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At least 19 recordsLinked to original sources

A comparison of the pharmacokinetics of human protamine sodium insulin with human isophane insulin following subcutaneous injection in normal subjects.

The pharmacokinetics of human protamine sodium insulin 0.6 mg% were compared with those of human isophane zinc insulin using the glucose clamp technique. The insulin preparations were administered subcutaneously at a dose of 0.5 U/kg in 7 normal subjects; a placebo injection served as control. Plasma insulin and C-peptide concentrations were then measured over 24 hours. After correction of the results to allow for endogenous insulin secretion the two insulin preparations gave similar values throughout the study except that protamine sodium insulin achieved an earlier peak in plasma insulin concentration (90 minutes) compared to isophane (120 minutes). When measured by an index of the dextrose infusion rate required to maintain euglycaemia the two insulin preparations gave similar values for the first 16 hours, maximum values being obtained during the fourth hour after administration. Using this index isophane zinc insulin gave higher values during the 17th, 19th and 21st hours following administration suggesting it may have a slightly more prolonged action than protamine sodium insulin.

Adult↗

Premixed insulin at ratio 3/7 and regular + isophane insulins at mixing ratios from 2/8 to 4/6 achieve the same metabolic control.

The insulin regimen with two daily injections is still that more frequently used. Often regular and NPH insulins are mixed at different ratios according to the patient's need; however, the mixture preparation can involve several errors. Efficacy, safety and compliance were evaluated comparing a premixture 3/7 (Actraphane HM) with extemporary mixtures of regular + NPH at mixing ratios ranging from 2/8 to 4/6, in a cross-over study of 8 weeks involving 20 insulin dependent diabetics. Metabolic control, hypoglycaemic episodes, insulin dose and proportions were similar with both treatments while a higher compliance was achieved with the premixture. In conclusion, premixture 3/7 and extemporary mixture (from 2/8 to 4/6) obtain the same efficacy and safety but the former shows a higher acceptability.

Adult↗

Effect of switching medically vulnerable patients with uncontrolled diabetes from isophane insulin human to insulin glargine.

PURPOSE: The purpose of this observational study was to determine if switching from isophane insulin human (NPH) to insulin glargine would improve glycemic control in a medically vulnerable population with uncontrolled diabetes. METHODS: A retrospective cohort review of patients' medical records was performed that recorded events occurring between January 1, 2001, and December 31, 2003. The cohort consisted of patients with diabetes in an adult medicine clinic at a county hospital. Patients were included if they were receiving NPH insulin for a minimum of six months and subsequently switched to insulin glargine for a minimum of six months. RESULTS: The study included 43 patients. There was no significant difference in mean glycosylated hemoglobin (HbA(1c)) between NPH insulin (9.6%) and insulin glargine (9.7%) regimens (p = 0.78, 95% confidence interval, -0.62%, 0.82%). Neither was there a significant difference in the frequency or severity of hypoglycemic episodes between the two treatments. Patients experienced significantly fewer diabetes-associated visits over six months while on insulin glargine. Refill frequency did not differ significantly when patients were receiving NPH insulin versus insulin glargine. When analyzing patient characteristics, those of Hispanic ethnicity experienced HbA(1c) values significantly higher than white patients. Several characteristics were associated with refill frequency. CONCLUSION: The results of our study indicate that both NPH- and glargine-based basal insulin regimens result in similar levels of glycemic control in a medically vulnerable population with diabetes, without significant differences in the number or severity of hypoglycemic episodes or in refill frequency.

Adult↗

Morning versus bedtime isophane insulin in type 2 (non-insulin dependent) diabetes mellitus.

Morning versus bedtime administration of NPH insulin was compared in 12 subjects with Type 2 diabetes and overt fasting hyperglycaemia. Subjects were studied at baseline (diet alone) and after 2 months on each of the two insulin programmes in a random crossover design, in which dosage was increased until at least one daily preprandial blood glucose was consistently in the range of 3.9 to 6.0 mmol l-1. Mean (+/- SEM) daily total insulin dosage was equivalent for the morning (0.36 +/- 0.03 units kg-1) and for the bedtime (0.37 +/- 0.03 units kg-1) insulin administration schedules. Glycaemic control was improved on both insulin regimens, but was better on bedtime than morning insulin. Fasting plasma glucose (mmol l-1) was 12.0 +/- 0.7 (baseline), 8.6 +/- 0.7 (morning), and 4.6 +/- 0.3 (bedtime), respectively. Mean 24 h plasma glucose (mmol l-1) was 13.3 +/- 1.3, 9.0 +/- 0.7, and 7.8 +/- 0.7. Glycated haemoglobin (%) was 7.65 +/- 0.35, 6.23 +/- 0.26, and 5.81 +/- 0.32. The improvement of basal glycaemia is a consequence of increased basal metabolic clearance of glucose (baseline, 47.6 +/- 3.1 ml m-2 min-1; morning 63.5 +/- 5.4, bedtime 103.5 +/- 7.1). There was no change in hepatic glucose output. It is concluded that bedtime administration of intermediate acting insulin results in increased basal insulinaemia, leading to improved basal glycaemia and consequent improved overall metabolic control, compared to morning insulin administration. Therefore, bedtime may be the preferable timing of insulin therapy for patients with Type 2 diabetes and overt fasting hyperglycaemia.

