OBJECTIVE -To assess safety, efficacy, and tolerability of pramlintide dose escalation with proactive mealtime insulin reduction, followed by insulin optimization, in patients with type 1 diabetes. RESEARCH DESIGN AND METHODS-This 29-week, double-blind, placebocontrolled study randomized 296 patients to pramlintide or placebo as an adjunct to insulin. During initiation, pramlintide was escalated from 15 to 60 g/meal (15-g increments) with recommended reductions (30 -50%) in mealtime insulin. Insulin was subsequently adjusted to optimize glycemic control. End points included safety and change in HbA 1c (A1C), postprandial glucose, insulin, weight, and tolerability. ; P Ͻ 0.0005) and weight (pramlintide Ϫ1.3 Ϯ 0.30, placebo ϩ1.2 Ϯ 0.30 kg; P Ͻ 0.0001). At week 29, insulin dose decreased by 28 and 4% in pramlintide-and placebo-treated groups, respectively. Nausea, reported by 63 and 36% of patients in pramlintide and placebo groups (P Ͻ 0.01), respectively, was predominately mild to moderate in intensity. Severe hypoglycemia rates were low in both groups (pramlintide 0.57 Ϯ 0.09, placebo 0.30 Ϯ 0.06 event rate/patient-year; P Ͻ 0.05), with increased rates observed in patients remaining at 30 g pramlintide. RESULTSCONCLUSIONS -Pramlintide dose escalation with reduced mealtime insulin was effective during therapy initiation in patients with type 1 diabetes. While both groups experienced equivalent A1C reductions relative to placebo, pramlintide-treated patients experienced reductions in postprandial glucose excursions and weight, not achievable with insulin therapy alone. Diabetes Care 29:2189 -2195, 2006A mylin, a glucoregulatory hormone cosecreted with insulin from pancreatic ␤-cells (1), regulates postprandial glucose appearance by slowing gastric emptying (2), suppressing postprandial glucagon secretion (3), and reducing food intake (4,5). These actions complement effects of insulin; thus, both hormones act together to maintain postprandial glucose homeostasis. Amylin is deficient in patients with type 1 diabetes and in insulin-using patients with type 2 diabetes (1).Pramlintide, the active ingredient in the SYMLIN (pramlintide acetate) injection (6), is an analog of amylin and the first noninsulin treatment for patients with type 1 diabetes since insulin was introduced. It is indicated as adjunct treatment in patients with type 1 and type 2 diabetes who use mealtime insulin and have not achieved desired glycemic control despite optimal insulin therapy. Through actions similar to those of amylin, pramlintide reduces postprandial glucose concentrations, improves overall glycemic control (HbA 1c [A1C]) (7,8), and results in significant weight reductions compared with insulin therapy alone (9).In previous studies, pramlintidetreated patients with type 1 diabetes experienced more nausea and severe hypoglycemia during therapy initiation than placebo-treated patients (7,8). Nausea was dose dependent, mostly mild or moderate in intensity, occurred early in therapy, and dissipated over time (7,8). Risk of insulin-induced...

AimsBasal insulin (BI) treatment initiation and dose titration in type 2 diabetes (T2DM) are often delayed. Such “clinical inertia” results in poor glycaemic control and high risk of long‐term complications. This survey aimed to determine healthcare professional (HCP) and patient attitudes to BI initiation and titration.MethodsAn online survey (July–August 2015) including HCPs and patients with T2DM in the USA, France and Germany. Patients were ≥18 years old and had been on BI for 6 to 36 months, or discontinued BI within the previous 12 months.ResultsParticipants comprised 386 HCPs and 318 people with T2DM. While >75% of HCPs reported discussing titration at the initiation visit, only 16% to 28% of patients remembered such discussions, many (32%–42%) were unaware of the need to titrate BI, and only 28% to 39% recalled mention of the time needed to reach glycaemic goals. Most HCPs and patients agreed that more effective support tools to assist BI initiation/titration are needed; patients indicated that provision of such tools would increase confidence in self‐titration. HCPs identified fear of hypoglycaemia, failure to titrate in the absence of symptoms, and low patient motivation as important titration barriers. In contrast, patients identified weight gain, the perception that titration meant worsening disease, frustration over the time to reach HbA1c goals and fear of hypoglycaemia as major factors.ConclusionA disconnect exists between HCP‐ and patient‐perceived barriers to effective BI titration. To optimize titration, strategies should be targeted to improve HCP–patient communication, and provide support and educational tools.

