Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality

Introduction Pre-diabetes comprises diverse subphenotypes linked to varying complications, type 2 diabetes, and mortality outcomes. This study aimed to explore these outcomes across different pre-diabetes subphenotypes.Research design and methods The dataset included adults without type 2 diabetes w...

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Main Authors: Tullaya Sitasuwan, Varisara Lapinee, Watip Tangjittipokin, Weerachai Srivanichakorn, Nattachet Plengvidhya, Chaiwat Washirasaksiri, Nutsakol Borrisut, Rungsima Tinmanee, Chayanis Kositamongkol, Pinyapat Ariyakunaphan
Format: Article
Language:English
Published: BMJ Publishing Group 2025-06-01
Series:BMJ Open Diabetes Research & Care
Online Access:https://drc.bmj.com/content/13/3/e004803.full
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author Tullaya Sitasuwan
Varisara Lapinee
Watip Tangjittipokin
Weerachai Srivanichakorn
Nattachet Plengvidhya
Chaiwat Washirasaksiri
Nutsakol Borrisut
Rungsima Tinmanee
Chayanis Kositamongkol
Pinyapat Ariyakunaphan
author_facet Tullaya Sitasuwan
Varisara Lapinee
Watip Tangjittipokin
Weerachai Srivanichakorn
Nattachet Plengvidhya
Chaiwat Washirasaksiri
Nutsakol Borrisut
Rungsima Tinmanee
Chayanis Kositamongkol
Pinyapat Ariyakunaphan
author_sort Tullaya Sitasuwan
collection DOAJ
description Introduction Pre-diabetes comprises diverse subphenotypes linked to varying complications, type 2 diabetes, and mortality outcomes. This study aimed to explore these outcomes across different pre-diabetes subphenotypes.Research design and methods The dataset included adults without type 2 diabetes with baseline HbA1c and fasting plasma glucose (FPG) measurements from Siriraj Hospital, Bangkok, Thailand. The participants were classified into six subphenotypes via the k-means clustering method on the basis of age, body mass index, FPG, HbA1c, high-density lipoprotein cholesterol and alanine aminotransferase levels. The incidences of type 2 diabetes, long-term vascular complications and mortality were compared among subphenotypes over a median follow-up of 8.8 years, employing Kaplan-Meier curves and Cox regression analysis adjusted for sex, statin use and hypertension status.Results Among the 4915 participants (mean age 60.1±10.1 years; 54.6% female), six clusters emerged: cluster 1, low risk (n=650; 13.2%); cluster 2, mild dysglycemia elderly (n=791; 16.1%); cluster 3, severe dysglycemia obese (n=1127; 22.9%); cluster 4, mild dysglycemia obese (n=963; 19.7%); cluster 5, severe dysmetabolic obese (n=337; 6.9%); and cluster 6, severe dysglycemia elderly (n=1042; 21.2%). Clusters were classified into diabetes risk subgroups: low risk (clusters 1 and 4) and high risk (clusters 3 and 5). Cluster 6 exhibited the highest risk, with significantly increased incidences of macrovascular complications (adjusted HR 2.22, 1.51–3.27) and type 2 diabetes (1.73, 1.42–2.12). In contrast, cluster 4 demonstrated the lowest risk, with significantly decreased incidences of new chronic kidney disease (0.65, 0.44–0.96), microvascular complications (0.62, 0.43–0.89) and mortality (0.25, 0.10–0.63).Conclusions Our pre-diabetes phenotyping approach effectively provides valuable insights into the risk of type 2 diabetes, vascular complications and mortality in individuals with pre-diabetes. Those with high-risk phenotypes should be prioritized for type 2 diabetes and cardiovascular interventions to mitigate risks.
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series BMJ Open Diabetes Research & Care
spelling doaj-art-938cfdf8e2a34eca91f94b95aebb33d52025-08-20T03:46:53ZengBMJ Publishing GroupBMJ Open Diabetes Research & Care2052-48972025-06-0113310.1136/bmjdrc-2024-004803Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortalityTullaya Sitasuwan0Varisara Lapinee1Watip Tangjittipokin2Weerachai Srivanichakorn3Nattachet Plengvidhya4Chaiwat Washirasaksiri5Nutsakol Borrisut6Rungsima Tinmanee7Chayanis Kositamongkol8Pinyapat Ariyakunaphan9Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandASEAN Institute for Health Development, Mahidol University, Salaya, ThailandDepartment of Immunology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDivision of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandDepartment of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandIntroduction Pre-diabetes comprises diverse subphenotypes linked to varying complications, type 2 diabetes, and mortality outcomes. This study aimed to explore these outcomes across different pre-diabetes subphenotypes.Research design and methods The dataset included adults without type 2 diabetes with baseline HbA1c and fasting plasma glucose (FPG) measurements from Siriraj Hospital, Bangkok, Thailand. The participants were classified into six subphenotypes via the k-means clustering method on the basis of age, body mass index, FPG, HbA1c, high-density lipoprotein cholesterol and alanine aminotransferase levels. The incidences of type 2 diabetes, long-term vascular complications and mortality were compared among subphenotypes over a median follow-up of 8.8 years, employing Kaplan-Meier curves and Cox regression analysis adjusted for sex, statin use and hypertension status.Results Among the 4915 participants (mean age 60.1±10.1 years; 54.6% female), six clusters emerged: cluster 1, low risk (n=650; 13.2%); cluster 2, mild dysglycemia elderly (n=791; 16.1%); cluster 3, severe dysglycemia obese (n=1127; 22.9%); cluster 4, mild dysglycemia obese (n=963; 19.7%); cluster 5, severe dysmetabolic obese (n=337; 6.9%); and cluster 6, severe dysglycemia elderly (n=1042; 21.2%). Clusters were classified into diabetes risk subgroups: low risk (clusters 1 and 4) and high risk (clusters 3 and 5). Cluster 6 exhibited the highest risk, with significantly increased incidences of macrovascular complications (adjusted HR 2.22, 1.51–3.27) and type 2 diabetes (1.73, 1.42–2.12). In contrast, cluster 4 demonstrated the lowest risk, with significantly decreased incidences of new chronic kidney disease (0.65, 0.44–0.96), microvascular complications (0.62, 0.43–0.89) and mortality (0.25, 0.10–0.63).Conclusions Our pre-diabetes phenotyping approach effectively provides valuable insights into the risk of type 2 diabetes, vascular complications and mortality in individuals with pre-diabetes. Those with high-risk phenotypes should be prioritized for type 2 diabetes and cardiovascular interventions to mitigate risks.https://drc.bmj.com/content/13/3/e004803.full
spellingShingle Tullaya Sitasuwan
Varisara Lapinee
Watip Tangjittipokin
Weerachai Srivanichakorn
Nattachet Plengvidhya
Chaiwat Washirasaksiri
Nutsakol Borrisut
Rungsima Tinmanee
Chayanis Kositamongkol
Pinyapat Ariyakunaphan
Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
BMJ Open Diabetes Research & Care
title Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
title_full Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
title_fullStr Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
title_full_unstemmed Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
title_short Identification of pre-diabetes subphenotypes for type 2 diabetes, related vascular complications and mortality
title_sort identification of pre diabetes subphenotypes for type 2 diabetes related vascular complications and mortality
url https://drc.bmj.com/content/13/3/e004803.full
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