[Experience with insulin-zinc suspension, a group of insulin preparations (lente insulins) with different effectiveness].
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In previous studies we demonstrated that mixing lente with soluble insulin of U40 strength in the syringe delays the onset of action of soluble insulin. Lente insulin of U100 as compared to U40 strength, contains a proportionally smaller amount of excess of zinc. The purpose of our study was to investigate the effect of premixing lente and soluble insulin of U100 strength on plasma insulin levels and glucose requirements during glucose clamping for 8 h in eight healthy volunteers. Soluble (0.22 U/kg) and lente (0.33 U/kg) insulin were administered once separately and once immediately after mixing in the syringe. In both instances the insulins were injected into two depots in contralateral thighs. The initial rise of plasma insulin levels from 0 to 2 h was not significantly different for both studies: from 11 +/- 1 to 25 +/- 4 mU/l and from 10 +/- 1 to 31 +/- 5 mU/l after premixing and separate administrations, respectively. However, the areas under the curves of the glucose infusion rates were significantly greater from 0 to 2 h after the separate injections of soluble plus lente than after premixing 3.25 +/- 0.70 vs. 1.84 +/- 0.56 mmol/kg, respectively (P less than 0.05). Plasma insulin levels and glucose requirements were significantly higher after premixing, compared with separate injections of soluble plus lente, from 300 to 480 and from 405 to 480 min, respectively. We conclude that mixing soluble with lente insulin of U100 strength in the syringe delays the onset of action of soluble insulin.
When mixed with lente insulin, regular insulin undergoes a slowing down in its absorption rate, which does not occur when it is mixed with isophane insulin. However, there is not sufficient evidence to state that this phenomenon affects the quality of the metabolic control in subjects treated with two daily mixtures of regular + intermediate insulins. This parallel study compared in a 12-month follow-up the results achieved in 154 insulin-dependent diabetics (IDD) treated with extemporary mixtures injected before breakfast and dinner, with the purpose of verifying whether the mixture regular + isophane offers specific advantages compared to regular + lente. The 79 IDD who have used isophane insulin and the 75 IDD treated with lente insulin had similar personal and clinical findings. During the 12-month study, the improvement of glucose profile, the number and the severity of hypoglycaemic episodes as well as the insulin requirement resulted almost overlapping with the two treatments. In conclusion, the results of this study confirm that the mixtures of regular + isophane insulins (Actrapid HM + Protaphane HM) and regular + lente insulins (Actrapid HM + Monotard HM) give the same guaranties of safety and efficacy, that the former shows a more rapid absorption rate and, finally, indicate that the ratio 30:70 between regular and intermediate insulins is that more frequently used.
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Six C-peptide-deficient diabetic patients, selected because of raised fasting blood glucose concentrations, participated in a randomised cross-over trial comparing twice-daily porcine soluble plus human ultralente with porcine soluble plus porcine lente insulins. As out-patients, overall mean blood glucose concentrations before and after breakfast were significantly lower during human ultralente therapy (7.2 +/- 0.8 vs 12.0 +/- 1.3, 11.1 +/- 1.0 vs 14.3 +/- 1.0 mmol/l, p less than 0.05), but were unchanged for the rest of the day. During overnight in-patient metabolic profiles a nadir in blood glucose occurred between 2-4 am with both insulin regimens (5.2 +/- 0.9 mmol/l ultralente, 6.5 +/- 1.3 mmol/l lente). Mean fasting and post-breakfast blood glucose levels were significantly lower with human ultralente as were fasting concentrations of glycerol and non-esterified fatty acids (p less than 0.05). Patients with poor overnight metabolic control and raised fasting blood glucose concentrations may benefit from human ultralente insulin, used as part of their twice-daily insulin regimen.
