Growth Differentiation Factor-15 as a Biomarker of Obese Pre-diabetes and Type 2 Diabetes Mellitus in Indian Subjects: A Case-control Study

2021 ◽  
Vol 17 ◽  
Author(s):  
Dipayan Roy ◽  
Purvi Purohit ◽  
Anupama Modi ◽  
Manoj Khokhar ◽  
Ravindra Kumar Gayaprasad Shukla ◽  
...  

Background: Type 2 diabetes mellitus (T2DM) is an ever-growing epidemic in India, and poses significant morbidity, mortality, and socioeconomic burden. Introduction: Growth differentiation factor-15 (GDF15) is a stress-responsive cytokine, increased in T2DM patients compared to control subjects without the disease. We aimed to assess whether serum GDF15 and adipose tissue GDF15 expression can differentiate between obese pre-diabetes and T2DM and control populations. Methodology: We recruited 156 individuals including 73 type 2 diabetes, 30 pre-diabetes, and 53 healthy controls. Clinical history, anthropometric measurements and biochemical profiling were done. Insulin resistance indices were calculated following HOMA models. Serum GDF15 was measured by sandwich ELISA. Visceral adipose tissue (VAT) expression of GDF15 was observed in 17 T2DM patients and 29 controls using SYBR Green chemistry in RT-PCR using GAPDH as housekeeping gene. The data were analyzed on R programming platform using RStudio. Results: Serum GDF15 was significantly higher (p<0.001) in T2DM subjects (median 1445.47 pg/mL) compared to prediabetes (627.85 pg/mL) and healthy controls (609.01 pg/mL). Using the ΔΔCt method, the VAT GDF15 expression was 1.54 fold and 1.57 fold upregulated in T2DM (n=17) compared to control subjects (n=29), and obese (n=12) compared to non-obese (n=34)subjects, respectively. The optimal cut-off point following the Youden’s index method was found to be 868.09 pg/mL. ROC curve analysis revealed that serum GDF15 had a sensitivity, specificity, and area under the curve (AUC) of 90.41%, 79.52%, and 0.892 respectively. GDF15 levels were significantly associated with age, BMI, HbA1c, fasting blood sugar, and insulin resistance indices. Conclusion: Hence, serum GDF15 is a biomarker for T2DM patients in our study population from Western India. However, larger prospective cohorts are necessary to validate this claim.

2019 ◽  
Vol 16 (4) ◽  
pp. 360-368
Author(s):  
Hani Zaidi ◽  
Rune Byrkjeland ◽  
Ida U Njerve ◽  
Sissel Åkra ◽  
Svein Solheim ◽  
...  

Background: Adipose tissue produces pro-inflammatory mediators involved in the atherosclerotic process. We investigated whether 12-month exercise training in patients with type 2 diabetes mellitus and coronary artery disease would reduce circulating levels and genetic expression of mediators in the interleukin-18, Caspase-1 and NLR pyrin domain containing 3 pathways. Correlations to glucometabolic variables; fasting glucose, HbA1c, duration of diabetes, insulin, C-peptide, insulin resistance (measured by homeostatic model assessment indexes – insulin resistance) and body mass index at baseline were further assessed. Methods: 137 patients (aged 41–81 years, 17.2% female participants) were included and randomized to a 12-month exercise programme or to a control group. Fasting blood and adipose tissue samples were taken at inclusion and after 12 months. Results: No statistically significant difference in changes of any variable between the intervention and the control group was found. At baseline, a positive correlation between insulin and homeostatic model assessment indexes – insulin resistance, interleukin-18 expression in adipose tissue and an inverse correlation between some glucometabolic variables and leukocyte expression of NLR pyrin domain containing 3 and Caspase-1 were observed. Conclusion: No significant effects of long-term exercise training were observed on the inflammasome-related mediators in our patients with combined coronary artery disease and type 2 diabetes mellitus. The observed correlations may indicate a pro-inflammatory state in adipose tissue by overweight and a compensatory downregulation of these mediators in circulating leucocytes.


