OBJECTIVETo describe the development and progression of neuropathy and related findings among patients with type 1 diabetes who participated in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study.RESEARCH DESIGN AND METHODSThe main diabetic peripheral neuropathy (DPN) outcome was assessed using clinical symptoms, signs, and nerve conduction study results during DCCT and repeated in EDIC year 13/14. Cardiovascular autonomic neuropathy (CAN) was assessed by R-R response to paced breathing, Valsalva ratio, and blood pressure response to standing during DCCT and in EDIC years 13/14 and 16/17. Additionally, symptoms reflecting neuropathic pain and autonomic function (including hypoglycemia awareness) were collected yearly in EDIC using standardized questionnaires; peripheral neuropathy was also assessed annually using the Michigan Neuropathy Screening Instrument. Assessments of genitourinary function were collected at EDIC year 10.RESULTSIntensive therapy during the DCCT significantly reduced the risk of DPN and CAN at DCCT closeout (64% and 45%, respectively, P < 0.01). The prevalence and incidence of DPN and CAN remained significantly lower in the DCCT intensive therapy group compared with the DCCT conventional therapy group through EDIC year 13/14.CONCLUSIONSThe persistent effects of prior intensive therapy on neuropathy measures through 14 years of EDIC largely mirror those observed for other diabetes complications. DCCT/EDIC provides important information on the influence of glycemic control, and the clinical course of diabetic neuropathy, and, most important, on how to prevent neuropathy in type 1 diabetes.

OBJECTIVE -To compare the efficacy and safety of continuous subcutaneous insulin infusion (CSII) and multiple daily injection (MDI) in older adults with insulin-treated type 2 diabetes and to assess treatment satisfaction and quality of life.RESEARCH DESIGN AND METHODS -Adults (n ϭ 107) Ն60 years of age (mean age 66 years) with insulin-treated type 2 diabetes (mean duration 16 years, BMI 32 kg/m 2 , and HbA 1C [A1C] 8.2%) were randomized to CSII (using insulin lispro) or MDI (using insulin lispro and insulin glargine) in a two-center, 12-month, prospective, randomized, controlled clinical trial. Efficacy was assessed with A1C, safety by frequency of hypoglycemia, and treatment satisfaction and quality of life with the Diabetes Quality of Life Clinical Trial Questionnaire and the 36-item short-form health survey, version 2.RESULTS -Forty-eight CSII subjects (91%) and 50 MDI subjects (93%) completed the study. Mean A1C fell by 1.7 Ϯ 1.0% in the CSII group to 6.6% and by 1.6 Ϯ 1.2% in the MDI group to 6.4%. The difference in A1C between treatment groups was not statistically significant (P ϭ 0.20). Eighty-one percent of CSII subjects and 90% of MDI subjects experienced at least one episode of minor (self-treated) hypoglycemia (P ϭ 0.17), and three CSII and six MDI subjects experienced severe hypoglycemia (P ϭ 0.49). Rates of severe hypoglycemia were similarly low in the two groups (CSII 0.08 and MDI 0.23 events per person-year, P ϭ 0.61). Weight gain did not differ between groups (P ϭ 0.70). Treatment satisfaction improved significantly with both CSII and MDI (P Ͻ 0.0001), and the difference between groups was not statistically significant (P ϭ 0.58).CONCLUSIONS -In older subjects with insulin-treated type 2 diabetes, both CSII and MDI achieved excellent glycemic control with good safety and patient satisfaction. Diabetes Care 28:1568 -1573, 2005I n the U.S., Ͼ20% of adults Ͼ65 years of age have diabetes (1). The risk of micro-and macrovascular complications increases in elderly patients with diabetes and is associated with higher hemoglobin HbA 1C (A1C) and longer duration of diabetes (2). In middle-aged adults with type 2 diabetes, intensive glycemic management can delay or prevent the development of microvascular and neuropathic complications (3,4). While the benefits of glycemic management are less clearly established in older adults, both the American Diabetes Association and the American Geriatrics Society recommend that older adults with good functional status maintain A1C levels Ͻ7% (5,6). Despite these recommendations, surveys have shown that only onethird of diabetic patients 65-74 years of age had A1C levels Ͻ7%. Of those using insulin, only 27% had A1C levels Ͻ7%, whereas nearly half had A1Cs Ͼ8% (7).While lifestyle changes and oral antidiabetes medications can improve glycemic control early in the course of type 2 diabetes, insulin is often required to reach A1C goals later in the course of disease. Intensive insulin therapy regimens employ either continuous subcutaneous insulin infusion (CSII) or mul...

