MD Conference Express ADA 2012 - (Page 21)

Take our survey and get access to a free eBook! A novel basal insulin that is under development, LY2605541, is engineered to be large in size, thereby delaying insulin absorption, reducing clearance, and resulting in prolonged duration of action [Hansen RJ et al. ADA 2012 Abstract 896-P]. Questions that remain on LY2605541 include its pharmacokinetic profile in type 1 diabetes, day-to-day reproducibility, lipid/hepatic mechanism and weight loss in the face of improved glycemic control, and titration. Dr. Bolli said the replacement of basal insulin is fundamental to insulin treatment of types 1 and 2 diabetes, and substitution of basal insulin becomes increasingly more important and challenging as b-cell mass or function deteriorates over time. Newer Bolus Insulins Luigi F. Meneghini, MD, University of Miami Miller School of Medicine, Miami, Florida, USA, discussed the evolution of rapid-acting insulin, limitations of current insulin preparations, and pipeline products. Home et al. recently reported [Diabetes Obes Metab 2012] that postprandial glucose excursions can inhibit achievement of good glycemic control and possibly have an effect on the risk of vascular comorbidities. Rapid-acting analogs offer an earlier onset and peak of biologic activity, a shorter duration of action, and less biologic variability (Figure 2), potentially leading to more physiologic insulin insulin replacement and better overall control than with human insulin. Figure 2. Potential Advantages of Rapid-Acting Insulin Analogs. Earlier onset and peak of biologic activity = Lower post prandial glucose Shorter duration of action = Less late prandial hypoglycemia Less biologic variability = Fewer glycemic fluctuations optimal timing of bolus administration in relation to meal consumption in adolescents and adults with type 1 diabetes, that a bolus of rapid-acting insulin prior to a meal results in significantly better postprandial glucose control than when the meal insulin bolus is given just prior to the meal or 20 minutes after meal initiation. [Cobry E et al. Diabetes Technol Ther 2010]. Insulin analogs are absorbed more quickly than human insulin in normal-weight healthy subjects or lean subjects with type 1 diabetes. However, most patients with type 2 diabetes using insulin are distinctly overweight or obese and require much larger insulin dosages [Lane WS et al. Endocr Pract 2009]. Gagnon-Auger et al. [Diabetes Care 2010] found that absorption of even a rapid-acting insulin analog such as lispro is substantially delayed and biologic activity considerably lower in obese subjects with type 2 diabetes. There are a number of innovative technologies being applied to provide a more physiologic insulin action profile. One such approach is the use of a fully human recombinant DNA-derived hyaluronidase enzyme (rHuPH20), which reduces resistance to bulk fluid flow following drug injection (insulin) and promotes drug dispersion to allow exposure to a greater capillary bed area. This approach accelerates absorption and peak biologic activity, as well as shortens the duration of action of either regular insulin or rapid-acting insulin analog preparations. [Frost GI. Expert Opin Drug Deliv 2007]. Another approach—inhaled insulin delivery—is generally well-tolerated and appears to be safe, at least in the short term [Muchmore DB, Gates JR. Diabetes Obes Metab 2006]. Inhaled insulin offers an alternative noninvasive option for premeal insulin administration, with glycemic efficacy slightly less than subcutaneous regular insulin and increased acceptability [Ceglia L et al. Ann Intern Med 2006]. A randomized, open-label, parallel-group study [NCT00309244] to assess the efficacy and safety of prandial Technosphere® inhaled insulin compared with twice-daily biaspart insulin found that change in HbA1C with inhaled insulin plus insulin glargine (0.68%; SE, 0.077; 95% CI, 0.83 to 0.53) was similar and noninferior to that with biaspart insulin (0.76%; SE, 0.071; 0.90 to 0.62). Patients had significantly less weight gain (p<0.05) and a reduced incidence of mild-to-moderate and severe hypoglycemic events on inhaled insulin plus insulin glargine than on biaspart insulin. The safety and tolerability profile was similar for both treatments, although there was an increased occurrence of cough and change in pulmonary function in the group that received inhaled insulin plus insulin glargine [Rosenstock J et al. Lancet 2010]. Concerns with respect to chronic lung exposure of high insulin concentrations still need to be carefully evaluated. 21 300 200 100 0 0 2 4 6 Time (hours) 8 10 Insulin Injection Reproduced with permission from LF Meneghini, MD. A Cochrane review of the effects of short-acting insulin analogs versus regular insulin, however, suggested only a modest benefit of short-acting insulin analogs in the majority of patients treated with insulin [Siebenhofer A et al. Cochrane Database Syst Rev 2006]. Clearly the timing of insulin bolus to meal is an important determinant of post-prandial glycemic control, and should favor rapidacting insulin analogs. It is clear, from a study on the Peer-Reviewed Highlights from the American Diabetes Association 72nd Annual Scientific Sessions http://www.mdconferencexpress.com http://www.surveymonkey.com/s/mdce_ada2012

Table of Contents for the Digital Edition of MD Conference Express ADA 2012

MD Conference Express ADA 2012
Contents
ORIGIN Trial Results
New Lessons in Hypertension and Diabetes
Closed-Loop Insulin Therapy in Young Children
The Precocious “AGE’ing” Effect of Type 1 Diabetes in Children
Abatacept in Patients with New-Onset Type 1 Diabetes: One-Year Follow-Up
Explaining the UKPDS Legacy Effect
Insulin and Cancer
Insulin Analogs
Dyslipidemia
Insulin Therapy
Incretin Therapies
Diabetes and Chronic Kidney Disease Guidelines Update
Managing Hyperglycemia in Hospitalized Patients
CVD Prevention and Treatment in Women With Diabetes
China Da Qing Study: Lifestyle Change in Women With IGT Extends Life
Markers of Macrovascular Complications in Pediatric Diabetes
Nonoperative Management of the Infected Diabetic Foot
Diabetic Retinopathy: Changing Prevalence and Severity Require Flexible Interventions
New ADA/EASD Position Statement Endorses a Patient-Centered Approach

MD Conference Express ADA 2012

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