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June 7, 2026Diabetes

Compared with MOD, the risk of subsequent albuminuria was significantly higher in SIRD (HR=2.12, 95% CI 1.21-3.71), SIDD (HR=3.26, 95% CI 1.60-6.64), and MARD (HR=1.82, 95% CI 1.07-3.08).

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Why the study?

Do distinct diabetes clusters predict the risk of incident albuminuria and differ in polygenic risk scores in a high-risk Indigenous American population?

Population

447 Indigenous Americans from the Southwestern US with diabetes diagnosed within 1 year

Comparison

Classification into diabetes clusters vs Mild obesity-related diabetes (MOD) cluster

Design

Cohort

Authors

MLMARIA JOSE RAMIREZ LUZURIAGAEAElsa Vazquez ArreolaWHWEN-CHI HSUEH

Discussion

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Overview

Phenotypic diabetes clusters in Indigenous Americans are similar to other populations, with severe insulin-resistant and severe insulin-deficient clusters carrying a higher risk of incident albuminuria.

Key Points

  • The aim is to characterize diabetes clusters and their association with complications in Indigenous Americans and evaluate differences in polygenic risk scores.
  • Diabetes clusters were identified using the k-means algorithm on data from 447 participants diagnosed with diabetes.
  • Clusters were analyzed for associations with complications using hazard ratios.
  • Polygenic risk scores were derived from genome-wide association study data, with standardized differences calculated.
  • Four diabetes clusters were identified: severe insulin-resistant diabetes (19.7%), mild obesity-related diabetes (42.5%), severe insulin-deficient diabetes (10.1%), and mild age-related diabetes (27.7%).
  • Risk of albuminuria was higher in severe insulin-resistant diabetes (HR=2.12), severe insulin-deficient diabetes (HR=3.26), and mild age-related diabetes (HR=1.82) compared to mild obesity-related diabetes.
  • Differences in polygenic risk scores indicated higher β-cell dysfunction in severe insulin-resistant (Δ 0.22) and severe insulin-deficient diabetes (Δ 0.26) compared to mild obesity-related diabetes.

Structured PICO

Do distinct diabetes clusters predict the risk of incident albuminuria and differ in polygenic risk scores in a high-risk Indigenous American population?

P
Population
447 Indigenous Americans from the Southwestern US with diabetes diagnosed within 1 year
I
Intervention
Classification into diabetes clusters (severe insulin-resistant diabetes [SIRD], mild obesity-related diabetes [MOD], severe insulin-deficient diabetes [SIDD], and mild age-related diabetes [MARD])
C
Comparator
Mild obesity-related diabetes (MOD) cluster
O
Outcome
Incident diabetes complications (albuminuria and severe albuminuria)surrogate

Phenotypic diabetes clusters in Indigenous Americans are similar to other populations, with severe insulin-resistant and severe insulin-deficient clusters carrying a higher risk of incident albuminuria.

Cite This Study

LUZURIAGA et al. (2026) studied this question.

synapsesocial.com/papers/6a250b0e7def13d035e1b095https://doi.org/10.2337/db26-2403-p
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Diabetes genetic clusters and clinical outcomes in American Indians2025
  2. 22396-P: Comparing Cluster-Based and Extreme-Value of Polygenic Risk Score Approaches to Stratify Patients with Type 2 Diabetes2026
  3. 3Diabetes Genetic Clusters and Clinical Outcomes in American Indians2025
  4. 42351-P: Assessment of Phenotypic Clustering of Incident and Prevalent Type 2 Diabetes: A MESA Pilot Study in the Definition, Etiology, Function: Integration to Enhance Type 2 Diabetes Treatment (DEFINE-Type 2 Diabetes) Consortium2026
  5. 5Clustering of diabetes: implications for personalized treatment2025