Impact of weight loss on cancer-related proteins in serum - results from a cluster randomised controlled trial of individuals with type 2 diabetes

Sep 21, 2026

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Type 2 diabetes is linked to higher risk across several cancer types, yet the biological intermediates remain unclear. This study examined whether intentional weight loss, as a diabetes intervention, disrupts circulating protein pathways associated with cancer development. Fasting serum samples from the DiRECT trial were analyzed using proteomics to compare baseline-to-1-year changes between the Counterweight-Plus program and best-practice care.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Background

Methods

Proteomic analysis

Statistical and Mendelian randomization analyses

Findings

Interpretation

Articles Impact of weight loss on cancer-related proteins in serum: results from a cluster randomised controlled trial of individuals with type 2 diabetes Caroline J. Bull,a,b,c,x Emma Hazelwood,a,b,x Danny N. Legge,c Laura J. Corbin,a,b Tom G. Richardson,a,b Matthew Lee,d James Yarmolinsky,a,b Karl Smith-Byrne,e David A. Hughes,a,b Mattias Johansson,d Ulrike Peters,f Sonja I. Berndt,g Hermann Brenner,h,i,j Andrea Burnett-Hartman,k Iona Cheng,l Sun-Seog Kweon,m,n Loic Le Marchand,o Li Li,p Polly A. Newcomb,f,q Rachel Pearlman,r Alex McConnachie,s Paul Welsh,t Roy Taylor,u Mike E. J. Lean,v Naveed Sattar,t Neil Murphy,d Marc J. Gunter,d,w Nicholas J. Timpson,a,b and Emma E. Vincenta,b,c,∗ aMRC Integrative Epidemiology Unit at the University of Bristol, Bristol, UK bPopulation Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK cSchool of Translational Health Sciences, Dorothy Hodgkin Building, University of Bristol, Bristol, UK dSection of Nutrition and Metabolism, International Agency for Research on Cancer, WHO, Lyon, France eCancer Epidemiology Unit, Oxford Population Health, University of Oxford, UK fPublic Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA gDivision of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA hDivision of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany iDivision of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany jGerman Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany kInstitute for Health Research, Kaiser Permanente Colorado, Denver, CO, USA lDepartment of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USAmDepartment of Preventive Medicine, Chonnam National University Medical School, Gwangju, KoreanJeonnam Regional Cancer Center, Chonnam National University Hwasun Hospital, Hwasun, Korea oUniversity of Hawaii Cancer Center, Honolulu, HI, USA pDepartment of Family Medicine, University of Virginia, Charlottesville, VA, USA qSchool of Public Health, University of Washington, Seattle, WA, USA rDivision of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA sRobertson Centre for Biostatistics, Institute of Health and Wellbeing, University of Glasgow, Glasgow, G12 8QQ, UK tSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, UK uTranslational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK vHuman Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary & Life Sciences, University of Glasgow, Glasgow, UK wDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College London, UK Summary Background Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown. We investigated the effect of a type 2 diabetes intervention, in the form of intentional weight loss, on circulating proteins associated with cancer risk to gain insight into potential mechanisms linking type 2 diabetes and adiposity with cancer development. Methods Fasting serum samples from participants with diabetes enrolled in the Diabetes Remission Clinical Trial (DiRECT) receiving the Counterweight-Plus weight-loss programme (intervention, N = 117, mean weight-loss 10 kg, 46% diabetes remission) or best-practice care by guidelines (control, N = 143, mean weight-loss 1 kg, 4% diabetes remission) were subject to proteomic analy

FAQs

Why investigate weight loss in people with type 2 diabetes for cancer risk?

Type 2 diabetes increases risk for multiple cancer types, but the underlying biological intermediates are not fully understood. The study evaluates whether intentional weight loss affects protein pathways linked to cancer development.

What data and analytic approach were used to assess changes in serum proteins?

Fasting serum samples from DiRECT participants were analyzed with Olink Oncology-II proteomics. Protein differences between baseline and 1 year were assessed using linear regression, followed by Mendelian randomization to evaluate cancer risk mechanisms.

Which proteins were modified by the weight-loss intervention?

Nine proteins showed modification in response to the intervention: glycoprotein NMB, furin, Wnt inhibitory factor 1, toll-like receptor 3, pancreatic prohormone, ERBB2 receptor tyrosine kinase 2, hepatocyte growth factor, endothelial cell-specific molecule 1, and RET proto-oncogene.

Sep 21, 2026

Uploaded by Himbo