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Pathophysiology-based phenotyping in type 2 diabetes: A clinical classification tool.

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  • 1Diabetes Research Centre, Department of Endocrinology, Centre for Individualized Medicine in Arterial Diseases, Odense University Hospital, Odense, Denmark.

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Summary

Type 2 diabetes is a heterogeneous disease with distinct pathophysiological subphenotypes. Identifying these subtypes, such as classical, insulinopenic, and hyperinsulinemic, can guide personalized treatment strategies for improved patient outcomes.

Keywords:
clinical diabetesindividualized treatmentinsulin secretioninsulin sensitivity and resistancepathophysiologytreatment guidelines

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Area of Science:

  • Endocrinology
  • Metabolic Diseases
  • Clinical Medicine

Background:

  • Type 2 diabetes mellitus (T2DM) is increasingly recognized as a complex condition with potential for diverse pathophysiological mechanisms.
  • Understanding these underlying differences is crucial for developing more effective and individualized treatment approaches.
  • This study investigates phenotypic heterogeneity within a large cohort of newly diagnosed T2DM patients.

Purpose of the Study:

  • To characterize distinct pathophysiological subphenotypes of type 2 diabetes.
  • To identify the prevalence of rare diabetes subtypes and classify the remaining patients based on insulin secretion and sensitivity.
  • To explore the clinical characteristics, including obesity and cardiovascular disease risk, associated with each identified T2DM subphenotype.

Main Methods:

  • A cohort of 5813 Danish patients with incident type 2 diabetes was analyzed.
  • Patients with rare subtypes (LADA, secondary, glucocorticoid-associated) were identified and excluded from further subtyping.
  • The remaining patients were subtyped using the homeostatic assessment model into insulinopenic, classical, or hyperinsulinemic phenotypes based on insulin sensitivity and beta-cell function.

Main Results:

  • Among 5813 patients, rare subtypes constituted a small percentage, with the majority having WHO-defined type 2 diabetes (93.7%).
  • Within the WHO-defined T2DM group, the classical phenotype was most prevalent (63.1%), followed by hyperinsulinemic (27.2%) and insulinopenic (9.7%).
  • Classical, insulinopenic, and hyperinsulinemic phenotypes differed significantly in obesity levels (waist circumference) and prevalence of cardiovascular disease at diagnosis, with hyperinsulinemic patients showing the highest CVD risk.

Conclusions:

  • Clinically diagnosed type 2 diabetes represents a heterogeneous group of patients with varying pathophysiological profiles.
  • Distinct subphenotypes (insulinopenic, classical, hyperinsulinemic) exhibit different clinical characteristics, including body composition and cardiovascular risk.
  • Future therapeutic strategies should move beyond a "one-size-fits-all" approach, aiming for targeted treatments based on individual pathophysiological subphenotypes to potentially improve patient prognosis.