Hyperlipidemia: a new therapeutic target for diabetic neuropathy

Abstract Emerging data establish dyslipidemia as a significant contributor to the development of diabetic neuropathy. In this review, we discuss how separate metabolic imbalances, including hyperglycemia and hyperlipidemia, converge on mechanisms leading to oxidative stress in dorsal root ganglia (DRG) sensory neurons. We conclude with suggestions for novel therapeutic strategies to prevent or reverse diabetes-induced nerve degeneration.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78728/1/j.1529-8027.2009.00237.x.pd

Altered sphingoid base profiles in type 1 compared to type 2 diabetes

Background: Sphingolipids are increasingly recognized to play a role in insulin resistance and diabetes. Recently we reported significant elevations of 1-deoxysphingolipids (1-deoxySL) - an atypical class of sphingolipids in patients with metabolic syndrome (MetS) and diabetes type 2 (T2DM). It is unknown whether 1-deoxySL in patients with diabetes type 1 (T1DM) are similarly elevated. Findings: We analyzed the long chain base profile by LC-MS after hydrolyzing the N-acyl and O-linked headgroups in plasma from individuals with T1DM (N = 27), T2DM (N = 30) and healthy controls (N = 23). 1-deoxySLs were significantly higher in the groups with T2DM but not different between T1DM and controls. In contrast to patients with T2DM, 1-deoxSL levels are not elevated in T1DM. Conclusions: Our study indicates that the 1-deoxySL formation is not per-se caused by hyperglycemia but rather specifically associated with metabolic changes in T2DM, such as elevated triglyceride levels. Electronic supplementary material The online version of this article (doi:10.1186/1476-511X-13-161) contains supplementary material, which is available to authorized users

Translating Glucose Variability Metrics into the Clinic via Continuous Glucose Monitoring: A Graphical User Interface for Diabetes Evaluation (CGM-GUIDE)

Background: Several metrics of glucose variability have been proposed to date, but an integrated approach that provides a complete and consistent assessment of glycemic variation is missing. As a consequence, and because of the tedious coding necessary during quantification, most investigators and clinicians have not yet adopted the use of multiple glucose variability metrics to evaluate glycemic variation. Methods: We compiled the most extensively used statistical techniques and glucose variability metrics, with adjustable hyper- and hypoglycemic limits and metric parameters, to create a user-friendly Continuous Glucose Monitoring Graphical User Interface for Diabetes Evaluation (CGM-GUIDE-). In addition, we introduce and demonstrate a novel transition density profile that emphasizes the dynamics of transitions between defined glucose states. Results: Our combined dashboard of numerical statistics and graphical plots support the task of providing an integrated approach to describing glycemic variability. We integrated existing metrics, such as SD, area under the curve, and mean amplitude of glycemic excursion, with novel metrics such as the slopes across critical transitions and the transition density profile to assess the severity and frequency of glucose transitions per day as they move between critical glycemic zones. Conclusions: By presenting the above-mentioned metrics and graphics in a concise aggregate format, CGM-GUIDE provides an easy to use tool to compare quantitative measures of glucose variability. This tool can be used by researchers and clinicians to develop new algorithms of insulin delivery for patients with diabetes and to better explore the link between glucose variability and chronic diabetes complications.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90437/1/dia-2E2011-2E0099.pd

Sexual dysfunction in women with type 1 diabetes in Norway: A cross-sectional study on the prevalence and associations with physical and psychosocial complications

