppressed. The hepatic protein expression profile revealed that rosiglitazone increased the downregulated total protein expression of insulin receptor substrate 1 (IRS-1) and IRS-2. Furthermore, the treatment suppressed the upregulated phosphorylation of IRS-1 at Ser307 and IRS-2 at Ser731. The results indicate that rosiglitazone ameliorates hepatic and systemic insulin resistance, hepatic inflammation, and fatty liver. Mechanistically, rosiglitazone suppressed hepatic protein overexpression of both phosphorylated nuclear factor- (NF-) κBp65 and inhibitory-κB kinase-α/β, a transcription factor that primarily regulates chronic inflammatory responses and the upstream NF-κB signal transduction cascades which are necessary for activating NF-κB, respectively. More importantly, rosiglitazone attenuated the decreases in adipose adiponectin mRNA level, plasma adiponectin concentrations, and hepatic protein expression of adiponectin receptor-1 and receptor-2. Thus, we can draw the conclusion that rosiglitazone elicits an adiponectin-mediated insulin-sensitizing action at the adipose tissue-liver axis in obese rats. Our findings may provide new insights into the mechanisms of action of rosiglitazone.

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Berberine Improves Glucose Homeostasis in Streptozotocin-Induced Diabetic Rats in Association with Multiple Factors of Insulin Resistance

ISRN Endocrinology ◽

10.5402/2011/519371 ◽

2011 ◽

Vol 2011 ◽

pp. 1-8 ◽

Cited By ~ 19

Author(s):

Yanfeng Chen ◽

Yanwen Wang ◽

Junzeng Zhang ◽

Changhao Sun ◽

Alfonso Lopez

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Glucose Homeostasis ◽

Tyrosine Phosphatase ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Blood Cholesterol ◽

Oral Glucose ◽

Dipeptidyl Peptidase 4 ◽

Multiple Factors

The present study was carried out to determine the effect of berberine on glucose homeostasis and several biomarkers associated with insulin sensitivity in male Wistar rats with intraperitoneal injection of streptozotocin (STZ)-induced diabetes. Rats with fasting blood glucose 16.7 mmol/L after 2 weeks of STZ injection were divided into two groups. One group was used as the diabetic control and another treated by gavage feeding with 100 mg/kg/d of berberine in water containing 0.5% carboxymethyl cellulose. A group of rats without receiving STZ was used as the normal control. After 7 weeks, berberine supplementation moderately but significantly lowered fasting blood glucose levels and improved oral glucose tolerance. Berberine lowered plasma free fatty acids and C-reactive protein levels without affecting plasma insulin levels. Diabetic rats treated with berberine showed significantly lower plasma triacylglycerol and cholesterol levels. Furthermore, berberine inhibited dipeptidyl peptidase-4 and protein tyrosine phosphatase-1B activities. In conclusion, berberine showed a dramatic effect of lowering blood cholesterol and triacylglycerols and improved moderately glucose homeostasis in STZ-induced diabetic rats in association with multiple factors related to insulin resistance.

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The Effect of Sanggua Drink Extract on Insulin Resistance through the PI3K/AKT Signaling Pathway

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/9407945 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Yu Cai ◽

Ying Wang ◽

Fei Zhi ◽

Qi-Chang Xing ◽

Yun-Zhong Chen

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Fasting Blood Glucose ◽

Diabetic Rats ◽

Hepatic Glycogen ◽

Insulin Sensitizer ◽

Radix Puerariae ◽

Glucose Water ◽

Protein Expressions

Treating type 2 diabetes mellitus (T2DM) using thiazolidinediones and biguanides can present several challenges for patients. Sanggua Drink (SGD) is a commonly used agent in traditional Chinese medicine, and it consists of Folium Mori, Fructus Momordicae Charantiae, Radix Puerariae Lobatae, and Rhizoma Dioscorea. The hypoglycemic effects and mechanisms of SGD extracts on insulin resistance in diabetic rats were investigated. SGD (1.24 g/kg orally) was verified in T2DM rats induced by a high-fat diet and streptozotocin. The results showed that SGD treatment was observed to reduce fasting blood glucose, water and food intake, total cholesterol triglycerides, and LDL, OGTT, FINS, HOMA-IR, GHb, and MDA and increase hepatic glycogen, HDL, SOD, CAT, and GSH-Px in diabetic rats. Simultaneously, SGD treatment by T2DM showed significantly ameliorated pathological changes and reduced inflammation in the pancreas. Treatment was also observed to increase gene and protein expressions of InsR, IRS-2, PI3K, AKT, and Glut4 in the livers of diabetic treated rats. These results suggest that SGD extracts have hypoglycemic properties and may alleviate insulin resistance in T2DM rats through the PI3K/AKT pathway. Therefore, SGD appears to be a promising insulin sensitizer.

