Mutations in the ABCC8 gene can cause autoantibody-negative insulin-dependent diabetes.

Activating mutations in genes KCNJ11 and ABCC8, which form the ATP-sensitive K+channel (K(ATP) channel), have been shown to cause transient or permanent neonatal diabetes. We describe here a rather different phenotype: two cases of adult diabetic patients-considered and treated as insulin-dependent diabetic patients since adolescence-who, in fact, turned out to be heterozygous for an ABCC8 mutation and able to successfully discontinue insulin while taking sulphonylurea treatment.

Incidence and characteristics of lower limb amputations in people with diabetes.

AIMS: To estimate the incidence, characteristics and potential causes of lower limb amputations in France. METHODS: Admissions with lower limb amputations were extracted from the 2003 French national hospital discharge database, which includes major diagnoses and procedures performed during hospital admissions. For each patient, diabetes was defined by its record in at least one admission with or without lower limb amputation in the 2002-2003 databases. RESULTS: In 2003, 17 551 admissions with lower limb amputation were recorded, involving 15 353 persons, which included 7955 people with diabetes. The crude incidence of lower limb amputation in people with diabetes was 378/100 000 (349/100 000 when excluding traumatic lower limb amputation). The sex and age standardized incidence was 12 times higher in people with than without diabetes (158 vs. 13/100 000). Renal complications and peripheral arterial disease and/or neuropathy were reported in, respectively, 30% and 95% of people with diabetes with lower limb amputation. Traumatic causes (excluding foot contusion) and bone diseases (excluding foot osteomyelitis) were reported in, respectively, 3% and 6% of people with diabetes and lower limb amputation, and were 5 and 13 times more frequent than in people without diabetes. CONCLUSIONS: We provide a first national estimate of lower limb amputation in France. We highlight its major impact on people with diabetes and its close relationship with peripheral arterial disease/neuropathy and renal complications in the national hospital discharge database. We do not suggest the exclusion of traumatic causes when studying the epidemiology of lower limb amputation related to diabetes, as diabetes may contribute to amputation even when the first cause appears to be traumatic.

A systematic review of the effectiveness of interventions to enhance the healing of chronic ulcers of the foot in diabetes.

The outcome of management of diabetic foot ulcers is poor and there is uncertainty concerning optimal approaches to management. We have undertaken a systematic review to identify interventions for which there is evidence of effectiveness. A search was made for reports of the effectiveness of interventions assessed in terms of healing, ulcer area or amputation in controlled clinical studies published prior to December 2006. Methodological quality of selected studies was independently assessed by two reviewers using Scottish Intercollegiate Guidelines Network (SIGN) criteria. Selected studies fell into the following categories: sharp debridement and larvae; antiseptics and dressings; chronic wound resection; hyperbaric oxygen (HBO); reduction of tissue oedema; skin grafts; electrical and magnetic stimulation and ultrasound. Heterogeneity of studies prevented pooled analysis of results. Of the 2251 papers identified, 60 were selected for grading following full text review. Some evidence was found to support hydrogels as desloughing agents and to suggest that a systemic (HBO) therapy may be effective. Topical negative pressure (TNP) may promote healing of post-operative wounds, and resection of neuropathic plantar ulcers may be beneficial. More information was needed to confirm the effectiveness and cost-effectiveness of these and other interventions. No data were found to justify the use of any other topically applied product or dressing, including those with antiseptic properties. Further evidence to substantiate the effect of interventions designed to enhance the healing of chronic ulcers is urgently needed. Until such evidence is available from robust trials, there is limited justification for the use of more expensive treatments and dressings.

Diabetic foot osteomyelitis.

