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Aim: Although newer technologies of insulin delivery in type 1 diabetes have facilitated an improvement in glycaemic control the risk of hypoglycaemia remains a threat. Therefore, it is important to define the thresholds of glycaemic variability below which the risk of hypoglycaemia can be eliminated or at least minimized., Methods: Randomized controlled trials conducted from 2017 to 2023 comparing Sensor-Augmented-Pumps and Augmented Insulin Delivery Systems (n = 16 and 22 studies, respectively) were selected. A weighted linear model of regression was used to compute the relationship between glycaemic variability and times spent below glucose range. The intercepts of regression lines with the abscissa axis (time below range = 0 %) defined the glycaemic variability thresholds., Results: Positive relationships were observed between the 2 metrics. The scatter plots indicated that the times spent below range never reached the value of 0 % and that the glycaemic variability never fell below 28 %. By extrapolating the regression lines, the glycaemic variability at intercepts with time below range < 70 mg/dL of 0 % was 30.1 % with sensor augmented pumps and 18.9 % with automated insulin delivery. For a time below range < 54 mg/dL of 0 % the respective glycaemic variability values were 32.7 % and 19.9 % (with sensor augmented pumps and automated insulin delivery, respectively)., Conclusions: Importantly, glycaemic variability targets and ambient hyperglycaemia are interdependent. Users of automated insulin delivery need to reach a glycaemic variability of 18 % to 20 % to minimize or eradicate the risk of hypoglycaemia. Such values are those observed in healthy non-diabetic people., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: L Monnier, C Colette, S Aouinti, N Molinari and D Owens declare that they have no conflict of interest relevant to this article; E Renard has received consulting and speaker fees from A.Menarini Diagnostics, Abbott, Air Liquide SI, Astra Zeneca, Beckton-Dickinson, Boehringer-Ingelheim, Cellnovo, Dexcom Inc, Insulet Inc., Johnson & Johnson, Medtronic, Medirio, Novo-Nordisk, Roche, Sanofi-Aventis and research support from Abbott, Dexcom Inc., Insulet Inc., Roche,Tandem Diabetes Care; P-Y Benhamou has received speaker fees from Abbott, Eli Lilly, Novo-Nordisk, served on advisory board panels for Abbott, Insulet, Eli Lilly, Novo-Nordisk and is chief medical officer for Diabeloop., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Near normal glycaemic control in diabetes consists to target daily glucose fluctuations and quarterly HbA1c oscillations in addition to overall glucose exposure. Consequently, the prerequisite is to define simple, and mathematically undisputable key metrics for the short- and long-term variability in glucose homeostasis. As the standard deviations (SD) of either glucose or HbA1c are dependent on their means, the coefficient of variation (CV = SD/mean) should be applied instead as it that avoids the correlation between the SD and mean values. A CV glucose of 36% is the most appropriate threshold between those with stable versus labile glucose homeostasis. However, when near normal mean glucose concentrations are achieved a lower CV threshold of <27 % is necessary for reducing the risk for hypoglycaemia to a minimal rate. For the long-term variability in glucose homeostasis, a CV HbA1c < 5 % seems to be a relevant recommendation for preventing adverse clinical outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

Aim: Diagnosis of nonalcoholic steatohepatitis (NASH) relies on liver biopsy. Noninvasive tools would be useful to target patients to refer for a biopsy. We aimed to determine the diagnostic value of the triglycerides and glucose (TyG) index, an insulin-resistance indicator, to predict NASH., Methods: Our study included grade II-III obese patients aged 18-65 years undergoing bariatric surgery and included in the COMET (COllection of MEtabolic Tissues) biobank (NCT02861781). Liver biopsies performed during bariatric surgery were collected from the biobank along with blood derivatives. Biopsies were analysed according to the steatosis, activity and fibrosis (SAF) scoring system to diagnose NASH, nonalcoholic fatty liver disease (NAFLD), and fibrosis. Logistic regression models were performed to identify factors predicting NASH, NAFLD, and fibrosis., Results: Of 238 analysed subjects (mean age 43±12 years, 33.6% men), 29% had type 2 diabetes. Steatosis was present in 67.2%, while NASH and advanced fibrosis (stage F3) were diagnosed in 18.1% and 2.9% respectively. TyG index was independently associated with NASH (odds ratio (OR): 4.7 [95% confidence interval: 2.3;9.5] P < 0.0001), NAFLD (OR: 2.0 [1.1;3.7] P = 0.03) and stages 2-3 fibrosis (OR: 4.0 [1.5;10.8] P = 0.007). NASH was also predicted by gamma-glutamyl transferase (GGT) with an area under the ROC curve: 0.79 [0.71;0.87 P = 0.04] for GGT and TyG index combined., Conclusion: In our cohort of severely obese patients, TyG index, when associated with GGT level, exhibited high diagnostic performance to predict NASH. Although validation in larger populations is needed, this result may be of considerable clinical value to predict need for liver biopsy., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests, (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Automated closed-loop (CL) insulin therapy has come of age. This major technological advance is expected to significantly improve the quality of care for adults, adolescents and children with type 1 diabetes. To improve access to this innovation for both patients and healthcare professionals (HCPs), and to promote adherence to its requirements in terms of safety, regulations, ethics and practice, the French Diabetes Society (SFD) brought together a French Working Group of experts to discuss the current practical consensus. The result is the present statement describing the indications for CL therapy with emphasis on the idea that treatment expectations must be clearly defined in advance. Specifications for expert care centres in charge of initiating the treatment were also proposed. Great importance was also attached to the crucial place of high-quality training for patients and healthcare professionals. Long-term follow-up should collect not only metabolic and clinical results, but also indicators related to psychosocial and human factors. Overall, this national consensus statement aims to promote the introduction of marketed CL devices into standard clinical practice., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

