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L Nosek

Publications and source records attributed to L Nosek.

5 recordsLinked to original sources

Dependency of the metabolic effect of sc-injected human regular insulin on intra-abdominal fat in patients with type 2 diabetes.

Ten patients with type 2 diabetes were enrolled in an isoglycemic glucose clamp study to determine the impact of intra-abdominal fat, subcutaneous abdominal fat and total abdominal fat on the metabolic effect of a single bolus (0.2 IU/kg) of sc-injected human regular insulin. The maximum metabolic effect associated highly and negatively with intra-abdominal fat (r = - 0.72, p < 0.02) and with the homeostasis model assessment insulin resistance score (HOMA, r = - 0.71, p < 0.03). Likewise, the total metabolic effect of sc-injected insulin correlated strongly and negatively with intra-abdominal fat (r = - 0.77, p < 0.01), HOMA (r = - 0.74, p < 0.02) and HbA (1c) (r = - 0.70, p < 0.03). Stepwise multiple regression analyses showed that the highest metabolic effect was only significantly predicted by intra-abdominal fat, indicating a high negative correlation with the maximum effect (beta = - 0.72) whereas time to maximum metabolic effect showed a strong (beta = 0.72) and positive correlation with HOMA. In combination with the HOMA, it is intra-abdominal fat, and not subcutaneous abdominal fat, which explains 50 - 75 % of the variability of the effect of sc human regular insulin in patients with type 2 diabetes.

Abdomen↗

Inhaled micronized crystalline human insulin using a dry powder inhaler: dose-response and time-action profiles.

AIM: The aim of this euglycaemic glucose clamp study was to investigate the pharmacokinetics, glucodynamics, safety and tolerability of micronized crystalline human insulin inhalation powder delivered by a Spiros dry powder inhaler system in healthy volunteers. METHODS: Thirteen healthy, non-smoking, male and female volunteers [age 30 +/- 7 years; BMI 23.5 +/- 2.7 kg/m(2); (mean +/- sd)] with normal pulmonary function participated in an open-label, randomised, 6-period crossover trial. Each volunteer received four single doses of inhaled insulin (60, 90, 120, 150 U) on separate occasions. For comparison, each volunteer also received two of three possible doses of subcutaneous (s.c.) injected regular human insulin (8, 14, or 20 U). RESULTS: Serum immunoreactive insulin following inhalation of insulin peaked an average of 60 min earlier compared with s.c. injected insulin (P < 0.0001). Following inhalation, the time to maximum glucose infusion rate occurred an average of 70 min earlier than with s.c. insulin: 187, 129, 161 and 162 min vs. 227, 241 and 241 min (P < 0.0001). The dose-response relationships for serum insulin pharmacokinetics and glucodynamics were linear for both inhaled and s.c. insulin. Relative bioavailability (based on serum insulin levels) ranged from 11.5 to 12.2% for the four doses of inhaled insulin and relative biopotency (based on glucose infusion rates) was 10.0 to 16.5%, respectively. Dosing was well tolerated by all volunteers. CONCLUSION: This study demonstrates that inhalation of human insulin via a dry powder inhaler system provides a promising alternative route for administration of insulin.

Administration, Inhalation↗