Aim To estimate the prevalence of sexual dysfunction in women with type 1 diabetes (T1D) compared with women without diabetes and to analyse associations between sexual dysfunction and the presence of chronic physical diabetes complications, diabetes distress and depression in women with T1D. Methods This cross-sectional study was conducted in Norway, and 171 women with T1D and 60 controls completed the Female Sexual Function Index (FSFI) and the Hospital Anxiety and Depression Scale (HADS). Diabetes distress was assessed with the Problem Areas in Diabetes (PAID) scale. Data on diabetes complications were retrieved from medical records. We performed logistic regression to estimate differences in the prevalence of sexual dysfunction (defined as FSFI ≤26.55) between women with T1D and women without diabetes and to examine associations of sexual dysfunction with chronic diabetes complications, diabetes distress and depression in women with T1D. Results The prevalence of sexual dysfunction was higher in women with T1D (50.3%) compared with the controls (35.0%; unadjusted odds ratio [OR] 1.89 [95% confidence interval (CI) 1.06–3.37]; adjusted OR 1.93 [1.05–3.56]). In women with T1D, sexual dysfunction was associated with both diabetes distress (adjusted OR 1.03 [1.01–1.05]) and depression (adjusted OR 1.28 [1.12–1.46]), but there were no clear associations with chronic diabetes complications (adjusted OR 1.46 [0.67–3.19]). Conclusions This study suggests that sexual dysfunction is more prevalent in women with T1D compared with women without diabetes. The study findings emphasize the importance of including sexual health in relation to diabetes distress and psychological aspects in diabetes care and future research.publishedVersio

Diabetes and obesity are the main metabolic drivers of peripheral neuropathy

ObjectiveTo determine the associations between individual metabolic syndrome (MetS) components and peripheral neuropathy in a large populationâ based cohort from Pinggu, China.MethodsA crossâ sectional, randomly selected, populationâ based survey of participants from Pinggu, China was performed. Metabolic phenotyping and neuropathy outcomes were performed by trained personnel. Glycemic status was defined according to the American Diabetes Association criteria, and the MetS using modified consensus criteria (body mass index instead of waist circumference). The primary peripheral neuropathy outcome was the Michigan Neuropathy Screening Instrument (MNSI) examination. Secondary outcomes were the MNSI questionnaire and monofilament testing. Multivariable models were used to assess for associations between individual MetS components and peripheral neuropathy. Treeâ based methods were used to construct a classifier for peripheral neuropathy using demographics and MetS components.ResultsThe mean (SD) age of the 4002 participants was 51.6 (11.8) and 51.0% were male; 37.2% of the population had normoglycemia, 44.0% prediabetes, and 18.9% diabetes. The prevalence of peripheral neuropathy increased with worsening glycemic status (3.25% in normoglycemia, 6.29% in prediabetes, and 15.12% in diabetes, P < 0.0001). Diabetes (odds ratio [OR] 2.60, 95% CI 1.77â 3.80) and weight (OR 1.09, 95% CI 1.02â 1.18) were significantly associated with peripheral neuropathy. Age, diabetes, and weight were the primary splitters in the classification tree for peripheral neuropathy.InterpretationSimilar to previous studies, diabetes and obesity are the main metabolic drivers of peripheral neuropathy. The consistency of these results reinforces the urgent need for effective interventions that target these metabolic factors to prevent and/or treat peripheral neuropathy.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/143679/1/acn3531_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/143679/2/acn3531.pd

Resting Heart Rate and Metabolic Syndrome in Patients With Diabetes and Coronary Artery Disease in Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

The relation between the metabolic syndrome (MetS) and resting heart rate (rHR) in patients with diabetes and coronary artery disease is unknown. The authors examined the cross-sectional association at baseline between components of the MetS and rHR and between rHR and left ventricular ejection fraction in the population from the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) randomized clinical trial. The mean rHR in the MetS group was significantly higher than in those without (68.4±12.3 vs 65.6±11.8 beats per min, P=.0017). The rHR was higher (P<.001 for trend) with increasing number of components for MetS. Linear regression analyses demonstrated that as compared to individuals without MetS, rHR was significantly higher in participants with MetS (regression coefficient, 2.9; P=.0015). In patients with type 2 diabetes and coronary artery disease, the presence of higher rHR is associated with increasing number of criteria of MetS and the presence of ventricular dysfunction.Prev Cardiol. 2010;13:112–116. © 2009 Wiley Periodicals, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79383/1/j.1751-7141.2010.00067.x.pd