Diabetes & Metabolism Journal

Original Articles

Complications
Objectively-Defined Sleep Regularity Is Associated with Macrovascular and Microvascular Complications among Individuals with Type 2 Diabetes Mellitus: A Cohort Study: Ying Zheng, Manrui Zhang, Hanzhang Wu, Jiahe Wei, Hui-Xin Wang, Torbjörn Åkerstedt, Xiaoyu Li, Xiao Tan; Received June 17, 2025 Accepted December 1, 2025 Published online April 17, 2026; DOI: https://doi.org/10.4093/dmj.2025.0530 [Epub ahead of print]

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Abstract PDF Supplementary Material PubReader ePub: Background
To assess the association of accelerometer-measured sleep regularity with macrovascular and microvascular complications among individuals with type 2 diabetes mellitus (T2DM).
Methods
A total of 3,862 participants with T2DM at baseline participated. The sleep regularity metrics measured by wrist-worn accelerometers include sleep regularity index (SRI) and standard deviation (SD) of sleep duration. Incident macrovascular complications including coronary heart disease (CHD) and stroke, microvascular complications including diabetic neuropathy, diabetic kidney disease, and diabetic retinopathy were recorded. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for macrovascular and microvascular complications.
Results
During a median follow-up of 7.2 years, 410 composite macrovascular and 615 composite microvascular events occurred. Compared to regular sleepers (the highest tertile of SRI), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.29; 95% CI, 1.01 to 1.66) and stroke (HR, 1.97; 95% CI, 1.08 to 3.58). Compared to regular sleepers (the lowest tertile of sleep duration SD), irregular sleepers were at higher risk of composite macrovascular complications (HR, 1.44; 95% CI, 1.12 to 1.84), CHD (HR, 1.40; 95% CI, 1.07 to 1.82), and stroke (HR, 2.07; 95% CI, 1.13 to 3.81). For microvascular complications, no significant association of sleep regularity metrics was found (all P>0.05). However, the dose-response analysis suggested a potential nonlinear association between SRI and diabetic neuropathy, with lower SRI consistently associated with higher risk of diabetic neuropathy (HR, 1.92; 95% CI, 1.28 to 2.88; 5th percentile vs. 50th percentile).
Conclusion
An irregular sleep pattern across days is clinically relevant for increasing the risk of macrovascular complications and diabetic neuropathy among individuals with T2DM.

Genetics
Exon Sequencing of HNF1β in Chinese Patients with Early-Onset Diabetes: Siqian Gong, Hong Lian, Yating Li, Xiaoling Cai, Wei Liu, Yingying Luo, Meng Li, Si-min Zhang, Rui Zhang, Lingli Zhou, Yu Zhu, Qian Ren, Xiuying Zhang, Jing Chen, Jing Wu, Xianghai Zhou, Xirui Wang, Xueyao Han, Linong Ji; Diabetes Metab J. 2025;49(2):321-330. Published online November 13, 2024; DOI: https://doi.org/10.4093/dmj.2024.0159

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Abstract PDF Supplementary Material PubReader ePub

Background
Maturity-onset diabetes of the young (MODY) due to variants of hepatocyte nuclear factor 1-beta (HNF1β) (MODY5) has not been well studied in the Chinese population. This study aimed to estimate its prevalence and evaluate the application of a clinical screening method (Faguer score) in Chinese early-onset diabetes (EOD) patients.
Methods
Among 679 EOD patients clinically diagnosed with type 2 diabetes mellitus (age at diagnosis ≤40 years), the exons of HNF1β were sequenced. Functional impact of rare variants was evaluated using a dual-luciferase reporter system. Faguer scores ≥8 prompted multiplex ligation-dependent probe amplification (MLPA) for large deletions. Pathogenicity of HNF1β variants was assessed following the American College of Medical Genetics and Genomics (ACMG) guidelines.
Results
Two rare HNF1β missense mutations (E105K and G454R) were identified by sequencing in five patients, showing functional impact in vitro. Another patient was found to have a whole-gene deletion by MLPA in 22 patients with the Faguer score above 8. Following ACMG guidelines, six patients carrying pathogenic or likely pathogenic variant were diagnosed with MODY5. The estimated prevalence of MODY5 in Chinese EOD patients was approximately 0.9% or higher.
Conclusion
MODY5 is not uncommon in China. The Faguer score is helpful in deciding whether to perform MLPA analysis on patients with negative sequencing results.

Citations

Citations to this article as recorded by

Transient neonatal diabetes mellitus as an early diagnostic clue to HNF1B-related disease – two case reports and a literature review
Marcin Kołbuc, Paweł Bednarek, Rafał Motyka, Tomasz Jarmoliński, Marzena Michalak-Kloc, Bodo B. Beck, Małgorzata Urbańska-Kosińska, Marcin Zaniew
Molecular and Cellular Pediatrics.2026;[Epub] CrossRef
Diabetes associated with HNF1B: beyond Occam’s razor—A case report
Carolina Sager-La Ganga, Clara Solà, Karen Castillo, Carme Figueredo, Ignacio Conget
Acta Diabetologica.2025; 62(8): 1347. CrossRef

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