bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Charcot foot
Authors: Jeffcoate W. , Lima J. , Nobrega L. 
Published: March 2003

Abstract Aims To review the clinical manifestations of the Charcot foot in diabetes mellitus, with particular reference to theories concerning aetiology. Methods Systematic review of the published literature, searching for the keywords ‘Charcot’, ‘foot and diabetes’ and ‘neuropathy’ on Medline, as well as by examination of the references in recent published reviews. Conclusions The Charcot foot of diabetes mellitus is a common problem, and yet is not widely recognized by non‐specialists. The failure of professionals to identify the condition in its early phases is probably largely responsible for the gross deformity which follows continued weight‐bearing. The condition is confined to those with severe peripheral neuropathy. It is thought to result from three factors: motor neuropathy leading to the development of abnormal forces within the foot, subsequent disorganization of the foot as a result of associated osteopenia and progressive destruction from continued weight‐bearing, enabled by reduced pain sensation. The cause of the osteopenia is not known, but it is associated with increased bone blood flow, which may be mainly the result of loss of sympathetic innervation. The importance of increased limb blood flow in the pathogenesis of the Charcot foot has been recognized for over a century. Paradoxically, the increased flow is associated with evidence of macrovascular disease, in that the prevalence of vascular calcification of pedal vessels approaches 90%. After an interval of many months, the condition tends to evolve: the increased blood flow lessens, the osteopenia is reduced and the disorganized bones become sclerotic. This tendency for the condition to evolve remains unexplained, since it would not be expected if the condition was caused solely by progressive denervation. As a result, it is suggested that another factor may be involved in the pathogenesis of the Charcot foot: an abnormal vasomotor reflex, analogous to reflex sympathetic dystrophy, occurring against a background of severe peripheral neuropathy. The resolution of the condition occurs because it is the reflex component of the hyperaemia which proves self‐limiting.
Iohexol as a marker of glomerular filtration rate in patients with diabetes: comparison of multiple and simplified sampling protocols
Authors: Pucci L. , Bandinelli S. , Pilo M. , Nannipieri M. , Navalesi R. , Penno G. 
Published: March 2003

SUMMARY Aims  To report on the reproducibility of iohexol glomerular filtration rate (GFR) estimation, to compare the plasma clearance of iohexol with that of[51Cr]EDTA and to evaluate the reliability of reduced sampling schedules in estimating GFR in Type 1 and Type 2 diabetes mellitus.Methods  Agreement was assessed in 15 Type 1 and 26 Type 2 diabetics with creatinine ranging from 53 to 564 μmol/l.Results  The regression between multiple‐sample iohexol and[51Cr]EDTA clearances was 0.999 in Type 1 and 0.987 in Type 2 diabetes (P < 0.0001 for both). A seven‐sample design and the three‐sample approach by Brøchner–Mortensen were validated by comparison with the full‐sample schedule in 87 patients (51 Type 1, 36 Type 2). Full‐sample GFR was 80.3 ± 43.8, seven‐sample 79.5 ± 43.9 (r = 0.990) and three‐sample 79.8 ± 45.2 ml.min−1.1.73 m−2 (r = 0.972). The coefficients of variation of GFR were 2.7 ± 1.4% and 3.8 ± 1.9% for the full‐sample and the seven‐sample approaches, respectively, and significantly higher for the three‐sample design (6.9 ± 3.4%, P = 0.0001).Conclusions  After iohexol injection, the Brøchner–Mortensen schedule does not provide an accurate estimate of GFR. The seven‐sample approach gives acceptable errors and allows a good estimate of GFR throughout a wide range of renal function.
Variability of glomerular filtration rate estimation using single injection methods in Type 1 diabetic patients
Authors: Siebenhofer A. , Meinitzer A. , Brandmair J. , Plank J. , Pieber T. R. 
Published: March 2003

