Summary. The relative efficacy of two twice-daily insulin regimens using highly purified insulins, once daily Ultratard with twice daily Actrapid (ultralente/ soluble) and twice daily Actrapid with twice daily Retard (soluble/isophane), has been studied in 12 diabetics in a cross-over study. Control was optimised as an out-patient, and assessed by in-patient 24 hour profiles. Similar day-time glucose control was achieved, but the mean overnight plasma glucose concentrations were more steady on ultralente/soluble (0100, 0300, 0500, 0700, 0800 h values 5. 6, 5.3, 5.8, 7.8, 10.4 mmol/1) than on soluble/isophane (4.3, 3.4, 5.2, 7.5, 12.2 mmol/1). The minimum overnight plasma glucose concentrations were lower (p < 0.05) on soluble/isophane (mean 2.8 mmo!/1) than on ukralente/soluble (mean 4.8 mmol/1), associated with higher (p < 0.05) nocturnal free plasma insulin levels after the evening soluble/isophane injection. The plasma glucose rise between 0700 and 0800 h was greater (p < 0.05) on soluble/isophane than on ultralente/soluble. The morning insulin injection should probably be taken immediately on rising, to prevent the pre-breakfast plasma glucose rise. The ultralente/ soluble combination gave similar day-time plasma glucose control to soluble/isophane with less nocturnal hypoglycaemia.Key words: Insulin therapy, hypoglycaemia, plasma insulin, diabetes control.There is increasing evidence that improved blood glucose control might prevent the long-term complications of diabetes [1]. Once daily injections of insulin * Present address: Prince Henry's H~ Melb~ Australia" Requests for offprints should be addressed to Dr. Turner fail to provide an insulin "pulse" to cover the evening meal [2,3]. A frequently used twice-daily regimen is a combination of soluble and isophane injections [4][5][6][7] with the morning soluble and isophane injections aiming to cover breakfast and lunch respectively, and the evening injections for the evening meal and the night respectively. An alternative insulin regimen is a constant basal insulin supplement with a long-acting ultralente insulin in order to provide normal basal plasma glucose concentrations, with additional twice-daily soluble insulin, before breakfast and before the evening meal, to cover meals [8]. To study the relative efficacy of the two insulin regimens, we have undertaken a cross-over study in insulin-requiting diabetics.
Patients and MethodsFifteen insulin-dependent (Type 1) diabetic patients gave informed consent for the study, but subsequently three were unable to comply with the 24 h studies. All patients had presented before age 45 years, and had no measurable plasma C-peptide ( < 0.06 nmol/1 after meals). Their mean age was 41 years (range 21-65 years) and mean ideal body weight 108% (range 95-128%).Ten patients had been treated with a soluble and isophane insulin regimen, and were initially studied on that regimen using the highly purified insulins Novo Actrapid MC and Nordisk Retard. Two were on other insulin regimens and were initially transferred to an ult...