Tracking the Change in Beta-cell Function and Insulin Sensitivity in Newly diagnosed, Untreated T2DM Patients

16 Mar, 22

Introduction

Beta-cell dysfunction and insulin resistance are the two predominant defects that lead to glucose intolerance. In recent years, researchers have been using the beta-cell function and insulin sensitivity to identify the subgroup of patients [ranging from pre-diabetes to overt type-2 diabetes mellitus (T2DM)] with glucose intolerance and to assess their risk of developing complications. It is therefore critical to re-evaluate the available data on standardized challenge tests and re-affirm the historical findings.

Aim

To re-examine beta-cell function and insulin sensitivity across a continuum from normal glucose tolerance (NGT) to early T2DM using highly specific insulin, C-peptide and intact proinsulin assays

Patient Profile

Individuals with NGT (n=104)
Individuals with impaired glucose tolerance (IGT; n=85)
Patients with newly diagnosed T2DM (n=554)

Methods

Study Design

Prospective study

Challenge tests

The study employed two different challenge tests as follows:
A standardised mixed meal tolerance test (MTT), performed after an overnight fast
A frequently sampled insulin-modified intravenous glucose tolerance test (FSIVGTT), performed on the second day over a 3-hour period

Assessments

The study participants were stratified as per their fasting plasma glucose (FPG) and body mass index (BMI)
Data from both the challenge tests were utilized to derive:
- Glucose, insulin, C-peptide and intact proinsulin profiles
- Various indices of beta-cell function, including the ‘gold-standard’ disposition index, and insulin sensitivity

Results

According to the MTT, increasing FPG was accompanied by progressively elevated and delayed postprandial glucose peaks. Parallelly, initial compensatory increases in fasting and postprandial insulin responses were followed with a progressive demise in overall beta-cell secretory capacity.
According to the FSIVGTT, persons with IGT had a major reduction in early insulin secretion in response to IV glucose, and a dramatic fall in insulin sensitivity.
Beyond pre-diabetes, ever-increasing fasting and postprandial hyperglycaemia predominantly resulted from a progressively decreasing beta-cell secretory function.

Conclusions

This study utilized improved assay technology and re-affirmed the changes in beta-cell function and insulin sensitivity in a large cohort of newly diagnosed untreated T2DM patients who had wide variation in their glucose tolerance.
Changes in insulin sensitivity were predominant at early stages i.e. at the lower levels of FPG observed between NGT and IGT.
Beta-cell function continued to diminish with increasing glycemia and hence could be used to determine the progression of disease.

Acta Diabetol. 2022;59:207–215.