Treating diabetes with islet transplantation: lessons from the past decade in Lille.

Type 1 diabetes (T1D) is due to the loss of both beta-cell insulin secretion and glucose sensing, leading to glucose variability and a lack of predictability, a daily issue for patients. Guidelines for the treatment of T1D have become stricter as results from the Diabetes Control and Complications Trial (DCCT) demonstrated the close relationship between microangiopathy and HbA1c levels. In this regard, glucometers, ambulatory continuous glucose monitoring, and subcutaneous and intraperitoneal pumps have been major developments in the management of glucose imbalance. Besides this technological approach, islet transplantation (IT) has emerged as an acceptable safe procedure with results that continue to improve. Research in the last decade of the 20th century focused on the feasibility of islet isolation and transplantation and, since 2000, the success and reproducibility of the Edmonton protocol have been proven, and the mid-term (5-year) benefit-risk ratio evaluated. Currently, a 5-year 50% rate of insulin independence can be expected, with stabilization of microangiopathy and macroangiopathy, but the possible side-effects of immunosuppressants, limited availability of islets and still limited duration of insulin independence restrict the procedure to cases of brittle diabetes in patients who are not overweight or have no associated insulin resistance. However, various prognostic factors have been identified that may extend islet graft survival and reduce the number of islet injections required; these include graft quality, autoimmunity, immunosuppressant regimen and non-specific inflammatory reactions. Finally, alternative injection sites and unlimited sources of islets are likely to make IT a routine procedure in the future.

Management of diabetic foot ulcers with a TLC-NOSF wound dressing.

OBJECTIVE: To evaluate the efficacy, tolerance and acceptability of UrgoStart Contact (Laboratoires Urgo), a new wound dressing impregnated with NOSF, as an MMP regulator in the management of neuropathic diabetic foot ulcers. METHOD: A multicentre, pilot, prospective, non-controlled open-label clinical trial. Adult patients with type 1 or 2 diabetes mellitus, who had a grade 1A (Texas classification), uninfected, neuropathic foot ulcer, 1-15cm2 in size and of 1-20 months' duration (mean 6.7 ± 5.2 months) were included in the study. The primary endpoint was the relative reduction of the wound surface area (%) at the end of the study. Secondary endpoints included rate of complete healing, and tolerability and acceptability of the dressing. The wound dressing was changed regularly at the investigator's discretion, in accordance with the wound status and exudate level. Patients were followed up every 2 weeks for a 12-week period. At each visit, patients underwent clinical assessments, and ulcer surface area was measured by planimetry and photographs. RESULTS: Thirty-four diabetic patients with a neuropathic foot ulcer were included but only 33 cases were analysed, as data were completely lost for one patient. At baseline, mean surface area was 2.7±2.4cm2. At the 12-week follow-up, the median surface area reduction was 82.7% (mean reduction 62.7 ± 49.9%) and in 10 of the 33 analysed patients (30%) the wound was healed. Only two of the seven documented local adverse events were deemed to be dressing related. According to the nursing staff, acceptability was considered very satisfactory, particularly in term of conformability and ease of use. CONCLUSION: This pilot study indicates that use of the new UrgoStart Contact dressing, combined with offloading and debridement,may help promote the healing process of the neuropathic diabetic foot ulcers, and was well tolerated and accepted.

A proof-of-concept study of the effectiveness of a removable device for offloading in patients with neuropathic ulceration of the foot: the Ransart boot.

AIM: To undertake a proof-of-concept study to determine whether a removable offloading device (the Ransart boot) for the management of diabetic foot ulcers (DFU) was as effective as reports of non-removable devices. RESEARCH DESIGN AND METHODS: This observational study used the Ransart boot for patients with DFU, in seven specialist centres. If a patient had two or more ulcers, one was selected as the index ulcer. Ulcers were classified by the University of Texas (UT) system. RESULTS: There were 135 patients (mean age 60.3 +/- 11.4 years); 96 (71.1%) male. Median ulcer duration at presentation was 90 [interquartile range (IQR) 30-1825] days. Seven were lost to follow-up, seven developed other major illnesses and four died; outcomes were documented in the remaining 117. Eighty-two (70.1% of 117) healed, after a median (IQR) 60 (43-99) days, while 22 (18.8%) ulcers were resolved by amputation (one major). The remaining 13 (11.1%) patients were judged non-compliant. There was a close correlation between ulcer classification at baseline and both time to healing (P < 0.001 chi(2)-test) and amputation (P < 0.001; Spearman's rank correlation coefficient). There was a positive correlation between ulcer duration at presentation and time to healing (P < 0.02), UT class (P < 0.01), glycated haemoglobin (P < 0.02) and amputation (P < 0.04). CONCLUSIONS: Time to healing and incidence of amputation were comparable with those previously reported for non-removable devices. Given that a removable device is much more acceptable to the patient, the effectiveness, cost and acceptability of the removable devices, such as the Ransart boot, need to be compared with a non-removable device in a randomized trial. Diabet. Med. 26, 778-782 (2009).

Comparison between Leukoscan (Sulesomab) and Gallium-67 for the diagnosis of osteomyelitis in the diabetic foot.

