Interaction of esomeprazole with insulin detemir and human albumin: A potential cause of hypoglycemia.

Insulin detemir (IDt) is long-acting insulin whose protraction mechanism is based on a covalently attached fatty acid to an insulin molecule. Utilizing the high affinity of fatty acids towards human serum albumin (HA), the modified detemir molecule binds with good affinity to HA, which functions as a reservoir that leads to a slow and prolonged release of insulin. However, questions were raised over potential interactions between other drugs and IDt through competitive binding on the binding site(s) of HA. In a previous study, concomitant use of esomeprazole (Esom) and erythromycin resulted in severe hypoglycemia, and thus: the drugs including Esom were suggested as enhancers of IDt action through displacing it from its binding site on HA. To further study this possibility, studies utilizing different techniques including, semipermeable membrane dialysis, capillary electrophoresis, UV,NMR spectroscopy, and molecular docking were carried out. Results from various techniques supported the simultaneous binding of Esom along with IDt to HA (i.e., binding in two different sites without signs of competition between the two). Moreover, capillary electrophoresis suggested an increase in the binding affinity of Esom to HA in the presence of IDt (1.9 × 103 Vs 2.7 × 104M-1). Perhaps most interesting was the observation that Esom could bind directly to IDt which was evidenced by all the employed techniques. Direct binding of Esom to IDt, might explain the enhancement in insulin action associated with the concomitant use of Esom. Therefore, Esom might represent a leading insulin-sensitizing compound that might lead to more effective insulin enhancing and less unwanted effects.

Effects of noopept on cognitive functions and pubertal process in rats with diabetes.

AIM: Type 1 diabetes (T1DM) is a common chronic disease in childhood. Increasing insulin resistance in puberty gives rise to higher doses of insulin usage in treatment. Of this reason new approaches in treatment are needed. Noopept researches suggest it to have anti-diabetic properties. We tried to determine the effects of noopept on pubertal diabetes. MAIN METHOD: The research was made with 60 prepubertal, 28 day-old, male, Sprague Dawley rats. The rats were divided into randomised 6 groups (n = 10/group). i) Control, ii) Diabetes Control, iii) Noopept Control, iv) Diabetes + Noopept, v) Diabetes + Insulin, vi) Diabetes + Insulin + Noopept. T1DM model was induced by streptozotocin on postnatal 28th day. 0.5 mg/kg noopept and 1 IU insulin were administered intraperitoneally for 14 days. Blood glucose and body weight measurements, puberty follow-up and MWM tests were performed. Hippocampus, hypothalamus and testis were evaluated histologically. Hypothalamic GnRH and kisspeptin were studied immunohistochemically. Serum LH, FSH and insulin, hippocampal homogenate NGF and BDNF levels were determined by ELISA. KEY FINDINGS: Delayed puberty was normalized by noopept (p < 0.05). Blood glucose levels were lower in noopept-administered diabetic groups (p < 0.05). Noopept decreased HOMA-IR in insulin administered diabetic group (p < 0.05). Number of degenerated cells in hippocampus and testis were higher in diabetes control group when compared with other groups (p < 0.05). GnRH immunoreactivity in Diabetes + Noopept group was increased when compared to insulin + noopept group (p = 0.018). There was no difference in kisspeptin, serum LH, FSH, hippocampal NGF-BDNF levels and spatial learning assessment among groups (p > 0.05). SIGNIFICANCE: Noopept may have positive effect in treatment of pubertal diabetes.

Comparison between the effect of regular human insulin and NPH with novo-rapid and levemir insulin in glycemic control in gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is one of the prevalent adverse conditions among pregnant women which needs delicate monitoring and control. GDM is a state in which the pregnant women's blood glucose level exceeds the normal range. Our goal was to determine the best therapeutic method to control the blood glucose level among GDM patients by comparing of the efficacy between two Insulin consisting, Novo-rapid + Levemir Insulin and Regular + NPH Insulin. METHOD: In this double-blind, randomized clinical trial study, we enrolled 100 women with GDM as an inpatient. In group A, patients underwent treating with Regular + NPH Insulin, and in group B, patients underwent treating with Novo-rapid + Levemir Insulin. Patient's demographic and clinical information gathered by specified several times during the study and analysis performed by SPSS21. RESULTS: Despite significant changes in the two groups patient's blood glucose levels; we could not find any remarkable differences between the two groups. In the case of patient and health care system satisfaction and the length of the hospitalization group, B was better than group A. CONCLUSION: Altogether, The Novo-rapid and Levemir Insulin in comparing with the Regular and NPH Insulin were practically advantageous due to the simple using method and short hospitalization period of the patient. Thus, we prefer and suggest this beneficial method (using Novo-rapid and Levemir Insulin) to reach therapeutic goals.

