Similar HbA1c reduction and hypoglycaemia with variable- vs fixed-time dosing of basal insulin peglispro in type 1 diabetes: IMAGINE 7 study.

Aims: To compare 24-hour fixed-time basal insulin peglispro (BIL) dosing with 8- to 40-hour variable-time BIL dosing for glycaemic control and safety in patients with type 1 diabetes. Primary outcome was non-inferiority of BIL variable-time dosing compared with fixed-time dosing for glycated haemoglobin (HbA1c) change after 12-week treatment (margin = 0.4%).

Basal insulin peglispro versus insulin glargine in insulin-naïve type 2 diabetes: IMAGINE 2 randomized trial.

Aims: To compare, in a double-blind, randomized, multi-national study, 52- or 78-week treatment with basal insulin peglispro or insulin glargine, added to pre-study oral antihyperglycaemic medications, in insulin-naïve adults with type 2 diabetes.

Material And Methods: The primary outcome was non-inferiority of peglispro to glargine with regard to glycated haemoglobin (HbA1c) reduction (margin = 0.4%).

Skin collagen pentosidine and fluorescence in diabetes were predictors of retinopathy progression and creatininemia increase already 6years after punch-biopsy.

Objective: Advanced glycation end products (AGEs) of collagens appear to contribute to microvascular complications in diabetes. Do high concentrations of AGEs in skin collagen predict accelerated progression of these complications after 6 years and indicate the need for tighter anti-diabetic treatment?

Design And Methods: We measured two AGE parameters in collagen extracted from skin punch-biopsies: pentosidine and fluorescence at 370/440nm, as markers and predictors of microvascular complications, in 30 patients with diabetes (14 type-1, 16 type-2) without renal insufficiency, and in age- and gender-matched normoglycemic controls, followed at Hôtel-Dieu in Paris.

Results: At the time of biopsy, marked increases in pentosidine (p=0.

Evolution of diabetes insulin delivery devices.

The first manufactured insulin pump was introduced in the 1970s and the first insulin pens in 1985; since then, many improvements have been made to both devices. The advantages of pens over syringes have been confirmed in numerous studies and include greater accuracy, ease of use, patient satisfaction, quality of life, and adherence. United States claims database analyses indicate that the improved adherence made possible by use of an insulin pen has the potential to reduce diabetes care costs when compared with using a vial and syringe.

Lacosamide in painful diabetic neuropathy: an 18-week double-blind placebo-controlled trial.

Unlabelled: The efficacy and tolerability of oral lacosamide (200, 400, and 600 mg/day) was evaluated in patients with painful diabetic neuropathy in a double-blind, randomized, placebo-controlled trial. The primary target dose to be confirmed was lacosamide 400 mg/day. Efficacy was assessed by changes in pain scale scores from baseline, with changes over the last 4 weeks of the 12-week maintenance period regarded as the primary endpoint.

Comparison of a multiple daily insulin injection regimen (basal once-daily glargine plus mealtime lispro) and continuous subcutaneous insulin infusion (lispro) in type 1 diabetes: a randomized open parallel multicenter study.

Objective: Insulin pump therapy (continuous subcutaneous insulin infusion [CSII]) and multiple daily injections (MDIs) with insulin glargine as basal insulin and mealtime insulin lispro have not been prospectively compared in people naïve to either regimen in a multicenter study. We aimed to help close that deficiency.

Research Design And Methods: People with type 1 diabetes on NPH-based insulin therapy were randomized to CSII or glargine-based MDI (both otherwise using lispro) and followed for 24 weeks in an equivalence design.

Basal-bolus therapy with insulin detemir using the 303 algorithm in the US PREDICTIVE 303 trial.

Introduction: The aim of this study was to compare a simplified patient-driven algorithm (303 Algorithm) to physician-driven adjustments in a subset of 193 patients with type 2 diabetes from the PREDICTIVE 303 study who were using basal-bolus insulin therapy.

Methods: PREDICTIVE 303 was a 26-week, randomized, phase 4 study, in which subjects were either instructed to adjust their insulin detemir dose every 3 days by +/-3 units if mean fasting plasma glucose (FPG) values were above 110 mg/dL or below 80 mg/dL (303 Algorithm), or had physicians adjust the insulin detemir dose according to usual practice (Standard-of-care).

Results: Patients in both groups achieved similar reductions in glycated hemoglobin (-0.

Cyclic relationships between diabetic nephropathy and cardiovascular risk factors.

The most common cause of death in diabetes is cardiovascular. Diabetic nephropathy has an important role in cardiovascular disease among susceptible diabetic patients. What is not well appreciated is that independent cardiovascular death risk factors (e.

Inhaled insulin: promises and concerns.

Since the introduction of Pfizer Exubera in the early 1990s, a number of other inhaled insulin solutions have been developed. This article provides an overview of inhaled insulin systems developed by Pfizer, Novo Nordisk, MannKind, and Lilly, three of which are currently in phase 3 trials. The strengths and weaknesses of each product, as well as the general technologies (liquid vs dry powder), are evaluated.

Improving glycemic control with insulin detemir using the 303 Algorithm in insulin naïve patients with type 2 diabetes: a subgroup analysis of the US PREDICTIVE 303 study.

Objective: PREDICTIVE 303 was a 26-week, prospective, randomized, open-label, multi-center study in patients with type 2 diabetes that investigated whether patient-driven adjustments of insulin detemir doses using the 303 Algorithm achieved similar glycemic control compared to standard-of-care, physician-driven adjustments in doses. This post hoc sub-analysis evaluates insulin naïve patients on oral anti-diabetic drugs (OADs) who were directed to start on once-daily insulin detemir as add-on therapy to any other glucose-lowering regimens.