OBJECTIVES: The diagnosis of osteomyelitis in patients with diabetic foot is difficult both clinically and radiologically. An early diagnosis is crucial to optimize therapeutic strategy. Among the diagnostic methods currently used, scintigraphy with ex-vivo labelled white blood cells is the gold standard, but cannot be performed in all centers; therefore 67Gallium citrate (67Ga) imaging in combination with a bone scintigraphy is still widely used. METHOD: The results of imaging 24 diabetic patients with 31 suspected osteomyelitic lesions using the antigranulocyte Fab' fragment (Sulesomab or LeukoScan or immunoscintigraphy) were prospectively compared with results from the bone scan coupled with 67Ga. The diagnosis of osteomyelitis was confirmed by either biopsy or follow-up, radiological imaging and clinical outcome. RESULTS AND CONCLUSION: Sulesomab correctly identified 12 of 18 osteomyelitic lesions while 67Ga was able to detect only 8 of 18. Therefore the sensitivity is 67% for Sulesomab and 44% for 67Ga. Among the 13 non-osteomyelitic lesions imaging with Sulesomab was able to rule out infection in 11 cases and 67Ga in 10 cases. The specificity is therefore 85% for Sulesomab and 77% for 67Ga. Image interpretation for Sulesomab in this group of patients is occasionally suboptimal when imaging is performed at 3 hours post injection. High vascular background in the early images may obscure infection especially in small bones. Practically, scintigraphy with Sulesomab is fast and simple due to ease of labeling, no ex-vivo handling of blood, low radiation and provides rapid diagnosis. The diagnosis of osteomyelitis obtained by the antibody fragment scintigraphy influences the management (guided biopsy) and therapy. In several patients, imaging with Sulesomab was able to rule out osteomyelitis, helping to avoid useless antibiotic therapy and its associated side effects.

Pregnancy induced hypertension in women with gestational carbohydrate intolerance: the diagest study.

OBJECTIVE: To determine the relationship between pregnancy induced hypertension (PIH) and gestational glucose intolerance. METHODS: A 50g, 1h glucose loading test was offered to all pregnant women between 24 and 28 weeks of gestation in 15 centres in northern France during 8 months in 1992. If the test was positive (> or =7.2 mmol/l), the woman underwent a 3h oral glucose tolerance test (OGTT) as soon as possible. Using the criteria of Carpenter and Coustan, gestational diabetes mellitus (GDM) was defined by two abnormal values (n=218) and gestational mild hyperglycemia (GMH) by one abnormal value (n=130). Each control group was defined by a 50g, 1h loading test result of <7.2 mmol/l (n=108).PIH included gestational hypertension (GH) and preeclampsia (PE). GH was defined as a diastolic pressure of more than 85 mmHg on at least two occasions arising during pregnancy. PE was defined as GH with proteinuria > or =500 mg/24h. RESULTS: The rate of PIH in the three groups (GDM; GMH and control group, C) was, respectively 17.0, 10.8, and 4.6%. All the six PE occurred in the GDM group. Univariate analysis showed significantly higher rate of hypertension in women with a history of PE, increasing body mass index before pregnancy (BMI) and glucose intolerance. In multivariate analysis with adjustment for primiparity, independent risk factors for PIH were a history of PE, BMI>27 and GDM, contrary to GMH and maternal age. CONCLUSIONS: PIH appears to be linked to the level of glucose intolerance during pregnancy, independently of other known factors of hypertension.

[Are the principles of treatment of chronic osteitis applicable to the diabetic foot?]. / Les principes du traitement de l'ostéite chronique sont-ils applicables au pied diabétique?

OBJECTIVE: The interest of the management of bone infections in the diabetic foot, inspired by the recommendations for the treatment of chronic osteitis, was assessed in this study. METHODS: Twenty bone infections in 17 diabetic patients with moderate to mild infections of the feet were confirmed by the results of X-ray and/or scintigraphic studies and bone surgery biopsy cultures revealing one or more bacteria sensitive to standard osteitis treatment (rifampicine + fluoroquinolone). The patients had received this treatment per os for a median duration of 6 months (3 to 10 months). Clinical follow-up was carried out during a consultation at 1, 3 and 6 months during treatment and then by telephone every six months after the end of treatment. Clinical success was defined as the disappearance of any local sign of infection and by the absence of relapse during the post-treatment follow-up period. The evolution of the bone infection was also assessed by the results of a control conducted 3 to 6 months after initiation of the antibiotic treatment. RESULTS: At the end of the treatment, all signs of infection had disappeared in 15/17 patients (88.2%) and no relapse had occurred in 14 (82.3%) patients at the end of a median post-treatment period of 22 months (12 to 41 months). Resection of necrotic bone was performed at the same time as the bone biopsy in 2 patients. The median duration of hospitalisation was of 14 days (3 to 53 days). During the study, a multi-resistant germ was isolated in 4 patients (1 Pseudomonas aeruginosa, 3 Staphylococcus aureus). During the post-treatment follow-up, 3 patients dies from causes unrelated to the infection treated. No serious adverse event was reported during the study. DISCUSSION: The results of this pilot study support the rationale of applying the treatment regimens of chronic osteitis to diabetic lesions of the feet, but are only applicable to comparable patients presenting with non-severe lesions of the feet. Moreover, the use of antibiotics with potent selection of resistance such as rifampicine and fluoroquinolone, requires that bone biopsies be taken, which is not easy in all the diabetic foot care centres. We are presently conducting a study to identify the sub-populations of diabetic patients who could benefit from such treatment.