Bone infection in the diabetic foot is always a complication of a preexisting infected foot wound. Prevalence can be as high as 66%. Diagnosis can be suspected in two mains conditions: no healing (or no depth decrease) in spite of appropriate care and off-loading, and/or a visible or palpated bone with a metal probe. The first recommended diagnostic step is to perform (and if necessary to repeat) plain radiographs. After a four-week treatment period, if plain radiographs are still normal, suspicion for bone infection will persist in case of bad evolution despite optimized management of off-loading and arterial disease. It is only in such cases that other diagnosis methods than plain radiographs must be used. Staphylococcus aureus is the most common pathogen cultured from bone samples, followed by Staphylococcus epidermidis. Among enterobacteriaceae, Escherichia coli, Klebsiella pneumonia and Proteus sp. are the most common, followed by Pseudomonas aeruginosa. Surprisingly, bacteria usually considered contaminant (as coagulase negative staphylococci (CNS) and Corynebacterium sp.) have been documented to be pathogens in the osteomyelitis of diabetic foot. Traditional approach to treatment of chronic osteomyelitis was by surgical resection of infected and necrotic bone. But new classes of antibiotics have both the required spectrum of activity and the capacity to penetrate and concentrate in the infected bone. Recently, several observations of osteomyelitis remission following non-surgical management with a prolonged course of antibiotics have been published. Lastly, combined approach with local bone excision and antibiotics has been proposed. Prospective trials should be undertaken to determine the relative roles of surgery and antibiotics in managing diabetic foot osteomyelitis.

Insulin therapy for type 2 diabetes: premixed or basal-prandial?

It is logical to begin type 2 insulin therapy with an injection of an intermediate-acting or a long-acting insulin at bedtime, but one should treat to target, i.e. aim at fasting glycaemias lower than 1.20 g/l to obtain an HbA(1c) close to 7%. Nevertheless, basal insulin therapy does not prevent progression to insulin-secretory deficiency. If necessary, recourse should be made to multiple-injection protocols, taking into account postprandial hyperglycaemia. For every level of HbA(1c), the suppression of postprandial hyperglycaemia, 1 point of HbA(1c) can be gained in theory, whereas reducing the fasting glycaemia to values of less than 1.10 g/l reduces HbA(1c) to close to 7%, whatever the initial level of HbA(1c). However, when a diabetic is clearly not controlled, the preprandial acting use of rapid analogues allows the fasting glycaemia to be improved significantly. Inversely, an early treatment with basal insulin, by correcting glucotoxicity, can also decrease postprandial hyperglycaemia. Many industry-sponsored studies comparing insulin therapy regimens show annoying biased interpretations of results. It does not seem pertinent to compare a single injection with two or even three injections, nor to compare an efficient titration with an inefficient titration or to eliminate oral drugs, in particular sulphonylureas combined with a basal insulin. If premix insulins can give satisfactory results in patients who maintain a sufficient residual insulin-secretion, we think it would be preferable to adopt the basal-prandial regimen and a step-by-step escalating therapy. The first stage consists in combining oral therapy with an injection of NPH insulin or a long-acting analogue at bedtime, aiming at a fasting glycaemia of less than 1.20 g/l. In the next stages, a single injection of rapid-acting insulin analogue is added each time. The main advantage of this regimen is to fix a target adapted to each injection and, as a result, to facilitate forced titration of the doses.

Should diabetic patients be asked to test their blood glucose 90 to 120 minutes after the beginning of their meals?

There are three distinct objectives in reducing the post-prandial blood glucose peaks: 1st to reduce the risk of foetal macrosomia in pregnancy, 2nd to reduce cardiovascular morbi-mortality, 3rd to lower the HbA1c. With 6-7 glycaemic controls per day and fractionning their meals, motivated women with gestational diabetes reach this goal. But there is no data today directly proving that post-prandial glycaemia is specifically related to the development of micro and macrovascular complications. So to reduce the cardiovascular risk, there are more arguments in favour of lowering HbA1c or prescribing statins than in prescribing a hypoglycaemic drug acting selectively on post-prandial glycaemia. Lastly, to reduce HbA1c near to the goal of 7%, the most important is to reduce the preprandial glycaemia below 1.20 g/l. The patients must be required to monitor their post-prandial glycaemia 2 hours after the beginning of the meal only when the aim is to lower the HbA1c below 7% or 6.5%, for example during pregnancy, or in case of discrepancy between glycaemia at 8 a.m. and 7 p.m. (below 1.20 g/)l and HbA1c (above 7%). In other cases, in type 2 diabetes, two glycaemias per day, fasting and vesperal, seems sufficient.