Circadian Rhythm↗

Treatment of diabetes mellitus in dogs using isophane insulin penfills and the use of serum fructosamine assays to diagnose and monitor the disease.

The objectives of the study were to test the use of a prefilled insulin syringe (Insulatard Novolet, isophane insulin, 100 IU/mL) in treating diabetic dogs and to test the clinical usefulness of serum fructosamine measurements in diagnosing and monitoring diabetes mellitus in dogs. For this study 15 dogs from throughout Norway with newly diagnosed diabetes mellitus were included and treated over a period of 180 days. All 15 dogs showed pretreatment hyperglycaemia. Of the 13 dogs tested, all showed elevated pretreatment serum fructosamine values. Within 2 weeks, 3 of the 15 included dogs had dropped out of the study. In 8 of the 12 remaining dogs, the clinical signs ceased within this period. Within a month, another dog was euthanised and one had died. Seven of the 10 remaining dogs were clinically normal. Three dogs had normal serum fructosamine concentrations, while in 6 dogs moderately or highly elevated serum fructosamine concentrations persisted. In one case serum fructosamine was not measured at this time. Increase in serum fructosamine concentration seemed to reflect hyperglycaemia and deteriorated clinical condition. Decrease in serum fructosamine concentration seemed to reflect improved glycaemic status and clinical condition. During the study period the owners did a total of approximately 3500 injections on their dogs. No reports of injection difficulties were received. This study documents that Insulatard Novolet is easy and safe to use in treating diabetic dogs and that serum fructosamine reflects long-term glucose concentrations in dogs. Serum fructosamine measurements provided a simple and easy way to diagnose persistent hyperglycaemia and monitor the treatment in diabetic patients.

Alkaline Phosphatase↗

The use of isophane insulin for the control of diabetes mellitus in dogs.

For this study 54 dogs with diabetes mellitus verified by anamnesis, clinical examinations and laboratory analyses were selected in 13 Danish and Swedish small animal clinics. After instruction the owners gave isophane insulin ("Insulin Protaphan Human") injections to the dogs morning and evening followed by a commercial or homemade meal rich in fibers. The veterinarians examined the treated dogs 5 times or more in the 90 day treatment period, preferably in the morning before injection and meal. In all 54 dogs the clinical symptoms disappeared a few days after isophane insulin injections, and 54% of the dogs were clinically healthy within 8 days. Within a month 96% of the dogs were normalized after therapy. Simultaneously the blood glucose levels were normalized in 64% of the dogs within 14 days and in further 21% within 30 days. The urine glucose levels were normalized in 64% of the dogs within 14 days and for further 19% within 30 days. At the end of the study 48 out of the 54 diabetic dogs were clinically healthy, alert and free from symptoms of diabetes. The average dose of isophane insulin was for greater dogs 0.44 units per kg bw twice a day, for small dogs 0.79. Six dogs had been destroyed in the trial period for various reasons. One owner had injection troubles. Another owner was hospitalized and had to get rid of the dog. One dog developed advanced breast cancer, 1 went fierce and 2 developed cataracts. Four dogs had by 1 or 2 occasions shown hypoglycemic symptoms, which quickly disappeared after appropriate adjustments of insulin dosing, feeding schedule and exercise programme.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Feed↗

Absorption of NPH (isophane) insulin in resting diabetic patients: evidence for subcutaneous injection in the thigh as the preferred site.

The absorption kinetics of NPH (isophane) insulin injected subcutaneously into the abdominal wall and subcutaneously (SC) and intramuscularly (IM) into the thigh was studied in 11 Type 1 diabetic patients. The thickness of the subcutaneous adipose tissue layer was measured by ultrasound. NPH (isophane) insulin injected IM into the thigh was absorbed faster than NPH insulin injected SC into the thigh (T50%, IM 8.0 +/- 0.6 h and SC 10.3 +/- 0.7 h, p less than 0.05). No difference in T50% values was found for injection into the abdominal wall (9.7 +/- 1.2h) compared with the thigh. The mean absorption rate from 1.5 to 13.5 h after injection was higher after injection IM into the thigh (6.4 +/- 0.3% of initial dose injected absorbed per h) than after SC injection into the thigh (5.2 +/- 0.3% h-1) and SC into the abdominal wall (5.1 +/- 0.3% h-1) (p less than 0.01). The most constant absorption rate was obtained after SC injection into the thigh (within-study day CV of the mean absorption rate 19.9 +/- 3.2% vs 34.4 +/- 3.2% after IM injection into the thigh and 27.1 +/- 4.9% after SC injection into the abdominal wall (p less than 0.02]. The study provides further evidence that the subcutaneous tissue of the thigh is the preferred injection site for NPH insulin.

