Association Between Insulin Resistance and Beta Cell Function With HbA1C in Diabetics

Study Overview
=================
Brief Summary
-----------------
Progression of T2DM is widely accepted to be contributed by two main components: beta cell function deterioration where insulin secretion is impaired and insulin resistance where insulin physiological response is reduced. Insulin resistance and beta cell function will be estimated through a mathematical model, homeostasis model assessment. Fasting insulin and C-peptide will be measured using liquid chromatography tandem mass spectrometry. Insulin resistance and beta cell function is then compared with the glycaemic control, HbA1C.

Detailed Description
-----------------
Primary objective • To investigate the association between the estimation of insulin resistance and beta cell function through homeostasis model assessment with HbA1C among oral anti-diabetics treatment non-responder. Secondary Objectives To compare the insulin resistance and beta cell function between the OAD treatment responders (negative control) and non-responders To investigate the relationship between plasma level of metformin and gliclazide with the estimation of beta cell function and insulin resistance To identify the proportion of patients with high insulin resistance and proportion of patients with low beta cell function To identify difference in insulin resistance and beta cell function of different ethnic groups in Sarawak To compare insulin resistance with cardiovascular disease risk using Framingham Risk Score and ASCVD risk estimation

Official Title
-----------------
Cross-Sectional Study on Association Between the Estimation of Insulin Resistance and Beta Cell Function Through Homeostasis Model Assessment With HbA1C Among Oral Anti-Diabetics Treatment Non-Responders

Conditions
-----------------
Diabetes Mellitus, Type 2

Intervention / Treatment
-----------------
* Diagnostic Test: Fasting insulin level
* Diagnostic Test: Plasma drug level


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Previously diagnosed to have T2DM, currently treated with oral anti-diabetics agents (either on maximum dose of Metformin only or with maximum dose of Gliclazide) for at least 3 months with no change in medications and dosage during the period of 3 months Exclusion Criteria: Patient that is on exogenous insulin, is on hormone replacement therapy or any steroids medications, with renal impairment with creatinine clearance less than 30ml/min and unable to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Metformin<br>Patients who are on either metformin 2g per day or metformin extended release 2g per day. Subject will be required to fast overnight. Fasting insulin levels and plasma drug levels will be measured. | Diagnostic Test: Fasting insulin level<br>* Fasting insulin and C-peptide level measured using LCMS which is then used to calculate the insulin resistance and beta cell function using homeostasis model assessment<br>Diagnostic Test: Plasma drug level<br>* Plasma trough level of metformin and gliclazide will be measured using LCMS to ensure true compliance.<br>|
| Metformin + Gliclazide<br>Patient who are on both metformin 2g per day or metformin extended release 2g per day and gliclazide 320mg per day or gliclazide modified release 120mg per day. Subject will be required to fast overnight. Fasting insulin levels and plasma drug levels will be measured. | Diagnostic Test: Fasting insulin level<br>* Fasting insulin and C-peptide level measured using LCMS which is then used to calculate the insulin resistance and beta cell function using homeostasis model assessment<br>Diagnostic Test: Plasma drug level<br>* Plasma trough level of metformin and gliclazide will be measured using LCMS to ensure true compliance.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HOMA estimation of insulin resistance and beta cell function | Insulin resistance and beta cell function is estimated through homeostasis model assessment | 1 day | 
| HbA1C | Glycaemic control of subjects assessed through HbA1C | 1 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Medication adherence | Assessed using Malaysian Medication Adherence Scale | 1 day | 
| Plasma metformin level | Measured using LCMS | 1 day | 
| Plasma gliclazide level | Measured using LCMS | 1 day | 
| Cardiovascular risk estimation | Framingham risk score and ASCVD risk estimation | 1 day | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Homeostasis Model Assessment, Insulin Resistance, Beta Cell Function, Liquid Chromatography Tandem Mass Spectrometry