Portfolio of Current Activities of the Department

A multidisciplinary approach is needed to understand the pathogenesis of type 2 diabetes:

Understanding the integrated pathophysiology, initiating the development of insulin resistance and progressive beta cell deterioration should broaden our capacity to identify novel therapeutic targets for the prevention and/or treatment of T2DM.  So we need to apply a multidisciplinary approach to study the pathogenesis of T2DM. As a prerequisite to study the proteomics & genomics of type 2 diabetes, we have standardized in-house, the culturing of human adipose tissue (subcutaneous fat) to study the modulations in various adipokines which contributes to the pathogenesis of insulin resistance, obesity and T2DM in Asian Indians.

1. Serum adiponectin is a useful biochemical marker for differentiating type 1 and type 2 diabetes : An accurate classification of diabetes is necessary for optimal treatment. For those with type 1 diabetes [T1DM], prompt classification is necessary to prevent more severe consequences surrounding uncontrolled blood glucose in the immediate post-diagnosis period and to allow a clinician to immediately start insulin and counsel regarding its proper use.

1. Evaluating a role for Retinol Binding Protein-4 (RBP-4) as a biomarker in patients with T2DM: One of my research focuses is on studying adipose tissue biology with special reference to a novel adipokine, RBP-4, which appears to be an important mediator of insulin resistance. We propose to look at whether RBP-4 along with modulations in other adipokines contributes to the pathogenesis of insulin resistance, obesity and T2DM in Asian Indians. 
   
   

we report that in Asian Indians, the circulatory levels of RBP4 and TTR are higher with increasing severity of glucose intolerance. Both RBP4 and TTR showed a significant association with obesity and T2DM and RBP4 additionally with insulin resistance. Further studies that address the precise mechanisms of the interrelationship of RBP4/TTR and T2DM, could aid in newer therapeutic measures for insulin resistance and type 2 diabetes. Prospective studies are needed to clarify the mechanisms of synthesis, secretion and accumulation as well as the etiological role of RBP4 in metabolic disorders.

1. Exploring the emerging biomarkers for early detection of beta cell dysfunction: Recent studies indicate that Asian Indians may be susceptible to early decline in beta cell function even during stages of mild dysglycemia. While the link between beta cell dysfunction and type 2 diabetes is very well established, there are few markers, ie., Betatrophin and secreted frizzled-related protein 4 (SFRP4) are emerging as newer biomarkers for early beta cell proliferation and beta cell dysfunction respectively.  We are currently exploring their role in assessing the early beta cell dysfunction.

2. Exploring the beneficial legacy effect of lifestyle intervention on adiposity and inflammation in overweight/obese people with prediabetes - A Randomized Control Trial:  This study is in collaboration with Emory University, we at MDRF implemented a randomized controlled trial, the Diabetes Community Lifestyle Improvement Program. While lifestyle intervention has been shown to offer persistent metabolic benefits, there are insufficient data on its influence on biomarkers such as adipokines and cytokines. We are currently investigating the biomarkers of adiposity (adiponectin, leptin) and proinflammation (tumour necrosis factor alpha [TNF ά], Interleukin -6 [IL-6]) and gut hormones in overweight/obese people with prediabetes randomized either to 4 months of intensive lifestyle management or standard care and followed till 12 months. The results from this study can form a basis for future translational research whereby these biomarkers can play an important role in prevention and intervention trials. 

3. Soluble (Pro) Renin Receptor in relation to Gestational Diabetes Mellitus:

Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with first recognition during pregnancy.  Most women with GDM are asymptomatic and GDM may go unnoticed for a considerable length of period. Hence it is recommended that early screening for GDM should be done since interventions, such as diet, exercise and medications (when indicated), if started early could improve maternal and fetal outcomes. In this context, use of biomarkers that can identify women with GDM would be useful.  Recently the soluble pro-renin receptor [s(Pro)RR] has been shown to  predict the development of gestational diabetes mellitus (GDM). We therefore investigated the association of s(Pro)RR levels in Asian Indians with GDM to see whether it can be used as a marker of GDM . This study shows the following findings. First, mean levels of the s(Pro)RR were significantly higher in subjects with GDM. Second, s(Pro)RR showed a significant correlation with fasting plasma glucose and glycated hemoglobin. Third, in the logistic regression, s(Pro)RR had a significant association with GDM  even after adjusting for age, BMI, fasting and 2hr plasma glucose, HbA1c and family history of type 2 diabetes.  Fourth, a s(Pro)RR  cut-point of 23.3 ng/ml had a sensitivity of 68% and specificity of 70%, for identifying GDM.

Use of biomarkers such as s(Pro)RR  can be used as an initial screening test to identify women who may need more definite diagnosis testing and thus help to substantially reduce the number of women who need to undergo definite testing. If it is also possible to detect women at higher risk of GDM early in pregnancy using such biomarkers, it could possibly help to improve the outcomes of women with GDM, although these would need longitudinal studies.

Grants Received by the Department

Grants Received by the Department