The use by diabetes patients of real-time continuous interstitial glucose monitoring (CGM) or the FreeStyle Libre ® (FSL) flash glucose monitoring (FGM) system is becoming widespread and has changed diabetic practice. The working group bringing together a number of French experts has proposed the present practical consensus. Training of professionals and patient education are crucial for the success of CGM. Also, institutional recommendations must pay particular attention to the indications for and reimbursement of CGM devices in populations at risk of hypoglycaemia. The rules of good practice for CGM are the precursors of those that need to be enacted, given the oncoming emergence of artificial pancreas devices. It is necessary to have software combining user-friendliness, multiplatform usage and average glucose profile (AGP) presentation, while integrating glucose and insulin data as well as events. Expression of CGM data must strive for standardization that facilitates patient phenotyping and their follow-up, while integrating indicators of variability. The introduction of CGM involves a transformation of treatment support, rendering it longer and more complex as it also includes specific educational and technical dimensions. This complexity must be taken into account in discussions of organization of diabetes care., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Aim: The benefits of retrospective continuous glucose monitoring (retroCGM) recording have been widely explored in clinical studies, and many diabetes physicians routinely use this examination. However, the method of interpretation of CGM recordings has never been precisely described., Method: An expert French panel of physicians met for two days to discuss several aspects of retroCGM use and to produce a position statement., Results: The guidelines cover the indications for retroCGM, the general organization and practical implementation of CGM recordings, a description of the different devices available and guidelines for the interpretation of retroCGM recordings., Conclusion: This consensus document should help clinicians in the proper use of retroCGM., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Aim: In the TELEDIAB-1 study, the Diabeo system (a smartphone coupled to a website) improved HbA1c by 0.9% vs controls in patients with chronic, poorly controlled type 1 diabetes. The system provided two main functions: automated advice on the insulin doses required; and remote monitoring by teleconsultation. The question is: how much did each function contribute to the improvement in HbA1c?, Methods: Each patient received a smartphone with an insulin dose advisor (IDA) and with (G3 group) or without (G2 group) the telemonitoring/teleconsultation function. Patients were classified as "high users" if the proportion of "informed" meals using the IDA exceeded 67% (median) and as "low users" if not. Also analyzed was the respective impact of the IDA function and teleconsultations on the final HbA1c levels., Results: Among the high users, the proportion of informed meals remained stable from baseline to the end of the study 6months later (from 78.1±21.5% to 73.8±25.1%; P=0.107), but decreased in the low users (from 36.6±29.4% to 26.7±28.4%; P=0.005). As expected, HbA1c improved in high users from 8.7% [range: 8.3-9.2%] to 8.2% [range: 7.8-8.7%] in patients with (n=26) vs without (n=30) the benefit of telemonitoring/teleconsultation (-0.49±0.60% vs -0.52±0.73%, respectively; P=0.879). However, although HbA1c also improved in low users from 9.0% [8.5-10.1] to 8.5% [7.9-9.6], those receiving support via teleconsultation tended to show greater improvement than the others (-0.93±0.97 vs -0.46±1.05, respectively; P=0.084)., Conclusion: The Diabeo system improved glycaemic control in both high and low users who avidly used the IDA function, while the greatest improvement was seen in the low users who had the motivational support of teleconsultations., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Objectives: New onset of diabetes after transplantation (NODAT) is a known complication of renal transplantation, but early glycaemic status after transplantation has not been described prospectively. This study aimed to assess blood glucose (BG) levels immediately following kidney transplantation in non-diabetic subjects and to explore their relationship to later graft outcomes and NODAT occurrence., Patients and Methods: Over a 9-month period, 43 consecutive non-diabetic patients who received a kidney transplant were prospectively investigated. During the first 4 days after transplantation, fasting BG was measured and the 24-h BG profile assessed by continuous glucose monitoring (CGM). Capillary BG was measured on hospital admittance and at least four times a day for CGM calibration thereafter. All adverse events were recorded, and fasting BG and HbA1c were assessed at 3, 6 and 12 months and at the last visit to our centre., Results: Immediately following renal transplantation, capillary BG was 12.2 ± 3.8 mmol/L. On day 1 (D1), fasting BG was 9.9 ± 4.3 mmol/L and decreased to 6.0 ± 1.5 mmol/L on D3. The CGM-reported mean 24-h BG (mmol/L) was 10.2±2.4 on D1, 7.7 ± 1.3 on D2 and 7.5 ± 1.1 on D3. From D1 to D4, 43% of patients spent>12h/day with BG levels>7.7 mmol/L. While morbidity during the 3 months following transplantation appeared unrelated to BG, the first post-transplantation capillary BG measurement and fasting BG on D1 tended to be higher in patients who developed diabetes 3 months later. Tacrolimus treatment was associated with a higher incidence of dysglycaemia at 3 and 6 months. After a mean follow-up of 72 months, NODAT was frequently seen (18.6%), and was associated with tacrolimus medication (P<0.01) and a higher rate of renal transplantation failure (RR: 3.6, P<0.02)., Conclusion: Hyperglycaemia appears to be a nearly constant characteristic immediately following transplantation in non-diabetic kidney recipients. Higher BG values could identify patients at risk for later post-transplant diabetes and graft failure., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Aim: Online continuous glucose monitoring (CGM) during physical exercise would be highly useful in patients with insulin-treated diabetes. For this reason, this study assessed whether such a goal could be reached with a subcutaneous 'needle-type' enzymatic sensor., Methods: Ten patients (five women/five men), aged 51 ± 12 years, with type 1 diabetes for 24 ± 11 years treated by continuous subcutaneous insulin infusion (CSII) for more than 1 year (HbA1c: 7.5 ± 0.8%) performed a 30-min bout of exercise at a constant high-intensity load (15% above their individual ventilatory threshold) on a cycle ergometer. All patients wore a subcutaneous 'needle-type' enzymatic glucose sensor linked to a portable monitor (Guardian(®) RT, Medtronic-MiniMed, Northridge, CA, USA) that had been inserted the previous evening. Sensor calibration was performed against capillary blood glucose immediately before the exercise. CGM values were recorded every 5 min from T(-10) to T(+30), then every 10 min during the recovery period from T(+30) to T(+90). These recorded values were compared with blood glucose assays performed on simultaneously collected venous samples., Results: Sensor functioning and tolerability raised no problems except for one sensor that could not be adequately calibrated. Data from this patient were excluded from the data analysis. An average blood glucose decrease of 63 ± 63 mg/dL (3.5 ± 3.5 mmol/L) (median decrease: 58 mg/dL [3.22 mmol/L]; range: -3 mg/dL [0.16 mmol/L] to 178 mg/dL [9.8 mmol/L]) occurred during exercise bouts, while CGM values decreased by 38 ± 49 mg/dL (2.11 ± 2.72 mmol/L) (median: 32 mg/dL [1.7 mmmol/L]; range: -15 mg/dL [0.83 mmol/L] to 58 mg/dL [3.22 mmol/L]). Cumulative paired glucose values (n = 135) could be analyzed. The correlation factor between CGM and blood glucose values was 0.957 with an intercept of 0.275. The mean difference between paired values according to Bland-Altman analysis was 10 ± 31 mg/dL (0.56 ± 1.72 mmol/L). Clarke error grid analysis showed 91% of paired points in A and B zones, while 0%, 9% and 0% of paired points were in the C, D and E zones, respectively., Conclusion: Blood glucose changes during intensive physical-exercise bouts performed by CSII-treated type 1 diabetes patients can be estimated with acceptable clinical accuracy by online CGM., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Aim: To review the recent clinical research related to the development of an artificial pancreas and the current perspectives for its home use., Methods: All clinical investigations assessing closed-loop insulin delivery systems in diabetic patients in the literature were collected and analyzed to identify any significant advances as well as bottlenecks., Results: The development of an artificial pancreas for ambulatory use offering an optimal substitute for insulin secretion has shown promising evolution over the past decade. The accumulated improvements achieved on the performance of insulin pumps using subcutaneous and intraperitoneal routes, continuous glucose monitoring and algorithms driving insulin infusion according to glucose measurement have led to numerous clinical trials recently, albeit only in a hospital setting so far. The key obstacles to achieving permanent normal glucose control are related to the delay of insulin action when infused subcutaneously or, at a lesser extent, into the peritoneal cavity, and blood glucose estimation made by subcutaneous interstitial measurement. These time lags impair the reactivity of the system, and suggest a need to develop complex algorithms aiming at their compensation. So far, manual interventions are needed at times of food intake to prevent hyper- or hypoglycaemic excursions when insulin changes rapidly., Conclusion: The most recent models using subcutaneous insulin infusion and glucose measurements linked by predictive control algorithms offer sufficient effectiveness and safety to consider their forthcoming use at home, during the night as a first step., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aim: Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family: in the presence of elevated blood glucose, it stimulates insulin secretion and inhibits glucagon production. In addition, GLP-1 slows gastric emptying. GLP-1 secretion has also been reported to potentially affect patients with type 2 diabetes (T2DM) compared with non-diabetics and, as enzymatic inactivation by dipeptidyl peptidase-4 (DPP-4) shortens the GLP-1 half-life to a few minutes, GLP-1 receptor agonists such as exenatide twice daily (BID) and liraglutide have been developed, and have become part of the management of patients with T2DM. This review focuses on the potential beneficial effects of these compounds beyond those associated with improvements in blood glucose control and weight loss, including changes in the cardiovascular and central nervous systems., Methods: This was a state-of-the-art review of the literature to evaluate the relationships between GLP-1, GLP-1 receptor agonists, weight and the cardiovascular system., Results: GLP-1 receptor agonists improve glucose control and do not significantly increase the risk of hypoglycaemia. Also, this new class of antidiabetic drugs was shown to favour weight loss. Mechanisms may involve central action, direct action by reduction of food intake and probably indirect action through slowing of gastric emptying. The relative importance of each activity remains unclear. Weight loss may improve cardiovascular outcomes in patients with T2DM, although GLP-1 receptor agonists may have other direct and indirect effects on the cardiovascular system. Reductions in myocardial infarct size and improvements in cardiac function have been seen in animal models. Beneficial changes in cardiac function were also demonstrated in patients with myocardial infarcts or heart failure. Indirect effects could involve a reduction in blood pressure and potential effects on oxidation. However, the mechanisms involved in the pleiotropic effects of GLP-1 receptor agonists have yet to be completely elucidated and require further study., Conclusion: These compounds may play an important role in the treatment of patients with T2DM as their potential effects go beyond glucose-lowering (weight loss, potential improvement of cardiovascular risk factors). However, to better understand their place in the management of T2DM, further experimental and clinical prospective studies are required., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

