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

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Diagnostic test: Fasting insulin level; Diagnostic test: Plasma drug level

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

• Study Type: Observational
• Enrollment (Actual): 255

Contacts and Locations

Study Locations

• Malaysia
  • Sarawak
    • Kuching, Sarawak, Malaysia, 93586
      • Clinical Research Centre, Sarawak General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

All T2DM patients under Sarawak General Hospital, Sarawak Heart Centre, Tanah Puteh Health Clinic, Jalan Masjid Health Clinic and Petra Jaya Health Clinic follow up during the period 3 July 2017 until 30 March 2018

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Metformin; 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; 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; Diagnostic test: Plasma drug level; Plasma trough level of metformin and gliclazide will be measured using LCMS to ensure true compliance.
Metformin + Gliclazide; 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; 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; Diagnostic test: Plasma drug level; Plasma trough level of metformin and gliclazide will be measured using LCMS to ensure true compliance.

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

Collaborators and Investigators

• Sponsor: Clinical Research Centre, Malaysia
• Collaborators: Ministry of Health, Malaysia
• Investigators: Principal Investigator: Aylwin Ming Wee Lim, Clinical Research Centre, Malaysia

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2017
• Primary Completion (ACTUAL): March 30, 2018
• Study Completion (ACTUAL): March 30, 2018

Study Registration Dates

• First Submitted: June 19, 2017
• First Submitted That Met QC Criteria: June 20, 2017
• First Posted (ACTUAL): June 22, 2017

Study Record Updates

• Last Update Posted (ACTUAL): July 19, 2018
• Last Update Submitted That Met QC Criteria: July 17, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Insulin Resistance; Homeostasis Model Assessment; Beta Cell Function; Liquid Chromatography Tandem Mass Spectrometry
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Hyperinsulinism; Diabetes Mellitus, Type 2; Insulin Resistance; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: NMRR-17-122-33927

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No