Review
Biochemistry & Molecular Biology
Toshiyuki Oshitari
Summary: Diabetic retinopathy is a tissue-specific neurovascular impairment in diabetic patients that affects the retina. Advanced glycation end-products (AGEs) are a major pathological factor causing neurovascular coupling impairments. Mechanisms such as AGE-receptor axis, reactive oxygen species, inflammation, and cell death pathways contribute to the impairment of neurovascular units. Neuronal cell death is directly associated with vision reduction in diabetic patients, highlighting the need for neuroprotective therapies targeting AGEs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Misganaw Asmamaw Mengstie, Endeshaw Chekol Abebe, Awgichew Behaile Teklemariam, Anemut Tilahun Mulu, Melaku Mekonnen Agidew, Muluken Teshome Azezew, Edgeit Abebe Zewde, Assefa Agegnehu Teshome
Summary: Hyperglycemia leads to protein glycation and accumulation of advanced glycation end products, which play a significant role in the development of diabetes complications. Their contribution occurs through receptor-mediated signaling cascade or direct extracellular matrix destruction.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Mariyam Khalid, Georg Petroianu, Abdu Adem
Summary: Persistent hyperglycemia in type 2 diabetes mellitus triggers a glycation reaction, resulting in the formation of AGEs. Binding of AGEs with its receptor RAGE activates various signaling pathways, leading to oxidative stress, inflammation, compromised insulin signaling, metabolic disturbances, pancreatic beta cell toxicity, and epigenetic modifications. This review summarizes the sources of AGEs, their role in metabolic dysfunction, and the AGEs/RAGE signaling cascade in type 2 diabetes mellitus and its associated complications.
Article
Endocrinology & Metabolism
Xue-Meng Zhang, Yuan Gao, Meng-Xue Yang, Xiao-Di Zheng, Rui Zhang, Yue-Yue Wu, Miao Zeng, Qian Yang, Zhi-Yan Yu, Jun Liu, Bing-Bing Zha, Bo Yang
Summary: Diabetic kidney disease (DKD) is a complication of diabetes, and early detection is crucial. This study found that the noninvasive lens AGEs fluorescence detection method can be used to predict the occurrence of DKD, providing clinical value in diagnosing DKD in patients with T2DM.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Elaf Al-Saoudi, Marie M. B. Christensen, Peter Nawroth, Thomas Fleming, Eva E. E. Hommel, Marit E. E. Jorgensen, Jesper Fleischer, Christian S. S. Hansen
Summary: In young adults with type 1 diabetes, increased levels of AGEs involving different metabolic pathways were associated with several measures of CAN and DSPN, suggesting that AGEs may play a diverse role in the pathogeneses of diabetic neuropathy.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Review
Endocrinology & Metabolism
Lin Mao, Ruili Yin, Longyan Yang, Dong Zhao
Summary: Atherosclerosis is a chronic inflammatory disease caused by factors like hyperglycemia, dyslipidemia, AGEs, inflammation, and insulin resistance. AGEs play a significant role in the pathogenesis of AS by affecting the function of VSMCs, contributing to the development and progression of the disease.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Endocrinology & Metabolism
Lingwen Ying, Yun Shen, Yang Zhang, Yikun Wang, Yong Liu, Jun Yin, Yufei Wang, Jingrong Yin, Wei Zhu, Yuqian Bao, Jian Zhou
Summary: This study found a positive association between AGEs levels and diabetic retinopathy (DR), with higher AGEs associated with more severe DR. The predictive value of AGEs for DR was similar to that of glycated hemoglobin A(1c) (HbA(1c), but AGEs showed higher efficacy in early screening for vision-threatening DR (VTDR). Non-invasive measurement of skin AGEs may be a more suitable indicator for poor prognosis of hyperglycemia compared to HbA(1c).
