title: The Relationship between Dyslipidemia and Acute Axonal Function in Type 2 Diabetes Mellitus In Vivo.
abstract: OBJECTIVE
  Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus. Treatment largely consists of symptom alleviation and there is a need to identify therapeutic targets for prevention and treatment of DPN. The objective of this study was to utilise novel neurophysiological techniques to investigate axonal function in patients with type 2 diabetes and to prospectively determine their relationship to serum lipids in type 2 diabetic patients.
  
  
  METHODS
  Seventy-one patients with type 2 diabetes were consecutively recruited and tested. All patients underwent thorough clinical neurological assessments including nerve conduction studies, and median motor axonal excitability studies. Studies were also undertaken in age matched normal control subjects(n = 42). Biochemical studies, including serum lipid levels were obtained in all patients. Patient excitability data was compared to control data and linear regression analysis was performed to determine the relationship between serum triglycerides and low density lipoproteins and excitability parameters typically abnormal in type 2 diabetic patients.
  
  
  RESULTS
  Patient mean age was 64.2±2.3 years, mean glycosylated haemoglobin (HbA1c%) was 7.8±0.3%, mean triglyceride concentration was 1.6±0.1 mmol/L and mean cholesterol concentration was 4.1±0.2mmol/L. Compared to age matched controls, median motor axonal excitability studies indicated axonal dysfunction in type 2 diabetic patients as a whole (T2DM) and in a subgroup of the patients without DPN (T2DM-NN). These included reduced percentage threshold change during threshold electrotonus at 10-20ms depolarising currents (TEd10-20ms)(controls 68.4±0.8, T2DM63.9±0.8, T2DM-NN64.8±1.6%,P<0.05) and superexcitability during the recovery cycle (controls-22.5±0.9, T2DM-17.5±0.8, T2DM-NN-17.3±1.6%,P<0.05). Linear regression analysis revealed no associations between changes in axonal function and either serum triglyceride or low density lipoprotein concentration when adjusted for renal function, a separate risk factor for neuropathy development. Our findings indicate that acutely, serum lipids do not exert an acute effect on axonal function in type 2 diabetic patients: TEd(10-20ms)(1.2(-1.4,3.8);P = 0.4) and superexcitability (2.4(-0.05, 4.8);P = 0.06).
  
  
  CONCLUSIONS
  These findings suggest that serum triglyceride levels are not related to axonal function in type 2 diabetic patients. Additional pathogenic mechanisms may play a more substantial role in axonal dysfunction prior to DPN development.
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Natalie C G
authors.initials: NC
authors.lastname: Kwai
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: William
authors.initials: W
authors.lastname: Nigole
authors.affiliation: Department of Endocrinology, Prince of Wales Hospital, Sydney, Australia.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Poynten
authors.affiliation: National Health and Medical Research Council Clinical Trials Centre, University of Sydney, Sydney, Australia.
authors.forename: Christopher
authors.initials: C
authors.lastname: Brown
authors.affiliation: Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors.forename: Arun V
authors.initials: AV
authors.lastname: Krishnan
mesh_terms: D000368:Aged; D001369:Axons / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000175:diagnosis*; D003929:Diabetic Neuropathies / Q000503:physiopathology; D050171:Dyslipidemias / Q000150:complications / Q000175:diagnosis*; D005260:Female; D005919:Glomerular Filtration Rate; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D016014:Linear Models; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D014280:Triglycerides / Q000097:blood
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; D008077:Lipoproteins, LDL; D014280:Triglycerides