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Decreased circulating BMP-9 levels in patients with Type 2 diabetes is a signature of insulin resistance

Clinical Science ◽

10.1042/cs20160543 ◽

2017 ◽

Vol 131 (3) ◽

pp. 239-246 ◽

Cited By ~ 17

Author(s):

Yong Luo ◽

Ling Li ◽

Xiaohui Xu ◽

Tong Wu ◽

Mengliu Yang ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Healthy Subjects ◽

Fasting Blood Glucose ◽

Oral Glucose ◽

Model Assessment ◽

Cross Sectional ◽

Lipid Infusion ◽

The Relationship

Bone morphogenetic protein 9 (BMP-9) has been demonstrated to improve glucose homoeostasis in diabetic mice. However, no report has demonstrated the relationship of circulating BMP-9 levels with insulin resistance (IR) or Type 2 diabetes mellitus (T2DM) in humans. The objective of the present study was to investigate the relationship between BMP-9 and IR in cross-sectional and interventional studies. Circulating BMP-9 levels were analysed by ELISA in 280 well-characterized individuals. Two-hour oral glucose tolerance test (OGTT) and euglycaemic–hyperinsulinaemic clamp (EHC) were performed in 20 healthy subjects. Acute IR was induced by lipid infusion for 4 h in 20 healthy volunteers. Real-time (RT)-PCR and Western blotting were used to assess mRNA and protein expression of BMP-9. The effect of a glucagon-like peptide-1 (GLP-1) receptor agonist (PEX168) on circulating BMP-9 was investigated in a 24-week treatment trial. Circulating BMP-9 levels were significantly higher in healthy subjects than in newly diagnosed patients with T2DM. Circulating BMP-9 negatively correlated with HbA1c, fasting blood glucose (FBG), OGTT, the area under the curve for glucose (AUCglucose) and homoeostasis model assessment of insulin resistance (HOMA-IR). Multivariate regression analyses showed that BMP-9 levels were independently associated with non-esterified fatty acid (NEFA) and AUCglucose. Both hyperinsulinaemia and lipid infusion decreased circulating BMP-9 levels. BMP-9 mRNA and protein expressions were significantly decreased in muscle and adipose tissues of T2DM patients. In the placebo treated group, BMP-9 levels continued to decline over time, whereas in the PEX 168 treated groups BMP-9 levels remained stable. Our data suggest that BMP-9 is likely to play an important role in IR in humans.

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Comparison of Frequency and Severity of Sleep-Related Breathing Disorders in Children with Simple Obesity and Paediatric Patients with Prader–Willi Syndrome

Journal of Personalized Medicine ◽

10.3390/jpm11020141 ◽

2021 ◽

Vol 11 (2) ◽

pp. 141

Author(s):

Agnieszka Lecka-Ambroziak ◽

Marta Wysocka-Mincewicz ◽

Anna Świercz ◽

Małgorzata Jędrzejczak ◽

Mieczysław Szalecki

Keyword(s):

Insulin Resistance ◽

Apnea Hypopnea Index ◽

Oral Glucose ◽

Prader Willi Syndrome ◽

Model Assessment ◽

Sleep Related Breathing Disorders ◽

Breathing Disorders ◽

Simple Obesity ◽

Rhgh Treatment ◽

Group 1

Sleep-related breathing disorders (SRBDs) can be present in children with simple obesity and with Prader–Willi syndrome (PWS) and influence an individual diagnostic and treatment approach. We compared frequency and severity of SRBDs in children with simple obesity and with PWS, both without and on recombinant human growth hormone (rhGH) treatment, and correlation of SRBDs with insulin resistance tests. A screening polysomnography-polygraphy (PSG), the oral glucose tolerance test (OGTT) and homeostasis model assessment of insulin resistance (HOMA-IR) were analysed in three groups of patients—with simple obesity (group 1, n = 30, mean age 14.2 years), patients with PWS without the rhGH therapy (group 2, n = 8, mean age 13.0 years) and during the rhGH treatment (group 3, n = 17, mean age 8.9 years). The oxygen desaturation index (ODI) was significantly higher in groups 2 and 3, compared to group 1 (p = 0.00), and hypopnea index (HI) was higher in group 1 (p = 0.03). Apnea–hypopnea index (AHI) and apnea index (AI) results positively correlated with the insulin resistance parameters in groups 1 and 3. The PSG values worsened along with the increasing insulin resistance in children with simple obesity and patients with PWS treated with rhGH that may lead to a change in the patients’ care.

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Twelve Weeks of Pioglitazone Therapy Significantly Attenuates Dysmetabolism and Reduces Inflammation in Continuous Ambulatory Peritoneal Dialysis Patients—A Randomized Crossover Trial

Peritoneal Dialysis International ◽

10.3747/pdi.2011.00116 ◽

2012 ◽

Vol 32 (5) ◽

pp. 507-515 ◽

Cited By ~ 10

Author(s):

Yun Li ◽

Qiong-Hong Xie ◽

Huai-Zhou You ◽

Jing Tian ◽

Chuan-Ming Hao ◽

...