Absorption↗

Chronic urticaria from isophane insulin therapy; sensitivity associated with noninsulin components in commercial preparations.

A young woman with diabetes mellitus developed chronic urticaria after changing from isophane been insulin suspension to isophane beef-pork insulin suspension. She reverted to treatment with her original insulin preparation, but urticaria failed to terminate. While in the hospital, her eruption began each afternoon at the site of insulin injection. Zinc single-peak beef insulin suspension, a purer preparation with different additives than isophane beef insulin, was substituted, and urticaria terminated rapidly. Intradermal skin testing using single-peak (purified) preparations indicated that the patient was sensitive to beef and pork forms of isophane insulin but not to beef and pork forms of zinc insulin. The patient later had a brief recurrence of urticaria following oral erythromycin and tetracycline therapy but did not develop lesions at sites of insulin injection.

Adult↗

[Action profile of a semisynthetic human isophane zinc insulin compared with customary isophane insulin].

Addition of zinc to a protamine-isophane insulin should probably allow to lengthen its duration of action. Therefore we compared the action of this new type of insulin (NPH Zn) with that of a classical protamine-isophane NPH insulin (NPH); both were manufactured by the same firm. Five healthy volunteers were connected to an artificial pancreas. 0.6 U/Kg of insulin was injected subcutaneously in the low left quarter of the abdominal wall. Insulin action was monitored by the glucose needs delivered by the artificial pancreas working in euglycemic glucose clamp mode. Each insulin were tested in every subject at a ten day interval. The peak plasma insulin levels were observed after 2 h 30 for the NPH insulin (40 +/- 17 microU/ml) and after 3 h (47 +/- 22 microU/ml) for the NPH Zn insulin. The glucose needs reached their top levels after 2 hours (102 +/- 19 mg.kg-1 x 15 min-1) for NPH insulin and after 3 hours (98 +/- 28 mg.kg-1 x 15 min-1) for NPH Zn; the glucose needs decreased on a parallel way for both insulins but a one hour delay for NPH Zn insulin was observed. Addition of zinc to isophane NPH insulin slightly modifies the pharmacokinecinetic parameters, moving forward one hour in the glucose delivery.

Adult↗

Insulin therapy in cats with diabetes mellitus.

Thirteen cats with diabetes mellitus were evaluated. Clinical signs included polydipsia, polyuria, polyphagia, lethargy, and weight loss. Results of physical examination included obesity, hepatomegaly, mild seborrhea sicca, muscle wasting, and dehydration. One cat walked plantigrade and was suspected of having a diabetic neuropathy. Persistent hyperglycemia, glucosuria, high liver enzyme activities, hypercholesterolemia, hyperproteinemia, and low electrolyte concentrations were the common laboratory findings. In 3 cats diabetes mellitus developed after megestrol acetate therapy; 2 of these cats required only temporary insulin treatment. In a 3rd cat, which had no history of receiving diabetogenic drug therapy, remission of diabetes mellitus also was observed. Serum insulin and plasma glucose concentrations were determined in 6 cats after administration of an intermediate-acting insulin (isophane insulin) and in 3 cats after administration of a long-acting insulin (protamine zinc insulin). The insulin concentration peaked 2 to 6 hours after the injection of intermediate-acting insulin and 6 to 12 hours after the injection of long-acting insulin. The lowest glucose concentration was recorded 4 to 8 hours after injection of intermediate-acting insulin, and 6 to 12 hours after injection of long-acting insulin. It was concluded that, although insulin therapy must be adjusted to the individual, the diabetic cat usually requires twice-daily administration of isophane insulin; however, the protamine zinc insulin can be given once daily for satisfactory control.

Adrenocorticotropic Hormone↗

Efficacy of insulin lispro in combination with NPH human insulin twice per day in patients with insulin-dependent or non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group.

