Differences in tissue-specific insulin resistance between South Asian and Nordic women with prediabetes after gestational diabetes.
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| Title: | Differences in tissue-specific insulin resistance between South Asian and Nordic women with prediabetes after gestational diabetes. |
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| Authors: | Kvist AAS; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway., Sharma A; Department of Endocrinology, Akershus University Hospital, Lørenskog, Norway., Qvigstad E; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway., Sattar N; School of Cardiovascular and Metabolic Health, University of Glasgow, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK., Gill JMR; School of Cardiovascular and Metabolic Health, University of Glasgow, BHF Glasgow Cardiovascular Research Centre, Glasgow, UK., Bjørnvall CD; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Kalleklev TL; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway., Shakya P; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway., van Hall G; Clinical Integrative Fluxomics Core, Clinical Biochemistry, Rigshospitalet & Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark., Norheim FA; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Lee-Ødegård S; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway., Birkeland KI; Institute of Clinical Medicine, University of Oslo, Oslo, Norway. k.i.birkeland@medisin.uio.no.; Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway. k.i.birkeland@medisin.uio.no.; Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway. k.i.birkeland@medisin.uio.no. |
| Source: | Diabetologia [Diabetologia] 2025 Dec; Vol. 68 (12), pp. 2696-2708. Date of Electronic Publication: 2025 Sep 24. |
| Publication Type: | Comparative Study; Journal Article |
| Language: | English |
| Journal Info: | Publisher: Springer Verlag Country of Publication: Germany NLM ID: 0006777 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-0428 (Electronic) Linking ISSN: 0012186X NLM ISO Abbreviation: Diabetologia Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Berlin Springer Verlag |
| MeSH Terms: | Diabetes, Gestational*/metabolism , Diabetes, Gestational*/ethnology , Insulin Resistance*/physiology , Insulin Resistance*/ethnology , Prediabetic State*/metabolism , Prediabetic State*/ethnology , South Asian People*/statistics & numerical data , Scandinavians and Nordic People*/statistics & numerical data, Adult ; Female ; Humans ; Pregnancy ; Adipose Tissue/metabolism ; Blood Glucose/metabolism ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/ethnology ; Diabetes Mellitus, Type 2/metabolism ; Glucose Clamp Technique ; Liver/metabolism |
| Abstract: | Competing Interests: Acknowledgements: The authors would like to thank the women who participated in the study, the study nurses Å. Halsne, S. Antonsen, S. Malayan, and the study coordinator E. Hillestad (Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway) for invaluable help during the implementation of the study. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Funding: Open access funding provided by University of Oslo (incl Oslo University Hospital). This study was funded by the Research Council of Norway, grant no. 273252, grant no. 340217 from South-Eastern Regional Health Authority, Norwegian Diabetes Association and Simon K. Fougner’s Family Foundation. SLØ is supported by the Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123). The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the manuscript; and did not impose any restrictions regarding the publication of the manuscript. Authors’ relationships and activities: NS has received consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novartis, Novo Nordisk, Pfizer, and Roche; speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Roche; and grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AASK was the main person responsible for data acquisition and wrote the first draft of the manuscript. FAN prepared samples for mRNA sequencing. AS, EQ and KIB contributed to the design. AASK and SL-Ø performed statistical analysis, and SL-Ø performed the bioinformatics. All authors contributed to analysis or interpretation of data, revised the manuscript critically and approved the final manuscript. KIB supervised the study performance, is the guarantor of this work and, as such, had the full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Aims/hypothesis: The aim of this work was to investigate tissue-specific insulin resistance in South Asian and Nordic women with previous gestational diabetes mellitus (pGDM) and to evaluate potential ethnic differences contributing to type 2 diabetes risk. Methods: A cross-sectional study using a two-step hyperinsulinaemic-euglycaemic clamp with a glucose tracer was conducted to assess insulin sensitivity in muscle, liver and adipose tissue in 19 South Asian and 16 Nordic women with pGDM and prediabetes (impaired glucose tolerance and/or impaired fasting glucose), along with 16 ethnicity-specific control women. We assessed inflammation and mitochondrial genes by mRNA sequencing of adipose tissue. Results: Both South Asian and Nordic women with pGDM showed reduced total glucose disposal (mainly due to muscle insulin resistance) and hyperinsulinaemia compared with the control group. Endogenous glucose production (mainly due to hepatic insulin resistance) was elevated in Nordics with pGDM, while South Asians with pGDM showed pronounced adipose tissue insulin resistance (reduced suppression of glycerol during clamp). mRNA sequencing of adipose tissue indicated increased tissue inflammation in South Asian women compared with Nordic women with pGDM. Furthermore, we observed a differential response to hyperinsulinaemia in South Asians vs Nordics related to mitochondrial mRNA, such as thymidine kinase 2 (TK2). Correlations between adiposity markers and insulin sensitivity also differed by ethnicity, suggesting that the pathways leading to type 2 diabetes may vary across populations. Conclusions/interpretation: South Asian and Nordic women with pGDM exhibited differences in insulin resistance profiles, with South Asians showing greater adipose tissue insulin resistance and inflammation. (© 2025. The Author(s).) |
