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      Prevalence of and Risk Factors for Diabetic Peripheral Neuropathy in Youth With Type 1 and Type 2 Diabetes: SEARCH for Diabetes in Youth Study

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          Abstract

          OBJECTIVE

          We assessed the prevalence of and risk factors for diabetic peripheral neuropathy (DPN) in youth with type 1 diabetes (T1D) and type 2 diabetes (T2D) enrolled in the SEARCH for Diabetes in Youth (SEARCH) study.

          RESEARCH DESIGN AND METHODS

          The Michigan Neuropathy Screening Instrument (MNSI) was used to assess DPN in 1,734 youth with T1D (mean ± SD age 18 ± 4 years, T1D duration 7.2 ± 1.2 years, and HbA 1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA 1c 9.4 ± 2.3%) who were enrolled in the SEARCH study and had ≥5 years of diabetes duration. DPN was defined as an MNSI exam score of >2. Glycemic control over time was estimated as area under the curve for HbA 1c.

          RESULTS

          The prevalence of DPN was 7% in youth with T1D and 22% in youth with T2D. Risk factors for DPN in youth with T1D were older age, longer diabetes duration, smoking, increased diastolic blood pressure, obesity, increased LDL cholesterol and triglycerides, and lower HDL cholesterol (HDL-c). In youth with T2D, risk factors were older age, male sex, longer diabetes duration, smoking, and lower HDL-c. Glycemic control over time was worse among those with DPN compared with those without for youth with T1D (odds ratio 1.53 [95% CI 1.24; 1.88]) but not for youth with T2D (1.05 [0.7; 1.56]).

          CONCLUSIONS

          The high rates of DPN among youth with diabetes are a cause of concern and suggest a need for early screening and better risk factor management. Interventions in youth that address poor glycemic control and dyslipidemia may prevent or delay debilitating neuropathic complications.

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          Most cited references19

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          Use of the Michigan Neuropathy Screening Instrument as a measure of distal symmetrical peripheral neuropathy in Type 1 diabetes: results from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications.

          The Michigan Neuropathy Screening Instrument (MNSI) is used to assess distal symmetrical peripheral neuropathy in diabetes. It includes two separate assessments: a 15-item self-administered questionnaire and a lower extremity examination that includes inspection and assessment of vibratory sensation and ankle reflexes. The purpose of this study was to evaluate the performance of the MNSI in detecting distal symmetrical peripheral neuropathy in patients with Type 1 diabetes and to develop new scoring algorithms.
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            Vascular factors and metabolic interactions in the pathogenesis of diabetic neuropathy.

            Diabetes mellitus is a major cause of peripheral neuropathy, commonly manifested as distal symmetrical polyneuropathy. This review examines evidence for the importance of vascular factors and their metabolic substrate from human and animal studies. Diabetic neuropathy is associated with risk factors for macrovascular disease and with other microvascular complications such as poor metabolic control, dyslipidaemia, body mass index, smoking, microalbuminuria and retinopathy. Studies in human and animal models have shown reduced nerve perfusion and endoneurial hypoxia. Investigations on biopsy material from patients with mild to severe neuropathy show graded structural changes in nerve microvasculature including basement membrane thickening, pericyte degeneration and endothelial cell hyperplasia. Arterio-venous shunting also contributes to reduced endoneurial perfusion. These vascular changes strongly correlate with clinical defects and nerve pathology. Vasodilator treatment in patients and animals improves nerve function. Early vasa nervorum functional changes are caused by the metabolic insults of diabetes, the balance between vasodilation and vasoconstriction is altered. Vascular endothelium is particularly vulnerable, with deficits in the major endothelial vasodilators, nitric oxide, endothelium-derived hyperpolarising factor and prostacyclin. Hyperglycaemia and dyslipidaemia driven oxidative stress is a major contributor, enhanced by advanced glycation end product formation and polyol pathway activation. These are coupled to protein kinase C activation and omega-6 essential fatty acid dysmetabolism. Together, this complex of interacting metabolic factors accounts for endothelial dysfunction, reduced nerve perfusion and function. Thus, the evidence emphasises the importance of vascular dysfunction, driven by metabolic change, as a cause of diabetic neuropathy, and highlights potential therapeutic approaches.
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              The SEARCH for Diabetes in Youth Study: Rationale, Findings, and Future Directions

              The SEARCH for Diabetes in Youth (SEARCH) study was initiated in 2000, with funding from the Centers for Disease Control and Prevention and support from the National Institute of Diabetes and Digestive and Kidney Diseases, to address major knowledge gaps in the understanding of childhood diabetes. SEARCH is being conducted at five sites across the U.S. and represents the largest, most diverse study of diabetes among U.S. youth. An active registry of youth diagnosed with diabetes at age <20 years allows the assessment of prevalence (in 2001 and 2009), annual incidence (since 2002), and trends by age, race/ethnicity, sex, and diabetes type. Prevalence increased significantly from 2001 to 2009 for both type 1 and type 2 diabetes in most age, sex, and race/ethnic groups. SEARCH has also established a longitudinal cohort to assess the natural history and risk factors for acute and chronic diabetes-related complications as well as the quality of care and quality of life of persons with diabetes from diagnosis into young adulthood. Many youth with diabetes, particularly those from low-resourced racial/ethnic minority populations, are not meeting recommended guidelines for diabetes care. Markers of micro- and macrovascular complications are evident in youth with either diabetes type, highlighting the seriousness of diabetes in this contemporary cohort. This review summarizes the study methods, describes key registry and cohort findings and their clinical and public health implications, and discusses future directions.
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                Author and article information

                Journal
                Diabetes Care
                Diabetes Care
                diacare
                dcare
                Diabetes Care
                Diabetes Care
                American Diabetes Association
                0149-5992
                1935-5548
                September 2017
                03 July 2017
                : 40
                : 9
                : 1226-1232
                Affiliations
                [1] 1Department of Neurology, University of Michigan, Ann Arbor, MI
                [2] 2Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC
                [3] 3Department of Epidemiology, Colorado School of Public Health, Aurora, CO
                [4] 4Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC
                [5] 5Division of Metabolism, Endocrinology and Diabetes, University of Michigan, Ann Arbor, MI
                [6] 6Santa Barbara, CA
                [7] 7Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA
                [8] 8Department of Pediatrics, University of Washington, Seattle, WA
                [9] 9Division of Endocrinology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH
                [10] 10Northwest Lipid Metabolism and Diabetes Research Laboratories, Department of Medicine, University of Washington, Seattle, WA
                [11] 11National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
                [12] 12Department of Epidemiology and Biostatistics and Center for Research in Nutrition and Health Disparities, Arnold School of Public Health, University of South Carolina, Columbia, SC
                Author notes
                Corresponding author: Eva L. Feldman, efeldman@ 123456umich.edu .
                Author information
                http://orcid.org/0000-0002-9162-2694
                Article
                0179
                10.2337/dc17-0179
                5566278
                28674076
                034b1af9-cd10-4283-8184-0113f268c4eb
                © 2017 by the American Diabetes Association.

                Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

                History
                : 30 January 2017
                : 2 June 2017
                Page count
                Figures: 1, Tables: 3, Equations: 0, References: 31, Pages: 7
                Funding
                Funded by: National Institute for Health Research, DOI http://dx.doi.org/10.13039/501100000272;
                Award ID: 1UC4DK108173-01
                Categories
                0106
                Pathophysiology/Complications

                Endocrinology & Diabetes
                Endocrinology & Diabetes

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