2016 ◽  
Vol 40 (1) ◽  
pp. 70 ◽  
Author(s):  
Ji Min Kim ◽  
Min Kyung Back ◽  
Hyon-Seung Yi ◽  
Kyong Hye Joung ◽  
Hyun Jin Kim ◽  
...  

2020 ◽  
Author(s):  
Halima Babiikir Eltahir ◽  
Elmahadi Mohamed Ali ◽  
Abdelrahim Osman Mohamed

Abstract Background:The pathogenesis of type 2 diabetes mellitus is due to two major abnormalities including insulin resistance and dysfunction, which lead to the inability to regulate blood glucose level. Adiponectin is a hormone secreted by the adipose tissue and it takes part in glucose metabolism with insulin-sensitising properties. Low levels of adiponectin leads to reduction of fatty acid oxidation decreased glucose uptake in skeletal muscle cells and increased level of free fatty acids leading to insulin resistance. Leptin is another adipokine produced by adipose tissue involved in the control of food intake via its action on the hypothalamus, suppressing appetite and stimulating energy expenditure. Leptin plays a critical role in pathophysiology of type 2 diabetes mellitus.The aim of the study was to investigate the association of serum adipokines levels with glycemic control and metabolic dyslipidemia in Sudanese patients with type 2 diabetes mellitus.Methods: This was a case control study. 202 patients with type 2 diabetes and 102 non-diabetic controls participated after signing written consent. Weight (kg) and height (m) were measured thenthe body mass index (kg/m2) was determined. Blood samples were collected after an overnight fasting. FBG, HbA1c and lipid profiles were measured using enzymatic methods. Adiponectin and leptin were measured using sandwich ELISA.Results: Adiponectin concentrations was significantly lower in patients with type 2 diabetes compared with the controls (p<0.001) and it was inversely correlated with HbA1c (Pearson Correlation -.160, P value = 0.005), total cholesterol and LDL levels (P = 0.05) and direct correlated HDL levels (P = 0.05). Leptin concentrations was significantly higher in patients with type 2 diabetes compared with the controls (p<0.002) and it was positively correlated with HbA1c (Pearson Correlation .155, P value = 0.02), total cholesterol and LDL levels (P = 0.05), there were no correlation with HDL and TG levels. Patients had significantly higher fasting blood glucose, HbA1c levels, total cholesterol and LDL levels compared with the controls. Conclusion: Patients with type 2 diabetes mellitus had decreased levels of serum adiponectin, high levels of serum leptin. There were significant correlations found between adiponectin and leptin levels with glycemic control and metabolic dyslipidemia


2003 ◽  
Vol 62 (3) ◽  
pp. 753-760 ◽  
Author(s):  
E. E. Blaak

Disturbances in pathways of lipolysis and fatty acid handling are of importance in the aetiology of obesity and type 2 diabetes mellitus. There is evidence that a lowered catecholamine-mediated lipolytic response may play a role in the development and maintenance of increased adipose tissue stores. Increased adipose tissue stores, a disturbed insulin-mediated regulation of lipolysis and subnormal skeletal muscle non-esterified fatty acid (NEFA) uptake under conditions of high lipolytic rate may increase circulating NEFA concentrations, which may promote insulin resistance and cardiovascular complications. In addition, a disturbance of NEFA uptake by adipose tissue postprandially is also a critical determinant of plasma NEFA concentration. Furthermore, evidence is increasing that insulin-resistant muscle is characterised by a lowered ability to oxidise fatty acids. A dysbalance between fatty acid uptake and fatty acid oxidation may in turn be a factor promoting accumulation of lipid intermediates and triacylglycerols within skeletal muscle, which is strongly associated with skeletal muscle insulin resistance. The present review describes the reported disturbances in pathways of lipolysis and skeletal muscle fatty acid handling, and discusses underlying mechanisms and metabolic consequences of these disturbances.


Author(s):  
Alexander A. Kremzer ◽  
Ivan M. Fushtey ◽  
Alexander A. Berezin

RELATION OF GROWTH-DIFFERENTIATION FACTOR-15 LEVELS AND NUMBER OF CIRCULATING ENDOTHELIAL PROGENITOR CELLS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS


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