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| Contributed Indexing: | Keywords: Adipose tissue; Euglycaemic clamp; Gestational diabetes; Glucose tracer; Insulin sensitivity; Nordics; Prediabetes; South Asians; Transcriptomics |
| Substance Nomenclature: | 0 (Blood Glucose) |
| Entry Date(s): | Date Created: 20250923 Date Completed: 20251107 Latest Revision: 20251117 |
| Update Code: | 20251117 |
| PubMed Central ID: | PMC12594657 |
| DOI: | 10.1007/s00125-025-06546-9 |
| PMID: | 40987939 |
| Database: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstract: | Competing Interests: Acknowledgements: The authors would like to thank the women who participated in the study, the study nurses Å. Halsne, S. Antonsen, S. Malayan, and the study coordinator E. Hillestad (Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Norway) for invaluable help during the implementation of the study. Data availability: The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request. Funding: Open access funding provided by University of Oslo (incl Oslo University Hospital). This study was funded by the Research Council of Norway, grant no. 273252, grant no. 340217 from South-Eastern Regional Health Authority, Norwegian Diabetes Association and Simon K. Fougner’s Family Foundation. SLØ is supported by the Novo Nordisk Fonden Excellence Emerging Grant in Endocrinology and Metabolism 2023 (NNF23OC0082123). The study funders were not involved in the design of the study; the collection, analysis, and interpretation of data; writing the manuscript; and did not impose any restrictions regarding the publication of the manuscript. Authors’ relationships and activities: NS has received consulting fees from AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Carmot Therapeutics, Eli Lilly, GlaxoSmithKline, Hanmi Pharmaceuticals, Menarini-Ricerche, Metsera, Novartis, Novo Nordisk, Pfizer, and Roche; speaker honoraria from Abbott Laboratories, AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, and Roche; and grant support paid to his university from AstraZeneca, Boehringer Ingelheim, Novartis, and Roche outside the submitted work. All other authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work. Contribution statement: AASK was the main person responsible for data acquisition and wrote the first draft of the manuscript. FAN prepared samples for mRNA sequencing. AS, EQ and KIB contributed to the design. AASK and SL-Ø performed statistical analysis, and SL-Ø performed the bioinformatics. All authors contributed to analysis or interpretation of data, revised the manuscript critically and approved the final manuscript. KIB supervised the study performance, is the guarantor of this work and, as such, had the full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.<br />Aims/hypothesis: The aim of this work was to investigate tissue-specific insulin resistance in South Asian and Nordic women with previous gestational diabetes mellitus (pGDM) and to evaluate potential ethnic differences contributing to type 2 diabetes risk.<br />Methods: A cross-sectional study using a two-step hyperinsulinaemic-euglycaemic clamp with a glucose tracer was conducted to assess insulin sensitivity in muscle, liver and adipose tissue in 19 South Asian and 16 Nordic women with pGDM and prediabetes (impaired glucose tolerance and/or impaired fasting glucose), along with 16 ethnicity-specific control women. We assessed inflammation and mitochondrial genes by mRNA sequencing of adipose tissue.<br />Results: Both South Asian and Nordic women with pGDM showed reduced total glucose disposal (mainly due to muscle insulin resistance) and hyperinsulinaemia compared with the control group. Endogenous glucose production (mainly due to hepatic insulin resistance) was elevated in Nordics with pGDM, while South Asians with pGDM showed pronounced adipose tissue insulin resistance (reduced suppression of glycerol during clamp). mRNA sequencing of adipose tissue indicated increased tissue inflammation in South Asian women compared with Nordic women with pGDM. Furthermore, we observed a differential response to hyperinsulinaemia in South Asians vs Nordics related to mitochondrial mRNA, such as thymidine kinase 2 (TK2). Correlations between adiposity markers and insulin sensitivity also differed by ethnicity, suggesting that the pathways leading to type 2 diabetes may vary across populations.<br />Conclusions/interpretation: South Asian and Nordic women with pGDM exhibited differences in insulin resistance profiles, with South Asians showing greater adipose tissue insulin resistance and inflammation.<br /> (© 2025. The Author(s).) |
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| ISSN: | 1432-0428 |
| DOI: | 10.1007/s00125-025-06546-9 |