Laboratory, nurse and patient assessment of Glucostix blood glucose reagent strips.

The new Glucostix (Ames) blood glucose reagent strips have been assessed for accuracy and acceptability by nurses using them on the ward and by patients at home. When used with a Glucometer II, Glucostix showed close correlation with blood glucose measured by Yellow Springs Analyser (r = 0.97, p less than 0.001). Using the strips without a meter patients achieved a good correlation with the Yellow Springs Analyser when measuring their own capillary blood glucose (r = 0.94, p less than 0.001). Ward nurses were less precise (r = 0.87, p less than 0.001) and this, perhaps, reinforces the importance of regular quality control to maintain the precision of blood glucose monitoring using reagent strips. Comparing Glucostix with BM Glycemie 1-44 strips, 14 of 15 nurses preferred Glucostix whereas patients showed no overall preference, 37% preferring BM Glycemie 1-44, 33% Glucostix, and 30% stating no preference. There were only minor differences between the two reagent strips. Both groups considered the Glucostix colour change to be easier to read, particularly when using the perforated bench readers, but some thought Glucostix needed more blood and that it was more difficult to remove from the pad. Thus, the Glucostix system provides an accurate measure of blood glucose and is an acceptable alternative to BM Glycemie 1-44 strips for use at home or on the ward.

Use of a pharmacologic indicator to compare compliance with tablets prescribed to be taken once, twice, or three times daily.

By use of an interview, return tablet count, and a pharmacologic indicator (low-dose phenobarbital), we compared compliance with tablets prescribed to be taken once, twice, or three times daily. One hundred seventy-nine patients with type II diabetes were randomly allocated to take one 2 mg phenobarbital tablet once, twice, or three times daily for 28 days. Phenobarbital level/dose ratios indicated that compliance was similar with once- and twice-daily regimens, and both were better than thrice-daily dosing. Mean return tablet counts suggested that compliance was best with the once-daily regimen; both twice- and thrice-daily regimens were similarly inferior. This difference between the techniques may be explained by the inadequacies of the residual tablet count, which identified only 13% of cases identified by phenobarbital. We conclude that compliance with the once-daily regimen was best, but that compliance with a twice-daily regimen was very similar, and both were superior to dosing three times a day.

Retinopathy in newly presenting non-insulin-dependent (type 2) diabetic patients.

One hundred and twenty-nine (97 M, 32 F) previously untreated non-insulin-dependent diabetic patients were studied. Meal and glucose (75 g) tolerance tests were performed on two separate days with glucose, C-peptide and insulin levels estimated during each with the inclusion of growth hormone during the meal test. In addition glycosylated haemoglobin (HbA1) and plasma creatinine levels were determined. Clinical evaluation included detailed ophthalmological examination following mydriasis. Differences between retinopaths (n = 21) and non-retinopaths (n = 108) were FPG 13.7 vs 11.6 (mmol/l) (p less than 0.01); HbA1: 12.9 vs 11.3 (%) (p less than 0.01); BMI: 25.2 vs 29.4 (kg/m2) (p less than 0.001); age 56.8 vs 52.4 (yr) (ns); creatinine: 91.2 vs 88.4 (mumol/l) (ns); systolic blood pressure: 152.4 vs 143.9 mmHg (ns); diastolic blood pressure 87.9 vs 87.7 mmHg (ns); fasting growth hormone: 4.6 +/- 0.9 vs 2.4 +/- 0.3 (mU/1) (p less than 0.01). Multivariate logistic analysis however revealed that systolic blood pressure in conjunction with the insulin response gave the most significant correlation with retinopathy. No significant correlation was observed with age, sex, diastolic blood pressure, creatinine, family history or smoking. The effect of disease duration could not be evaluated. B-cell function appears central to microvascular complications in non-insulin dependent diabetes mellitus.

Pharmacokinetics of subcutaneously administered human, porcine and bovine neutral soluble insulin to normal man.

Highly purified neutral soluble human, porcine and bovine insulin (0.075 U/kg body weight) were administered randomly by subcutaneous injection to six normal men. Somatostatin by continuous intravenous infusion (100 micrograms/h) was used to suppress endogenous insulin secretion. The effects of the three species of insulins on plasma glucose, immunoreactive insulin (IRI), C-peptide and intermediary metabolite concentrations were essentially similar. The onset of hypoglycaemic action of bovine insulin was delayed compared to human and porcine insulin due possibly to a lower receptor binding of the bovine insulin. No local or systemic adverse reactions to the insulins were observed.

Comparison of highly purified semi-synthetic insulin and highly purified porcine insulin in the treatment of type I diabetes: interim report of a multi-centre randomised single blind study.

