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Diabetes Research
06.02.2018

Prostate Cancer: Poor Prognosis in Men with Diabetes

Men with type 2 diabetes are less likely to develop prostate cancer than patients without diabetes. However, the mortality rate is higher. Researchers of Helmholtz Zentrum München and experts of the German Center for Diabetes Research (DZD) from Tübingen and of the Urology Department of Tübingen University Hospital were able to show that in the affected individuals the androgen receptor and the mitogenic forms of the insulin receptor were more strongly expressed. This could explain why patients with diabetes have a poorer prognosis for prostate cancer. The results were published in the journals ‘Molecular Metabolism’ and ‘Endocrine Related Cancer’.

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Prostate cancer and type 2 diabetes are among the most common diseases in men. Although studies indicate that people with diabetes suffer more frequently from cancer, men with diabetes do not increasingly suffer from prostate cancer. On the contrary, meta-analyses of studies have shown that diabetes patients are less likely to develop this carcinoma. However, the mortality rate is higher. This is also confirmed by current research carried out by researchers at the Institute for Diabetes Research and Metabolic Diseases (IDM) of Helmholtz Zentrum München at the University of Tübingen, a partner of the DZD, in cooperation with the Department of Urology at Tübingen University Hospital.

The research team recently analyzed the data of patients who had their prostate removed due to cancer. As expected, among them were fewer patients with diabetes than in the general population. However, prostate cancer patients with diabetes were significantly more likely to have metastases in the lymph nodes. In addition, the proportion of patients who are at very high risk according to the guidelines of the National Comprehensive Cancer Network (NCCN) was significantly higher among those with diabetes.

But how do prostate carcinomas differ in men with and without diabetes? What makes prostate carcinoma in patients with metabolic disease so aggressive? The researchers investigated these questions in another study. For this purpose, they analyzed 70 tumor samples from patients without diabetes and 59 samples from patients with type 2 diabetes.

Since male sex hormones (androgens) play an important role in the development of prostate cancer, the scientists investigated the androgen signaling chain. “We conducted a gene expression analysis of key proteins and found that in men with diabetes, the androgen receptor (AR) was increased", said Dr. Martin Heni, who led the study at the IDM. The signaling pathway mediated by AR was also activated.

The scientists identified another difference: "Insulin receptors of isoform A are increasingly expressed in the prostate carcinomas of patients with diabetes," said Dr. Stefan Lutz, first author of the study. These can bind insulin-like growth factors (IGFs). This contributes to increased cell growth and cell division. Normally, adults mainly express the isoform B, which does not bind IGF. In addition, in patients with diabetes, the steroid biosynthesis in the tumor is also altered. Less protective estrogen receptor ligands are formed. This further strengthens the androgen signaling pathway in tumors.

“Our research provides new insights into why prostate cancer is so aggressive in men with type 2 diabetes," said Dr. Heni, summarizing the results. “Prostate carcinoma in men with type 2 diabetes has a poorer prognosis and must therefore be diagnosed and treated earlier and more comprehensively than prostate cancer in nondiabetics," said Professor Arnulf Stenzl, MD, head physician of the Urology Department of Tübingen University Hospital.

Further Information

Original Publications:
Lutz, SZ et al. (2017): Androgen receptor overexpression in prostatecancer in type 2 diabetes. Molecular Metabolism, DOI: 10.1016/j.molmet.2017.11.013

Lutz, SZ et al. (2018): Higher prevalence of lymph node metastasis in prostate cancer in patients with diabetes. Endocrine-Related Cancer, DOI: 10.1530/ERC-17-0465

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,300 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The primary research objective of the research groups working in the Institute for Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Zentrum München at the University of Tübingen is personalized prediction of diabetes risk and diabetes prevention as well as personalized therapy. Here special focus is placed on gene-environment interaction. 

The German Center for Diabetes Research (DZD) is a national association that brings together experts in the field of diabetes research and combines basic research, translational research, epidemiology and clinical applications. The aim is to develop novel strategies for personalized prevention and treatment of diabetes. Members are Helmholtz Zentrum München – German Research Center for Environmental Health, the German Diabetes Center in Düsseldorf, the German Institute of Human Nutrition in Potsdam-Rehbrücke, the Paul Langerhans Institute Dresden of the Helmholtz Zentrum München at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Zentrum München at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich.

Founded in 1805, the University Hospital Tuebingen is one of the leading centres of German university medicine. As one of 33 University Hospitals in Germany, it contributes to a successful combination of top-level medicine, research, and teaching. More than 400,000 in- and outpatients from around the world benefit from this connection of science and practice each year, since the clinics, institutes, and centres unite specialists from all fields under one roof. Its experts collaborate across disciplines and offer state-of-the-art research-based treatment to all patients. The University Hospital does research to improve diagnostics, therapies, and healing processes. Many new cutting-edge treatments are clinically tested and applied in Tuebingen. Neurosciences, Oncology and Immunology, Infection Biology, Vascular Medicine and Diabetes are focus areas of research at the University Hospital Tuebingen. It is a reliable partner in four of the six German Centres for Health Research (DZG) created by the Federal Government.

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