Keyword(s):

Insulin Resistance ◽

Peritoneal Dialysis ◽

Continuous Ambulatory Peritoneal Dialysis ◽

Crossover Trial ◽

Fasting Blood Glucose ◽

High Risk Patient ◽

Model Assessment ◽

Serum Triglycerides ◽

Once Daily ◽

Randomized Crossover Trial

BackgroundThe aim of the present study was to investigate the effect of oral pioglitazone (PIO) on lipid metabolism, insulin resistance, inflammation, and adipokine metabolism in continuous ambulatory peritoneal dialysis (CAPD) patients.MethodsIn this randomized crossover trial, 36 CAPD patients with serum triglyceride levels above 1.8 mmol/L were randomly assigned to receive either oral PIO 15 mg once daily or no PIO for 12 weeks. Then, after a 4-week washout, the patients were switched to the alternative regimen. The primary endpoint was change in serum triglycerides during the PIO regimen compared with no PIO. Secondary endpoints included changes in other lipid levels, homeostatic model assessment of insulin resistance (HOMA-IR), adipocytokines, and C-reactive protein (CRP).ResultsAll 36 CAPD patients (age: 64 ± 11 years; 33% men; 27.8% with diabetes mellitus) completed the study. Comparing patients after PIO and no PIO therapy, we found no significant differences in mean serum triglycerides (3.83 ± 1.49 mmol/L vs 3.51 ± 1.98 mmol/L, p = 0.2). However, mean high-density lipoprotein (0.94 ± 0.22 mmol/L vs 1.00 ± 0.21 mmol/L, p = 0.004) and median total adiponectin [10.34 μg/mL (range: 2.59 – 34.48 μg/mL) vs 30.44 μg/mL (3.47 – 93.41 μg/mL), p < 0.001] increased significantly. Median HOMA-IR [7.51 (1.39 – 45.23) vs 5.38 (0.97 – 14.95), p = 0.006], mean fasting blood glucose (7.31 ± 2.57 mmol/L vs 6.60 ± 2.45 mmol/L, p = 0.01), median CRP [8.78 mg/L (0.18 – 53 mg/L) vs 3.50 mg/L (0.17 – 26.30 mg/L), p = 0.005], and mean resistin (32.70 ± 17.17 ng/mL vs 28.79 ± 11.83 ng/mL, p = 0.02) all declined. The PIO was well tolerated, with only one adverse event: lower-extremity edema in a patient with low residual renal function.ConclusionsBlood triglycerides were not altered after 12 weeks of PIO 15 mg once daily in CAPD patients, but parameters of dysmetabolism were markedly improved, including insulin resistance, inflammation, and adipokine balance, suggesting that PIO could be of value for this high-risk patient group. Larger, more definitive studies are needed to confirm these findings.

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The Relationship between Insulin Resistance and the Cardiovascular Biomarker Growth Differentiation Factor-15 in Obese Patients

Clinical Chemistry ◽

10.1373/clinchem.2010.153726 ◽

2011 ◽

Vol 57 (2) ◽

pp. 309-316 ◽

Cited By ~ 73

Author(s):

Greisa Vila ◽

Michaela Riedl ◽

Christian Anderwald ◽

Michael Resl ◽

Ammon Handisurya ◽

...

Keyword(s):

Insulin Resistance ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Oral Glucose ◽

Model Assessment ◽

Obese Patients ◽

Growth Differentiation Factor 15 ◽

Homeostatic Model Assessment ◽

Homeostatic Model ◽

The Relationship

BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-responsive cytokine linked to obesity comorbidities such as cardiovascular disease, inflammation, and cancer. GDF-15 also has adipokine properties and recently emerged as a prognostic biomarker for cardiovascular events. METHODS We evaluated the relationship of plasma GDF-15 concentrations with parameters of obesity, inflammation, and glucose and lipid metabolism in a cohort of 118 morbidly obese patients [mean (SD) age 37.2 (12) years, 89 females, 29 males] and 30 age- and sex-matched healthy lean individuals. All study participants underwent a 75-g oral glucose tolerance test; 28 patients were studied before and 1 year after Roux-en-Y gastric bypass surgery. RESULTS Obese individuals displayed increased plasma GDF-15 concentrations (P < 0.001), with highest concentrations observed in patients with type 2 diabetes. GDF-15 was positively correlated with age, waist-to-height ratio, mean arterial blood pressure, triglycerides, creatinine, glucose, insulin, C-peptide, hemoglobin A1c, and homeostatic model assessment insulin resistance index and negatively correlated with oral glucose insulin sensitivity. Age, homeostatic model assessment index, oral glucose insulin sensitivity, and creatinine were independent predictors of GDF-15 concentrations. Roux-en-Y gastric bypass led to a significant reduction in weight, leptin, insulin, and insulin resistance, but further increased GDF-15 concentrations (P < 0.001). CONCLUSIONS The associations between circulating GDF-15 concentrations and age, insulin resistance, and creatinine might account for the additional cardiovascular predictive information of GDF-15 compared to traditional risk factors. Nevertheless, GDF-15 changes following bariatric surgery suggest an indirect relationship between GDF-15 and insulin resistance. The clinical utility of GDF-15 as a biomarker might be limited until the pathways directly controlling GDF-15 concentrations are better understood.

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