AbstractAim  Single‐injection inulin clearance (SIIC) methods without urine collection have often been compared with classical constant‐infusion inulin clearance methods. Therefore, we used repeated SIIC measurements to prove the hypothesis of a possible overestimation or variability of inulin clearance in Type 1 diabetic patients.Methods  Two SIIC periods, glomerular filtration rate 1 and 2 (GFR 1, GFR 2) were performed consecutively on the same day. In diabetic patients, GFR 3 was measured several days later at the same time of day as the GFR 1 had been done. The calculation used a two‐compartment modelling system (TCM) which showed excellent agreement to ratio of dose over area under the curve (D/AUC) calculation.Results  Twelve normotensive Type 1 diabetic patients (mean and sd), age 39 (10.7) years, diabetes duration 20 (10.7) years, HbA1c 8.5% (0.82%), albuminuria 13.8 (15.7) mg/24 h and six controls, age 26 (2.6) years were examined. Healthy controls showed an excellent repeatability between GFR 1 111.8 (11.44) and GFR 2 110.8 (11.41) ml.min−1.1.73 m2−1. However, in diabetic patients there was a highly significant decrease between GFR 1 129.4 (11.86) and GFR 2 118.1 (13.05) ml.min−1.1.73 m2−1. GFR 1 with 129.4 (11.86) ml.min−1.1.73 m2−1 did not differ significantly from GFR 3 with 129.9 (12.40) ml.min−1.1.73 m2−1 in diabetic patients (P < 0.839).Conclusions  In contrast to normal subjects, in Type 1 diabetic patients single‐injection inulin clearance technique showed a clinically relevant decrease in GFR on two repeated measurements on the same day. Overestimation of GFR by the first inulin clearance may be caused by incomplete inulin distribution in the slow compartment.Diabet. Med. 18, 464–468 (2001)
The influence of isolated small nerve fibre dysfunction on microvascular control in patients with diabetes mellitus
Authors: Pfützner A. , Forst T. , Engelbach M. , Margin T. , Goitom K. , Löbig M. , Beyer J. , Kunt T. 
Published: March 2003

AbstractAim The aim of the study was to investigate the influence of isolated small nerve fibre dysfunction on microvascular skin blood flow and transcutaneous oxygen tension in patients with diabetes mellitus.Methods  Small nerve fibre dysfunction was assessed by the measurement of thermal and pain perception thresholds. Patients with evidence of large fibre disturbances as evaluated by means of vibration perception threshold were excluded from the study. Microvascular blood flow was investigated with laser‐Doppler‐fluxmetry (LDF) following stimulation with acetylcholine and mild thermal injury.Results  Diabetic patients with small nerve fibre injury showed a significantly reduced increase in the laser‐Doppler‐flux signal following the application of acetylcholine compared with patients without neuropathy or healthy control subjects (2.8 arbitrary units (AU) (1.3–5.5) vs. 7.2 AU (4.1–25.5); P = 0.007 and vs. 8.5 AU (3.0–17.0), P = 0.02, respectively). The increase in LDF following thermal injury was also diminished in patients with small nerve fibre dysfunction compared with patients without neuropathy or the control group (29.8 AU (17.2–46.5) vs. 51.2 AU (29.5–93.5); P = 0.02 and vs. 54.6 AU (39.7–97.7); P = 0.004, respectively). In addition, they showed a significantly reduced transcutaneous oxygen tension compared with the other groups (42.9 mmHg (41.6–55.5) vs. 56.1 mmHg (49.2–60.8); P = 0.04 and vs. 59.0 mmHg (54.6–80.3), P = 0.03, respectively).Conclusions  Our study confirms an association between small nerve fibre injury and skin microvascular dysfunction. It further underlines the concept of neurovascular disturbances in the pathogenesis of neurotrophic foot ulceration.Diabet. Med. 18, 489–494 (2001)
Audit of influenza and pneumococcal vaccination uptake in diabetic patients attending secondary care in the Northern Region
Authors: Wahid S. T. , Nag S. , Bilous R. W. , Marshall S. M. , Robinson A. C. J. 
Published: March 2003

AbstractAims  To document uptake of influenza and pneumococcal vaccination in diabetic patients attending secondary care in the Northern Region, and to explore influencing factors.Methods  Diabetic patients attending out‐patients in Middlesbrough, Gateshead and Newcastle were questioned from October 1999 to March 2000. Physicians enquired about influenza and pneumococcal vaccination status using a standardized questionnaire. Data collected included age, year of diagnosis, duration of diabetes, type of diabetes, and the presence of other recognized indications for vaccination.Results  Two hundred and sixty‐eight diabetic patients, 42% (113/268) with Type 1 diabetes, 34% (91/268) with ischaemic heart disease, 10% (26/268) with chronic pulmonary disease (CPD) and 10% (27/268) with chronic renal disease, were questioned. Thirty‐five percent (93/268) of patients received both influenza and pneumococcal vaccines, 24% (64/268) received only influenza vaccine, and none received pneumococcus vaccine alone. Most vaccinees received advice about influenza and pneumococcal vaccination from their general practitioner (90% (142/157) and 87% (81/93), respectively). A large number of non‐vaccinees were unaware of the need for influenza and pneumococcal vaccination (69% (76/111) and 91% (159/175), respectively). Using multiple logistic regression co‐existing CPD increased the odds of receiving influenza (odds ratio (OR) (95% confidence interval (CI)) = 1.99 (1.07–14.12)) or pneumococcal (OR = 3.77 (1.69–21.76)) vaccination. Furthermore, each 1‐year increase in age increased the chance of receiving influenza or pneumococcal vaccination by 22% (OR = 1.22 (1.09–1.67) and 29% (OR = 1.29 (1.07–1.72)), respectively.Conclusions  Vaccination rates in these diabetic patients are unsatisfactory. Secondary care health professionals might increase rates by raising the topic in consultations.Diabet. Med. 18, 599–603 (2001)
Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb‐threatening diabetic foot infection
Authors: Pellizzer G. , Strazzabosco M. , Presi S. , Furlan F. , Lora L. , Benedetti P. , Bonato M. , Erle G. , De Lalla F. 
Published: March 2003