Percutaneous transluminal angioplasty in severe diabetic foot ischemia: outcomes and prognostic factors.

OBJECTIVES: To evaluate the outcomes of severe ischemic diabetic foot ulcers for which percutaneous transluminal angioplasty (PTA) was considered as the first-line vascular procedure. Factors associated with successful PTA were sought. RESEARCH DESIGN AND METHODS: In 32 consecutive diabetic patients with foot ulcers and severe limb ischemia, PTA was performed if feasible; if not, primary bypass grafting was done when feasible. All patients were followed until healing or for at least one year. Patients with worsening ulcers after PTA underwent bypass grafting. Clinical and angiographic factors influencing outcomes after PTA were sought by univariate and multivariate analysis. RESULTS: PTA was done in 25 of the 32 (78%) patients, and considered clinically successful in 13 (52%). After 1 year, the healing rate was 70% and the limb salvage rate 90%. Successful PTA was significantly associated with a higher post-PTA transcutaneous oxygen pressure (P = 0.03) and presence of at least one patent pedal vessel (P = 0.03) in the univariate analysis; only a patent pedal vessel was significant in the multivariate analysis. CONCLUSION: Primary PTA in diabetic patients with severe ischemic foot ulcers provides similar outcomes to usual results obtained in severe ischemia in absence of diabetes. The presence of one patent pedal vessel on arteriography before PTA is the best prognostic factor.

Diabetic foot ulcer and multidrug-resistant organisms: risk factors and impact.

AIMS: The primary objective was to characterize factors allowing the colonization of diabetic foot wounds by multidrug-resistant organisms (MDRO), and the secondary objective was to evaluate the influence of MDRO colonization/infection on wound healing. METHODS: In 180 patients admitted to a specialized diabetic foot unit, microbiological specimens were taken on admission. Potential risk factors for MDRO-positive specimens were examined using univariate and multivariate analyses. Prospective follow-up data from 75 patients were used to evaluate the influence of MDRO colonization/infection on time to healing. RESULTS: Eighteen per cent of admission specimens were positive for MDRO. MDRO-positive status was not associated with patient characteristics (age, sex, type of diabetes, complications of diabetes), wound duration, or wound type (neuropathic or ischaemic). In the multivariate analysis, the only factors significantly associated with positive MDRO status on admission were a history of previous hospitalization for the same wound (21/32 compared with 48/148; P = 0.0008) or the presence of osteomyelitis (22/32 compared with 71/148; P = 0.025). In the longitudinal study of 75 wounds, MDRO-positive status on admission or during follow-up (6 months at least or until healing, mean 9 +/- 7 months) was not associated with time to healing (P = 0.71). CONCLUSION: MDROs are often present in severe diabetic foot wounds. About one-third of patients with a history of previous hospitalization for the same wound, and 25% of patients with osteomyelitis, had MDRO-positive specimens. This suggests that hygiene measures, or isolation precautions in the case of admission of patients presenting with these characteristics, should be aggressively implemented to prevent cross-transmission. Positive MDRO status is not associated with a longer time to healing.

[Understanding patients to promote self-regulation in Type 2 diabetes: how to live with an illness beginning before its onset?]. / Comprendre les patients pour promouvoir l'autorégulation dans le diabète de type 2: vivre avec une maladie évolutive qui commence avant son début.

The characteristics of Type 2 diabetes raise major questions on patients' behaviours and their determinants. The goal of this paper is to integrate recent empirical results of behavioural sciences and modern medical therapeutics in diabetes. We should consider all factors which may influence behavioural self-care while refer less to the normative logic of compliance. Behavioural sciences have demonstrated that various central factors should be considered to promote health behaviours in Type 2 diabetes: namely negative emotions, coping, personal models of illness and risk perception. All these concepts may constitute targets of practical interventions. These can either improve the quality of life, modify or individualise diabetes constraints, improve the focus of medical information given to the patient, favour a better acceptation of illness or a more active role towards diabetes. Self-monitoring of blood glucose and introduction of insulin may influence psychological determinants of self-care behaviours. These arguments are followed by a set of recommendations for the clinician and the researcher.

