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Correlation of insulin resistance, beta cell function and insulin sensitivity with serum sFas and sFasL in newly
Hemant Kumar1, Manish Mishra, Surabhi Bajpai
1Department of Medicine, Institute of Medical Sciences, Banaras Hindu University, Varanasi, 221 005, India.
Abstract:
Pancreatic beta cell dysfunction and reduced insulin sensitivity are fundamental factors associated with glucotoxicity, lipotoxicity and oxidative stress in type 2 diabetic patients (T2DM). Diabetic milieu can induce apoptosis in several types of cells. The aim of present study was to compare circulating soluble apoptotic markers (sFas and sFas-L) with HOMA-IR, HOMA-%S, HOMA-%B in the serum of newly diagnosed T2DM and healthy subjects. For this study, 94 T2DM and 60 healthy subjects were enroled and evaluated for various parameters. Biochemical quantifications were performed with Syncron CX5 auto-analyzer. The levels of serum sFas-L, TNF-α and IL-6 were estimated by flowcytometry. The fasting serum insulin and sFas quantified by ELISA. HOMA-IR, HOMA-%S and HOMA-%B were calculated with HOMA calculator v2.2.2. The levels of TC, TG, LDL-C, VLDL-C were augmented and HDL declined significantly (P < 0.001) in diabetics. The levels of serum insulin, TNF-α, IL-6, sFas, HOMA-IR were raised (P < 0.001) and sFas-L, HOMA-%S and HOMA-%B were decreased significantly (P < 0.001) in T2DM subjects than healthy. In diabetics, serum sFas was positively correlated with HOMA-IR (r = 0.720, P < 0.001) and negatively with HOMA-%B (r = -0.642, P < 0.001) significantly while serum sFasL was negatively correlated with HOMA-IR (r = -0.483, P < 0.001) and positively with HOMA-%B (r = 0.466, P < 0.001) significantly. Further, the multivariate stepwise regression analysis shows that HOMA-IR contributes significantly to the variance of sFas and sFasL. Our findings suggest that the pancreatic beta cell dysfunction along with increased insulin resistance appears to be associated with apoptotic markers.
Insights
Type 2 diabetes is linked to increased insulin resistance and pancreatic beta cell dysfunction, indicated by elevated apoptotic markers like sFas. These markers correlate with insulin resistance and beta cell function in diabetic patients.
Area of Science:
- Endocrinology
- Metabolic Disorders
- Immunology
Background:
- Type 2 diabetes mellitus (T2DM) is characterized by pancreatic beta cell dysfunction and insulin resistance.
- Glucotoxicity, lipotoxicity, and oxidative stress contribute to T2DM pathogenesis.
- Apoptosis plays a role in the progression of T2DM.
Purpose of the Study:
- To compare circulating soluble apoptotic markers (sFas and sFas-L) with insulin resistance (HOMA-IR) and beta cell function (HOMA-%B, HOMA-%S) in newly diagnosed T2DM patients and healthy individuals.
- To investigate the relationship between apoptotic markers and metabolic parameters in T2DM.
Main Methods:
- Serum levels of sFas, sFas-L, insulin, TNF-α, and IL-6 were measured in 94 T2DM patients and 60 healthy controls.
- Biochemical parameters including lipids were quantified.
- Insulin resistance and beta cell function were calculated using the Homeostatic Model Assessment (HOMA) calculator.
- Flow cytometry and ELISA were used for marker quantification.
Main Results:
- T2DM patients exhibited significantly higher levels of serum insulin, TNF-α, IL-6, sFas, and HOMA-IR compared to healthy subjects.
- Conversely, sFas-L, HOMA-%S, and HOMA-%B were significantly lower in T2DM patients.
- Serum sFas positively correlated with HOMA-IR and negatively with HOMA-%B in T2DM.
- Serum sFas-L showed a negative correlation with HOMA-IR and a positive correlation with HOMA-%B.
- Multivariate analysis indicated HOMA-IR significantly influences sFas and sFas-L levels.
Conclusions:
- Pancreatic beta cell dysfunction and increased insulin resistance in T2DM are associated with elevated apoptotic markers.
- sFas and sFas-L may serve as potential indicators of apoptosis and disease progression in T2DM.
- These findings highlight the role of apoptosis in the pathophysiology of T2DM.
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