DIABETES RESEARCH AND CLINICAL PRACTICE
(2021)
Review
Biochemistry & Molecular Biology
Kirti Parwani, Palash Mandal
Summary: Metabolic syndrome can lead to diabetic nephropathy, and excess sugar can induce the formation of advanced glycation end products (AGEs), which activate pro-inflammatory markers and induce endoplasmic reticulum stress. Accumulation of AGEs, reactive oxygen species, and activation of protein kinase C are considered to contribute to the development and progression of diabetic nephropathy.
ARCHIVES OF PHYSIOLOGY AND BIOCHEMISTRY
(2023)
Article
Multidisciplinary Sciences
Gao-Xiang Wang, Ze-Bin Fang, Jun-Tong Li, Bao-Li Huang, De-Liang Liu, Shu-Fang Chu, Hui-Lin Li
Summary: This study aimed to investigate the correlation between serum albumin and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). The results showed a significant negative correlation between serum albumin levels and DR, suggesting that serum albumin levels can be used as a reference point for long-term follow-up of patients with T2DM.
Review
Immunology
Martina Maurelli, Paolo Gisondi, Giampiero Girolomoni
Summary: Advanced glycation end products (AGEs) are biologically active compounds that react with proteins to generate reactive aldehydes. They accumulate in tissues during ageing and in various metabolic and inflammatory disorders such as type 2 diabetes, obesity, cardiovascular diseases, chronic renal insufficiency, and psoriasis. The interaction of AGEs with their receptors (RAGEs) leads to cellular signaling, oxidative stress, and activation of inflammatory mediators. AGEs may play a pathogenic role in the intersection of inflammatory and metabolic diseases and could be a potential target for therapeutic strategies.
Article
Ophthalmology
Johanna Rankenberg, Stefan Rakete, Brandie D. Wagner, Jennifer L. Patnaik, Christian Henning, Anne Lynch, Marcus A. Glomb, Ram H. Nagaraj
Summary: The levels of AGEs in human lens capsules during cataract surgery were found to be similar between diabetic and non-diabetic patients, except for significantly higher levels of glucosepane in diabetic patients, which may explain the similar incidence of posterior capsule opacification between the two groups.
EXPERIMENTAL EYE RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Mieke Steenbeke, Reinhart Speeckaert, Stephanie Desmedt, Griet Glorieux, Joris R. Delanghe, Marijn M. Speeckaert
Summary: Patients with chronic kidney disease (CKD) are more prone to oxidative stress and chronic inflammation, resulting in increased production and decreased clearance of advanced glycation end products (AGEs). AGEs may contribute to decreased kidney function and increased all-cause mortality in CKD patients. Interaction between AGEs and their cell-bound receptor RAGE activates nuclear factor kappa-B (NF-kappa B), leading to cell dysfunction and increased production of inflammatory cytokines. Alterations in the AGE-RAGE system are associated with the development of various chronic kidney diseases. Soluble RAGE (sRAGE) acts as a decoy receptor to inhibit membrane-bound RAGE activation and AGE-RAGE-related toxicity. The ratio of AGEs to sRAGE may be a useful tool for predicting the prognosis of kidney diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Deepesh D. Gaikwad, Nilima S. Bangar, Mayura M. Apte, Armaan Gvalani, Rashmi S. Tupe
Summary: This study discovers that the interaction between aldosterone and glycated albumin in diabetic nephropathy can cause oxidative stress, reduce levels of antioxidants and glycation detoxifying enzymes, and result in renal cell damage.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2022)
Editorial Material
Biochemistry & Molecular Biology
Afreen Khanam, Saheem Ahmad, Arbab Husain
Summary: This article discusses the pathophysiological significance of advanced glycation end products (AGEs) and their receptor in diabetic nephropathy (DN).