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Ultralente insulin has replaced protamine zinc insulin as the treatment of choice in treatment of diabetes mellitus in cats. There is variability in effectiveness of ultralente insulin and problems with glycemic control develop in some cats. Alternative insulin preparations are sought when ultralente insulin is ineffective. Twelve cats with insulin-dependent diabetes mellitus were treated with lente insulin. Clinical signs improved in 8 cats given lente insulin every 12 hours. Lente insulin was ineffective in 4 cats. Three of these cats were subsequently found to have an insulin resistant disorder. In 1 cat, lente insulin was ineffective because of short duration of action. Lente insulin is a viable treatment alternative when ultralente insulin is ineffective in achieving glycemic control. Ultralente insulin is still the insulin of choice for the initial treatment of diabetes in cats, because of the potential to establish glycemic control with once-a-day treatment.
The effects of sequential administration through one needle of human soluble and human lente insulin on plasma insulin levels and action profiles, assessed with glucose clamping, were studied in six healthy volunteers. Insulin kinetics after administration of human soluble insulin (0.22 IU/kg) alone were compared with those after sequential administration of 1) human soluble insulin followed by human lente insulin and 2) human lente insulin followed by human soluble insulin. Total insulin dose in both sequences was 0.55 IU/kg, 40% of which was short-acting insulin. Plasma insulin levels were not significantly different at any time point between 0 and 240 min after soluble insulin compared with either combination. Although insulin levels were slightly but significantly lower at 30 and 105 min after lente followed by soluble insulin compared with soluble followed by lente insulin, these differences probably reflect chance occurrences. Glucose requirements were not significantly different after either of the three administrations. We therefore conclude that the unwanted retarding effect after mixing of human soluble insulin with human lente insulin in the syringe on the onset of action of the soluble insulin can be prevented by sequential subcutaneous injection of these insulins with two syringes through one needle.
The miscibility of human semisynthetic regular and lente insulins (Actrapid human/Monotard human) and human biosynthetic regular and NPH insulins (Humulin regular/Humulin NPH) was studied in vitro and in 16 insulin-dependent diabetic patients. In vitro a decrease of regular insulin was found immediately after mixture with semisynthetic lente insulin in proportions 1:4, 1:3, 1:2, 1:1, and 2:1. This was not found after mixture with human biosynthetic regular and NPH insulins. Free insulin and blood glucose were determined over 8 h after the morning injection of regular/lente (n = 9) or regular/NPH (n = 7) insulins in proportions used by the patients (approximately 1:2) mixed in one syringe or in separate syringes. Mixing the regular/lente preparations in one syringe immediately before injection resulted in a significant loss of the early rise in free insulin (P less than .01), with a tendency to a higher free insulin in the afternoon. A corresponding change in the blood glucose profile was seen. No changes were observed in free insulin or blood glucose after mixing regular and NPH preparations compared with separate injections. We conclude that mixing human semisynthetic regular and lente insulins (Actrapid human/Monotard human) instantly results in a decrease of regular insulin, probably due to formation of a longer-acting preparation, whereas no such changes occur with human biosynthetic regular and NPH insulins (Humulin regular/Humulin NPH).
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The goals of this study were to compare the efficacy of once-daily administered Glargine insulin to twice-daily administered Lente insulin in cats with diabetes mellitus and to describe the use of a high-protein, low-carbohydrate diet designed for the management of diabetes mellitus in cats. All cats with naturally occurring diabetes mellitus were eligible for inclusion. Baseline testing included a physical examination, serum biochemistry, urinalysis and urine culture, serum thyroxine concentration, and serum fructosamine concentration. All cats were fed the high-protein, low-carbohydrate diet exclusively. Cats were randomized to receive either 0.5 U/kg Lente insulin q12h or 0.5 U/kg Glargine insulin q24h. Re-evaluations were performed on all cats at weeks 1, 2, 4, 8, and 12, and included an assessment of clinical signs, physical examination, 16-hour blood glucose curve, and serum fructosamine concentrations. Thirteen cats completed the study (Lente, n = 7, Glargine, n = 6). There was significant improvement in serum fructosamine and glucose concentrations in all cats but there was no significant difference between the 2 insulin groups. Four of the 13 cats were in complete remission by the end of the study period (Lente, n = 3; Glargine, n = 1). The results of the study support the use of once-daily insulin Glargine or twice-daily Lente insulin in combination with a high-protein, low-carbohydrate diet for treatment of feline diabetes mellitus.