A common treatment regimen for patients with either insulin-dependent diabetes mellitus (IDDM) or non-insulin-dependent diabetes mellitus (NIDDM) is a combination of rapid-acting insulin and intermediate-acting insulin administered twice each day. It is usually recommended that regular human insulin be injected 30 to 45 minutes before a meal. In practice, patients often inject regular human insulin closer to mealtime, causing a higher post-prandial serum glucose level and an increased potential for hypoglycemia in the postabsorptive period. Insulin lispro, a rapid-acting insulin analogue, is best injected just before a meal because of its more rapid absorption and shorter duration of action. In 707 randomized patients, 379 with IDDM and 328 with NIDDM, we studied the effect of twice-daily insulin lispro or regular human insulin in combination with NPH human insulin (isophane insulin) on premeal, 2-hour postprandial, and bedtime glycemic control. Assessments were based on the results of a seven-point blood glucose profile, the insulin dose (by formulation and time of administration), the incidence and frequency of hypoglycemic episodes, and the glycated hemoglobin value. Treatment with insulin lispro resulted in lower postprandial glucose levels and smaller increases in glucose level after the morning and evening meals compared with treatment with regular human insulin. Overall glycemic control, frequency of hypoglycemic events, and total insulin dose were not different between the two groups. Insulin lispro in combination with NPH human insulin in a twice-per-day regimen allows injection closer to mealtime and improves post-prandial glycemic control without increasing the risk of hypoglycemia.

Adolescent↗

Hyperparathyroidism and coexisting diabetes mellitus. Altered carbohydrate metabolism.

Hyperparathyroidism was diagnosed in a 67-year-old diabetic man treated for 20 years with isophane insulin suspension, 40 to 45 units/day. It was also diagnosed in a 64-year-old diabetic with severe retinopathy and vascular disease, who was not dependent on insulin. In the first case, removal of a parathyroid adenoma resulted in frequent hypoglycemic attacks, which led to a reduction of the administration of insulin isophane suspension to 20 units/day. In the second case, there was a notable improvement in the glucose tolerance testing that followed surgery, accompanied by a decrease in total plasma insulin response from 17,838 to 5,605 units, by planimetry. These observations suggest that hyperparathyroidism worsens coexisting diabetes mellitus and that one must be aware of increased insulin sensitivity and the possibility of severe hypoglycemia in cases that require insulin after surgical correction of the hypercalcemic state.

Aged↗

[Treatment of type 2 diabetes. Early detection of secondary oral treatment failure is important].

As type II diabetes is caused by decreased insulin secretion and increased insulin resistance, treatment must be aimed at the correction of these abnormalities. To this end, oral hypoglycaemic agents (OHAs) are used once adverse lifestyle factors have been suitably modified. New OHAs are being developed, or have already been approved. Subsequent treatment failure, after an initially satisfactory response, occurs in 5-10 per cent of patients on OHAs, and is currently treated with a combination of an OHA for daytime use and NPH insulin (isophane insulin) for use at bedtime. This yields metabolic control at least as good as that obtained with intensive insulin treatment, and at less risk of weight gain.

Administration, Oral↗

Absorption of isophane (NPH) insulin and its clinical implications.

Absorption of 125I-NPH insulin (125I-isophane insulin) (40 IU/ml) was studied in eight diabetics given 50% and 150% of their normal daily dose of insulin. Insulin absorption correlated with plasma insulin (r = 0.97, p less than 0.001) and blood glucose (r = -0.87, p less than 0.01) concentrations. Absorption was slower at higher doses, so that trebling the insulin dose only doubled the amount absorbed over the first 24 hours. The plasma elimination half time (t12) of insulin was about five minutes. Thus, the disappearance of radiolabelled insulin is a reliable and quantitative index of insulin absorption; subcutaneous degradation, if present, is minimal and constant. Changes in dise of intermediate-acting insulin further increases the large variation in insulin absorption. This implies that minor adjustments of intermediate insulin dosage are probably futile.

Absorption↗

[Advances in insulin treatment. Evaluation of isophane or lente insulin, mixed with rapid insulin and injected twice-a-day].

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.

Adolescent↗

Insulin detemir: new drug. A second long-acting insulin analogue: many uncertainties, few advantages.

(1) The standard treatment for type 1 diabetes is intensive insulin therapy, consisting of at least 3 daily injections of different insulins, one of which is a long-acting insulin. (2) Insulin detemir is the second long-acting human insulin analogue to be marketed in Europe (after insulin glargine) for the treatment of diabetes in adults and children over 6 years of age. Its action lasts about 12 hours. (3) Insulin detemir was evaluated in around 10 comparative trials, all unblinded, examining the effect of insulin detemir in terms of global glycaemic control (HbA1c level). None of these trials examined whether insulin detemir prevented complications of diabetes. (4) About 10 trials, involving more than 3000 patients, showed that insulin detemir, insulin isophane and insulin glargine have similar efficacy in treating both type 1 and type 2 diabetes. (5) The short-term adverse effect profile of insulin detemir is similar to that of isophane insulin. There is slightly less weight gain with insulin detemir, but injection site reactions occur more frequently. The long-term adverse effects of insulin detemir are not known. (6) Insulin detemir is a clear solution, leading to a risk of confusion with ordinary human insulin or a fast-acting insulin analogue. (7) In practice, isophane insulin remains the first choice long-acting insulin for patients with type 1 or type 2 diabetes.

Diabetes Mellitus, Type 1↗