Aim: This study aimed to assess the effectiveness of continuous glucose monitoring (CGM) for glucose control in type 1 diabetic patients treated by continuous subcutaneous insulin infusion (CSII) and presenting with frequent hypoglycaemic episodes., Methods: Thirteen patients with type 1 diabetes (diabetes duration: 25±15 years; CSII duration: 5.5±7.0 years), with more than six recorded capillary blood glucose (CBG) values <60 mg/dL, according to their metres for the past 14 days, were offered the permanent use of a CGM device (Guardian RT(®), Medtronic) plus ongoing self-monitoring of blood glucose (SMBG) for 12 weeks, followed by a 12-week crossover period of SMBG only, or vice versa. Glucose control, determined by recorded 14-day CBG values <60 mg/dL and HbA(1c) levels, and quality of life according to the Diabetes Quality of Life (DQOL) questionnaire, were assessed at baseline, and after 12- and 24-week follow-ups., Results: Four patients withdrew from the study during the first period (of whom three were using CGM). In the nine study completers, the number of low CBG values decreased significantly from 13.9±9.2 to 7.6±6.8 (P=0.011) when patients used CGM, in either the initial or final trial period, while a decrease in HbA(1c) from 8.3±0.7 to 7.7±0.6% (P=0.049) was also observed, in contrast to the absence of any significant differences during the SMBG-only period. DQOL scores were also essentially unaffected., Conclusion: This pilot observational study supports the hypothesis that CGM use can significantly improve overall glucose control while reducing hypoglycaemic episodes in hypoglycaemia-prone type 1 diabetic patients treated by CSII., (Copyright © 2010 Elsevier Masson SAS. All rights reserved.)

The effectiveness of a specific educational programme involving the use of a real-time glucose-sensor system (Guardian RT) to improve glucose control was investigated in patients with poorly controlled type 2 diabetes despite insulin therapy. Ten patients participated in a randomized crossover study comparing two 3-month periods, during which glucose levels were monitored by either self-monitoring of blood glucose (SMBG) alone or by Guardian RT (restricted to 1 week per month) in addition to SMBG. Only four of the enrolled patients completed both periods, while dropouts were mainly due to technical difficulties in using the device. All six patients who completed the first 3-month period showed a reduction in glycated haemoglobin (HbA(1c)) level whatever the mode of glucose monitoring (study effect). A further reduction in HbA(1c) level was observed in two of the three patients using the Guardian RT during the second period. Less frequent symptomatic hypoglycaemic episodes were noted during the 3-month period with the device in the four patients who completed both study periods. These limited, but promising, results of this pilot study appear to justify the initiation of a larger study to assess the use of a real-time glucose sensor in carefully selected patients with type 2 diabetes., (Copyright 2010 Elsevier Masson SAS. All rights reserved.)

For years, external insulin pumps have enjoyed proven efficacy as an intensive diabetes treatment to improve glycaemic control and reduce hypoglycaemia. Since the last ALFEDIAM guidelines in 1995, however, basal-bolus treatment using a combination of long- and short-acting insulin analogues have emerged and could challenge, at a lower cost, the efficacy of pumps using rapid-acting insulin analogues, considered the 'gold standard' of insulin treatment. Nevertheless, given its theoretical and practical advantages, some patients will derive more benefit from pump treatment. These cases have been carefully evaluated in the literature by a panel of experts appointed by ALFEDIAM to determine the indications for pump treatment. In patients with type 1 diabetes, persistent elevated HbA(1c) despite multiple daily injections (MDI), and repeated hypoglycaemia and high glycaemic variability, represent the most validated indications. In patients with type 2 diabetes, pump treatment may be indicated in cases of MDI failure to achieve HbA(1c) targets. Absolute contraindications are rare, and comprise severe psychiatric disorders, rapidly progressing ischaemic or proliferative retinopathy before laser treatment and exposure to high magnetic fields. Relative contraindications are mostly related to the patient's lack of compliance or inability to cope with the treatment, and need to be evaluated individually to clearly assess the benefit/risk ratio for the given patient. However, as these conditions are progressive, there should also be annual reassessment of the appropriateness of pump treatment. Specific education on pump treatment initially and throughout the follow-up, delivered by experienced medical and paramedical teams, are the best guarantees of treatment efficacy and safety., (Copyright (c) 2010 Elsevier Masson SAS. All rights reserved.)

