Screening for diabetic retinopathy by ophthalmologists and endocrinologists with pupillary dilation and a nonmydriatic digital camera.

PURPOSE: To assess the effects of pupillary dilation on image quality and certitude of screening diabetic retinopathy by trained endocrinologists using a digital nonmydriatic camera. DESIGN: Prospective, comparative, observational case series. METHODS: One hundred fifty patients with diabetes attending a hospital-based photographic screening clinic had five-field (45 degree) digital retinal imaging and mosaic construction, first through dark-adapted pupils, then after a single application of tropicamide 1%. The 600 sets of images (150 patients, 300 eyes, before and after dilation) were graded independently and in a blinded manner by two endocrinologists and two ophthalmologists, with the consensual opinion on dilated images of the latter serving as the gold standard. The criteria of evaluation were assessment of image quality and certitude of detecting and grading retinopathy. RESULTS: Of 300 eyes, pharmacological mydriasis improved image quality, with an increase in the number of eyes with five good images from seven to 160 and good-quality mosaics from 99 to 233. Dilation allowed better identification of maculopathy in the second eye because there was a decrease in ungradeable central images from 127 to 15 eyes. Dilation increased the number of eyes having retinopathy detected with certainty from 153 to 252 and graded with certainty from 173 to 277. No adverse effects were recorded. CONCLUSIONS: Single application of tropicamide 1% significantly improves image quality and certitude of screening diabetic retinopathy with nonmydriatic camera by endocrinologists.

Chronotropic incompetence to exercise separates low body weight from established anorexia nervosa.

Chronotropic incompetence (CI), characterized by an attenuated heart rate (HR) response to exercise could participate to the limitation of exercise capacity in anorexia nervosa (AN). Therefore, we evaluated the role of cardiac sympathetic responsiveness in AN patients. In addition, the ambulatory value of autonomic control using spectral analysis of heart rate variability (HRV) was determined and correlated to maximal exercise performance. Twenty-two patients hospitalized for weight loss and suspicion of AN were included in the study. All performed a symptom-limited exercise test with measurement of gas exchange for chronotropic response to exercise evaluation. Holter ECG recordings allowed daytime and night-time spectral domain HRV analysis in order to evaluate the alteration of sympathetic control of HR in free-living conditions. CI defined as a failure to achieve 80% of heart rate reserve (%HRR) was observed in 13 (59%) patients (CI+). This group presented a higher body mass deficit than the group without CI (CI-; -35.1 +/- 8.7% versus -26.1 +/- 10.7%; P<0.05). Obviously, patients with a lower body mass index (BMI < 16 kg m(-2), n = 14) revealed a more severe limitation to maximal exercise with a lower peak HR, a lower peak Vo(2), and a lower maximal O(2) pulse (P<0.05). BMI was significantly correlated to peak Vo(2), maximal HR, and %HRR achieved at peak exercise. Daytime HRV parameters reflecting the sympathetic autonomic equilibrium (LF nu, LF/HF ratio) were significantly lower in CI+ patients. Blunted sympathetic response to maximal exercise is frequent and correlated to weight deficit. The present data suggest a major autonomic derangement in AN characterized by a cardiac sympathetic withdrawal.

Assessment of a new insulin preparation for implanted pumps used in the treatment of type 1 diabetes.

BACKGROUND: Implanted insulin pumps using the peritoneal route provide long-term improvement of glucose control compared with subcutaneous insulin therapy in type 1 diabetes (T1D) patients. The stability of insulin preparation is critical for a safe use in implanted pumps. Insuman implantable(®) (400 IU/mL) (Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany), a recombinant human insulin, has been developed as a replacement for Insuplant(®) (Aventis Pharma, Frankfurt am Main, Germany), a semisynthetic insulin, the only one used so far. The aim of the study was to demonstrate the noninferiority of Insuman versus Insuplant, in terms of safety and effectiveness when used in implanted pumps. SUBJECTS AND METHODS: The patients enrolled, currently treated for T1D by the Medtronic MiniMed (Northridge, CA) implantable pump model 2007 with Insuplant, were randomized into two study arms and received either Insuman or Insuplant for four pump refill cycles. Each pump refill cycle was 40±5 days. The co-primary end points included glycated hemoglobin (HbA1c) change from baseline and pump infusion accuracy. RESULTS: In total, 169 patients were randomized. Noninferiority of Insuman versus Insuplant was demonstrated both for the HbA1c change from baseline (as a percentage) with intergroup difference of 95% confidence interval (-0.36;+0.11) and for the infusion accuracy assessed by the measured percentage of error at pump refill, as shown by intergroup difference of 95% confidence interval (-5.81; -0.50), in per-protocol populations, although the insulin daily dose was similar. Severe hypoglycemia occurred at least once in 12 versus 11 patients, respectively, and metabolic or technical adverse events were comparable. CONCLUSIONS: Findings suggest that Insuman can safely and effectively replace Insuplant in implanted pumps.