AbstractAims  The results of ulcer swabbing vs. deep tissue biopsy have been compared prospectively in 29 diabetic patients with limb‐threatening foot infection, to investigate the effectiveness and reliability of each method, and to evaluate whether any of the two could be more suitable for the microbiological follow‐up of severe lesions.Methods  Microbiological samples were collected by using both methods at fixed intervals after therapy commencement (i.e. at day 0, 7, 14, and 30). Statistical comparison was performed between the results of each sampling procedure after the end of follow‐up.Results  At enrolment, the mean number of isolates per patient was 2.34 by swabbing and 2.07 by tissue biopsy sampling; the rate of isolation for anaerobes with the two methods was 35% and 25%, respectively; no statistical differences could be observed between the two procedures in terms of either species or frequency of isolation. Anaerobic species were never detected after the first 2 weeks of appropriate treatment, and those ulcers which were still active at day 30 yielded almost exclusively Gram‐positive bacteria. At the end of follow‐up, deep tissue cultures appeared to exhibit a higher diagnostic sensitivity with respect to swabs.Conclusions  Swabbing and deep tissue cultures appear to be equally reliable for the initial monitoring of antimicrobial treatment in severe diabetic foot infection. However, our experience seems to suggest that deep tissue might be more sensitive than swabbing for monitoring those isolates that have been selected for antibiotic resistance, i.e. those from ulcers that are still active after 30 days of treatment.Diabet. Med. 18, 822–827 (2001)
Assessing diabetic control — reliability of methods available in resource poor settings
Authors: Rotchford A. P. , Rotchford K. M. , Machattie T. , Gill G. V. 
Published: March 2003

AbstractAims and methods To examine the reliability of random venous or capillary blood glucose testing, random urine glucose testing, and a current symptom history in predicting a high HbA1c in Type 2 diabetic patients taking oral hypoglycaemic agents in a poorly controlled rural African population.Results For a cut‐off point for HbA1c of ≥ 8%, for random venous plasma glucose of ≥ 14 mmol/L (present in 47.2% of subjects), specificity was 97.1% (95% CI 85.1–99.9), sensitivity 56.8% (48.8–64.5) and positive predictive value (PPV) 98.9% (94.2–99.9). HbA1c≥ 8% is predicted by a random capillary blood glucose of 17 mmol/L (present in 28.4% of subjects) with specificity 100% (90.0–100.0), PPV 100% (93.7–100.0) and sensitivity of 34.3% (27.2–42.1). HbA1c≥ 8% is predicted by the presence of heavy glycosuria (≥ 55 mmol/L) (present in 35.6%) with specificity 94.1% (80.3–99.3), sensitivity of 41.9% (34.1–49.9) and PPV 97.1% (89.9–99.6). Polyuria/nocturia (present in 31.3%) was the only symptom found to be associated with poor control, with a specificity for predicting HbA1c of ≥ 8% of 81.5% (61.9–93.7), PPV 89.1% (76.4–96.4) and sensitivity 30.6% (22.9–39.1).Conclusions Where resources are short, random glucose testing can be used to detect a significant proportion of those with the worst control with a high degree of specificity enabling primary care staff to modify treatment safely. Where facilities are limited capillary blood or urine testing with reagent strips, may be substituted for venous plasma testing in the laboratory. A symptom history was insufficient to replace biochemical testing, but where this is unavailable, urinary symptoms may be helpful.Diabet. Med. 19, 195–200 (2002)
Cystic fibrosis‐related diabetes: the role of peripheral insulin resistance and β‐cell dysfunction
Authors: Yung B. , Noormohamed F. H. , Kemp M. , Hooper J. , Lant A. F. , Hodson M. E. 
Published: March 2003

AbstractAims The goal of this study was to identify the glycaemic status and investigate the roles of peripheral insulin resistance (IR) and pancreatic β‐cell dysfunction in the pathogenesis of cystic fibrosis‐related diabetes (CFRD) in adult cystic fibrosis (CF) patients with no previous history of glycaemic disturbances.Methods The glucose tolerance status of 68 CF patients was determined using 2‐h oral glucose tolerance tests (OGTTs). Peripheral IR was measured using the homeostasis model assessment for insulin resistance (HOMA‐IR) in the CF group and 46 normal healthy control subjects. Pancreatic β‐cell function, calculated as the ratio between the 30‐min increment in plasma insulin and the corresponding 30‐min post‐OGTT plasma glucose concentration, was also measured in a subset of 30 CF patients and 16 normal healthy controls. Extended 180‐min OGTTs, with frequent plasma glucose and insulin sampling, were also undertaken in 24 CF patients and eight normal healthy controls to determine glucose‐induced insulin response.Results Of the 68 CF patients studied, 41, 18 and nine were found to have normal, impaired and diabetic glucose tolerances, respectively. The mean HOMA‐IR values (mU/mmol) in the CF patients, as a whole, were not significantly different compared with the normal healthy controls (CF 2.2 ± 1.1 vs. control 1.8 ± 0.9; NS). Within the CF group, glycaemic status had no impact on HOMA‐IR (mU/mmol): 2.2 ± 1.2 (normal glucose tolerance); 2.0 ± 1.0 (impaired glucose tolerance); and 2.3 ± 1.1 (diabetic glucose tolerance). β‐cell function (mU/mmol) was not only significantly lower in the CF group (CF 1.65 ± 1.8; P < 0.001) but also in the CF group with normal glucose tolerance (2.25 ± 2.10; P < 0.01) compared with healthy control (4.98 ± 2.38). Mean plasma glucose concentrations were generally higher and mean plasma insulin concentrations lower in the CF group as a whole when compared with normal healthy controls. Within the CF group, there was a progressive decline in glucose‐induced insulin release with worsening glycaemic status.Conclusions A lack of difference in peripheral IR, measured using HOMA‐IR, in the CF group and healthy controls or within the CF group with differing glycaemic status suggests that IR does not have a significant role in the pathogenesis of CFRD. Pancreatic β‐cell function, already subnormal in CF patients with OGTT‐defined normal glucose tolerance status, deteriorated further with worsening glycaemic status. This suggests that insulinopenia plays a prominent role in the pathogenesis of glucose intolerance and subsequent development of CFRD.
No evidence for accumulation of insulin glargine (LANTUS®): a multiple injection study in patients with Type 1 diabetes
Authors: Heise T. , Bott S. , Rave K. , Dressler A. , Rosskamp R. , Heinemann L. 
Published: March 2003

AbstractAimsInsulin glargine is a long‐acting insulin analogue that is metabolically active for at least 24 h. We investigated the multiple‐dose pharmacokinetic properties of insulin glargine to determine whether daily injections lead to the accumulation of circulating insulin levels and a corresponding decrease in blood glucose levels in patients with Type 1 diabetes.MethodsFifteen patients using preprandial insulin lispro (mean age 36 ± 9 years, body mass index 24.6 ± 2.2 kg/m2) completed the study. Each patient’s optimal insulin glargine dose was determined during a dose‐finding phase. After a washout period, patients were treated over 12 days with a constant daily dose of insulin glargine injected in the abdominal subcutaneous adipose tissue at 22:00 h, and with preprandial insulin lispro. Free serum insulin (FSI) and blood glucose concentrations were assessed hourly after the first, fourth, and eleventh injection, after which patients fasted for 24 h and did not use any other insulin preparation.ResultsThere were no changes in daily insulin doses during the dose‐finding phase (insulin glargine: initial dose 24 ± 6 IU, mean change 0 ± 3 IU; insulin lispro: 18 ± 9 IU, 0 ± 7 IU). The time course of FSI was comparable on the three pharmacokinetic study days. Notably, the trough FSI at the end of the sampling periods was almost identical (day 1, 79 ± 56 pmol/l, day 4, 77 ± 56 pmol/l, day 11, 86 ± 60 pmol/l). No changes occurred in any of the pharmacokinetic parameters studied.ConclusionsThere is no evidence that insulin glargine accumulates after multiple injections over 12 days. These results indicate that the predetermined dose of insulin glargine will not need to be reduced after commencing treatment because of a risk of accumulation.
Clinical outcome of diabetes patients hospitalized with foot ulcers, Dar es Salaam, Tanzania
Authors: Gulam‐Abbas Z. , Lutale J. K. , Morbach S. , Archibald L. K. 
Published: March 2003