Methods: Patients in the 303 Algorithm group were instructed to adjust their detemir dose every 3 days based on mean fasting plasma glucose (FPG) values using a simple algorithm: mean FPG < 80 mg/dL, reduce dose by 3 units; between 80-110mg/dL, no change; > 110mg/dL, increase by 3 units.

The usage of a simplified self-titration dosing guideline (303 Algorithm) for insulin detemir in patients with type 2 diabetes--results of the randomized, controlled PREDICTIVE 303 study.

The Predictable Results and Experience in Diabetes through Intensification and Control to Target: An International Variability Evaluation 303 (PREDICTIVE 303) Study (n = 5604) evaluated the effectiveness of insulin detemir, a long-acting basal insulin analogue, using a simplified patient self-adjusted dosing algorithm (303 Algorithm group) compared with standard-of-care physician-driven adjustments (Standard-of-care group) in a predominantly primary care setting, over a period of 6 months. Insulin detemir was to be started once-daily as add-on therapy to any other glucose-lowering regimens or as a replacement of prestudy basal insulin in patients with type 2 diabetes. Investigator sites rather than individual patients were randomized to either the 303 Algorithm group or the Standard-of-care group.

Continuous intraperitoneal insulin infusion does not increase the risk of organ-specific autoimmune disease in type 1 diabetic patients: results of a multicentric, comparative study.

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.

[Inhaled insulin, new perspective for insulin therapy].

Since the discovery of insulin and its use in diabetes care, patients, physicians and nurses dream of another way of insulin administration than the subcutaneous injections actually used. Different types of insulin administration have been evaluated and, particularly, that using the pulmonary route. The use of this alternative method to deliver insulin may result in improved patient compliance, facilitate intensified therapies and avoid the delay of initiating insulin administration because patient's reluctance.

Association between a protein polymorphism in the start codon of the vitamin D receptor gene and severe diabetic retinopathy in C-peptide-negative type 1 diabetes.

Context: The vitamin D (VD) receptor (VDR) is extensively expressed in retina. The plasma concentration of 1,25-dihydroxyvitamin D3 has been inversely correlated with the severity of diabetic retinopathy (DR), which raises the possibility that VD, through its antiinflammatory, antioxidant, antiproliferative, and antiangiogenic properties, may protect diabetic retina. The TaqI VDR polymorphism has been associated with severe DR.

The T-786C and C774T endothelial nitric oxide synthase gene polymorphisms independently affect the onset pattern of severe diabetic retinopathy.

Genetic factors could be implicated in the pathogenesis of severe diabetic retinopathy (DR). Recently, we reported a strong association between the eNOS4b/a endothelial nitric oxide synthase (eNOS) polymorphism and severe DR. To examine whether T-786C and C774T eNOS polymorphisms are involved in severe DR, 254 Caucasians with longstanding C-peptide-negative type 1 diabetes, 128 patients with absent/mild DR (control group), and 126 patients with preproliferative/proliferative DR (study group) were genotyped.

Insulin detemir used in basal-bolus therapy in people with type 1 diabetes is associated with a lower risk of nocturnal hypoglycaemia and less weight gain over 12 months in comparison to NPH insulin.

Aim: The aim of this study was to compare the long-term safety and efficacy of twice-daily insulin detemir or NPH insulin as the basal component of basal-bolus therapy in people with type 1 diabetes.

Methods: A multicentre, open-label, parallel-group study was conducted over 12 months and completed by 308 people (from an original randomized cohort of 428). Patients were randomized in a 2:1 ratio to receive insulin detemir or NPH insulin before breakfast and dinner, with insulin aspart at mealtimes.

Combined improvements in implantable pump technology and insulin stability allow safe and effective long term intraperitoneal insulin delivery in type 1 diabetic patients: the EVADIAC experience.

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.

Effects of dipeptide administration on hypoglycaemic counterregulation in type 1 diabetes.

Objectives: To investigate if a dipeptide made of glutamine and alanine is able to contribute to the recovery from insulin-induced hypoglycaemia in type 1 diabetes.

Research Design And Methods: Fifteen adult type 1 patients were randomly assigned to study group (n=7): intravenous infusion of 20 g Dipeptiven in normal saline (i.e.

Inhaled insulin for the treatment of diabetes: projects and devices.

A non-invasive alternative to insulin injections would represent a major improvement for Type 1 and 2 insulin-treated patients. The lung is the only route which allows bio-availability of insulin, approaching 10% without absorption enhancers. However, the reproducibility of the plasma response to the pulmonary insulin is similar to subcutaneous insulin analogues, that is to say, relatively poor.

Accuracy of the continuous glucose monitoring system in inpatient and outpatient conditions.

Objective: To evaluate in inpatient and outpatient conditions, using only non-calibration data, the accuracy of the Continuous Glucose Monitoring System (CG-MS).

Research Design And Methods: Twelve, 21 and 20 type 1 diabetic patients participated in 3- day inhospital, 6-day ambulatory (i.e.

[How I explore...glycemic kinetics by continuous glucose monitoring].

The improvement of diabetic patients' glycaemic status requires an increase of fingerstick blood glucose measurements. Among the possibilities available to assess diabetes' control, we will consider new systems of continuous interstitial glucose monitoring. After a brief description of the devices presently commercialized, we will discuss their indications and their limitations, as well as their future prospects in a possible "closed loop" insulin delivery according to blood glucose level.

Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart.

Objective: Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals.

Research Design And Methods: This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively.