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A quarter of all patients hospitalized and up to a third of all patients in clinical trials are people with diabetes mellitus. Despite the almost complete reduction of coma incidence, diabetes is a major challenge for the health system due to its epidemic spread and unresolved issues regarding the prevention of complications.
In recent years, numerous pharmacological innovations have led to a significant expansion of treatment options, however the problem of mortality and organ complications is not yet solved. In addition, it became clear, that some of the most important complications occur independently of blood glucose, and can not be avoided by intensive glycemic treatment. Therefore, research aims at finding weaknesses in the causal chain “hyperglycaemia - vascular injury - organ failure”.
Therefore, the section of endocrinology, 5th medical department, employs clinical and preclinical studies to analyze mechanisms of diabetic small vessel damage.
- In patients, the relationship between major risk factors and the natural course of diabetic retinopathy is analyzed in large cohorts with type 1 and type 2 diabetes.
- In diabetic animal models, mechanisms causing damage to the neurovascular unit, are investigated. Through targeted approaches, patient-relevant surrogate endpoints are modified in the models.
- In preclinical models, changes of the neurovascular unit, caused by the isolated injury of photoreceptors, are examined, analyzed and evaluated for their similarities to diabetic retinopathy.
- Due to pathogenetic relation to Alzheimer's disease, mechanisms are investigated in animal models to understand similarities between eye and brain damage in people with diabetes.
- Our group is interested in glucose-independent mechanisms of small vessel damage, in particular the effects on immune cells of the retina. These include aspects of sugar memory ("metabolic memory").
- In a nematode model, mechanisms of neuron-specific damages caused by glucose and reactive metabolites are analyzed, in order to establish a connection to neuronal damages in the diabetic retina.
- In pre-diabetic patients with WHO grade III obesity, endothelial dysfunction and markers of metabolic syndrome are studied to understand mechanisms of non-hyperglycaemic metabolic damage of vessels.
- Jörgens K, Stoll SJ, Pohl J, Fleming TH, Sticht C, Nawroth PP, Hammes HP, Kroll J: High tissue glucose alters intersomitic blood vessels in zebrafish via methylglyoxal targeting the VEGF receptor signaling cascade. Diabetes, 64: 213-225, 2015.
- McVicar CM, Ward M, Colhoun LM, Guduric-Fuchs J, Bierhaus A, Fleming T, Schlotterer A, Kolibabka M, Hammes HP, Chen M, Stitt AW. Role of the receptor for advanced glycation endproducts (RAGE) in retinal vasodegenerative pathology during diabetes in mice. Diabetologia, 58: 1129-1137, 2015.
- Busch S, Kannt A, Kolibabka M, Schlotterer A, Wang Q, Lin J, Feng Y, Hoffmann S, Gretz N, Hammes HP . Systemic treatment with erythropoietin protects the neurovascular unit in a rat model of retinal neurodegeneration. PLoS One, 9: e102013, 2014.
- Hu J, Popp R, Frömel T, Ehling M, Awwad K, Adams RH, Hammes HP, Fleming I. Müller glia cells regulate Notch signaling and retinal angiogenesis via the generation of 19,20-dihydroxydocosapentaenoic acid. J Exp Med, 211: 281-295, 2014.
- Hammes HP, Kerner W, Hofer S, Kordonouri O, Raile K, Holl RW; DPV-Wiss Study Group. Diabetic retinopathy in type 1 diabetes-a contemporary analysis of 8,784 patients. Diabetologia, 54: 1977-1984, 2011.
- Hammes HP, Feng Y, Pfister F, Brownlee M. Diabetic retinopathy: targeting vasoregression. Diabetes, 60: 9-16, 2011.
- Queisser MA, Yao D, Geisler S, Hammes HP, Lochnit G, Schleicher ED, Brownlee M, Preissner KT. Hyperglycemia impairs proteasome function by methylglyoxal. Diabetes, 59: 670-678, 2010.
- Sjølie AK, Klein R, Porta M, Orchard T, Fuller J, Parving HH, Bilous R, Chaturvedi N; DIRECT Programme Study Group. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomized placebo-controlled trial. Lancet, 372: 1385-1393, 2008.
- Pfister F, Feng Y, vom Hagen F, Hoffmann S, Molema G, Hillebrands JL, Shani M, Deutsch U, Hammes HP. Pericyte migration: a novel mechanism of pericyte loss in experimental diabetic retinopathy. Diabetes, 57: 2495-2502, 2008.