Aim: The objective of the present study was to investigate the genetic association of the fat-mass-and-obesity-associated (FTO) gene in obese women in the presence of the known influential role of the insulin receptor substrate 2 (IRS-2) gene., Methods: This case-control study was carried out in the Languedoc-Roussillon region of France, and included lean control women (n=128), and women (n=119) of various degrees of obesity (body mass index [BMI] mean+/-S.D.: 39.3+/-7.4kg/m(2)) and a prevalence of 26.9% of the metabolic syndrome (MetS). For the FTO gene, genotyping was performed by sequence-specific oligonucleotide-polymerase chain reaction (SSO-PCR) on the single nucleotide polymorphism (SNP) rs1421085 (C/T) while, for IRS-2, the rs1805097 (G/A) corresponding to variant Gly1057Asp was genotyped by direct sequencing., Results: The FTO gene (homozygous C/C) was significantly associated to both simple and morbid obesity (P<0.026 and P<0.0034, respectively), with odds-ratios (ORs) of 2.58 (95% CI: 1.1-6.0) and 4.1 (95% CI: 1.6-10.5), respectively, independent of IRS-2. MetS was also associated with FTO (P<0.032, OR: 3.1, 95% CI: 1.1-8.5), but not with IRS-2. Genotypes of FTO were correlated with insulin resistance, and homozygous C/C was positively correlated with an increase in insulin resistance over the value predicted by the increase in BMI., Conclusion: These data confirm the influential role of the FTO gene in obesity in the French female population and, in addition, revealed the role of FTO in insulin resistance and MetS. These effects appeared to be independent of IRS-2, which is directly involved in insulin action. This study may offer new insights into the genetic determinants of obesity and MetS in women.

Aim: The objective of this review was to assess the safety and efficacy of bariatric surgery in patients with severe obesity and late-stage type 2 diabetes (T2D)., Methods: A review of the literature looked for reported data on outcomes of bariatric surgery when performed in patients with T2D treated by oral medications or insulin. Recent updates in our understanding of the effects of bariatric surgery on glucose homoeostasis were also examined., Results: Data on the outcomes of bariatric surgery in advanced T2D are scarce. Having either T2D for more than 10 years or more advanced forms of the disease, according to antidiabetic therapy, is associated with less weight loss after bariatric surgery. Improvement of diabetes control is also less than seen in earlier forms of T2D, and resolution of the disease is less likely to occur. However, a reduction in oral medications or insulin doses has been documented. Residual beta-cell function is suggested to be a possible determining factor for therapeutic changes or cessation, while reductions in both weight-related and non-weight-related insulin resistance can be expected. Beneficial effects on co-morbidities and overall mortality due to the excess weight loss may also be seen., Conclusion: Bariatric surgery in patients with severe obesity and late-stage T2D is currently justified by the expected benefits due to the excess weight loss. However, specific studies are needed to better assess the effects of such surgery on glucose control and the associated outcomes., (Copyright 2009 Elsevier Masson SAS. All rights reserved.)

A 30-year-old man with a history of skin and recurrent oral ulceration over 1 year developed loss of visual acuity in the right eye. The diagnosis of acute frosted branch angiitis was based on retinal vasculitis associated with retinal edema and hemorrhages, confirmed using fluorescein angiography (venous leakage and extensive staining of the vein walls). General examination revealed pseudofolliculitis and recurrent oral ulcers. The diagnosis of Behçet's disease was based on the international criteria. The patient was treated with prednisolone and colchicine, which were effective with a normalization of the fundus 1 month later. The initial presentation of Behçet's disease as frosted branch angiitis is exceptional, the main differential diagnosis being herpetic infections, which must be ruled out.

The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.

The obesity epidemic is of some concern in women of reproductive age. Maternal obesity is associated with many pregnancy complications, especially gestational diabetes and hypertensive disorders of pregnancy. Delivery in obese women is characterized by a high caesarean-section rate and an increased risk of anaesthetic and postoperative complications. Weight retention after birth may increase the risk of type 2 diabetes in the long term. Foetal risks include macrosomia, malformations and increased perinatal mortality, with the long-term infant health marked by a higher risk of obesity and metabolic disorders. Optimal management includes preconception counselling, pregravid weight-loss programmes, monitoring of gestational weight gain, repeated screening for pregnancy complications and long-term follow-up to minimize the social and economic consequences of pregnancy in overweight women.

Aim: To review clinical use of implantable insulin pumps and to suggest indications for this therapy., Methods: The EVADIAC group performed a review of published reports on implantable insulin pumps for the last 15 years and analyzed its own centralized database. From this update, a position statement on indications of this therapy is drawn., Results: Published papers mostly report safety and effectiveness data from observational cumulated experiences of 15-350 patient-years. While HbA(1c) reduction does not reach statistical significance in all reported studies, improvement of blood glucose stability and reduction of severe hypoglycaemia appear as constant characteristics of this therapy. When compared to subcutaneous insulin therapy in randomized controlled studies, implantable pumps allow significantly reduced blood glucose fluctuations and improved quality of life in both type 1 and type 2 diabetic patients, and a significant weight decrease in type 2 diabetic patients. While the EVADIAC registry shows the reduced occurrence of pump-pocket complications thanks to preventive measures and a lower incidence of catheter obstructions following improvements of catheter design, underdelivery due to insulin aggregation in pumps remains a recurrent although reversible issue. Determinants of increased anti-insulin antibody production in some patients remain elusive but impact on blood glucose control is limited in most cases., Conclusion: From analyzed data, the EVADIAC group states that implantable pumps can be safely indicated and provide metabolic improvements in type 1 diabetic patients who remain far from targeted HbA(1c) below 7% and/or experience large fluctuations of blood glucose including recurrent severe hypoglycaemia, in spite of intensive follow-up and education when treated by subcutaneous insulin.

Aim: Restoration of long-term normal blood glucose control in diabetic patients supports the elaboration of an artificial beta cell. The possibility of implantation of the three crucial components of such a system (insulin delivery device, glucose sensor and controller) is analyzed., Methods: The Long-Term Sensor System project, aiming at a fully implantable artificial beta cell, assessed the feasibility of glucose control by the combined implantation of a pump for peritoneal insulin delivery and a central intravenous glucose sensor close to the right atrium, connected via a subcutaneous lead. It was initiated in 10 Type 1 diabetic patients in our clinic from 2000. Data obtained during this experience are reviewed and confronted to reported closed-loop trials using other approaches., Results: No significant complication related to prolonged implantation of intravenous sensors occurred and the combined implants were well tolerated. Glucose measurement by the intravenous sensors correlated well with meter values (r=0.83-0.93, with a mean absolute deviation of 16.5%) and accuracy has been sustained for an average duration of 9 months. Uploading of pump electronics by algorithms designed for closed-loop insulin delivery allowed in-patient 48 hour-trials aiming at automated glucose control. Glucose control was similar to that reported by investigations combining subcutaneous sensors to wearable pumps for subcutaneous insulin infusion. The benefits of more physiological insulin kinetics due to intra-peritoneal delivery have been hampered by the slow response time of intravenous sensors., Conclusion: Although the concept of a fully implantable artificial beta cell has been validated as feasible, the limited performance in achieving glucose control requests improvements in the sensor structure to increase its longevity and decrease sensor delay.