Assessment of patient-led or physician-driven continuous glucose monitoring in patients with poorly controlled type 1 diabetes using basal-bolus insulin regimens: a 1-year multicenter study.

OBJECTIVE: The benefits of real-time continuous glucose monitoring (CGM) have been demonstrated in patients with type 1 diabetes. Our aim was to compare the effect of two modes of use of CGM, patient led or physician driven, for 1 year in subjects with poorly controlled type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes aged 8-60 years with HbA(1c) ≥ 8% were randomly assigned to three groups (1:1:1). Outcomes for glucose control were assessed at 1 year for two modes of CGM (group 1: patient led; group 2: physician driven) versus conventional self-monitoring of blood glucose (group 3: control). RESULTS: A total of 257 subjects with type 1 diabetes underwent screening. Of these, 197 were randomized, with 178 patients completing the study (age: 36 ± 14 years; HbA(1c): 8.9 ± 0.9%). HbA(1c) improved similarly in both CGM groups and was reduced compared with the control group (group 1 vs. group 3: -0.52%, P = 0.0006; group 2 vs. group 3: -0.47%, P = 0.0008; groups 1 + 2 vs. group 3: -0.50%, P < 0.0001). The incidence of hypoglycemia was similar in the three groups. Patient SF-36 questionnaire physical health score improved in both experimental CGM groups (P = 0.004). Sensor consumption was 34% lower in group 2 than in group 1 (median [Q1-Q3] consumption: group 1: 3.42/month [2.20-3.91] vs. group 2: 2.25/month [1.27-2.99], P = 0.001). CONCLUSIONS: Both patient-led and physician-driven CGM provide similar long-term improvement in glucose control in patients with poorly controlled type 1 diabetes, but the physician-driven CGM mode used fewer sensors.

No loss of chance of diabetic retinopathy screening by endocrinologists with a digital fundus camera.

OBJECTIVE: To compare the efficacy of the diabetic retinopathy (DR) screening with digital camera by endocrinologists with that by specialist and resident ophthalmologists in terms of sensitivity, specificity, and level of "loss of chance." RESEARCH DESIGN AND METHODS: In a cross-sectional study, 500 adult diabetic patients (1,000 eyes) underwent three-field retinal photography with a digital fundus camera following pupillary dilatation. Five endocrinologists and two ophthalmology residents underwent 40 h of training on screening and grading of DR and detection of associated retinal findings. A κ test compared the accuracy of endocrinologist and ophthalmology resident screening with that performed by experienced ophthalmologists. Screening efficiency of endocrinologists was evaluated in terms of "loss of chance," i.e., missed diagnoses that required ophthalmologist referrals. RESULTS: The mean weighted κ of DR screening performed by endocronologists was similar to that of ophthalmology residents (0.65 vs. 0.73). Out of 456 DR eyes, both endocrinologists and ophthalmology residents misdiagnosed only stage 1 DR (36 and 14, respectively), which did not require ophthalmologist referral. There were no significant differences between endocrinologists and ophthalmology residents in terms of diabetic maculopathy and incidental findings except for papillary cupping and choroidal lesions, which were not the main purpose of the study or of the training. CONCLUSIONS: The endocrinologist with specific training for DR detection using a three-field digital fundus camera with pupillary dilatation can perform a reliable DR screening without any loss of chance for the patients when compared with identical evaluation performed by experienced ophthalmologists.