CURRENT PROTEIN & PEPTIDE SCIENCE
(2023)
Article
Nutrition & Dietetics
Rui Liu, Mengyao Zhang, Li Xu, Jingjin Liu, Pingan Yang, Min Li, Jie Qin
Summary: The study showed that fAGEs levels increased with the duration of diabetes in patients with T2DM, and were significantly correlated with HbA1c. The continuous increase of fAGEs might lead to elevated levels of HbA1c, UACR, and CIMT in patients with T2DM.
FRONTIERS IN NUTRITION
(2022)
Letter
Endocrinology & Metabolism
Erika B. Parente, Stefan Mutter, Lena M. Thorn, Valma Harjutsalo, Per-Henrik Groop
Article
Endocrinology & Metabolism
Patrik Smidtslund, Fanny Jansson Sigfrids, Anni Ylinen, Nina Elonen, Valma Harjutsalo, Per-Henrik Groop, Lena M. Thorn
Summary: This study aims to investigate the prognosis after a first-ever myocardial infarction (MI) in individuals with type 1 diabetes and how different MI- and diabetes-related factors affect the prognosis and risk of secondary cardiovascular events. The study found that individuals with type 1 diabetes have a high cardiovascular and diabetes-related mortality after their first-ever MI, and poor kidney function is associated with high mortality and excessive risk of secondary cardiovascular events.
Article
Clinical Neurology
Victoria Lillback, Marco Savarese, Niina Sandholm, Peter Hackman, Bjarne Udd
Summary: In this retrospective study, the disease progression of 137 TMD patients over 15 years was observed. The main symptoms of TMD patients were walking difficulties and weakness in distal lower limbs. The progression of the weakness was moderate and cardiomyopathy was not developed due to the titin defect alone. These findings provide important information for the accurate identification and therapeutic intervention of TMD.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Anniina Tynjala, Valma Harjutsalo, Fanny Jansson Sigfrids, Per-Henrik Groop, Daniel Gordin
Summary: This study investigated the association between long-term glycemic variability and arterial stiffness in patients with type 1 diabetes. The results showed that the variability of HbA1c was significantly correlated with arterial stiffness. Importantly, this association was independent of the HbA1c mean.
CARDIOVASCULAR DIABETOLOGY
(2023)
Article
Clinical Neurology
Heli Viljakainen, Elina Engberg, Emma Dahlstrom, Sohvi Lommi, Jari Lahti
Summary: Sleep duration has been associated with obesity, especially bedtime discrepancy between school and non-school days in children. Later bedtime on non-school nights and delay in bedtime compared with school nights are associated with higher BMIz and WtHr, also predicting higher WtHr longitudinally. Promoting early bedtimes, especially on weekends, should be considered to prevent obesity in school-aged children.
JOURNAL OF SLEEP RESEARCH
(2023)
Article
Endocrinology & Metabolism
Minna Harsunen, Jani Haukka, Valma Harjutsalo, Nina Mars, Anna Syreeni, Taina Harkonen, Annemari Karajaemaki, Jorma Ilonen, Mikael Knip, Niina Sandholm, Paivi Johanna Miettinen, Per-Henrik Groop, Tiinamaija Tuomi
Summary: Contrary to the presumption that type 1 diabetes leads to an absolute insulin deficiency, this study found that many individuals with type 1 diabetes still have circulating C-peptide years after diagnosis. The study also identified the correlation between age at diagnosis and decline in C-peptide secretion, as well as the association between polygenic risk scores, clinical factors, and random serum C-peptide concentrations.