Aim: The purpose of this national multicenter prospective study by the French EVADIAC group was to investigate the possibility that continuous intraperitoneal insulin infusion using an implanted pump (CIpii) increases the risk of autoimmune disease in type 1 diabetic patients as it increased anti-insulin immunogenicity., Methods: Prevalence of clinical (Hashimoto's disease, hyperthyroidism, gastric atrophic disease and vitiligo) and subclinical (presence of anti-thyroperoxidase antibodies, anti-intrinsic factor antibodies, abnormal TSH levels) autoimmune diseases was estimated by comparing two groups of patients already treated by either CIpii (n=154) or external pump (CSII) (n=121) for an average of 6 years. Incidence of autoimmune disease was determined by comparing the same measurements one year after inclusion., Results: No significant difference was observed for the total prevalence of clinical and subclinical auto-immune thyroid and gastric di-seases (35.6% and 3.2% respectively in the CIpii group versus 40.4% and 2.6% in the CSII group). No significant difference for the incidence of clinical and subclinical auto-immune diseases was observed: 7.2% and 0% in CIpii and 7.3% and 1.7% in CSII., Conclusion: As previously shown AIA (anti-insulin antibodies) levels were higher in CIpii than in CSII (32.9% vs 20.2%, P<0.0001) but no correlation was observed with either clinical or subclinical autoimmune disease. This large-scale study eliminates the possibility that CIpii increases the risk of autoimmune disease.

Aim: The GlucoDay allows continuous glucose monitoring by subcutaneous microdialysis in sedentary conditions. To validate it when glycaemia may undergo rapid and dramatic changes, we investigated its accuracy during two exercise sessions with markedly different glucose disposal rates., Methods: Nine male diabetic patients, aged 32-61, treated by insulin pumps, first underwent a standard maximal exercise-test designed for determining the maximal oxygen consumption and the first ventilatory threshold (Vt1). Then two 30 min steady-state workloads at 15% below and 15% above the Vt1 were performed in random order with the GlucoDay, and measurement of CHO oxidation rates was made by indirect calorimetry., Results: CHO oxidation during exercise at +15% Vt1 was higher (+943.5 mg/min, ie +45.5%, P<0.01) than during exercise at -15% Vt1 No hypoglycaemia occurred. Due to breakages of 39% of subcutaneous probes, eleven steady-state sessions in 7 subjects allowed to compare 141 paired glucose (sensor vs. venous) determinations. The Clarke error grid situates 92.9% of glucose values within the A zone and 6.4% within the B zone, while only one pair of values (0.7%) falls in the D zone. Venous glucose tended to decrease more rapidly than sensor glucose during exercise. Bland-Altman plots evidence for a few cases of underestimation of venous glucose at high intensity., Conclusions: This study showed satisfactory accuracy of the GlucoDay during exercise. A slight lag time in sensor values likely explains a few discrepancies that do not appear as clinically meaningful. Reduction of probe fragility and confirmed sensor accuracy in hypoglycaemia would further support applicability of GlucoDay at exercise.

Unlabelled: Extreme subcutaneous insulin resistance is a rare syndrome characterized by a severe resistance to subcutaneous (S/C) insulin together with persistence of normal or near normal intravenous (IV) insulin sensitivity. Its pathophysiology is unknown, although increased insulin degrading activity has been reported in the S/C adipose tissue fraction in some cases. Until now, proposed treatments have been disappointing. We report 4 cases who were successfully treated by intraperitoneal (IP) route., Methods: The diagnosis of subcutaneous insulin resistance was based upon following combined conditions: resistance to hypoglycaemic action of subcutaneous insulin but normal or near normal sensitivity to IV or IP insulin., Results: 4 patients among those followed by EVADIAC group met these criteria: 3 with type 1 diabetes (C peptide=0), the last one with unexplained non insulin-deficient diabetes (no anti-GAD antibodies, C peptide=5 ng/ml). All of them had been treated with subcutaneous insulin therapy without success despite huge doses (up to 4000 IU/day in two patients). The 3 type 1 diabetic patients presented with a history of repeated ketoacidosis episodes. A treatment of insulin mixed with aprotinin had been proposed to 2 patients without success. The IV insulin sensitivity was proved to be normal in two patients by euglycaemic clamp data. A skin biopsy was performed in 1 patient. An accumulation of insulin in the derma was revealed with no increase of degradation products of insulin. In these 4 patients, a dramatic improvement of diabetes control was obtained by IP insulin delivery from an implantable pump (HbA1c decrease by at least 3%)., Conclusion: Although pathophysiology of the subcutaneous insulin resistance syndrome remains unexplained, our data show that intra-peritoneal insulin therapy from an implantable pump allows diabetes control in patients affected by this uncommon but severely disabling condition.

Intensive insulin therapy aiming at normoglycemia in order to prevent long-term complications is not questionable for the management of type 1 diabetes mellitus nowadays. The gold standard mode of insulin therapy in this view is CSII using fast-acting analogues. Whether this reference method can be challenged by MDI using recently available long- and fast-acting analogues remains an open question. Use of fast-acting analogues provides similar benefits on post-meal glucose control either by MDI or by CSII. Long-acting analogues glargine and detemir have shown better effectiveness on basal blood glucose control, including improved stability and reduced occurrence of hypoglycemic episodes, than NPH and ultralente. Reported comparisons between CSII and MDI using glargine have been limited until now. While some of them have shown that CSII allowed both lower HbA1(c) and incidence of hypoglycemia, similar effects have been obtained in other experiences. From present data, it appears that CSII remains the most effective mode of intensive insulin therapy although it may be challenged in patients with stable basal insulin needs. Nevertheless, individual factors seem to be decisional in the choice between CSII and MDI using long-acting analogues, among which patient ability and will to use an insulin pump are critical.

