Neurophysiological changes in the central and peripheral nervous system of streptozotocin-diabetic rats. Course of development and effects of insulin treatment.
(9/1279)
Diabetes mellitus can affect both the peripheral and the central nervous system. However, central deficits are documented less well than peripheral deficits. We therefore compared the course of development of neurophysiological changes in the central and peripheral nervous systems in streptozotocin-diabetic rats. Sciatic nerve conduction velocities and auditory and visual evoked potentials were measured prior to diabetes induction, and then monthly after diabetes induction for 6 months. In addition, the effect of insulin treatment was examined. Treatment was initiated after a diabetes duration of 6 months and was continued for 3 months. During treatment, evoked potentials and nerve conduction were measured monthly. In a third experiment, conduction velocities in ascending and descending pathways of the spinal cord were examined after 3 and 6 months of diabetes. Impairments of sciatic nerve conduction velocities developed fully during the first 2-3 months of diabetes. In contrast, increased latencies of auditory and visual evoked potentials developed only after 3-4 months of diabetes, and progressed gradually thereafter. Insulin treatment, initiated 6 months after induction of diabetes, improved both nerve conduction velocities and evoked potential latencies. Conduction velocities in the spinal cord tended to be reduced after 3 months of diabetes and were significantly reduced after 6 months of diabetes. The present study demonstrates that in streptozotocin-diabetic rats the course of development of peripheral and central neurophysiological changes differs. Peripheral impairments develop within weeks after diabetes induction, whereas central impairments take months to develop. Insulin can reverse both peripheral and central neurophysiological alterations. (+info)
The 10-year incidence of renal insufficiency in people with type 1 diabetes.
(10/1279)
OBJECTIVE: To describe the 10-year decrease in estimated creatinine clearance and the incidence of renal insufficiency and end-stage renal disease in a cohort of people with type 1 diabetes. RESEARCH DESIGN AND METHODS: A population-based cohort of individuals with younger-onset diabetes (diagnosed at < 30 years old and taking insulin) participated in an examination during 1984-1986 (n = 891), a 6-year follow-up examination during 1990-1992 (n = 765), and a 10-year follow-up examination during 1995-1996 (n = 634). Serum creatinine and risk factors were measured during standardized protocols at each examination. Estimated adjusted creatinine clearance was computed by a modification of the Cockroft-Gault formula. A clinically meaningful change was defined as a decrease in the estimated annual creatinine clearance of > or = 3 ml.min-1.1.73 m-2.year-1. Renal insufficiency was defined by the development of a serum creatinine of 2.0 mg/dl or greater after the 1984-1986 examination. RESULTS: The 10-year estimated incidence of an annual decrease in the creatinine clearance of > or = 3 ml.min-1.1.73 m-2 for the cohort was 52.5%, and the cumulative 10-year incidence of renal insufficiency and end-stage renal failure was 14.4%. In univariate analyses, incidence of a decrease in the estimated creatinine clearance of > or = 3 ml.min-1.1.73 m-2.year-1 and the incidence of renal insufficiency were both related to higher glycosylated hemoglobin; higher diastolic blood pressure; the presence of microalbuminuria and gross proteinuria; more severe retinopathy; and a history of loss of tactile sensation or temperature sensitivity at baseline. In logistic regression analysis, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, higher glycosylated hemoglobin and higher diastolic blood pressure were associated with decreasing estimated creatinine clearance. In logistic regression analyses, after adjusting for the presence of microalbuminuria and gross proteinuria at baseline, the incidence of renal insufficiency was independently associated with age, glycosylated hemoglobin, hypertension, and serum HDL cholesterol. CONCLUSIONS: These data suggest that a public health approach aimed at controlling glycemia, blood pressure, and serum lipids might result in reducing the rate of decline in renal function and development of renal insufficiency in people with type 1 diabetes. (+info)
Impact of peripheral neuropathy on bone density in patients with type 1 diabetes.
(11/1279)
OBJECTIVE: To investigate whether peripheral neuropathy (PN), as part of the microangiopathic complex, affects bone mineral density (BMD) of the peripheral or the axial skeleton in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Three study groups were examined. Group 1 comprised 21 males with type 1 diabetes and severe PN with a mean (range) duration of diabetes of 28 (9-59) years and an HbA1c of 8.2% (6.3-10.4). Group 2 comprised 21 male type 1 diabetic patients with absent or mild PN matched to patients of group 1 regarding age, weight, and duration of diabetes. Group 3 comprised 21 control subjects. BMD was measured by dual-energy x-ray absorptiometry (DEXA) and by quantitative ultrasound of the calcaneus. PN was determined by biothesiometry. Levels of physical activity were assessed through guided questionnaires. RESULTS: In group 1, BMD was significantly reduced at all measured sites, compared with an expected Z score of 0 (spine, -1.01 +/- 0.34; femur, -0.94 +/- 0.25; forearm, -1.10 +/- 0.36). To a lesser extent, but still significantly, group 2 also showed reduced BMD values (spine, -0.60 +/- 0.26; femur, -0.55 +/- 0.25; forearm, -1.05 +/- 0.36), whereas group 3 had normal BMD values (-0.23 +/- 0.25, -0.10 +/- 0.21, -0.07 +/- 0.25, respectively). Group 1 had lower mean BMD levels than group 2 and group 3 at all measured sites, but a significant difference was found only between groups 1 and 3 at the site of the femur (analysis of variance, P < 0.05). Broadband ultrasound attenuation (BUA) of the calcaneus was significantly reduced in group 1 compared with groups 2 and 3 (108 +/- 3 vs. 115 +/- 2 and 115 +/- 2). Significant correlations between all DEXA measurements and BUA were demonstrated in both groups 1 and 2 (r values between 0.54 and 0.75). No significant differences in physical activity levels or body composition were demonstrated between the two patient groups. CONCLUSIONS: The present results suggest that in patients with type 1 diabetes, PN may be an independent risk factor for reduced BMD in the affected limbs as well as in the skeleton in general. (+info)
Epidemiology of Diabetes Interventions and Complications (EDIC). Design, implementation, and preliminary results of a long-term follow-up of the Diabetes Control and Complications Trial cohort.
(12/1279)
OBJECTIVE: The Diabetes Control and Complications Trial (DCCT) demonstrated the powerful impact of glycemic control on the early manifestations of microvascular complications. Contemporary prospective data on the evolution of macrovascular and late microvascular complications of type 1 diabetes are limited. The Epidemiology of Diabetes Interventions and Complications (EDIC) study is a multicenter, longitudinal, observational study designed to use the well-characterized DCCT cohort of > 1,400 patients to determine the long-term effects of prior separation of glycemic levels on micro- and macrovascular outcomes. RESEARCH DESIGN AND METHODS: Using a standardized annual history and physical examination, 28 EDIC clinical centers that were DCCT clinics will follow the EDIC cohort for 10 years. Annual evaluation also includes resting electrocardiogram. Doppler ultrasound measurements of ankle/arm blood pressure, and screening for nephropathy. At regular intervals, a timed 4-h urine is collected, lipid profiles are obtained, and stereoscopic fundus photographs are taken. In addition, dual B-mode Doppler ultrasound scans of the common and internal carotid arteries will be performed at years 1 and 6 and at study end. RESULTS: Written informed consent was obtained from 96% of the DCCT subjects. The participants, compared with nonparticipants, tended to have better glycemic control at the completion of the DCCT and were more likely to have their diabetes care provided by DCCT personnel. The EDIC baseline measurement stratified by sex delineates multiple cardiovascular disease risk factor differences such as age (older in men), waist-to-hip ratio (higher in men). HDL cholesterol (lower in men), hypertension (more prevalent in men), and maximum intimal-medial thickness of common and internal carotid arteries (thicker in men). Of the original conventional treatment group, 69% have changed to continuous subcutaneous insulin infusion or multiple daily injections. Although the mean HbA1c difference between the intensive and conventional treatment groups narrowed at EDIC years 1 and 2, HbA1c remained significantly lower in the intensive group. Of all expected clinic visits, 95% were completed, and the quality of EDIC data is very similar to that observed in the DCCT. CONCLUSIONS: Although obvious problems exist in extended follow-up studies of completed clinical trials, these are balanced by the value of continued systematic observation of the DCCT cohort. In contrast to other epidemiologic studies, EDIC will provide 1) definitive data on type 1 as distinct from type 2 diabetes; 2) reliance on prospective rather than on cross-sectional analysis; 3) long-term follow-up in a large population; 4) consistent use of objective, reliable measures of outcomes and glycemia; and 5) observation of patients from before the onset of complications. (+info)
Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings.