AbstractAims To determine the prevalence rate, clinical features, risk factors, and clinical outcome of foot ulcers in diabetes patients admitted to Muhimbili National Hospital, Dar es Salaam, Tanzania.Methods A prospective cohort study of newly hospitalized, adult diabetes patients with foot ulcers was conducted during January 1997 to December 1998 (study period). Detailed clinical and epidemiological data were recorded for each patient, followed by a comprehensive physical examination. Clinical outcome was documented.Results Of 627 diabetes patients evaluated during the study period, 92 (15%) had foot ulcers. Of these 92 patients, 30 (33%) were selected for surgery (minor and major amputations); the rest were managed conservatively. Patients who underwent surgery were more likely than those who did not to have gangrene (P < 0.001) or neuropathy (P < 0.01). On stratification by severity of ulcers, patients with Wagner score ≥ 4 were significantly more likely than those < 4 to have neuroischaemic foot lesions (P < 0.001) or delayed presentation to hospital (P < 0.001). The overall mortality rates for amputees and non‐amputees were similar (29%); the highest in‐patient mortality rate (54%) was observed among patients with severe (Wagner grade ≥ 4) ulcers who did not undergo surgery.Conclusions Diabetic foot ulcers are associated with significant morbidity and mortality in Tanzania. Mortality rates among patients with severe ulcers remain high despite surgery. Thus, surgery undertaken during the less severe stages of ulcers may improve patient outcome. Education of patients should underscore the importance of foot care and consulting a doctor during the early stages of foot ulcer disease.
Adherence to oral hypoglycaemic agents prior to insulin therapy in Type 2 diabetes
Authors: Evans J. M. M. , Donnan P. T. , Morris A. D. 
Published: March 2003

AbstractAim To investigate whether patients require insulin as a result of poor adherence to oral hypoglycaemic agents (OHAs) in Type 2 diabetes.Methods A diabetes information system and a database of drugs dispensed for the study period 1993–1996 were used in Tayside, Scotland (population 400 000). Patients aged over 34 years with Type 2 diabetes who had at least 6 months exclusive therapy with OHAs (sulphonylureas or metformin) prior to insulin treatment were identified. Intended duration of every OHA prescription was calculated from prescription details. Adherence was estimated by dividing total intended duration of OHA therapy by study time for each patient, and compared between those who did and did not convert to insulin.Results There were 2537 patients on sulphonylureas (51% male, mean age 67 years). There was improved adherence in the 262 patients who commenced insulin, who had mean adherence of 88.3% (95% confidence interval (CI) 85.9–90.6%) compared with the remaining 2275 patients whose mean adherence was 87.4% (95% CI 86.7–88.2%). In a logistic regression analysis, the adjusted odds ratio (OR) for commencing insulin was 1.20 (95% CI 1.07–1.35) for a quartile increase in adherence. There were 1519 patients on metformin (49% male, mean age 64 years). Mean adherence was 79.7% (95% CI 76.4–83.1%) and 83.1% (95% CI 82.0–84.1%) in 169 patients who did and 1350 who did not commence insulin, respectively, with an adjusted OR for a quartile increase in adherence of 0.91 (95% CI 0.78–1.07).Conclusion Despite suboptimal adherence to OHAs in Type 2 diabetes, this is not associated with subsequent requirement for insulin.Diabet. Med. 19, 685–688 (2002)
The pathogenesis and management of painful diabetic neuropathy: a review
Authors: Spruce M. C. , Potter J. , Coppini D. V. 
Published: March 2003

AbstractPainful diabetic neuropathy has always been a challenging complication of diabetes mellitus. Emerging theories suggest that early dysaesthesia associated with painful neuropathy may act as a marker for the development of the ‘at risk’ foot, allowing preventative clinical strategies to be undertaken. The mechanisms of neuropathic pain are complex. The authors’ intentions are to help members of the diabetes care team better understand and appreciate the diverse symptoms reported by patients. The various treatments available for painful neuropathy are discussed in detail. Robust comparative studies on such treatments are, however, unavailable and the authors have designed a logical approach to management based on best current evidence and their own clinical experience.