Objective: To report a long-term multicentre experience with implantable insulin pumps in type 1 diabetic patients, and to test safety and accuracy of the systems following improvements in infused insulin solutions and peritoneal catheter., Research Design and Methods: Forty MiniMed Implantable Pumps model 2001 were consecutively implanted over a two-month period in type 1 diabetic volunteers. The systems were equipped by a new compliant sideport catheter and were refilled at 45-day intervals with HOE 21 PH ETP insulin batches showing enhanced physical stability in vitro. Safety was assessed from the incidence of acute adverse events and effectiveness from quarterly HbA(1c) assays. Accuracy of delivery was measured at each pump refill by comparing residual insulin in the pump reservoir with expected amount according to programmed infusion. The study lasted until pump battery depletion or premature pump explantation., Results: Cumulated experience was 106 patient-years. Premature explantations occurred in 3 cases, due to one electronic pump failure and two "pump-pocket" infections. Near-normal insulin delivery was sustained until expected battery depletion in 13 cases. Forty underdelivery events occurred in 24 pumps, but 36 among them were related to pump slowdowns due to insulin aggregation in pumps that were promptly solved by an outpatient NaOH rinse procedure. Only 4 underdeliveries were caused by catheter obstructions that required laparoscopy to remove peritoneal tissue overgrowth around the catheter. Over pump lifetime, HbA(1c) was 7.2 +/- 0.2% in the 13 patients with no underdelivery and 7.7 +/- 0.5% in the other ones. Only one severe hypoglycemia and one ketoacidosis occurred during the whole study., Conclusion: Our current experience with improved implantable pumps and insulin solutions shows both long-term safety and effectiveness of this treatment in type 1 diabetic patients following improvement in infused insulin solutions and catheter. This therapy may be a good alternative for patients that experience frequent severe hypoglycemia with intensive subcutaneous insulin therapy.

Use of portable pumps is increasing to achieve intensive insulin treatment. Beside unpredictable insulin absorption and insufficient reactivity to changes of insulin flow rate due to the subcutaneous route, this therapy is however limited by the lack of information on blood glucose level provided by self-blood glucose monitoring. Thus, patient interpretation only leads to speculative adaptation of pump flow rate. The lack of alert toward the risk of hypoglycemia or hyperglycemic ketogenic deviations can lead to the occurrence of deleterious metabolic distorsions, among which severe hypoglycemia stands in first rank. Starting experiences of continuous recording of interstitial glucose level by portable systems using glucose-oxidase allow on short time durations the identification of daily periods of poor metabolic control. Retrospective availability of information gives the possibility of more adequate treatment adaptations than conventional capillary blood glucose monitoring, but does not allow immediate prevention of metabolic events. Only devices providing real time or near-real time information to the patient can fulfill this function. However, the absence of tight parallelism between variations of interstitial and blood glucose levels may lead to erroneous decisions. A true continuous real time information on blood glucose level on long-term seems only expectable from implantable glucose sensors. Still under investigation, these systems should be able to insure vigilance toward the risk of hypo- and hyperglycemia on weekly or monthly periods. Initially used as complementary to capillary self-monitoring, their reliability should allow their use as substitutes for conventional monitoring, except for measurements aimed at signal calibration. Pump control by the sensor signal is conceivable if it corresponds to a direct, continuous, real time measurement of blood glucose, and subject to a simultaneous improvement of insulin infusion modes.

Background: The management of abdominal fat accumulation and metabolic disorders in HIV1-infected patients, by an aerobic training program, is considered., Methods: Seventeen lipodystrophic and 2 dyslipidemic (without body modification) adults were studied before and after 4 months of training. The training load was individualized on a ventilatory threshold basis, determined during a maximal exercise test on cycle ergometer. Total (TAT), Visceral (VAT) and Subcutaneous Adipose Tissue (SAT) were assessed by CT-scan. Total (TC) and High Density Lipoprotein (HDL-C) Cholesterol, Triglycerides (TG), lactate (La), insulin and glucose were measured after a 12-hour-overnight fast. LDL, TC/HDL, TG/HDL, HOMA-insulin resistance index and coronary heart disease (CHD) relative risk (RR(CHD)) were calculated., Results: Besides a significant improvement of aerobic fitness, trained patients exhibited a reduction in TAT (-12.8%, p < 0.001), specially at the visceral level (- 12%, p < 0.01) and in TC, TG and La (- 23%, - 43% and - 19% respectively, p < 0.01). HDL-C was increased (+ 6%, p < 0.01). All these effects were above changes that could be expected by a possible regression to the mean artefact. Both TC/HDL and TG/HDL were reduced (p < 0.01) and the estimated RR(CHD) decreased by approximately 13% (p < 0.01). No significant training effect was observed on the 9 available HOMAs. Significant correlations were found between changes in blood lipid values and baseline measures (r range - 0.55 to - 0.79, p < 0.05), indicating a larger improvement when baseline lipid parameters were higher., Conclusion: Aerobic training reduced visceral fat, lipid disorders, basal blood lactate and CHD markers in HIV patients. Training effects were particularly important for patients with marked dyslipidemia.

The project to finalize a 'closed loop' insulin delivery according to blood glucose level, i.e. an implanted artificial beta cell, is born from the development of the first miniaturized portable insulin pumps during the 1970s. Continuous improvements in micro-electronics, as well as in the development of biomaterials and stable insulin solutions, have led to the availability of implantable pumps able to infuse insulin by the peritoneal route, in a continuous and programmable way, for several years. These systems represent the most efficient and physiological mode of insulin therapy at the present time. More recently, we have demonstrated during clinical trials that intravascular, implantable, glucose sensors using glucose-oxidase were able to measure with good accuracy real-time blood glucose for several months. The combination of these two devices to form a prototype of implantable artificial beta cell, designated as Long Term Sensor System, allowed us to perform the first trials of closed-loop insulin delivery according to sensor signal for periods of 48 hours in type 1 diabetic patients. This mode of functioning appeared to be feasible and able to establish glucose control closer to physiology than the use of implantable pumps in open-loop, i.e. by adapting insulin delivery according to capillary blood glucose. Although algorithms tuning automated insulin delivery are improvable, the success of these initial trials materializes the perspective of a possible restoration of physiological insulin function by the mean of an implanted artificial beta cell in diabetic patients.

Background: To assess the efficacy on blood glucose control of continuous peritoneal insulin infusion from implantable pump (CPII) compared with continuous subcutaneous infusion using insulin lispro (CSII-IL) in type 1 diabetic patients., Methods: Fourteen type 1 diabetic patients (5 males and 9 women, age 50.6 +/- 12.8, diabetes duration 28.0 +/- 13.4 years) were treated with CSII-IL and CPII. Capillary blood glucose (BG) was monitored and recorded at least 4 times per day during 2 study periods of 45 days: using CSII-IL (period A), and from 45th to 90th day after implantation (period B). HbA1C was measured at the end of each period., Results: Both daily BG levels (145 +/- 18 vs 153 +/- 17 mg/dl, p<0.01) and preprandial BG levels (139 +/- 20 vs 147 +/- 22 mg/dl, p<0.05) were lower in period B. Although postprandial BG values tended to be lower in period B, this reduction did not reach statistical significance (149 +/- 20 vs 157 +/- 16 mg/dl, p=0.07). Meanwhile, SD of all BG values was lower with CPII (69 +/- 11 vs 79 +/- 17 mg/dl, p<0.01) and HbA1c levels were lower at the end of period B (7.3 +/- 0.9 vs 7.8 +/- 0.9%, p=0.04). Low blood glucose index was comparable during both periods (2.8 +/- 1.6 vs 3.1 +/- 1.5, p=0.4)., Conclusion: CPII may provide a better BG control and stability than CSII-IL. However, a long-term randomized prospective study is needed to confirm these improvements.

Low-dose oral contraceptives can be used by a great number of women with IDDM or a previous gestational diabetes mellitus. Others hormonal contraceptives (progestogen-only preparations) are less convenient and the compliance is poor with an increasing risk of gynaecologic side effects. The safety of this contraceptives as regards vascular diabetic complications is not evaluated well. Nulliparous patients with progressive complications can use barrier methods of contraception after education. Macroprogestative contraception is a adequate choice for women within forties. For multiparous diabetic women, intra-uterine devices represent the first choice.

Clinical data in the 1980s showed a close relationship between the conceptional glycated hemoglobin and the occurrence of spontaneous early abortions and fetal malformations. Blood glucose level during pregnancy was similarly correlated with the risk of fetal macrosomia, due to significant links between birthweight, fetal hyperinsulinemia and mean maternal blood glucose. Tight blood glucose control from conception to term was shown to be able to lower the risk of fetal malformations and perinatal mortality to that of the offspring of a non diabetic mother. Prerequisites include: 1) contraception until tight blood glucose control, 2) close partnership between diabetologist and obstetrician, 3) assessment of diabetic complications. Seldom, coronary heart disease or advanced nephropathy contraindicate pregnancy. Uncontrolled proliferative or pre-proliferative retinopathy, or macular edema, are temporary contraindications to pregnancy. Laser photocoagulation must then be performed before tightening blood glucose control. A complete review of diabetes management is associated with therapeutic intensification. Blood glucose objectives allow as limits: 70 to 100 mg/dl before meals, up to 140 mg/dl one hour and 120 mg/dl two hours after meals. HbA1c allowing conception is close to 7%. Blood glucose monitoring requires 6-7 measurements per day. The most efficient insulin regimens include 3 to 4 shots per day. The distribution between regular and NPH or lente insulins is adapted individually. Lispro insulin, now appearing as safe, may be used to improve post-meal blood glucose control. Insulin pumps may be useful in case of late-night poor control or frequent hypoglycemic events. Patient acceptance of this option is unavoidable to obtain a benefit. Preconceptional insulin therapy must be maintained until pregnancy term. Follow-up must be intensified after twenty fourth week. Labor and delivery, cesarean section, fetal maturation by corticosteroids and use of i.v. betamimetic drugs require continuous i.v. insulin delivery. The continuation of intensive insulin management in post-partum is encouraged.

Insulinresistance, commonly associated with polycystic ovarian syndrome (PCOS), raises many unresolved debates about its prevalence, mechanism and true pathological role. Low insulin sensibility may have multiple origins among them genetic molecular defects in pathways of cellular insulin effects. A weight gain and android distribution of fat mass may reveal or increase insulin resistance and hyperinsulinemia. The preexisting unbalanced ovarian steroidogenesis secondary to abnormalities in gene coding for enzymes of P450C17 alpha might be the necessary support facilitating the stimulatory effect of hyperinsulinemia or other factors (LH, IGF1) on ovarian androgens. In practice, the phycisian has to know how to evaluate and to treat insulin resistance in view of its implication in dysovulation and, later on, metabolic and cardiovascular risks. Nutritional education and regular physical exercice are the necessary approaches. The efficacy and indications of metformin and thiazolidinediones have to be further evaluated.

Complications at implantation site of implantable insulin pumps may lead to premature removal. To elucidate the origins and the outcomes of these local adverse events. We investigated seromas of the 'pump-pocket' that have been detected for an eight month-period during the follow-up of such-treated forty type 1 diabetic patients. At the start of study period, skin bacterial flora was sampled at umbilicus and groin, and isolated strains of Staphylococcus epidermidis were preserved in specific vials at -20 degrees C. Each time a seroma was detected at transcutaneous 45 days-refill of pump reservoir, it was sampled for bacterial cultures. Isolated strains of S. epidermidis from seroma were genetically compared to preserved strains of corresponding patients using Pulsed-Field Gel Electrophoresis (PFGE) after genomic restriction by SmaI. Among the ten seromas that occurred after a mean time of 9.9 months since implantation, S. epidermidis were isolated in five cases. Genetic comparison of isolated strains could be performed in three cases. Compared strains showed identical (in 2 cases) or closely related (in one case) PFGE profiles. While the five aseptic seromas resolved with rest, four infected cases required explantations after one to nineteen months in spite of antibiotic therapy and the fifth one persisted without impairment under long-term antibiotics. Our results suggest that seeding from the skin flora is a key-factor determining the severity of pump-pocket complications. We recommend that bacterial investigations of pump-pocket seromas should be systematically performed, while prophylactic measures might include antibiotic cover for each puncture of the pump-pocket.

External pump treatment improves glycemic control, particularly thanks to the continuous basal rate. The pharmacokinetics of the short-acting insulin analog lispro allow a better control of post-prandial hyperglycemia than regular insulin. The use of the short-acting insulin analog in the pump improves HbA1c and blood glucose stability, without increasing the risk of hypoglycemia. Frequent blood glucose self-monitoring is required in order to optimize insulin adjustments, using the retro-active method. Systematic monitoring of urine ketones is also required, for an early detection of any interruption in insulin delivery. Under these conditions, this modality of intensified treatment seems very efficient.

Insulin resistance, which is found in 85-95% of non-insulin-dependent diabetes mellitus (NIDDM) patients, results from three factors: genetic background (which has been widely investigated), nutritional status (mostly obesity and fat distribution) and exercise. Upper body obesity, which can be found in 85% of these subjects, can increase muscular insulin resistance through several mechanisms, the best known being a free fatty acid-induced decrease in intracellular free CoA/acylCoA that inhibits the stimulatory effect of insulin on glycolysis, glucose transport across cell membrane, and glycogen storage. However, muscle insulin resistance in NIDDM exists before adiposity and is likely to induce it. Actually, muscles of subjects at risk for NIDDM exhibit a very early defect in both glycogen storage ability and free fatty acid oxidation capacity that can impair fuel utilization and increase fat storage. Regular exercise induces muscular metabolic changes which can compensate for those diabetogenic defects and thus prove useful in the management of NIDDM. Moreover, exercise has been shown to prevent subjects at risk for NIDDM from developing overt diabetes.