Supplementation of vitamin E in NIDDM leads to enrichment of LDL and LDL subfractions and reduced susceptibility to oxidation. Despite a greater percentage increase in vitamin E content in small dense LDL, it remained substantially more susceptible to oxidation than was buoyant LDL. This suggests that dense, LDL may gain less protection against oxidation from antioxidant supplementation than does larger, more buoyant LDL. In contrast to previous reports, vitamin E supplementation did not reduce glycation of intracellular or plasma proteins.

OBJECTIVETo compare two self-titration algorithms for initiating and escalating prandial insulin lispro in patients with type 2 diabetes inadequately controlled on basal insulin. RESEARCH DESIGN AND METHODSThe trial was designed as two independent, multinational, parallel, open-label studies (A and B), identical in design, to provide substantial evidence of efficacy and safety in endocrine and generalist settings. Subjects were 18-85 years old (study A: N = 528; study B: N = 578), on basal insulin plus oral antidiabetic drugs for ‡3 months, and had an HbA 1c 7.0% to £12.0% (>53.0 to £107.7 mmol/mol). Once optimized on insulin glargine, subjects were randomized to one of two self-titration algorithm groups adjusting lispro either every day (Q1D) or every 3 days (Q3D) for 24 weeks. The primary outcome was the change in HbA 1c from baseline. The primary and secondary objectives were evaluated for the overall population and subjects ‡65 years old. . The incidence and rate of hypoglycemia were similar for Q3D and Q1D in both studies. In general, no clinically relevant differences were found between the two algorithms in subjects ‡65 years old in either study. RESULTS Baseline CONCLUSIONSPrandial insulin lispro can effectively and safely be initiated, by either of two selftitrated algorithms, in a variety of practice settings.

OBJECTIVE -Hypoglycemia is a common acute complication of diabetes therapy. The GlucoWatch biographer provides frequent and automatic glucose measurements with an adjustable low-glucose alarm. We have analyzed the performance of the biographer low-glucose alarm relative to hypoglycemia as defined by blood glucose Յ3.9 mmol/l. RESEARCH DESIGN AND METHODS -The analysis was based on 1,091 biographer uses from four clinical trials, which generated 14,487 paired (biographer and blood glucose) readings.RESULTS -The results show that as the low-glucose alert level of the biographer is increased, the number of true positive alerts (alarm sounds and blood glucose Յ3.9 mmol/l) and false positive alerts (alarm sounds but blood glucose Ͼ3.9 mmol/l) increased. When analyzed as a function of varying low-glucose alert levels, the results show receiver operator characteristic curves consistent with a highly useful diagnostic tool. Setting the alert level from 1.1 to 1.7 mmol/l above the level of concern is likely to optimize the trade-off between true positives and false positives for each user. When the same blood glucose data are analyzed for typical monitoring practices (two or four measurements per day), the results show that fewer hypoglycemic events are detected than those detected with the biographer.CONCLUSIONS -The frequent and automatic nature of the biographer readings allows more effective detection of hypoglycemia than that achieved with current medical practice. Diabetes Care 24:881-885, 2001H ypoglycemia is a common acute complication of diabetes therapy. The frequency of severe hypoglycemia has been shown to increase with more intensive treatment. Increasing the frequency of glucose measurements, regardless of the technique used, makes it possible to detect a greater number of hypoglycemic events. However, as many as seven glucose measurements per day may fail to detect hypoglycemic events (1).A device providing automatic readings could make frequent monitoring easier and enable an alarm to be sounded in response to glucose readings below userselected alert levels. Such an alarm could reduce the risk of hypoglycemia, making intensive therapy safer and more acceptable for patients. The GlucoWatch biographer (Cygnus, Redwood City, CA) provides frequent, automatic, and noninvasive glucose measurements-up to three readings per hour for as long as 12 h after a blood glucose measurement for calibration. Clinical studies in controlled and home environments have demonstrated high accuracy and precision (2,3). The results presented here evaluate the hypoglycemia alert performance in a large and demographically diverse patient population using the biographer both in controlled and normal daily environments. The accuracy and precision results from these studies have been described (4).The performance of the hypoglycemia alert depends on the selection of a low-glucose alert level that will trigger an audible alarm. The performance of the alert function can be best evaluated by an analysis of the receiver operator characteri...