A recent survey confirms the efficacy and the safety of implanted insulin pumps during long-term use in poorly controlled type 1 diabetes patients.

BACKGROUND: This article reports a prolonged trial with insulin pumps implanted in patients with type 1 diabetes showing poor glucose control and a high rate of complications. METHODS: We reviewed data from 181 patients undergoing implanted insulin pump therapy. Analysis included hemoglobin A1c (HbA1c) values, body weight, and diabetes complications status. RESULTS: At implantation, the mean age was 43 (range, 19-72) years, mean duration of diabetes was 22.2 (2-52) years, and mean body weight was 68.6 (43-104) kg. The complication status involved retinopathy (62% of patients), neuropathy (34.6%), nephropathy (26%), and cardiovascular disease (14%). Patients' previous insulin treatment regimen was multiple daily injections (17.1%) or continuous subcutaneous insulin infusion (82.9%). HbA1c levels significantly dropped from 7.9 ± 1.2% to 7.6 ± 1.2% after 1 year (P < 0.01) and remained within the range of 7.5-7.6% for up to 5 years. No significant variation of body weight or complications status occurred. CONCLUSIONS: Implanted insulin pump therapy demonstrates long-term benefits in type 1 diabetes patients who have poor prognosis under intensive subcutaneous treatment.

[Generic carbamazepine-induced subacute adrenal insufficiency?]. / Décompensation surrénalienne subaiguë induite par un médicament générique de la carbamazépine?

Iatrogenic causes of adrenal insufficiency in Addison's disease are exceptional. We report the case of a patient with a history of epilepsy (taking carbamazepine, Tégrétol LP) and Addison's disease (treated by hydrocortisone (HDC) 30 mg/d, Dectancyl 0,5 mg/d, Florinef 50 mg/d). Recent digestive disorders required emergency hospitalization. The physical examination was normal and laboratory tests showed hyponatremia, hyperkalemia, and elevated serum ACTH. The course was rapidly favorable after rehydration and up-titration of the drug regimen. No triggering factor was identified, but the Tégrétol LP had been replaced for 3 months by a generic drug with the same quantity of active ingredients and the same bioavailability, but with a different excipient (the generic drug was not encapsulated). Could these differences have increased the serum level of carbamazepine and lead to more rapide HDC metabolism by enzymatic induction? Could poorer digestive tolerance have decreased HDC absorption? The hypothesis of carbamazepine overdosage is unlikely because the assay remained within the therapeutic range and hyperkaliemia would favor adrenal decompensation. In conclusion, this single case cannot prove drug interaction but does point out the importance of being prudent when modifying a well--tolerated regimen in a patient with Addison's disease.

Alteration of the QT rate dependence in anorexia nervosa.

Myocardial repolarization has been evaluated in patients with anorexia nervosa (AN) with conflicting results. The authors postulated that dynamic alterations in QT interval adaptation could characterize these patients. This study compared QT dynamicity along RR intervals from 24-hour ECG data of patients with and without AN. Twenty-five patients (23 women) fulfilling the Diagnostic and Statistical Manual (DSM IV) criteria for AN were included in the study. All underwent 24-hour ECG Holter recordings, allowing QT and RR measurements, and heart rate variability (HRV) analysis in free-living conditions. A group of 25 sex- and age-matched healthy subjects served as controls. Compared with controls, AN patients presented with relative bradycardia, more particularly during night periods but neither mean QT nor corrected mean QT length (calculated using Bazett formula) over the 24 hours of monitoring differed. However, QT/RR slope was found significantly enhanced compared with normals (-2.00 +/- 0.53 vs - 1.42 +/- 0.40) (P = 0.006): QT length related to heart rate was found longer for a heart rate <55 beats/min in AN. Mean 24-hours QT length appears unaltered in AN in the absence of electrolytic disorders. However, the QT/RR relationship was enhanced reflecting the specific autonomic imbalance encountered in this population. The clinical implications of such findings need to be discussed since an equivalent enhancement of QT/RR slope has been described after myocardial infarction in patients presenting life-threatening ventricular arrhythmias.