Clinical experience with a new device that will simplify insulin injections.

In order to test clinically a newly developed, simple, and convenient device for giving multiple injections of short-acting insulin (Actrapid HM, Novo, Bagsvaerd, Denmark), 16 type I diabetic patients previously stabilized on intensified conventional therapy regimens participated in a randomized crossover study for a period of 6 wk. The patients used conventional syringes for injections of short-acting insulin during one period and the new device during the other. Conventional syringes were used for injections of basal insulin during both periods. Metabolic control was assessed by twice-weekly blood glucose profiles, HbA1c, and the frequency of hypoglycemic reactions; no significant differences were found during the two treatment periods. No infections at the injection sites were seen. Patients' evaluation of the new device was very positive.

Oral contraception and insulin sensitivity: in vivo assessment in normal women and women with previous gestational diabetes.

The sensitivity to insulin (euglycemic clamp technique) was assessed in previous gestational diabetic women (n = 6) and nondiabetic women (n = 6) before and twice during low-dose triphasic oral contraceptive administration (ethinyl estradiol and levonorgestrel) for 6 months. Both groups had normal plasma glucose and insulin levels during oral glucose tolerance tests before and during treatment. In vivo peripheral insulin action was measured during insulin infusion of 40 mU/m2 X min with plasma glucose clamped at fasting levels. Before treatment glucose infusion rates were identical in both groups [1.56 +/- 0.12 (SEM) mmol/m2 X min and 1.51 +/- 0.09 mmol/m2 X min, respectively]. After hormonal treatment for 6 months the amount of glucose infused decreased significantly in the previously gestational diabetic women (1.10 +/- 0.12 mmol/m2 X min, P = 0.01), whereas the decrease was less pronounced in the nondiabetic women (1.30 +/- 0.22 mmol/m2 X min, P = 0.09). The decrease in insulin sensitivity was not sufficient to alter glucose tolerance either in the previous gestational diabetic women nor in the nondiabetic women.

Effect of porcine gastric inhibitory polypeptide on beta-cell function in type I and type II diabetes mellitus.

The effect of highly purified natural porcine GIP on C-peptide release was examined in six type I (insulin-dependent) diabetics (IDD) with residual beta-cell function, six type II non-insulin-dependent) diabetics (NIDD), and six normal subjects. All subjects were normal weight. From -120 minutes to 180 minutes glucose or insulin was infused IV to achieve a constant plasma glucose level of 8 mmol/L. On two separate days GIP (2 pmol/kg/min) or isotonic NaCl at random were infused from 0 to 30 minutes. After 10 minutes of GIP infusion plasma IR-GIP concentrations were in the physiologic postprandial range. At 30 minutes a further increase in IR-GIP to supraphysiologic levels occurred. In all subjects plasma, C-peptide increased more after 10 minutes of GIP infusion (IDD, 0.48 +/- 0.05; NIDD, 0.79 +/- 0.11; normal subjects, 2.27 +/- 0.29 nmol/L) than on the corresponding day with NaCl infusion (IDD, 0.35 +/- 0.03; NIDD, 0.62 +/- 0.08; normal subjects, 1.22 +/- 0.13 nmol/L, P less than .05 for all). The responses of the diabetics were significantly lower than that of the normal subjects (P less than .001 for both groups). No further increase in C-peptide occurred during the remaining 20 minutes of the GIP infusion in the diabetic subjects (IDD, 0.49 +/- 0.05; NIDD, 0.83 +/- 0.10 nmol/L). In the presence of a plasma glucose concentration of 8 mmol/L, physiologic concentrations of porcine GIP caused an immediate but impaired beta-cell response in IDD and NIDD patients.

Elevated maternal serum alpha-fetoprotein caused by midtrimester amniocentesis: a prognostic factor.

In a prospective investigation, 247 patients underwent ultrasonically guided midtrimester amniocentesis. Maternal serum alpha-fetoprotein (AFP) was measured before and after the procedure. In 229 patients, preamniocentesis AFP exceeded 19 micrograms/liter. Forty-eight (21.0%) of these displayed a significant elevation of AFP induced by the procedure, indicating fetal-maternal bleeding. This event was correlated with anterior placental location (P less than .025) and was followed by a significantly reduced mean fetal birth weight (3143 versus 3385 g, P less than .05). In addition, a nonsignificant (.10 less than P less than .20) doubling of the risk of giving birth to a child small for gestational age was observed. These findings suggest that amniocentesis represents a potential hazard to the fetus. The implications in relation to the widening indications for amniocentesis are discussed.

Cortisol, glucose, and hemodynamic responses to surgery after naloxone administration.

