Islet Function Phenotyping-Based Heterogeneity in New-Onset Type 2 Diabetes: Clinical Importance and Baseline Metabolic Phenotype in a Large-Sample Cohort.

Authors

Jun Guo, Manman Song, Yu Zhou, Xiaoming Wu, Congqing Pan

Published in

Advances in therapy. Oct 26, 2026. Epub Oct 26, 2026.

Abstract

As a result of a variety of pathophysiological mechanisms, type 2 diabetes displays notable clinical heterogeneity. However, large cohorts of newly diagnosed patients are still needed to validate systematic classification based on basic clinical indicators and its clinical significance. Patients with new-onset type 2 diabetes were divided into four pathophysiological subtypes based on HOMA-IR and HOMA-β. Each subtype's clinical traits, metabolic profiles, and cross-sectional complication risk were assessed.
A total of 21,340 patients who had just received a diagnosis of type 2 diabetes and were not receiving treatment were included. HOMA-IR and HOMA-β were computed. The overall medians were used as cut points to split patients into four groups: group 1, high resistance low secretion (HRLS); group 2, high resistance high secretion (HRHS); group 3, low resistance low secretion (LRLS); and group 4, low resistance high secretion (LRHS). The groups were compared in terms of prognosis, islet function, metabolic markers, and demographics.
There were notable clinical and metabolic variations among the four groups. The HRLS group (n = 2743) had the highest risk of complications, the lowest disposition index, and the worst metabolic indicators. With the highest insulin levels and a moderate disposition index, the HRHS group (n = 7935) demonstrated typical metabolic syndrome. The LRLS group (n = 7927) demonstrated severe insulin secretory defects, as evidenced by their moderate disposition index, good sensitivity, and poor secretion. The LRHS group (n = 2735) had the highest disposition index and the least severe metabolic abnormalities. All intergroup comparisons had a p value < 0.001.
Type 2 diabetes subtypes with different pathophysiological mechanisms and clinical prognoses can be effectively identified by simple classification based on HOMA-IR and HOMA-β, which offers a useful framework for precision medicine.

PMID:
42932135
Bibliographic data and abstract were imported from PubMed on 27 Oct 2026.

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