S. Franc

The Diabeo Software Enabling Individualized Insulin Dose Adjustments Combined With Telemedicine Support Improves HbA1c in Poorly Controlled Type 1 Diabetic Patients A 6-month, randomized, open-label, parallel-group, multicenter trial (TeleDiab 1 Study)

OBJECTIVE To demonstrate that Diabeo software enabling individualized insulin dose adjustments combined with telemedicine support significantly improves HbA1c in poorly controlled type 1 diabetic patients. RESEARCH DESIGN AND METHODS In a six-month open-label parallel-group, multicenter study, adult patients (n = 180) with type 1 diabetes (>1 year), on a basal-bolus insulin regimen (>6 months), with HbA1c ≥8%, were randomized to usual quarterly follow-up (G1), home use of a smartphone recommending insulin doses with quarterly visits (G2), or use of the smartphone with short teleconsultations every 2 weeks but no visit until point end (G3). RESULTS Six-month mean HbA1c in G3 (8.41 ± 1.04%) was lower than in G1 (9.10 ± 1.16%; P = 0.0019). G2 displayed intermediate results (8.63 ± 1.07%). The Diabeo system gave a 0.91% (0.60; 1.21) improvement in HbA1c over controls and a 0.67% (0.35; 0.99) reduction when used without teleconsultation. There was no difference in the frequency of hypoglycemic episodes or in medical time spent for hospital or telephone consultations. However, patients in G1 and G2 spent nearly 5 h more than G3 patients attending hospital visits. CONCLUSIONS The Diabeo system gives a substantial improvement to metabolic control in chronic, poorly controlled type 1 diabetic patients without requiring more medical time and at a lower overall cost for the patient than usual care.

A Comprehensive Description of Muscle Symptoms Associated with Lipid-Lowering Drugs

AbstractA spectrum of disease from myalgia to rhabdomyolysis exists as classic side-effect of lipid-lowering treatment (LLT). While myopathy has generated considerable interest, mild musculo-skeletal symptoms are poorly assessed. Objective: To report on the muscular side-effects of LLT with a particular focus on the overlooked milder ones. Methods: Hyperlipidemic patients under LLT and complaining of muscle symptoms were asked to complete a self administered questionnaire. Among the 815 adult hyperlipidemic patients under LLT and referred to the cardiovascular prevention unit of La Pitie Hospital, 165 patients answered that they experienced, or had experienced, muscle symptoms which they attributed to the LLT. One hundred and thirty three of these completed and returned a self-administered questionnaire. Results: A clear chronological link between symptoms and the LLT was revealed, either because they appeared soon after drug initiation or because of an improvement after drug withdrawal.While cramps and stiffness were the most frequent symptoms, tendonitis-associated pain was surprisingly common, reported in almost half the cases. Pain was often diffuse with a focus on a given location, mainly lower limbs. 39% of patients had used analgesics for pain relief. Unpredictably, a majority of patients reported pain during rest and the lying position. In a number of cases, a family history of pain under LLT was revealed. Conclusion: The impact of these mild symptoms on daily activities might not be negligible in a subset of patients. The role and importance of a genetic background predisposing to low-grade myopathy deserves further investigation.

Complete surgical lymph node resection does not prevent authentic recurrences of medullary thyroid carcinoma

BACKGROUND Medullary thyroid carcinoma is a rare tumour derived from the thyroid parafollicular calcitonin‐secreting cells. Calcitonin is a very specific marker of this cancer that allows preoperative diagnosis. Serum calcitonin assay is particularly useful to define the postoperative state of patients (cured, apparently cured, not cured) and, because of its great sensitivity, it has a major place in the postoperative follow‐up.