Comparison of two diagnostic tests for gestational diabetes in predicting macrosomia.

OBJECTIVES: To validate a diagnostic test for gestational diabetes which predicts the risk of macrosomia. METHODS: A prospective study was carried out among 354 women at risk for gestational diabetes to compare two glucose tests diagnosing pregnancies at risk of macrosomia. The "practical" test consisted in glucose measurement in the fasting state and two hours after an usual breakfast and the "reference" test was the test proposed in France (O'Sullivan test with or without a 100 g oral glucose tolerance test). Both tests were made between the 24(th) and 28(th) week of gestation. Women at high risk for macrosomia were treated. The first assessment criterion was macrosomia (babies large for gestational age). Because of the presence of women treated for gestational diabetes in our sample, the sensitivity and specificity of the tests in diagnosing pregnancies at risk of macrosomia were calculated using either the incidence of macrosomia observed in our population, or the incidence of macrosomia observed theoretically in the absence of treatment (22% in literature). RESULTS: Macrosomia was diagnosed in 49 neonates (14%). The "practical" test was significantly more sensitive than the reference test (respectively 46.9% versus 16.3%, p=0.0001 in the first case, and 54.3% versus 20.1%, p=0.0001 in the second case). The "reference" test was significantly more specific than the "practical" test (respectively 80% versus 68.2%, p=0.0001 in the first case, and 80.6% versus 70%, p=0.0001 in the second case). CONCLUSION: Our study shows that the simplified "practical" test is more sensitive than the "reference" test currently used in France in screening women at risk of macrosomia.

Functional intensified insulin therapy with short-acting insulin analog: effects on HbA1c and frequency of severe hypoglycemia. An observational cohort study.

OBJECTIVES: To assess the effect of a particular insulin regimen called "functional insulin therapy" using a short-acting insulin analog on the risk of severe hypoglycemia and the HbA(1c) level among patients already under intensive insulin therapy. DESIGN: A cohort of 110 patients with type 1 diabetes receiving intensive insulin therapy with regular insulin for several years was followed during one year after initiation of functional insulin therapy (FIT) with a short-acting insulin analog. The glycemic control was assessed by the mean value of the last three HbA(1c) assays before the initiation of FIT and then by the mean of the following three. The number of severe hypoglycemic episodes/patient/year during the year preceding and the year following the initiation of FIT was recorded. RESULTS: The mean HbA(1c) level decreased on average by 0.7 percent during the 12-month study (p=0.0001) and the number of episodes of severe hypoglycemia fell to 75% of its previous level (p<0.05). CONCLUSION: Substitution of intensive insulin therapy using regular insulin for functional insulin therapy using short-acting insulin analog may improve glycemic control and reduce the risk of severe hypoglycemia.

Outcome of severe diabetic foot ulcers after standardised management in a specialised unit.

OBJECTIVE: The primary objective was to evaluate the efficacy in terms of limb salvage and healing time of standardised multidisciplinary management for high-grade diabetic foot ulcers. The secondary objective was to retrospectively identify the factors that influenced time to healing. STUDY DESIGN AND METHODS: Over a 2-year period, 157 patients with diabetic foot ulcers were managed in our specialised unit using a standard treatment strategy; 118 were followed until healing or for at least 7 months (range, 7-29) after hospital discharge and form the basis for this study. Predetermined criteria were used to diagnose and manage the lesions. The number of major amputations and the time to healing were the main outcome measures. Univariable and multivariable analyses were done retrospectively to look for factors associated with time to healing. RESULTS: The limb salvage rate was 97.5% and the healing rate was 50% after 10 months and 70% after 16 months. Factors significantly associated with healing time were arterial disease without bypass surgery (p<0.001) and renal replacement therapy (p<0.05). Osteomyelitis, as managed in this study, did not increase the healing time (p > 0.6). CONCLUSION: In high-grade diabetic foot ulcers, standardised conservative management with second-line bone-sparing surgery, if needed, yields an acceptable limb salvage rate. With combined medical and surgical treatment, osteomyelitis is not a poor prognosis factor.

