MD Conference Express ADA 2012 - (Page 15)
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Endogenous Glucose Production (mg/kg/min)
study that showed the peripheral delivery of a novel hepatopreferential insulin analog (insulin 327) leads to delayed suppression of lipolysis, greater effect on liver glucose metabolism, and reduced effect on nonhepatic glucose uptake compared with regular insulin delivered by the same route. Dogs with arterial, portal, and hepatic vein catheters were studied after an 18-hour fast. 3H-glucose was infused from -140 min. After a basal period (-40 to 0 min), somatostatin and basal portal glucagon were infused (0 to 300 min). At the same time, insulin 327 or human insulin (HI) was infused into a peripheral vein (7.2 or 1.8 pmol/kg/min, respectively; n=5/group), and euglycemia was maintained by glucose infusion. Suppression of lipolysis was delayed with insulin 327 compared with HI: during the first hour, plasma nonesterified fatty acid levels (µmol/L) decreased by 91±37 versus 419±42, respectively, and blood glycerol levels (µmol/L) fell by 0±7 versus 39±5, respectively. Arterial insulin 327 and HI levels increased to 10,870±2543 and 95±8 pmol/L, respectively (Figure 2). Figure 1. IDeg: Glucose-Lowering Effect at Steady State.
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IDeg 100 U/mL 0.8 U/kg IDeg 200 U/mL 0.6 U/kg IDeg 100 U/mL 0.6 U/kg IDeg 100 U/mL 0.4 U/kg
improve prandial glucose control. It has a history of more than 60 years of safe clinical use. The aim of this study was to compare rapid-acting analog insulin that is formulated with rHuPH20 versus insulin lispro alone on glycemic control parameters, safety, and tolerability in an intensive basalbolus insulin therapy in patients with type 1 diabetes [Phase II Study Evaluating Pharmacokinetics and Postprandial Glycemic Response of Subcutaneously Injected Humalog and Humlin R With/Without Co Injected Recombinant Human Hyaluronidase Following Liquid Meal in Type1 Diabetes Mellitus Patients; NCT00774800]. The results were presented by Irl B. Hirsch, MD, University of Washington School of Medicine, Seattle, Washington, USA. Figure 2. Glucose Appearance and Utilization.
Human Insulin Insulin 327
3-3H glucose
SRIF+Basal Portal Glucagon Glucose to maintain euglycemia Human insulin (1.8 pmol/kg/min) or Insulin 327 (7.2 pmol/kg/min)
150 100
50 0
Glucose infusion rate (mg/kg/min)
4
8
Glucose Utilization (mg/kg/min)
3
6 4 2 0 -40 0 60 120 180 Time (minutes) 240 300
2
n=21
n=37
1
n=16 n=22
Reproduced with permission from DS Edgerton, PhD.
0 Day 6
Reproduced with permission from T Heise, MD.
Day 7
Relative to the basal period, insulin 327 suppressed net hepatic glucose balance and glucose production (mg/kg/ min; last 3 h) by 1.9±0.1 and 1.7±0.1, respectively, while HI reduced them by only 0.5±0.6 and 1.1±0.3. On the other hand, insulin 327 increased nonhepatic glucose uptake and glucose utilization (mg/kg/min; last 3 h) by only 1.0±0.4 and 1.5±0.3, respectively, while HI increased them by 2.4±1.2 and 2.5±1.1. Liver-preferential insulin analogs may provide a therapeutic benefit by functionally restoring the physiological insulin gradient at the liver compared with peripheral tissues. Recombinant human hyaluronidase (rHuPH20) is a genetically engineered soluble version of the naturally occurring human hyaluronidase enzyme that is used to accelerate absorption and action of insulin and, thus,
After a 4- to 6-week run-in using prandial glulisine plus glargine (BID), 117 subjects (mean: age 42.6±14 years; BMI, 27.3±4.4 kg/m2; HbA1C, 6.7% to 8.3%) were randomly assigned (double-blind crossover) to lispro plus rHuPH20 or aspart plus rHuPH20 versus lispro alone for 2 12-week intensive management periods; prandial doses were given immediately before meals. The primary endpoint of HbA1C noninferiority (0.4% margin) was achieved with no treatment difference (95% CI, -0.05 to 0.15). Overall hypoglycemic rates (≤70 mg/dL or symptoms) were reduced 5% (p=0.035), and events <56 mg/dL were reduced 7% (p=0.045). Total daily insulin dose (54±27 for analogPH20 versus 56±27 U for lispro; p=0.057) and weight gain difference (-0.57 lb; p=0.27) showed favorable trends. No meaningful differences in adverse events, immunogenicity, or injection-site pain were noted. Flatter daytime glucose profiles and an 82% reduction in postprandial glucose excursions suggest that analog-PH20 offers improved postprandial glucose control.
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Peer-Reviewed Highlights from the American Diabetes Association 72nd Annual Scientific Sessions
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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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