Glycaemic control in type 2 diabetic patients on chronic haemodialysis: use of a continuous glucose monitoring system

BACKGROUND The proportion of diabetic patients undergoing haemodialysis is rapidly increasing. Glucose control among such patients is difficult to assess. We aimed to evaluate the clinical performance of a continuous glucose monitoring system (CGMS) in type 2 diabetic patients on chronic haemodialysis. METHODS We used a 4-day CGMS to monitor glucose levels in 19 haemodialysed type 2 diabetic patients (HD T2) including 2 days with and 2 days without dialysis session, and 39 non-HD T2 in a double-centre study. RESULTS The glucose concentration according to the glucose meter and CGMS were correlated in HD T2 patients (r = 0.90, P < 0.0001) and in non-HD T2 patients (r = 0.81, P < 0.0001). The relative absolute difference (RAD) between glucose determined by a glucose meter and glucose determined by the CGMS did not differ between HD T2 and non-HD T2 patients (9.2 +/- 10.5 vs. 8.2 +/- 7.6%; P = 0.165). Glycated haemoglobin (A1c) and mean glucose concentration were strongly correlated in non-HD T2 patients (r = 0.71; P < 0.0001) but weakly correlated in HD T2 patients (r = 0.47; P = 0.042). Fructosamine was correlated with the mean glucose concentration in non-HD T2 (r = 0.67; P < 0.0001) but not in HD T2 patients (r = 0.04; P = 0.88). CONCLUSION CGM is a validated marker of glycaemic control in HD diabetic patients. This tool showed that A1c and fructosamine, despite being good markers of glycaemic control in non-HD diabetic patients, are of poor value in HD diabetic patients.

Real-life application and validation of flexible intensive insulin-therapy algorithms in type 1 diabetes patients

AIMS Flexible intensive insulin therapy (FIT) has become the reference standard in type 1 diabetes. Besides carbohydrate counting (CHO), it requires the use of algorithms to adjust prandial insulin doses to the number of CHO portions. As recourse to standard algorithms is usual when initiating FIT, the use of personalized algorithms would also allow more precise adjustments to be made. The aim of the present study was to validate personalized prandial algorithms for FIT as proposed by Howorka et al. in 1990. METHODS We conducted a 4-month observational study of 35 patients with type 1 diabetes, treated with FIT for at least 6 months, who were already using Howorkas prandial algorithms (meal-related and correctional insulin doses for blood glucose increases induced by CHO). These patients were asked to use a personal digital assistant (PDA) phone with an electronic diary (instead of a paper one) to take advantage of the computerized data-collection system to assess the quality of postprandial metabolic control. RESULTS Whatever the number of CHO portions, mean postprandial blood glucose values remained close to the target of 7.8mmol/L, and the compensatory algorithm allowed precise correction of preprandial hyperglycaemia. In fact, the algorithms for meal-related and correctional insulin doses at the end of the study did not differ significantly from those initially calculated, but they generally differed from one patient to another. CONCLUSION In type 1 diabetic patients treated with FIT, the use of individualized parameters permits fast and accurate adjustment of mealtime insulin doses, leading to good control of the postprandial state.

Reimbursement for continuous glucose monitoring: a European view.

Different systems for continuous glucose monitoring (CGM) are available on the European market. There is no unlimited reimbursement for CGM use in any European country, but in some countries, reimbursement exists for certain clinical indications. The aim of this commentary is to describe the different reimbursement situations across Europe for this innovative but costly technology, as a prelude to establishing more uniform use. From the perspective of many scientists and clinicians, a number of randomized controlled trials have demonstrated the efficacy of real-time CGM versus self-monitoring of blood glucose, at least for hemoglobin A1c reduction. Nevertheless, according to many health care professionals and potential CGM users, national health services and health insurance organizations are reluctant to reimburse CGM. Imminent technological and manufacturing developments are expected to reduce the day-to-day costs of CGM.

In Vitro and In Vivo Modulation of Alternative Splicing by the Biguanide Metformin

Major physiological changes are governed by alternative splicing of RNA, and its misregulation may lead to specific diseases. With the use of a genome-wide approach, we show here that this splicing step can be modified by medication and demonstrate the effects of the biguanide metformin, on alternative splicing. The mechanism of action involves AMPK activation and downregulation of the RBM3 RNA-binding protein. The effects of metformin treatment were tested on myotonic dystrophy type I (DM1), a multisystemic disease considered to be a spliceopathy. We show that this drug promotes a corrective effect on several splicing defects associated with DM1 in derivatives of human embryonic stem cells carrying the causal mutation of DM1 as well as in primary myoblasts derived from patients. The biological effects of metformin were shown to be compatible with typical therapeutic dosages in a clinical investigation involving diabetic patients. The drug appears to act as a modifier of alternative splicing of a subset of genes and may therefore have novel therapeutic potential for many more diseases besides those directly linked to defective alternative splicing.