LANCET DIABETES & ENDOCRINOLOGY
(2023)
Review
Endocrinology & Metabolism
Niina Sandholm, Emma H. Dahlstrom, Per-Henrik Groop
Summary: Diabetic kidney disease (DKD) is a severe complication of diabetes, affecting a significant portion of patients. While elevated blood glucose levels play a key role in DKD, it is a complex disease with both genetic and environmental factors contributing to its development. Genome-wide association studies (GWASs) have been valuable in identifying genetic risk factors for DKD, and recent advancements in sequencing techniques have allowed for the discovery of rare genetic variants. Epigenome-wide association studies have also been conducted to explore the role of DNA methylation in DKD. This review aims to summarize the identified genetic and epigenetic risk factors for DKD.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Endocrinology & Metabolism
Aleksi Tarkkonen, Tor-Bjorn Claesson, Marika I. Eriksson, Carol Forsblom, Lena M. Thorn, Paula Summanen, Per-Henrik Groop, Jukka Putaala, Daniel Gordin, Juha Martola
Summary: Using magnetic resonance imaging, we found that the optic tracts of individuals with type 1 diabetes were smaller than those of healthy controls, suggesting that chronic hyperglycemia also damages the optic tract. This damage was associated with various metabolic measures as well as diabetic complications such as eye disease, kidney disease, neuropathy, and cerebral microbleeds.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Multidisciplinary Sciences
Om Prakash Dwivedi, Karina Barreiro, Annemari Karajamaki, Erkka Valo, Anil K. Giri, Rashmi B. Prasad, Rishi Das Roy, Lena M. Thorn, Antti Rannikko, Harry Holthoefer, Kim M. Gooding, Steven Sourbron, Denis Delic, Maria F. Gomez, Per-Henrik Groop, Tiinamaija Tuomi, Carol Forsblom, Leif Groop, Maija Puhka
Summary: By genome-wide sequencing of 200 urinary extracellular vesicle (uEV) mRNA samples from clinical studies, we identified potential candidate biomarkers and mechanisms for studying diabetic kidney disease (DKD) in Type 1 diabetes (T1D), which were validated in both Type 1 and 2 diabetes. The sequencing results revealed over 10,000 mRNAs with similarity to the kidney transcriptome. Thirteen upregulated genes predominantly expressed in proximal tubules, correlated with hyperglycemia and involved in cellular/oxidative stress homeostasis were found in T1D DKD groups. We constructed a transcriptional stress score based on six of these genes (GPX3, NOX4, MSRB, MSRA, HRSP12, and CRYAB), which reflected long-term decline of kidney function and could identify individuals with early decline even in normoalbuminuric patients.
Review
Cardiac & Cardiovascular Systems
Francesco Cosentino, Subodh Verma, Philip Ambery, Marianne Bach Treppendahl, Martin van Eickels, Stefan D. Anker, Michele Cecchini, Paola Fioretto, Per-Henrik Groop, David Hess, Kamlesh Khunti, Carolyn S. P. Lam, Isabelle Richard-Lordereau, Lars H. Lund, Paul McGreavy, Philip N. Newsome, Naveed Sattar, Scott Solomon, Franz Weidinger, Faiez Zannad, Andreas Zeiher
Summary: Metabolic comorbidities are common in cardiorenal disease and are associated with increased risk of poor outcomes of COVID-19 infection. Recognition and treatment of cardiometabolic diseases, as well as improving lifestyle and developing new biomarkers, are essential for prevention and management.
EUROPEAN HEART JOURNAL
(2023)
Article
Multidisciplinary Sciences
Raija Lithovius, Stefan Mutter, Erika B. Parente, Ville-Petteri Makinen, Erkka Valo, Valma Harjutsalo, Per-Henrik Groop
Summary: Effective treatment can prevent kidney complications in women with type 1 diabetes, but there may be underprescription in some cases. Data analysis of prescriptions and their relationship with kidney health can provide insights to optimize treatment.
SCIENTIFIC REPORTS
(2023)
Article
Endocrinology & Metabolism
M. I. Eriksson, A. Syreeni, N. Sandholm, E. H. Dahlstrom, D. Gordin, T. Tatlisumak, J. Putaala, Per-Henrik Groop, J. Martola, L. M. Thorn
Summary: This study aimed to evaluate the association between haptoglobin genotype and cerebral small-vessel disease (SVD). The results showed no significant association between haptoglobin genotype and SVD.
ACTA DIABETOLOGICA
(2023)
