One hundred years of insulin: Is it time for smart?

Abstract

Smarter understanding of diabetes pathophysiology and pharmacology of insulin therapy can lead to better clinical outcomes. Rather than looking for an insulin formulation that is considered “best” for a general population, it could be appropriate to seek the “smart” insulin choice, tailored to the specific clinical situation. Different treatment goals should be considered, with pros and cons to each. Ideally, insulin therapy in most diabetic dogs should mimic a “basal‐bolus” pattern. The “intermediate”‐acting insulin formulations might provide better “bolus” treatment in dogs than the rapid‐acting formulations used in people. In patients with some residual beta cell function such as many diabetic cats, administering only a “basal” insulin might lead to complete normalisation of blood glucose concentrations. Insulin suspensions (neutral protamine Hagedorn, neutral protamine Hagedorn/regular mixes, lente and protamine zinc insulin) as well as insulin glargine U100 and detemir are “intermediate”‐acting formulations that are administered twice daily. For a formulation to be an effective and safe “basal” insulin, its action should be roughly the same every hour of the day. Currently, only insulin glargine U300 and insulin degludec meet this standard in dogs, whereas in cats, insulin glargine U300 is the closest option.

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“…In this sense, the initial long-term insulin regimen adopted can follow the same standards regardless of a PRDM diagnosis. Low twice-daily doses of intermediated or long-acting insulin suspensions or insulin analog solutions can be applied to try to cover the patient’s basal and post-prandial insulin requirements, taking into account local regulatory rules, costs, patient’s size, and owner‘s issues, for example [ 29 , 124 , 132 ]. Alternatively, a basal–bolus insulin treatment system can be proposed for particular cases, trying to better cover basal and post-prandial insulin requirements [ 132 ].…”

“…Low twice-daily doses of intermediated or long-acting insulin suspensions or insulin analog solutions can be applied to try to cover the patient’s basal and post-prandial insulin requirements, taking into account local regulatory rules, costs, patient’s size, and owner‘s issues, for example [ 29 , 124 , 132 ]. Alternatively, a basal–bolus insulin treatment system can be proposed for particular cases, trying to better cover basal and post-prandial insulin requirements [ 132 ]. The insulin dose to stabilize a patient with diabetes is assumed as the difference between the patient’s needs and the patient’s insulin production [ 9 ].…”

“…In this way, it is difficult to assume a general standardized suggestion regarding the initial insulin dose in IRD cases since the patient’s insulin-resistance degree (i.e., presence of interferences of insulin action on target cells) and residual beta-cell secretory capacity are unknown. Starting doses of insulin recommended in actual guidelines can be used according to the veterinarian’s description [ 29 , 124 , 132 , 133 ]. Dietary management of patients with diabetes is also highly advisable and has serial benefits for the patient [ 29 , 124 ].…”

“…Trying to help the patient with diabetes deliver her puppies can be particularly challenging [ 10 ] despite gratifying, and progressive insulin resistance and increased risk for DKA are expected closer to the full-term pregnancy with resultant increased risk for the mother and puppies, especially in older bitches [ 10 , 66 , 67 ]. Insulin doses and regimens can be reviewed according to the patient’s needs [ 27 , 29 , 124 , 132 ]. Perfect glucose control was quite unlikely in a study with gestational diabetes in dogs [ 10 ]; however, the patients were treated with insulin suspensions (NPH or intermediate porcine insulin), in a median dose of 0.65 U/kg q12h (range: 0.4–1.5 U/kg, q12h), and eventually more aggressive doses could have performed better.…”

“…Despite being quite different conditions, the insulin resistance pattern induced by the diestrus and glucocorticoid excess due to hypercortisolism was shown to be similar [ 95 ]. Regarding basal–bolus protocols, long-acting insulin analogs (e.g., glargine 300U, degludec) are the best options to employ as basal insulin, while intermediate-acting insulin such as NPH is considered the best option to employ as bolus insulin due to physiological insulin secretion patterns in a dog [ 132 , 151 ]. However, a basal–bolus protocol using NPH as basal insulin, and the short-acting analog lispro as bolus insulin, was helpful in improving glycemic control in a group of poorly regulated diabetic dogs [ 152 ].…”