Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults
Background/Objectives: Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver dis...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/13/1/101 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832588957673586688 |
|---|---|
| author | Eman Alshawaf Sulaiman K. Marafie Mohamed Abu-Farha Ahmed N. Albatineh Tahani Alramah Aldana Albuhairi Yafa Al Qassar Reem Zinoun Rawan Shalabi Sarah Behbehani Dalal Mohammed Fahad Alajmi Mohammed A. Abdalla Ebaa Al-Ozairi Mohammad Shehab Muhammad Abdul-Ghani Fahd Al-Mulla Jehad Abubaker |
| author_facet | Eman Alshawaf Sulaiman K. Marafie Mohamed Abu-Farha Ahmed N. Albatineh Tahani Alramah Aldana Albuhairi Yafa Al Qassar Reem Zinoun Rawan Shalabi Sarah Behbehani Dalal Mohammed Fahad Alajmi Mohammed A. Abdalla Ebaa Al-Ozairi Mohammad Shehab Muhammad Abdul-Ghani Fahd Al-Mulla Jehad Abubaker |
| author_sort | Eman Alshawaf |
| collection | DOAJ |
| description | Background/Objectives: Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D. The primary outcomes of this study are obesity, insulin resistance, MAFLD, and T2D, while the secondary outcome is hypertension; Methods: This is a cross-sectional study involving 450 participants, who were divided based on their obesity status into people with obesity (n = 182) and those without obesity (n = 265). Circulating Ism1 levels were measured by ELISA and were compared between the groups. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver was evaluated using Fibroscan; Results: Our results showed a significant reduction in circulating Ism1 levels in individuals with obesity (<i>p</i>-value = 0.002). Ism1 levels were negatively associated with the odds of T2D, possibly suggesting a protective role. Additionally, individuals with higher CAP scores demonstrated significantly lower Ism1 levels, and the Spearman’s rank correlation revealed a negative association between Ism1 and both CAP scores (r = −0.109, <i>p</i>-value = 0.025) and insulin resistance (r = −0.141, <i>p</i>-value = 0.004). Logistic regression analysis further supported Ism1 as an independent significant protective factor against obesity-related metabolic dysfunction. This significance persisted after adjusting for several confounders. Furthermore, our ROC results indicate that circulatory Ism1 levels possess significant diagnostic capability for identifying individuals with obesity-related metabolic imbalances with an area under the curve of 0.764 (95% CI = 0.718, 0.811). Finally, the adjusted multinomial analysis suggested that higher levels of Ism1 may play a protective role against pre-diabetes (AOR = 0.88, 95% CI = 0.838, 0.925) and T2D (AOR = 0.87, 95% CI = 0.814, 0.934); Conclusions: This study suggests that reduced Ism1 levels are linked to increased insulin resistance, MAFLD, and T2D in obese individuals. Our findings further corroborate the protective role of Ism1 and highlight its potential utility as a biomarker for monitoring obesity-related metabolic diseases. |
| format | Article |
| id | doaj-art-280a7fdacc584f2bad151ce8f667cd36 |
| institution | Kabale University |
| issn | 2227-9059 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj-art-280a7fdacc584f2bad151ce8f667cd362025-01-24T13:24:01ZengMDPI AGBiomedicines2227-90592025-01-0113110110.3390/biomedicines13010101Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti AdultsEman Alshawaf0Sulaiman K. Marafie1Mohamed Abu-Farha2Ahmed N. Albatineh3Tahani Alramah4Aldana Albuhairi5Yafa Al Qassar6Reem Zinoun7Rawan Shalabi8Sarah Behbehani9Dalal Mohammed10Fahad Alajmi11Mohammed A. Abdalla12Ebaa Al-Ozairi13Mohammad Shehab14Muhammad Abdul-Ghani15Fahd Al-Mulla16Jehad Abubaker17Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Community and Population Health, College of Health, Lehigh University, Bethlehem, PA 18015, USADepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Translational Research, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Translational Research, Dasman Diabetes Institute, Dasman 15462, KuwaitClinical Research Unit, Dasman Diabetes Institute, Dasman 15462, KuwaitDivision of Gastroenterology, Department of Internal Medicine, Mubarak Alkabeer University Hospital, Kuwait University, Kuwait City 31470, KuwaitDepartment of Translational Research, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Translational Research, Dasman Diabetes Institute, Dasman 15462, KuwaitDepartment of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Dasman 15462, KuwaitBackground/Objectives: Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D. The