OBJECTIVETo evaluate the impact of former intensive versus conventional insulin treatment on neuropathy in Diabetes Control and Complications Trial (DCCT) intensive and conventional treatment subjects with type 1 diabetes 13–14 years after DCCT closeout, during which time the two groups had achieved similar A1C levels.RESEARCH DESIGN AND METHODSClinical and nerve conduction studies (NCSs) performed during the DCCT were repeated during the Epidemiology of Diabetes Interventions and Complications (EDIC) study by examiners masked to treatment status on 603 former intensive and 583 former conventional treatment subjects. Clinical neuropathy was defined by symptoms, sensory signs, or reflex changes consistent with distal polyneuropathy and confirmed with NCS abnormalities involving two or more nerves among the median, peroneal, and sural nerves.RESULTSThe prevalence of neuropathy increased 13–14 years after DCCT closeout from 9 to 25% in former intensive and from 17 to 35% in former conventional treatment groups, but the difference between groups remained significant (P < 0.001), and the incidence of neuropathy remained lower among former intensive (22%) than former conventional (28%) treatment subjects (P = 0.0125). Analytic models of incident neuropathy that adjusted for differences in NCS results at DCCT closeout showed no significant risk reduction associated with former intensive treatment during follow-up (odds ratio 1.17 [95% CI 0.84–1.63]). However, a significant persistent treatment group effect was observed for several NCS measures. Longitudinal analyses of overall glycemic control showed a significant association between mean A1C and measures of incident and prevalent neuropathy.CONCLUSIONSThe benefits of former intensive insulin treatment persisted for 13–14 years after DCCT closeout and provide evidence of a durable effect of prior intensive treatment on neuropathy.

OBJECTIVEWe 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 METHODSThe 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 HbA1c 9.1 ± 1.9%) and 258 youth with T2D (age 22 ± 3.5 years, T2D duration 7.9 ± 2 years, and HbA1c 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 HbA1c.RESULTSThe 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]).CONCLUSIONSThe 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.

OBJECTIVE -To evaluate the impact of prior intensive diabetes therapy on neuropathy among former Diabetes Control and Complications Trial (DCCT) participants.RESEARCH DESIGN AND METHODS -At the conclusion of the DCCT, subjects in the intensive group were encouraged to maintain intensive therapy, and subjects in the conventional group were encouraged to begin intensive therapy. Thereafter, we annually assessed neuropathy as part of the Epidemiology of Diabetes Intervention and Complications (EDIC) study. Neuropathy was defined using the Michigan Neuropathy Screening Instrument (MNSI). We recorded potential adverse consequences of neuropathy.RESULTS -At the first EDIC examination, 1,257 subjects participated in the neuropathy assessment. Consistent with DCCT results, the former intensive group showed a lower prevalence of neuropathy than the conventional group based on positive questionnaire (1.8 vs. 4.7%; P ϭ 0.003) or examination (17.8 vs. 28.0%; P Ͻ 0.0001) results. Despite similar levels of glycemic control, symptoms and signs of neuropathy remained less prevalent among the former intensive group compared with the conventional group. At the beginning of the EDIC study, prior intensive therapy reduced the odds of having symptoms and signs of neuropathy using MNSI criteria by 64% (P ϭ 0.0044) and 45% (P Ͻ 0.0001), respectively, with similar odds reductions observed for both neuropathic symptoms (51%, P Ͻ 0.0001) and neuropathic signs (43%, P Ͻ 0.0001) across 8 years of EDIC follow-up.CONCLUSIONS -The benefits of 6.5 years of intensive therapy on neuropathy status extended for at least 8 years beyond the end of the DCCT, similar to the findings described for diabetic retinopathy and nephropathy. Diabetes Care 29:340 -344, 2006T he Diabetes Control and Complications Trial (DCCT) used a combination of self-reported symptoms, detailed neurological examinations, and nerve conduction studies to identify symptoms, signs, or electrophysiological evidence of distal symmetrical peripheral neuropathy (1,2). The primary neurological end point in the DCCT was the development of "confirmed clinical neuropathy" between baseline and completion of the DCCT, whereas "definite clinical neuropathy" (symptoms and signs consistent with clinical neuropathy as determined by a board-certified neurologist) served as a secondary end point (1-3). Intensive therapy, designed to achieve glycemic levels as close as possible to the nondiabetic range, reduced the risk of developing confirmed clinical neuropathy by 60 -69%, with similar reductions noted for definite clinical neuropathy (1-3).The Epidemiology of Diabetes Intervention and Complications (EDIC) study is an epidemiologic follow-up of the DCCT cohort (4). The primary study goal is to examine the long-term effects of prior intensive compared with conventional therapy on the development and progression of diabetes complications and cardiovascular disease in type 1 diabetes. Surveillance of neuropathy in the EDIC study is performed annually by the EDIC nurse coordinator or diabetologist ...