The correlation of structural and binding affinity of insulin analog to the onset of action for diabetic therapy

Background: These days, insulin analog production has been improved and becoming popular. The advantages of insulin analog have been extensively reviewed in terms of effectiveness compared to human insulin. Each of the insulin analog industries has claimed their safety and efficacy based on in vivo and in vitro to overcome type 2 diabetes. Hereby, we report on the identification of highly effective analog-based insulin on structure and binding affinity computationally, to confirm its potential and give a broader point of view to insulin analog users. Methods: Five types of insulin analogs, Aspart, Glargine, Detemir, Lispro and Degludec, were analyzed. We grouped and clustered the sequence by alignment to identify the closeness and sequence similarity between samples, continued by superimposing analysis and undertaking binding affinity identification utilizing of a docking analysis approach. Results: Lispro had the least sequence similarity to other types, close to Aspart (96%) and Glargine (90.5%), while Detemir and Degludec showed 100% similarity we decide to only use Degludec for the next analysis. Furthermore, Lispro, Aspart, and Glargine exhibited structural similarity strengthened by the lack of significant difference in the RMSD data. Importantly, Aspart had the highest binding affinity score (-66.1 +/- 7.1 Kcal/mol) in the docking analysis to the insulin receptor (INSR) and similar binding site areas to human insulin. Conclusion: Our finding revealed that the strength of insulin analogs towards insulin receptors is identic with its rapid mechanism in the human body. Keywords: computation, docking, insulin analog, sequence similarity, structure Abstrak Latar belakang: Saat ini, produksi analog insulin meningkat dan menjadi popular. Keuntungan analog insulin telah ditinjau secara ekstensif dalam hal efektivitas dibandingkan dengan insulin manusia. Masing-masing industri analog insulin mengklaim keamanan dan kemanjurannya berdasarkan in vivo dan in vitro untuk mengatasi diabetes tipe 2. Kami melaporkan identifikasi insulin analog yang efektif berdasarkan struktur dan afinitas pengikatan secara komputasi, untuk mengonfirmasi potensi serta memberikan sudut pandang yang lebih luas kepada pengguna insulin analog. Metode: Lima jenis analog insulin, Aspart, Glargine, Detemir, Lispro, dan Degludec, dianalisis. Kami membandingkan dan mengelompokkan urutan tersebut dengan penyelarasan untuk mengidentifikasi kedekatan dan kesamaan urutan antar sampel dilanjutkan dengan superimposing analysis dan melakukan identifikasi binding affinity menggunakan pendekatan analisis docking. Hasil: Lispro memiliki kemiripan sekuen paling rendah dengan jenis lainnya, mendekati Aspart (96%) dan glargine (90,5%), sedangkan Determir dan Degludec menunjukkan kemiripan 100% sehingga kami menggunakan Degludec untuk analisis selanjutnya. Selain itu, Lispro, Aspart, dan Glargine menunjukkan kesamaan struktural yang diperkuat oleh rendahnya nilai signifikansi pada data RMSD. Perlu digarisbawahi bahwa Aspart memiliki skor afinitas pengikatan tertinggi (-66.1 +/- 7.1 kkal / mol) dalam analisis docking ke reseptor insulin (INSR) dan memiliki area pengikatan yang serupa dengan insulin manusia. Kesimpulan: Penemuan kami mengungkapkan bahwa kekuatan insulin analog sejalan dengan laju mekanismenya di dalam tubuh manusia Kata kunci: komputasi, docking, insulin analog, kemiripan sekuen, struktur

DIVE/DPV registries: benefits and risks of analog insulin use in individuals 75 years and older with type 2 diabetes mellitus

IntroductionThe aims of this study were to characterize insulin-treated individuals aged ≥75 years with type 2 diabetes using basal insulin analogs (BIA) or regular insulins (human insulin (HI)/neutral protamine Hagedorn (NPH)) and to compare the benefits and risks.Research design and methodsThe analysis was based on data from the DPV (Diabetes-Patienten-Verlaufsdokumentation) and DIVE (DIabetes Versorgungs-Evaluation) registries. To balance for confounders, propensity score matching for age, sex, diabetes duration, body mass index and hemoglobin A1c (HbA1c) as covariates was performed.ResultsAmong 167 300 patients aged ≥75 years with type 2 diabetes (mean age, 80.3 years), 9601 subjects used insulin regimens with basal insulin (HI/NPH or BIA). Of these 8022 propensity score-matched subjects were identified. The mean diabetes duration was ~12 years and half of the patients were male. At the time of switch, patients provided with BIA experienced more dyslipidemia (89.3% vs 85.9%; p=0.002) and took a greater number of medications (4.3 vs 3.7; p<0.001) and depression was more prevalent (8.4% vs 6.5%; p=0.01). Aggregated to the most actual treatment year, BIA was associated with a higher percentage of patients using basal-supported oral therapy (42.6% vs 14.4%) and intensified conventional insulin therapy (44.3% vs 29.4%) and lower total daily insulin doses (0.24 IU/kg/day vs 0.30 IU/kg/day; p<0.001). The study did not reveal significant differences in efficacy (HbA1c 7.4% vs 7.3%; p=0.06), hospitalizations (0.7 vs 0.8 per patient-year (PY); p=0.15), length of stay (16.3 vs 16.1 days per PY; p=0.53), or rates of severe hypoglycemia (4.07 vs 4.40 per 100 PY; p=0.88), hypoglycemia with coma (3.64 vs 3.26 per 100 PY; p=0.88) and diabetic ketoacidosis (0.01 vs 0.03 per 100 PY; p=0.36).ConclusionBIA were used in more individually and patient-centered therapy regimens compared with HI/NPH in patients with a mean age of 80 years. Both groups were slightly overtreated with mean HbA1c <7.5%. The risk of severe hypoglycemia was low and independent of insulin type. Further analyses of elderly patients with type 2 diabetes are needed to provide evidence for best practice approaches in this age group.