primary outcomes of this study are obesity, insulin resistance, MAFLD, and T2D, while the secondary outcome is hypertension; Methods: This is a cross-sectional study involving 450 participants, who were divided based on their obesity status into people with obesity (n = 182) and those without obesity (n = 265). Circulating Ism1 levels were measured by ELISA and were compared between the groups. Insulin resistance was assessed using the homeostasis model assessment of insulin resistance (HOMA-IR), and fatty liver was evaluated using Fibroscan; Results: Our results showed a significant reduction in circulating Ism1 levels in individuals with obesity (<i>p</i>-value = 0.002). Ism1 levels were negatively associated with the odds of T2D, possibly suggesting a protective role. Additionally, individuals with higher CAP scores demonstrated significantly lower Ism1 levels, and the Spearman’s rank correlation revealed a negative association between Ism1 and both CAP scores (r = −0.109, <i>p</i>-value = 0.025) and insulin resistance (r = −0.141, <i>p</i>-value = 0.004). Logistic regression analysis further supported Ism1 as an independent significant protective factor against obesity-related metabolic dysfunction. This significance persisted after adjusting for several confounders. Furthermore, our ROC results indicate that circulatory Ism1 levels possess significant diagnostic capability for identifying individuals with obesity-related metabolic imbalances with an area under the curve of 0.764 (95% CI = 0.718, 0.811). Finally, the adjusted multinomial analysis suggested that higher levels of Ism1 may play a protective role against pre-diabetes (AOR = 0.88, 95% CI = 0.838, 0.925) and T2D (AOR = 0.87, 95% CI = 0.814, 0.934); Conclusions: This study suggests that reduced Ism1 levels are linked to increased insulin resistance, MAFLD, and T2D in obese individuals. Our findings further corroborate the protective role of Ism1 and highlight its potential utility as a biomarker for monitoring obesity-related metabolic diseases.https://www.mdpi.com/2227-9059/13/1/101obesitypre-diabetesdiabetesMAFLDmetabolic diseasesIsthmin-1 |
| spellingShingle | Eman Alshawaf Sulaiman K. Marafie Mohamed Abu-Farha Ahmed N. Albatineh Tahani Alramah Aldana Albuhairi Yafa Al Qassar Reem Zinoun Rawan Shalabi Sarah Behbehani Dalal Mohammed Fahad Alajmi Mohammed A. Abdalla Ebaa Al-Ozairi Mohammad Shehab Muhammad Abdul-Ghani Fahd Al-Mulla Jehad Abubaker Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults Biomedicines obesity pre-diabetes diabetes MAFLD metabolic diseases Isthmin-1 |
| title | Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults |
| title_full | Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults |
| title_fullStr | Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults |
| title_full_unstemmed | Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults |
| title_short | Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults |
| title_sort | circulating isthmin 1 levels and their relationship with diabetes and metabolic diseases in kuwaiti adults |
| topic | obesity pre-diabetes diabetes MAFLD metabolic diseases Isthmin-1 |
| url | https://www.mdpi.com/2227-9059/13/1/101 |
| work_keys_str_mv | AT emanalshawaf circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT sulaimankmarafie circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT mohamedabufarha circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT ahmednalbatineh circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT tahanialramah circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT aldanaalbuhairi circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT yafaalqassar circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT reemzinoun circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT rawanshalabi circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT sarahbehbehani circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT dalalmohammed circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT fahadalajmi circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT mohammedaabdalla circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT ebaaalozairi circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT mohammadshehab circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT muhammadabdulghani circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT fahdalmulla circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults AT jehadabubaker circulatingisthmin1levelsandtheirrelationshipwithdiabetesandmetabolicdiseasesinkuwaitiadults |