TY  - JOUR
AB  - BACKGROUND: Diabetic kidney disease (DKD) is a chronic kidney condition that arises from prolonged hyperglycaemia that can progress to kidney failure, severe morbidity, and mortality if left untreated. It is the major cause of chronic kidney disease among people who have diabetes, accounting for a significant percentage of patients with end-stage kidney disease who require kidney replacement therapy. MAIN BODY: In DKD, numerous dysbalanced metabolic, haemodynamic, inflammatory signalling pathways, and molecular mediators interconnect, creating a feedback loop that promotes general kidney damage. Hyperglycaemia is the primary trigger for DKD and leads gradually to oxidative stress, inflammation, extracellular matrix deposition and fibrosis, glomerular hypertension, and intrarenal hypoxia. Key interconnected metabolic pathways are the hyperglycaemia-mediated polyol, hexosamine, protein kinase C, and advanced glycation end-products pathway hyperactivity. Concurrently, hyperglycaemia-induced renin-angiotensin-aldosterone system stimulation, alters the kidney intraglomerular haemodynamic leading to inflammation through Toll-like receptors, Janus kinase/signal transducer and activator of transcription, and nuclear factor-kappa B, transforming growth factor-beta-mediated excessive extracellular matrix accumulation and fibrosis. The resulting death signals trigger apoptosis and autophagy through Hippo, Notch, and Wnt/β-catenin pathway activation and microRNA dysregulation. These signals synergistically remodel the kidneys culminating in intrarenal hypoxia, podocyte dysfunction, hyperfiltration, epithelial-mesenchymal transition, and loss of kidney function. The resulting renal failure further upregulates these death pathways and mediators, giving rise to a vicious cycle that further worsens DKD. CONCLUSION: This review provides an overview of the primary molecular mediators and signalling pathways leading to DKD; their interconnectivity at the onset and during DKD progression, the central role of transforming growth factor-beta via different pathways, the Hippo pathway kidney-specific response to hyperglycaemia, and how all mediators and transduction signals result in a vicious circle that exacerbates renal failure. The review gives therapeutic sights to these pathways as druggable targets for DKD management. Understanding these molecular events underlying the pathogenesis of DKD can bridge basic research and clinical application, facilitating the development of innovative management strategies.
AU  - Efiong, E.E.
AU  - Maedler, K.*
AU  - Effa, E.*
AU  - Osuagwu, U.L.*
AU  - Peters, E.*
AU  - Ikebiuro, J.O.*
AU  - Soremekun, C.
AU  - Ihediwa, U.*
AU  - Niu, J.
AU  - Fuchs, M.
AU  - Bazireh, H.
AU  - Bassey, A.L.*
AU  - Amadi, P.U.*
AU  - Dong, Q.
AU  - Kimani, N.M.*
AU  - Chukwuanukwu, R.C.*
AU  - Tuenter, E.*
AU  - Sharma, S.
AU  - Grallert, H.
C1  - 74865
C2  - 57642
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - Decoding diabetic kidney disease: A comprehensive review of interconnected pathways, molecular mediators, and therapeutic insights.
JO  - Diabetol. Metab. Syndr.
VL  - 17
IS  - 1
PB  - Bmc
PY  - 2025
ER  - 

TY  - JOUR
AB  - Background: Although the population-based German disease management programs (DMPs) for diabetes mellitus (DM) and coronary heart disease (CHD) are among the biggest worldwide, evidence on the effectiveness of these programs is still inconclusive or missing, particularly for high risk patients with comorbidities. The objective of this study was therefore to analyze the impact of DMPs on process and outcome parameters in patients with both, type 2 DM and CHD. Methods: Analyses are based on two postal surveys of patients from the KORA myocardial infarction registry (southern Germany) with type 2 DM and on two postal validation studies with patients' general physicians (2006, n = 312 and 2011, n = 212). The association between DMP enrollment (being enrolled in either DMP-DM or DMP-CHD) and guideline care (defined by several process indicators) at baseline (2006) and its development until follow-up (2011) was analyzed using logistic regression models accounting for the repeated measurements structure. The impact of DMP enrollment/guideline care on cumulated (quality-adjusted) life years ((QA)LYs) over a 4-year time horizon (2006-2010) was assessed using multiple linear regression methods. Logistic regression models were applied to analyze the association between DMP status and patient self-management at follow-up. Results: Being enrolled in a DMP was associated with better guideline care at baseline [OR = 2.3 (95 % CI 1.27-4.03)], but not at follow-up [OR = 0.80 (95 % CI 0.40-1.58); p value for time-interaction <0.01]. DMP enrollment was not significantly [+0.15 LYs (95 % CI -0.07, 0.37); +0.06 QALYs (95 % CI -0.15, 0.26)], but treatment according to guideline care significantly [+0.40 LYs (95 % CI 0.21-0.60); +0.28 QALYs (95 % CI 0.10-0.45)] associated with higher (quality-adjusted) survival over the 4-year follow-up period. DMP enrollees further reported a somewhat better self-management than patients not being enrolled into a DMP. Conclusions: The results of this study concerning the effectiveness of DMPs in patients with DM and CHD are mixed, but are weakly in favor of DMPs. However, we found a clear positive impact of guideline care on quality adjusted survival in this patient group. The development of the association between DMP enrollment and guideline care over the follow-up time indicates some external effects, which should be the subject of further investigations.
AU  - Laxy, M.
AU  - Stark, R.G.
AU  - Meisinger, C.
AU  - Kirchberger, I.
AU  - Heier, M.
AU  - von Scheidt, W.*
AU  - Holle, R.
C1  - 46874
C2  - 39005
TI  - The effectiveness of German Disease Management Programs (DMPs) in patients with type 2 diabetes mellitus and coronary heart disease: Results from an observational longitudinal study.
JO  - Diabetol. Metab. Syndr.
VL  - 7
IS  - 1
PY  - 2015
ER  -