(13/1279)
OBJECTIVE: To determine the frequency and constellations of anatomic, pathophysiologic, and environmental factors involved in the development of incident diabetic foot ulcers in patients with diabetes and no history of foot ulcers from Manchester, U.K., and Seattle, Washington, research settings. RESEARCH DESIGN AND METHODS: The Rothman model of causation was applied to the diabetic foot ulcer condition. The presence of structural deformities, peripheral neuropathy, ischemia, infection, edema, and callus formation was determined for diabetic individuals with incident foot ulcers in Manchester and Seattle. Demographic, health, diabetes, and ulcer data were ascertained for each patient. A multidisciplinary group of foot specialists blinded to patient identity independently reviewed detailed abstracts to determine component and sufficient causes present and contributing to the development of each patient's foot ulcer. A modified Delphi process assisted the group in reaching consensus on component causes for each patient. Estimates of the proportion of ulcers that could be ascribed to each component cause were computed. RESULTS: From among 92 study patients from Manchester and 56 from Seattle, 32 unique causal pathways were identified. A critical triad (neuropathy, minor foot trauma, foot deformity) was present in > 63% of patient's causal pathways to foot ulcers. The components edema and ischemia contributed to the development of 37 and 35% of foot ulcers, respectively. Callus formation was associated with ulcer development in 30% of the pathways. Two unitary causes of ulcer were identified, with trauma and edema accounting for 6 and < 1% of ulcers, respectively. The majority of the lesions were on the plantar toes, forefoot, and midfoot. CONCLUSIONS: The most frequent component causes for lower-extremity ulcers were trauma, neuropathy, and deformity, which were present in a majority of patients. Clinicians are encouraged to use proven strategies to prevent and decrease the impact of modifiable conditions leading to foot ulcers in patients with diabetes. (+info)
Postural characteristics of diabetic neuropathy.
(14/1279)
OBJECTIVE: To explore the posturographic correlates of diabetic neuropathy by comparing the performances of three groups of diabetic patients (severe, moderate, and absent neuropathy) with those of normal subjects and four clinical control groups. RESEARCH DESIGN AND METHODS: Using the Interactive Balance System (Tetrax, Ramat Gan, Israel), based on the assessment of the interaction of vertical pressure fluctuations on four independent platforms, one for each heel and toe part, respectively, posturographic examinations were given to 28 diabetic patients (8 with severe, 12 with moderate, and 8 with no peripheral neuropathy), 30 normal control subjects, and a clinical control group of 52 patients (14 with stage II Parkinson's disease, 13 with brain damage, 7 with whiplash, and 19 with peripheral vestibular pathology). The following posturographic parameters were evaluated; 1) general stability; 2) Fourier analysis showing patterns of sway intensity within eight frequency bands between 0.1 and 3 Hz; 3) weight distribution; 4) synchronization of sway; and 5) performance patterns for eight positions, requiring closure of eyes and standing on an elastic surface, as well as left, right, back, and downward head turns. RESULTS: For positions with closed eyes, diabetic patients with severe and moderate neuropathy were significantly less stable than normal subjects and diabetic patients without neuropathy, but diabetic patients with severe and moderate neuropathy turned out to be as equally unstable as clinical control subjects. However, for sway intensity within the band of 0.5 to 1.00 Hz on positions with lateral head turn with occluded vision, neuropathic diabetic patients performed significantly worse than did both normal and clinical control subjects. The same posturographic parameter also differed significantly between normal subjects and diabetic patients without neuropathy. CONCLUSIONS: As reported in previous studies, general instability in diabetic neuropathy is not a sufficiently characteristic correlate of the syndrome. On the other hand, spectral analysis of sway on stressful positions involving head turning appears to differentiate diabetic neuropathy from other disorders involving postural disturbances. (+info)
Relationship between neuropathy, hypertension and red blood cell Na/K ATPase in patients with insulin-dependent diabetes mellitus.