This is an interim report of a long term single-blind study of the effects of changing diabetic patients treated with highly purified porcine insulin to semi-synthetic human insulins of identical formulation. Twenty four insulin dependent diabetics were randomly allocated to continue with porcine insulin (n = 11) or human insulin (n = 13). There were no significant changes within the groups nor differences between the groups in mean preprandial capillary blood glucose, glycosylated haemoglobin or insulin dose during the first 24 weeks of the study. Insulin antibody levels remained low and did not differ between the groups. No local or systemic adverse reactions were observed. In this group of patients conversion to human insulin did not result in a change in diabetic control or insulin dose.

Study of porcine and human isophane (NPH) insulins in normal subjects.

The plasma glucose, C-peptide and insulin responses to subcutaneously administered highly purified porcine, 'semi-synthetic' and 'biosynthetic' human isophane (NPH) insulin and diluting medium as control in normal male subjects were evaluated. Porcine and semi-synthetic human NPH insulins were administered at two dose levels of 0.15 and 0.30 U/kg body weight and biosynthetic human NPH at 0.15 U/kg body weight only. At the low dose level the three insulin preparations resulted in a similar maximal hypoglycaemic effect within 3-5 h after administration. However, over the remainder of the 11 h post-injection period, the plasma glucose level was lower after semi-synthetic human insulin. In contrast, at the 0.30 U/kg dose level, there was no difference in the early or late hypoglycaemic response between porcine and semi-synthetic human NPH insulins of equivalent pharmaceutical formulation. The clinical relevance of these findings needs further evaluation. The data suggest that for the 'intermediate-acting' NPH insulin preparations, both the species of insulin, nature and quantity of the retarding protein and their subsequent interaction may determine their time-action characteristics.

Glycosylated serum albumin: an intermediate index of diabetic control.

Glycosylated hemoglobin (HbA1) is widely used as an index of glycemic control in diabetic patients. However, due to the long survival time of erythrocytes (120 days), it remains elevated for several weeks after improved control. Other plasma proteins are similarly glycosylated, and as glycosylated serum albumin (GSA) has a shorter half-life (20 days), it should detect glycemic changes earlier. Fasting blood glucose (FBG), GSA, and HbA1 were measured weekly in newly diagnosed diabetic patients (N = 12) for 8 wk after beginning treatment. After 4 wk, a similar fall in FBG and GSA levels, i.e., 72% and 58% respectively, was observed. In contrast, HbA1 fell significantly less (P less than 0.01), by only 39% of its initial value. By 8 wk there was no significant difference between the percentage reduction in the three indices of control. Therefore, GSA provides the clinician with earlier objective evidence of the metabolic response to therapeutic intervention and can be regarded as an intermediate index of diabetic control.

The clinical pharmacology of human insulin (Novo) in normal subjects.

Neutral regular human insulin (Novo) (derived from porcine insulin) and porcine insulin were administered by subcutaneous (s.c.) injection into the anterior abdominal wall in two different groups of six normal male subjects. The insulin dosage was 0.075 IU/kg body wt; diluting medium was used to obtain control values. In one group, somatostatin was administered by continuous intravenous infusion (100 micrograms/h) to inhibit pancreatic beta-cell secretion. The plasma glucose, C-peptide, and insulin (immunoreactive) responses to human insulin and porcine insulin were identical in the studies with and without somatostatin. Although the incremental plasma insulin values achieved with the two insulins were similar in the two studies, the hypoglycemic effect was accentuated in the presence of somatostatin, with a delayed recovery toward normoglycemia. The human insulin and porcine insulin were well tolerated in all subjects and there were no unwanted side effects.

A study of the comparative safety and efficacy of neutral soluble human (semi-synthetic) and porcine monocomponent insulin in non-diabetic subjects.

Neutral soluble human (semi-synthetic) and porcine insulin and diluting medium were administered subcutaneously in a randomized fashion to six fasting normal male subjects. The plasma glucose, C-peptide and insulin response was observed for a period of two hours before and six hours after injection of insulin (0.075 m/kg) into the anterior abdominal wall. The hypoglycaemic response was identical for the two insulins with the plasma glucose values reaching a nadir at 90--120 minutes and returning to within 10% of basal levels by six hours. Also similar peak plasma insulin values were achieved with human and porcine insulin by 50--60 minutes post-injection. The C-peptide response following the administration of both insulins suggested equal suppression of endogenous beta cell secretion. The two insulins were well tolerated with no immediate or delayed allergic reactions in any subject. These results suggest that human (semi-synthetic) and porcine soluble monocomponent insulins under the described experimental conditions are bioequivalent.