Recent results from the prospective population-based KORA F4/FF4 study have linked environmental risk factors with the onset of distal symmetrical polyneuropathy (DSPN) for the first time. Researchers of the German Diabetes Center (DDZ) in cooperation with Helmholtz Munich were able to determine that people with obesity are at greater risk of developing DSPN.

Type 2 diabetes is one of the most common causes of polyneuropathy. However, there is mounting evidence from preclinical, clinical, and epidemiological studies that points to inflammation and oxidative stress also being triggering mechanisms. Endothelial dysfunction or microangiopathy are also considered effector pathways that connect metabolic and age-related damage with neuropathic damage.

“Considering that these mechanisms can also be triggered by environmental risk factors, the lack of available data related to environmental pollution as a potential determinant of DSPN was surprising,” says Professor Dr. Christian Herder from the German Diabetes Center (DDZ) who, together with his colleague in Munich, Professor Dr. Annette Peters, was responsible for coordinating the study. The aim of the research group was therefore to investigate long-term environmental exposure and the onset of DSPN while simultaneously assessing potential exposures and testing the hypothesis that obese people are at greater risk of DSPN than those without obesity. For this reason, the KORA F4/FF4 study* investigated four environmental factors “low ambient temperature”, “lack of green spaces”, “high levels of street noise”, and “high levels of air pollution” in 423 people without DSPN aged 62–81.

Obesity is Associated with the Severity of DSPN
Distal symmetrical polyneuropathy is characterized by sensory and movement disorders and pain that tend to begin in the lower extremities with the symptoms increasing over time. It can cause people with diabetes to develop diabetic foot syndrome and can even lead to amputation. There is mounting evidence that people who are obese or with related comorbidities who have not been diagnosed with diabetes represent a susceptible subgroup in the population. “This was also shown to be the case in the probands of the KORA study who developed DSPN,” explains Professor Herder. “They tended to be older, have a higher BMI and waist circumference, and have a higher rate of cardiovascular disease than those who did not develop DSPN”.

Air Pollution as the Number One Risk Factor
Of the environmental factors assessed by the study, air pollution, and especially super-fine particles, was most strongly associated with the onset of DSPN. However, as environmental factors do take effect separate from one another, but rather display interdependencies, they should be viewed together. “Only then can the assessment of the joint effects provide a comprehensive picture of the risk of disease,” says Herder. The joint analysis of all exposures also identified additive effects with a 1.4 times greater risk of DSPN based on lower ambient temperature during the warmer months of the year, lack of green spaces near the participant’s place of residence, and higher noise levels and ultra-fine particle concentrations – regardless if people with or without obesity were affected. However, people with obesity appear to be more susceptible to most exposures, resulting in a 2-fold increase of the DSPN risk when all four risk factors were assessed within the scope of a joint model.

Effects of the Results
The study added sensorimotor neuropathy to the growing list of diseases whose prevalence is increased by environmental risk factors, particularly air pollution. These findings underscore the need for coordinated societal and political intervention to reduce the environmental risk for everyone while following a uniform approach to disease prevention by simultaneously focusing on lifestyle, socioeconomic, and environmental factors. “In this equation, obesity represents the primary modifiable risk factor. “For this reason, prevention and treatment of the disease and all its complications is of immense importance in Germany and is a task that must fall to policymakers as well as those providing treatment” demands Professor Michael Roden, Director of the Department of Endocrinology & Diabetology, University Hospital Düsseldorf and Director of the German Diabetes Center (DDZ).

Original publication:
Herder C, Peters A, et al. Environmental risk factors of incident distal sensorimotor polyneuropathy: Results from the prospective population-based KORA F4/FF4 study. Science of The Total Environment 2023;858(3):159878; https://doi.org/10.1016/j.scitotenv.2022.159878

* KORA: Cooperative Health Research in the Augsburg region; population-based studies, including KORA F4 (2006-2008) and KORA FF4 (2013-2014), both of which are follow-up studies of the population-based KORA S4 study (1999-2001) conducted in the city of Augsburg and the adjacent districts of Augsburg and Aichach-Friedberg in Southern Germany.

Contact: 
Isabelle Keller 
Press officer DDZ 
isabelle.keller(at)ddz.de  
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The German Diabetes Center (DDZ) serves as the German reference center for diabetes. Its objective is to contribute to the improvement of prevention, early detection, diagnosis and treatment of diabetes mellitus. At the same time, the research center aims at improving the epidemiological data situation in Germany. The DDZ coordinates the multicenter German Diabetes Study and is a point of contact for all players in the health sector. In addition, it prepares scientific information on diabetes mellitus and makes it available to the public. The DDZ is part of the Leibniz Association (Wissenschaftsgemeinschaft Gottfried Wilhelm Leibniz, WGL) and is a partner of the German Center for Diabetes Research (DZD e.V.). www.ddz.de/en 

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 Munich – 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 Helmholtz Munich at the University Medical Center Carl Gustav Carus of the TU Dresden and the Institute for Diabetes Research and Metabolic Diseases of Helmholtz Munich at the Eberhard-Karls-University of Tuebingen together with associated partners at the Universities in Heidelberg, Cologne, Leipzig, Lübeck and Munich. www.dzd-ev.de/en