Insulin‐based strategies to prevent hypoglycaemia during and after exercise in adult patients with type 1 diabetes on pump therapy: the DIABRASPORT randomized study

To validate strategies to prevent exercise‐induced hypoglycaemia via insulin‐dose adjustment in adult patients with type 1 diabetes (T1D) on pump therapy.

Accuracy of a new patch pump based on a microelectromechanical system (MEMS) compared to other commercially available insulin pumps: results of the first in vitro and in vivo studies.

Background: The JewelPUMP™ (JP) is a new patch pump based on a microelectromechanical system that operates without any plunger. The study aimed to evaluate the infusion accuracy of the JP in vitro and in vivo. Methods: For the in vitro studies, commercially available pumps meeting the ISO standard were compared to the JP: the MiniMed® Paradigm® 712 (MP), Accu-Chek® Combo (AC), OmniPod® (OP), Animas® Vibe™ (AN). Pump accuracy was measured over 24 hours using a continuous microweighing method, at 0.1 and 1 IU/h basal rates. The occlusion alarm threshold was measured after a catheter occlusion. The JP, filled with physiological serum, was then tested in 13 patients with type 1 diabetes simultaneously with their own pump for 2 days. The weight difference was used to calculate the infused insulin volume. Results: The JP showed reduced absolute median error rate in vitro over a 15-minute observation window compared to other pumps (1 IU/h): ±1.02% (JP) vs ±1.60% (AN), ±1.66% (AC), ±2.22% (MP), and ±4.63% (OP), P < .0001. But there was no difference over 24 hours. At 0.5 IU/h, the JP was able to detect an occlusion earlier than other pumps: 21 (19; 25) minutes vs 90 (85; 95), 58 (42; 74), and 143 (132; 218) minutes (AN, AC, MP), P < .05 vs AN and MP. In patients, the 24-hour flow error was not significantly different between the JP and usual pumps (–2.2 ± 5.6% vs –0.37 ± 4.0%, P = .25). The JP was found to be easier to wear than conventional pumps. Conclusions: The JP is more precise over a short time period, more sensitive to catheter occlusion, well accepted by patients, and consequently, of potential interest for a closed-loop insulin delivery system.

Can Postprandial Blood Glucose Excursion Be Predicted in Type 2 Diabetes

OBJECTIVE We investigated the relationship between carbohydrate intake and postprandial blood glucose (BG) levels to determine the most influential meal for type 2 diabetic subjects treated with basal insulin and needing prandial insulin. RESEARCH DESIGN AND METHODS Three-day BG profiles for 37 type 2 diabetic subjects, with A1C levels of 7.7%, treated with sulfonylurea and metformin, and well titrated on insulin glargine, were analyzed using a continuous glucose monitoring system. Food intake from 680 meals was recorded and quantified during continuous glucose monitoring. RESULTS The median BG excursion (ΔBG) was higher at breakfast than at lunch or dinner (111 [81; 160] vs. 69.5 [41.5; 106] and 82.5 mg/dl [53; 119] mg/dl, P < 0.0001). There was a weak overall correlation between ΔBG and carbohydrate intake. Correlation improved when mealtime was taken into account. Simple relationships were established: ΔBG (mg/dl) = 65 × carbohydrate/body weight + 73 for breakfast (R2 = 0.20, P < 0.0001); the slope was reduced by half at lunch and by one-third at dinner. Twelve relevant variables likely to affect ΔBG were integrated into a polynomial equation. This model accounted for 49% of ΔBG variability. Two groups of patients were identified: responders, in whom ΔBG was well correlated with carbohydrate intake (R2 ≥ 0.30, n = 8), and nonresponders (R2 < 0.30, n = 29). Responders exhibited a greater insulinopenic profile than nonresponders. CONCLUSIONS The carbohydrate intake in responders clearly drives ΔBG, whereas, in nonresponders, other factors predominate. This sort of characterization should be used to guide therapeutic choices toward more targeted care with improved type 2 diabetes management.