MD Conference Express ADA 2011 - (Page 31)

• • Severe retinopathy: OR=5.057 (95% CI, 1.380 to 18.537; p=0.014) Maculopathy: OR=4.443 (95% CI, 1.925 to 10.253; p<0.001) have unpredictable sleep patterns and eating behaviors [Danne T. Diabetes Care 2007]. Figure 1. Dose-Dependent Pharmacodynamics of Regular Insulin. Glucose Infusion Rate (mg/minute) 800 The data from the two studies suggest that OSA may play an important role in the development of both diabetic neuropathy and retinopathy. Prospective studies are needed to confirm this hypothesis. In addition, research is needed to determine the impact of treating OSA on both diabetic complications. 600 0.3 U/kg 400 200 0.05 U/kg 0 2 4 6 8 10 12 14 Insulin Delivery: Special Needs of Adolescents Written by Rita Buckley 0 Time (hours) Reproduced with permission from W. Tamborlane, MD. In youth with type 1 diabetes (T1DM), increasing insulin resistance and decreased adherence to diabetes management tasks often occur during the adolescent years, leading to deterioration of glycemic control [Maffeis C et al. Pediatr Diabetes 2011]. William V. Tamborlane, MD, Yale School of Medicine, New Haven, Connecticut, USA, discussed the pharmacokinetic and pharmacodynamic properties of insulin, the need for fast-acting insulin in the pediatric T1DM population, and the latest approaches for accelerating the time-action profile of insulin. Insulin sensitivity is reduced, even in healthy lean adolescents as they progress through puberty. This insulin resistance, which appears to be related to the pubertyassociated rise in growth hormone levels, is exaggerated in teenagers with T1DM, especially adolescents who are overweight or obese [American Diabetes Association. Diabetes Care 2006]. There is a need for faster-acting insulins to address the challenges of insulin resistance in the pediatric population. Adolescents with T1DM require large (ie, 0.2–0.3 U/kg) premeal bolus doses of rapid-acting insulin to overcome peripheral resistance in puberty. But, there are negative clinical consequences that are associated with this strategy. They include delayed peak, with early postmeal hyperglycemia, and prolonged duration that suppresses hepatic glucose production, causing late postmeal hypoglycemia, especially after the last meal of the day (Figure 1). The timely delivery of insulin in doses that match the increase in blood glucose after and between meals is a therapeutic challenge [Stote R et al. J Diabetes Sci Technol 2010]. Rapid-acting insulin analogs offer the possibility of immediate preprandial or even postprandial administration in children and adolescents, who often While rapid-acting insulin analogs have a more suitable pharmacokinetic and pharmacodynamic profile than soluble human regular insulin [Heller S et al. Diabetes Metab Res Rev 2011], even current insulins work too slowly and last too long for external closed-loop systems—once again resulting in exaggerated postmeal excursions, especially after breakfast, and vulnerability to late postmeal hypoglycemia, particularly after dinner. More rapidly absorbed insulins can increase bioavailability and achieve greater within-subject consistency of bolus doses (Figure 2). Several approaches are being tested to accelerate the time-action profiles of fast-acting insulins. They include faster insulins; warming of the infusion site; coformulation with hyaluronidase; and alternate routes (microneedle infusion sets, inhaled insulin, and intraperitoneal insulin pumps). Figure 2. Pharmacodynamics of Regular Versus RapidActing Insulin Analogs. Regular Glucose Infusion Rate (mg/minute) Glucose Infusion Rate (mg/minute) 800 600 400 0.3 U/kg 0.05 U/kg 800 Analog 0.3 U/kg 0.05 U/kg •Sharper & higher peaks •Earlier onset •Shorter duration 600 400 200 200 0 0 2 4 6 8 10 12 14 0 0 2 4 6 8 10 12 14 Time (hours) Time (hours) Reproduced with permission from The American Diabetes Association, [Lys(B28), Pro(B29)]human insulin. A rapidly absorbed analogue of human insulin. Howey DC et al; vol. 43, 396-402, March 1994. The present status of these strategies varies. The first and only recombinant human hyaluronidase enzyme, 31 Peer-Reviewed Highlights from the American Diabetes Association 71st Annual Scientific Sessions http://www.mdconferencexpress.com

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