Dose-dependent delay of the hypoglycemic effect of short-acting insulin analogs in obese subjects with type 2 diabetes: a pharmacokinetic and pharmacodynamic study.

Abstract

OBJECTIVE:

Injected volume and subcutaneous adipose tissue blood flow (ATBF) affect insulin absorption. Pharmacokinetics of short-acting insulin analogs were established by assessing injection of small doses in lean subjects, healthy or with type 1 diabetes. In obese patients, however, daily dosages are larger and ATBF is decreased. This study assessed the kinetics of a short-acting insulin analog in obese subjects with type 2 diabetes.

RESEARCH DESIGN AND METHODS:

Euglycemic clamps after subcutaneous lispro injections were performed. Six healthy control subjects received 10 units. Seven obese (BMI 38.3 ± 7.0 kg/m(2)) subjects with type 2 diabetes received 10, 30, and 50 units. Plasma lispro was measured by specific radioimmunoassay and ATBF by the (133)Xe-washout technique.

RESULTS:

ATBF was 64% lower in subjects with type 2 diabetes than in control subjects. After 10 units injection, time to lispro plasma peak (T(max)) was similar (48.3 vs. 55.7 min; control subjects versus type 2 diabetic subjects), although maximal concentration (C(max))/dose was 41% lower in subjects with type 2 diabetes, with lower and delayed maximal glucose infusion rate (GIR(max): 9.0 vs. 0.6 mg/kg/min, P < 0.0001, 69 vs. 130 min, P < 0.0001, respectively). After 30- and 50-unit injections, T(max) (88.6 and 130.0 min, respectively) and time to GIR(max) (175 and 245 min) were further delayed and dose related (r(2) = 0.51, P = 0.0004 and r(2) = 0.76, P < 0.0001, respectively).

CONCLUSIONS:

Absorption and hypoglycemic action of increasing dosages of lispro are critically delayed in obese subjects with type 2 diabetes.

• Authors: Maude Gagnon-Auger, Patrick du Souich, Jean-Patrice Baillargeon, Elisabeth Martin, Pascal Brassard, Julie Ménard, Jean-Luc Ardilouze
• Journal: Diabetes care (Diabetes Care) Vol. 33 Issue 12 Pg. 2502-7 (Dec 2010) ISSN: 1935-5548 [Electronic] United States
• PMID: 20841613 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Hypoglycemic Agents
• Insulin
• Insulin Lispro

Topics

• Adolescent
• Adult
• Aged
• Diabetes Mellitus, Type 2 (blood, complications)
• Female
• Humans
• Hypoglycemic Agents (blood, pharmacokinetics)
• Injections, Subcutaneous
• Insulin (analogs & derivatives, blood, pharmacokinetics)
• Insulin Lispro
• Male
• Middle Aged
• Obesity (complications)
• Young Adult