Quantitation of Insulin Analogues in Serum Using Immunoaffinity Extraction, Liquid Chromatography, and Tandem Mass Spectrometry.

Insulin analysis is used in combination with glucose, C-peptide, beta-hydroxybutyrate, and proinsulin determination for the investigation of adult hypoglycemia. The most common cause is the administration of too much insulin or insulin secretagogue to a diabetic patient or inadequate caloric intake after administration of either. Occasionally there is a question as to whether hypoglycemia has been caused by an exogenous insulin-whether by accident, intent, or even malicious intent. While traditionally this was confirmed by a low or undetectable C-peptide in a hypoglycemic specimen, this finding is not entirely specific and would also be expected in the context of impaired counter-regulatory response, fatty acid oxidation defects, and liver failure-though beta-hydroxybutyrate levels can lend diagnostic clarity. For this reason, insulin is often requested. However, popular automated chemiluminescent immunoassays for insulin have distinctly heterogeneous performance in detecting analogue synthetic insulins with cross-reactivities ranging from near 0 % to greater than 100 %. The ability to detect synthetic insulins is vendor-specific and varies between insulin products. Liquid Chromatography and Tandem Mass Spectrometry (LC-MS/MS) offers a means to circumvent these analytical issues and both quantify synthetic insulins and identify the specific type. We present an immunoaffinity extraction and LC-MS/MS method capable of independent identification and quantitation of native sequence insulins (endogenous, Insulin Regular, Insulin NPH), and analogues Glargine, Lispro, Detemir, and Aspart with an analytical sensitivity for endogenous insulin of between 1 and 2 µU/mL in patient serum samples.

A clinical update of using albumin as a drug vehicle - a commentary.

Human serum albumin (HSA) has emerged as a versatile carrier for therapeutic agents, primarily for treating diabetes and cancer, improving the pharmacokinetic profile of the drug or delivering the drug to the pathogenic site addressing diseases with unmet medical needs. Market approved products include fatty acid derivatives of human insulin or the glucagon-like-1 peptide (Levemir, Tresiba, and Victoza) which bind physically to the respective binding sites of HSA thus extending their half-life. For cancer treatment, the paclitaxel albumin nanoparticle Abraxane has been approved for treating metastatic breast cancer, non-small cell lung cancer, and advanced pancreatic cancer. Finally, the albumin-binding prodrug of doxorubicin, Aldoxorubicin, which binds covalently to the cysteine-34 position of circulating albumin, is in advanced clinical trials with a registration phase 3 trial for soft tissue sarcoma initiated in Q1 2014.

Insulin analogue levemir and development of pancreatic adenocarcinoma: a case report and literature review.

There is an association between insulin analogues, glargine, lispro and aspart and the incidence of malignancies. A 76 year-old female patient with history of diabetes, hypertension and hyperlipidemia presented with flank pain after using insulin Levemir as part of her management. CT abdomen revealed pancreatic mass and endoscopic ultrasound- guided FNA aspiration biopsy showed pancreatic adenocarcinoma. It was not clear whether the insulin analogue initiated the tumor or helped the growth of pre-existing malignant foci. Then we concluded that case presented raises an indicator of possible association between using insulin analogue and initiation of malignancies, or stimulation of malignant foci.

[Basal insulin analogue versus traditional NPH insulin in basal bolus therapy of children and adolescents with type 1 diabetes].

The efficacy and safety of a combination of ultrashort acting insulin aspart (Novorapid) with determir (Levemir) and glargin (Lantus) versus the traditional NPH-insulin (Protafan) used in basal bolus therapy were evaluated in 112 children and adolescents with type 1 diabetes 12 and 24 weeks after treatment. According to the type of basal insulin, the patients were divided into 3 groups. A significant decrease in HbA1c levels was revealed in the group of detemir-treated patients. The analogues of basal insulin significantly reduced the risk of hypoglycemias, by simultaneously improving the quality of glycemia control. Their use could cause a significant decrease in the fasting plasma level of glucose, by completely refusing 6.00 extra insulin doses. In the detemir group, the daily dose was increased, by lowering the amount of basal insulin. The dose of dietary insulin underwent changes in the glargin group. Body mass index remained unchanged in the detemir group over 24 weeks of treatment.