Sixty Type 1 (insulin dependent) and sixty Type 2 (non insulin dependent) diabetic patients attending a diabetology unit were examined in search of limited joint mobility, Dupuytren's disease, flexor tenosynovitis and carpal tunnel syndrome, in comparison with two populations of 60 non diabetic controls matched for sex and age with the Type 1 and the Type 2 diabetic patients. Microangiopathic and neuropathic complications, glycaemic control, blood pressure and tobacco consumption were simultaneously assessed in 39 of the 60 type 1 and in all the type 2 diabetic patients. The prevalence of the various soft tissue hand lesions was higher in both diabetic populations (respectively Type 1 and Type 2) than in their control populations: Limited joint mobility: 33.3 and 26.7% vs 5.0 and 8.3% (both p < 0.01); Dupuytren's disease: 35.0 and 30.0% vs 6.7 and 10.0% (both p < 0.01); flexor tenosynovitis: 23.3 and 16.7% vs 0.0 and 3.3% (p < 0.01 and p < 0.05); carpal tunnel syndrome: 26.7 and 15.0% vs 3.3 and 5% (p < 0.01 and NS). The prevalence of limited joint mobility in Type 1 diabetes was independently associated with increasing age (p < 0.05) and to lower extent with increasing duration of diabetes (p = 0.05), whereas the prevalence of Dupuytren's disease only correlated with increasing age in both types of diabetes (p < 0.05). In Type 2 diabetes, the prevalence of flexor tenosynovitis also increased independently with age (p < 0.05), and the prevalence of limited joint mobility increased in the opposite way to the body mass index after adjustment on age, duration of diabetes and sex (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Independently of its initial mechanism, Type 2 diabetes associates in various degrees disorders in insulin sensibility and secretion. The dissociated insulin resistance among tissues explains the predictable imperfection of insulin therapy in this disease due to frequent weight increase and the potential risks of insulin on atherogenesis raised on the basis of experimental studies. All diabetic subjects are not equally insulin resistant and do not have the same insulin secretory capacity evaluated in practice by means of the response of insulin or C peptide plasma levels to various secreting agents. Intensity and duration of hyperglycaemia, muscular mass, physical activity and way of life, age, weight and fat patterning, the presence of complications, acceptance, education feasibility and compliance are essential in selecting towards insulin therapy. Meanwhile, as the results of the prospective studies in progress become available, it seems that insulin should be restricted to the smallest useful dosage possible and that weight change should be carefully checked within the weeks following initiation of insulin. The future of insulin therapy in Type 2 diabetes requires (1) better selection of patients showing a demonstrated beneficial effect of insulin, (2) the association of insulin with new molecules capable of reducing its dosage and preventing its deleterious effects, (3) a change in the mode of insulin administration, with an appropriate balance between comfort and efficacy, (4) change in the insulin structure towards analogues or compounds related to insulin but with less perverted effects.

The feasibility of the continuous intraperitoneal insulin infusion from implantable programmable systems was evaluated in 17 Type 1 (insulin-dependent) diabetic patients currently treated by external pumps. Eight subjects were using a continuous subcutaneous insulin infusion (cumulated experience: 7.4 patients x years) and nine subjects had a cumulated experience of 61.4 patients x years of continuous intra peritoneal insulin delivery by external pumps. The two studied implantable systems (A and B) were delivering the same pH neutral surfactant-stabilized semi-synthetic human insulin, but at the respective concentrations of 400 units per ml in group A (n = 12) and of 100 units per ml in group B (n = 5), via a peritoneal catheter. The pump was implanted in a subcutaneous pocket created in the abdominal wall under general anesthesia. The reported trial of implantable programmable systems is 21 patient x years with an individual experience of 1.2 +/- 0.4 years (mean +/- SD). A sustained and stable glycaemic control was obtained, as indicated by the haemoglobin A1c: 7.4 +/- 1.3% (normal range: 4.3-6.1%), the mean blood glucose: 7.4 +/- 2.1 mM.l-1, the standard deviation of blood glucose values: 3.4 +/- 0.4 mM.l-1 and the percentages of 13.1 +/- 4.5% and 6.1 +/- 6.1% of blood glucose values respectively over 11 mM.l-1 and under 2.8 mM.l-1 after one year. The only metabolic event to occur was one episode of ketoacidosis secondary to a catheter obstruction. No hypoglycaemic coma occurred contrasting with incidences of 0.54 and 0.05 per patient x year during subcutaneous external and intraperitoneal pumps respectively (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Sixteen patients suffering from symptoms suggestive of idiopathic reactive hypoglycaemia and reproducible during an oral glucose tolerance test when plasma glucose was less than or equal to 2.8 mM, were included in an acute, double-blind and cross-over study to test the efficacy of Miglitol (Bay m1099), a new alpha-glucosidase inhibitor versus placebo. Patients were randomized to ingest 100 mg Miglitol or placebo together with a sucrose solution (45 g/m2 body surface), one week apart. During four hours, plasma glucose levels were continuously monitored and plasma insulin and gastric inhibitory polypeptide (GIP) levels were measured at 30-minute intervals; serum C-peptide concentration was determined at 0, 30, 60 minutes and then every hour. The post-load rise in plasma glucose was significantly blunted by Miglitol, as shown by the reduced plasma glucose peak, the diminished early (0-120 min) area under the glycaemic curve and the decreased rate of plasma glucose rise. Thereafter, plasma glucose nadir was significantly raised and rate of plasma glucose fall was slowed by Miglitol with a concomitant improvement in the hypoglycaemic index. Insulin secretion was dampened as indicated by parallel reduction of plasma insulin and serum C-peptide peaks; morever, early area under the insulin curve and total (0-240 min) area under the C-peptide curve were significantly reduced. Decrease of plasma GIP peak and total area under the GIP curve were also significant. During sucrose tolerance test with Miglitol, hypoglycaemic symptoms were significantly alleviated but intestinal side-effects were common. Blunting the insulin response to glucose directly by delaying glucose absorption and indirectly through reducing GIP secretion, may be a valuable therapeutic approach in reactive hypoglycemia; nevertheless, long-term study with Miglitol are needed, due to the poor intestinal tolerance of this drug in the present acute study.

Disclosure of microalbuminuria gives a hope to improve renal and perhaps cardiovascular outcome of diabetes mellitus by the mean of an early treatment. We studied in 30 diabetic patients for each sex, consecutively admitted to hospital the efficacy of a colorimetric tablet-test for quick screening of microalbuminuria. The results obtained from a 24 hours-urine collection are compared to those observed with a reference radio-immunologic method. In this population whose prevalence for microalbuminuria over 15 micrograms/mn is 30%, the test shows a sensibility and a negative predictive value of 100%, but a specificity and a positive predictive value of about 40%. Else, intensity of positivity follows systolic blood pressure and creatininemia increase. If the good and cheap screening value of the test can be acknowledged, its positivity needs however a precise evaluation by a reference assay before therapeutic decision.