title: People with type 1 diabetes using short acting analogue insulins are less dehydrated than those with using human soluble insulin prior to onset of diabetic ketoacidosis.
abstract: Diabetic ketoacidosis (DKA) is associated with disturbances of acid base, fluid balance and electrolytes. Much of the established literature states that the fluid deficit in someone presenting with DKA is in the region of 6-8 l of fluid (about 100 ml/Kg), and this needs to be the fluid volume that is replaced in the first 24 h following admission to hospital. The physiology of fluid loss in DKA is complex. In summary, however, as blood glucose levels rise, the renal threshold for active glucose reabsorbtion is exceeded leading to glucose loss in the urine. This leads to an osmotic diuresis, and thus dehydration if oral intake is insufficient. Further losses are accounted for by hyperventilation, sweating and vomiting. With the older insulins--such as soluble human insulins, the duration of action was 8-10 h, with a peak of action at approximately 2-4 h after subcutaneous injection. Because very low insulin concentrations are sufficient to prevent ketone production, and because insulin concentrations would stay sufficiently high enough to do this, ketones would not be formed for up to 10 h after the last injection. Furthermore, concentrations of ketones sufficiently high enough to make a person unwell may take several more hours to develop. However, during this time, as insulin concentrations declined, blood glucose levels would increase, eventually overcoming the renal threshold, causing the renal diuresis and subsequent dehydration. Thus, on human soluble insulin, there is the opportunity to become profoundly dehydrated prior to the onset of significant ketoacidosis. The new rapid acting analogue insulins have durations of action of between 4 and 6 h. Thus the individual would become absolutely insulin deficient relatively quicker than with human soluble insulin. In this circumstance, the blood glucose would not have time to rise as high as with human soluble insulin deficiency before significant ketosis develops, thus leading to a lesser degree of dehydration. New rapid acting insulin analogues are becoming more widely used. This suggests that the volumes needed to replace those lost prior to the onset of significant DKA may be lower.
authors.affiliation: Elsie Bertram Diabetes Centre, Norfolk and Norwich University Hospital NHS Foundation Trust, Colney Lane, Norwich, Norfolk NR4 7UY, UK. ketan.dhatariya@nnuh.nhs.uk
authors.forename: Ketan
authors.initials: K
authors.lastname: Dhatariya
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003681:Dehydration / Q000209:etiology*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D016883:Diabetic Ketoacidosis / Q000209:etiology* / Q000517:prevention & control; D005947:Glucose / Q000032:analysis; D006801:Humans; D007328:Insulin / Q000031:analogs & derivatives / Q000627:therapeutic use*; D008954:Models, Biological; D008962:Models, Theoretical; D012995:Solubility
chemical_list: D001786:Blood Glucose; D007328:Insulin; D005947:Glucose