(15/1279)
Hypertension has been proposed as an independent risk factor for diabetic neuropathy. In insulin-dependent diabetic (IDDM) patients suffering from neuropathy, red blood cell (RBC) Na/K ATPase is decreased. Such a decrease might be involved in the physiopathology of hypertension and therefore be the link between hypertension and neuropathy. To confirm this hypothesis, we studied 104 IDDM patients with a long duration of disease by looking at the association between neuropathy and hypertension and by comparing RBC Na/K ATPase activity in subgroups. The independent risk factors associated with neuropathy were hypertension, triglyceride level, diabetes duration and low RBC Na/K ATPase activity. Contrary to our expectations, Na/K ATPase was not decreased in hypertensive patients (294 +/- 16 nmol Pi/mg prot/h vs 303 +/- 9), but those treated with angiotensin converting enzyme (ACE) inhibitor had higher RBC Na/K ATPase activity than those treated with calcium blockers (355 +/- 15 nmol Pi/mg prot/h vs 216 +/- 10). These results confirm the association between neuropathy and hypertension, on the one hand, and neuropathy and decreased Na/K ATPase, on the other, and show that hypertension in IDDM patients was not associated with decreased RBC Na/K ATPase. Moreover, ACE inhibitor treatment in IDDM patients, whether hypertensive or not, was associated with higher levels of RBC Na/K ATPase, which could account for its beneficial effect on diabetic neuropathy. (+info)
Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers.
(16/1279)
OBJECTIVE: To identify risk factors for lower-extremity amputation (LEA) in individuals with diabetes and to estimate the incidence of LEA. RESEARCH DESIGN AND METHODS: This is a prospective study of 776 U.S. veterans in a general medicine clinic in Seattle, Washington. The outcome was first LEA during follow-up. Potential risk factors evaluated in proportional hazards models included, among others, peripheral vascular disease (PVD), sensory neuropathy, former LEA, foot deformities and ulcers, diabetes duration and treatment, and hyperglycemia. RESULTS: Associated with an increased risk for LEA were PVD defined as transcutaneous oxygen < or = 50 mmHg (relative risk [RR] = 3.0, 95% CI 1.3-7.1), insensitivity to monofilament testing (RR = 2.9, odds ratio = 1.1-7.8), lower-extremity ulcers (RR = 2.5, CI 1.1-5.4), former LEA, and treatment with insulin when controlling for duration of diabetes and other factors in the model. PVD defined as absent or diminished lower-extremity pulses or an ankle arm index < or = 0.8 was also associated with a significantly higher risk of LEA in separate models. Foot ulcers were associated with an increased ipsilateral risk of amputation. The age-adjusted incidence among men only for LEA standardized to the 1991 U.S. male diabetic population was 11.3/1,000 patient-years. CONCLUSIONS: This prospective study shows that peripheral sensory neuropathy, PVD, foot ulcers (particularly if they appear on the same side as the eventual LEA), former amputation, and treatment with insulin are independent risk factors for LEA in patients with diabetes. (+info)