How type 1 diabetic patients with good or poor glycemic control cope with diabetes-related stress.

OBJECTIVE: To determine the link between glycemic control and the strategies adopted by patients in coping with diabetes-related stress. MATERIAL AND METHODS: In a cross-sectional study of 122 type 1 diabetic patients, glycemic control was evaluated on the basis of the last mean annual HbA(1c) level, and a comparison was made of two groups of patients, i.e., those with "good control" (HbA(1c)<7.5%) and "poor control" (HbA(1c) > 8.5%). Sociodemographic were collected for all patients by the referring physician. The nature of the diabetes-related stress and the coping strategies adopted by patients were determined by analyzing validated self-assessment questionnaires. RESULTS: Comparison showed that there was no significant difference between the two groups in terms of the patients' age, level of education, age at onset, duration of the diabetes, or the nature of diabetes-related stress factors. In contrast, the difference between the groups was significant in that patients in the "well controlled" group carried out more home blood glucose tests (p<0.02), had fewer complications (p<0.003), and made greater use of so-called "task oriented" strategies (p=0.023), regardless of the existence of any complications. CONCLUSIONS: Even though the nature of the diabetes-related stress appears to be the same for the two groups, type 1 diabetic patients with good glycemic control manage their condition differently (more frequent home blood glucose tests) and use coping strategies that place greater emphasis on problem solving.

[Type 2 diabetes: what therapeutic strategy?]. / Diabète de type 2: quelle stratégie thérapeutique?

GOAL OF TREATMENT: Prevention of diabetic micro and macroangiopathy is the goal of treatment in type 2 diabetes mellitus. A well-controlled glucose level is the key to prevention of microangiopathy; there is no threshold level. Antihypertensive treatment, with the goal of blood pressure below 130/80 mmHg is also beneficial in preventing aggravation of microangiopathy. For macroangiopathy, prevention is based in priority on treatment of other risk factors for cardiovascular disease; the threshold level for drug treatment and the therapeutic objective are those defined for secondary prevention in non-diabetic patients, i.e. blood pressure below 140/80 mmHg and LDL cholesterol under 1.30 g/l. The beneficial effect of lower glucose levels on preventing macrovascular risk was not formally demonstrated by the UKPDS, probably because the difference between the control and the treatment group HbA1c levels was minimal, 0.9 points. REVISITING STRATEGY: It is thus time to revisit the preventive strategy for type 2 diabetes mellitus, i.e. step-by-step increments, as currently proposed for worsening glucose levels. Metformine should be prescribed if the HbA1c is above normal in order to achieve the demonstrated benefit in prevention of microangiopathy and in the hope, motivated by pathophysiology data, of preventing insulin failure. Slow-release insulin at bedtime should be added to the oral hypoglycemiants if fasting glucose exceeds 1.60 or 1.80 g/l, even if the HbA1c remains below 8%. NEW HYPOGLYCEMIANTS: The role of these new agents in this more "aggressive" strategy remains to be defined. Glinides will have to demonstrate their superiority over sulfamides (fewer episodes of hypoglycemia with comparable efficacy) to justify their high cost. Glitazones will have to demonstrate a beneficial effect in second intention combination with metformine on cardiovascular morbidity mortality in type 2 diabetes patients with a metabolic insulin-resistance syndrome and visceral obesity. OBSERVANCE: Since patients with type 2 diabetes mellitus are often taking 3 to 6 tablets to control their glucose level, 3 to control blood pressure, plus another to lower the lipid level and finally one more for an antiplatelet effect reducing the number of tablets and patient education will most certainly help improve therapeutic observance.