Glargine and degludec: solution behaviour of higher dose synthetic insulins

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers (“multi-hexamerisation”). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24–40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes

Inpatient Diabetology: The New Frontier

Tight glycemic control is now an imperative of outpatient diabetes care. The inpatient arena remains under the influence of an ineffective paradigm characterized by tolerance for hyperglycemia and a reluctance to use insulin intensively. This article is a call to action against the lip service paid to inpatient diabetes care. The compelling in vitro and in vivo evidence for the benefit of intensive insulin-mediated glycemic control is summarized. The linchpin of current inpatient care is a commonly used insulin sliding scale. This autopilot approach as the sole mode of treatment for inpatient hyperglycemia has been strongly condemned. Nevertheless, it continues to survive. The evidence supports the compelling argument that the adverse effect of hyperglycemia on hospital length of stay, morbidity, and mortality is substantial. Clinicians, nurses, administrators, and insurers ought to look critically at the prevailing paradigm and spearhead the much-needed revolution in inpatient diabetology. The issue of glycemic targets, the need for noninvasive blood glucose monitoring, and the role of nursing staff in this revolution are raised. We call for the banning of the insulin sliding scale use as the sole diabetes order. Also, the use of basal insulin via continuous intravenous insulin infusion or subcutaneous insulin analogs should be embraced. Educating nurses, house staff, and other frontline professionals in the adverse consequences of the current paradigm is essential. Inpatient glycemic control matters; clinical and financial outcomes are at stake. It behooves the health care system and the diabetic public to address the contemporary state of inpatient diabetology as soon as possible