Expression of Sirtuin 1 and Sirtuin 6 and its correlation in patients with Type 2 Diabetes Mellitus

Diabetes mellitus is a heterogenous, and chronic metabolic disorder characterized by alteration in carbohydrate metabolism resulting in secondary alterations in protein and lipid metabolism. Epigenetic modification is a novel mechanism that has been extensively studied to understand the cause of insulin resistance in T2DM. Epigenetic modification of genome leads to permanent change in gene expression from one generation to another generation. Sirtuin family is a NAD+-dependent histone deacetylase, and is one of such epigenetic modification.  The novel research target Sirtuin 6 improves the decreased sensitivity of beta cell functioning to the levels of glucose through various mechanism. One such pathway is suppression of the thioredoxin interacting protein (TXNIP), which is engaged in β-cell apoptosis.  Another such mechanism is via inhibition of FOXO1 expression, involved in maintaining the glucose sensing ability of pancreatic β-cell and systemic glucose tolerance. Sirtuin 1 also plays a crucial role in regulating histone and DNA methylation through the recruitment of other nuclear enzymes to the chromatin, such as histone 3 lysine 9 (H3K9) and H4K16. Sirtuin 1 can also deacetylate numerous transcription factors to regulate the expression of target genes either positively or negatively, including tumour protein 53 (p53), forkhead box O (FOXO), nuclear factor kappa B (NF-kB) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a).Therefore, in the present study we show the expression of Sirtuin 1 and Sirtuin 6, with a novel attempt to study the pharmacological correlation, that is differences in Sirtuin levels in patients on various antidiabetic and oral hypoglycaemic therapy.

Objectives

1.     To analyse the expression of Sirtuin 1 and Sirtuin 6 levels in type 2 diabetic mellitus.

2.     To correlate Sirtuin 1 and Sirtuin 6 levels in patients on different antidiabetic and oral hypoglycaemic therapy.

3.     To compare Insulin resistance by HOMA

**Methodology:**Patients who meet the inclusion criteria with diabetes will be divided into two groups based on their HbA1c levels according to ADA guidelines, Patients with controlled diabetes (HbA1c ≤ 7) and Patients with uncontrolled diabetes (HbA1c >7). After a written informed consent from the study participants, through a case record form basic demographic details and past medical history will be collected. In case of diabetic subjects, detailed history about the duration of diabetes and history of medication on which the patient is on and family history of diabetes will also be noted. After explaining the procedure, 6ml of peripheral blood will be collected from the patient. The following investigation will be carried out, HbA1c, fasting Insulin & FBS, Lipid profile, Thyroid profile: to rule out subclinical hypothyroidism, SIRTUIN levels 1 and 6 – ELISA kits, Insulin resistance will be calculated using the homeostatic model assessment of insulin resistance (HOMA-IR) index = (Insulin (µIU/mL) × Fasting Blood Glucose (mg/dL)/405.