Radha Saraswathy1, Sudhaa Anand1, Sree Kumar Kunnumpurath2, R Jones Kurian3, Alan David Kaye4, Nalini Vadivelu5. 1. Biomolecules and Genetics Division, School of Bio Sciences and Technology, Vellore Institute of Technology University, Vellore, India. 2. Consultant in Pain Medicine, Department of Anesthesiology, Epsom and St Helier University Hospitals NHS Trust, Carshalton, UK. 3. Consultant Anaesthetist and Pain Medicine, Department of Anesthesiology, East Surrey Hospital, Red Hill, UK. 4. Departments of Anesthesiology and Pharmacology, Louisiana State University Health Sciences Center, New Orleans, LA. 5. Department of Anesthesiology, Yale University School of Medicine, New Haven, CT.
Abstract
BACKGROUND: Recent decades have seen an increase in our understanding of a number of pathophysiological processes associated with type 2 diabetes mellitus (DM). Despite increases in understanding and treatment options, diabetic neuropathy remains a significant problem and is associated with tremendous morbidity and mortality. In this regard, oxidative DNA damage is postulated to play a role in diabetes-mediated neuropathic pathogenesis. METHODS: In this pilot investigation, we studied the extent of chromosomal damage utilizing chromosomal aberration (CA) assay in cultured lymphocytes of patients in 3 subgroups: patients with diabetic neuropathy, patients with type 2 DM and no neuropathy, and a control group. RESULTS: The patients with diabetic neuropathy showed a statistically significantly higher rate of CA (P<0.001, 0.086 ± 0.04) compared to the DM patients without neuropathy (0.03 ± 0.02). Samples from subjects with diabetic neuropathy were evaluated to check for mutations in the AKR1B1 gene (exon 1). A significant number of mutations appeared after DNA sequencing within the AKR1B1 gene. Of 50 diabetic neuropathy patient samples analyzed, 10 revealed mutations. CONCLUSION: Our results suggest that painful diabetic neuropathy is a condition with enhanced genomic instability characterized by increased CA and possible mutations. Exon 1 of the gene AKR1B1 showed significant mutations in patients with painful diabetic neuropathy.
BACKGROUND: Recent decades have seen an increase in our understanding of a number of pathophysiological processes associated with type 2 diabetes mellitus (DM). Despite increases in understanding and treatment options, diabetic neuropathy remains a significant problem and is associated with tremendous morbidity and mortality. In this regard, oxidative DNA damage is postulated to play a role in diabetes-mediated neuropathic pathogenesis. METHODS: In this pilot investigation, we studied the extent of chromosomal damage utilizing chromosomal aberration (CA) assay in cultured lymphocytes of patients in 3 subgroups: patients with diabetic neuropathy, patients with type 2 DM and no neuropathy, and a control group. RESULTS: The patients with diabetic neuropathy showed a statistically significantly higher rate of CA (P<0.001, 0.086 ± 0.04) compared to the DMpatients without neuropathy (0.03 ± 0.02). Samples from subjects with diabetic neuropathy were evaluated to check for mutations in the AKR1B1 gene (exon 1). A significant number of mutations appeared after DNA sequencing within the AKR1B1 gene. Of 50 diabetic neuropathypatient samples analyzed, 10 revealed mutations. CONCLUSION: Our results suggest that painful diabetic neuropathy is a condition with enhanced genomic instability characterized by increased CA and possible mutations. Exon 1 of the gene AKR1B1 showed significant mutations in patients with painful diabetic neuropathy.
Authors: S Tesfaye; L K Stevens; J M Stephenson; J H Fuller; M Plater; C Ionescu-Tirgoviste; A Nuber; G Pozza; J D Ward Journal: Diabetologia Date: 1996-11 Impact factor: 10.122
Authors: Bernhard O Boehm; Peter Möller; Josef Högel; Bernhard R Winkelmann; Wilfried Renner; Silke Rosinger; Ursula Seelhorst; Britta Wellnitz; Winfried März; Julia Melzner; Silke Brüderlein Journal: Diabetes Date: 2008-07-23 Impact factor: 9.461