The adrenocortical, hyperglycemic, and hemodynamic responses to cholecystectomy or vagotomy were studied in 16 patients under halothane and N2O/O2 anesthesia. The patients were randomly divided into two groups: eight patients received naloxone in doses used clinically (2.5 microgram/kg i.v.) just before induction of anesthesia, while eight subjects received placebo. The results showed insignificant differences in plasma concentrations of cortisol and glucose between groups. Nor did blood pressure, heart rates, and inspired halothane concentrations differ significantly between groups. Thus, inhibition of opiate receptors and endorphins by naloxone in an otherwise clinically effective dosage does not influence the adrenocortical, hyperglycemic, or hemodynamic responses to surgical stress. We therefore conclude from our data that opiate receptors and endorphins are not involved in the initial phase of the endocrine-metabolic responses to surgery nor are they part of the neural mechanisms mediating stress-induced analgesia.

Preconceptional treatment with insulin infusion pumps in insulin-dependent diabetic women with particular reference to prevention of congenital malformations.

Severe congenital malformations occur more often in infants of diabetic mothers than in infants of non-diabetic mothers. Fetuses exhibiting early fetal growth delay are in increased risk to be malformed and the early fetal growth rate seems to be related to the degree of metabolic control around the time of conception and in the early pregnancy. Nine insulin-dependent diabetic women (White classes B-F) were treated by means of continuous subcutaneous insulin infusion (CSII) initiated at least two months prior to conception and continued throughout pregnancy in order to evaluate the influence of optimized metabolic control on the course and outcome of diabetic pregnancy. Eleven conventionally treated pregnant diabetics (White classes B-D) served as controls. In the pump group the mean blood glucose values in the 4 weeks immediately before and after the conception were 7.7 +/- 0.2 mmol/l and 8.0 +/- 0.3 mmol/l, respectively, the HbA1c was 7.3 +/- 0.5% at the time of conception and 6.9 +/- 0.2% 6-10 weeks later. In the control group the HbA1c 6-10 weeks after conception was 7.2 +/- 0.5%. In the pump group two fetuses exhibited early growth delay while all of the 11 fetuses in the control group were of normal early growth. There were no malformations in either group. All pregnancies were uncomplicated except for one case of toxaemia in the control group. Thus, during CSII treatment the metabolic control was improved in all patients. A possible beneficial effect of this improved control on the early fetal growth delay was not demonstrated. Both groups are, however, still small and definite conclusions must await further results.

Prevalence of microalbuminuria in children with type 1 (insulin-dependent) diabetes mellitus.

The prevalence of microalbuminuria was determined in children aged 7 to 18 years with Type 1 (insulin-dependent) diabetes of more than 2 years' duration. All patients (n = 102) attending 2 diabetes clinics were asked to collect 2 overnight timed urine samples for albumin analysis by radioimmunoassay. Complete urine collection was obtained in 97 patients (95%). Overnight urinary albumin excretion rates were also measured in 36 healthy children matched for age and sex. Nineteen of the 97 patients (20%) had microalbuminuria, i.e. overnight urinary albumin excretion rates above the upper normal level (14 micrograms/min) in both urine collections. Microalbuminuria was only demonstrated in patients aged greater than or equal to 15 years, prevalence 37% (19/52 patients). Arterial blood pressure was elevated, mean 122/84 +/- 11/9mmHg, in the microalbuminuric group (19 patients) compared to the age-matched normoalbuminuric diabetic group (33 patients), mean 117/74 +/- 10/10mm Hg, p less than 0.001. The prevalence of simplex retinopathy was identical in these two groups, i.e. 25%. Glycosylated haemoglobin was slightly higher in the microalbuminuric patients, p less than 0.10. Our cross-sectional study reveals a high prevalence (37%) of persistent microalbuminuria, a stage highly predictive of later development of diabetic nephropathy, in Type 1 diabetic children aged greater than or equal to 15 years.

Comparison of continuous subcutaneous insulin infusion with multiple insulin injections using the NovoPen.

Twenty-one patients with insulin-dependent diabetes mellitus (IDDM) participated in a 20-week randomized cross-over comparison of continuous subcutaneous insulin infusion (CSII) with intensified conventional treatment (ICT) using the NovoPen. The Medix or the Auto-Syringe pumps were used for CSII and, during ICT with NovoPen, conventional plastic syringes were used for injections of intermediate-acting insulin at bedtime. At entry HbA1c, was 8.7 +/- 0.4% (mean +/- SE) in CSII patients and 8.8 +/- 0.5% in the ICF group. HbA1c declined significantly in both groups (ICT 7.6 +/- 0.2%; CSII 7.6 +/- 0.2%) though there was no significant difference between the responses. Overall mean blood glucose was slightly but significantly lower during CSII than during ICT (CSII: 7.6 +/- 0.2 mmol/l; ICT: 8.7 +/- 0.4 mmol/l, p less than 0.05). The number of hypoglycaemic episodes did not differ significantly between patients treated with NovoPen and CSII. At the end of the study, a questionnaire revealed that all but one patient preferred ICT with NovoPen to conventional therapy. Given the choice for future treatment, 6 patients chose CSII, 12 patients preferred ICT with NovoPen and 1 was unsure.

Danish patients' attitudes to scientific-ethical questions. An interview study focusing therapeutic trials.

One hundred and fourteen in- and out-patients from a department of internal medicine were interviewed, on the basis of a questionnaire with the following key questions: 1) Their attitudes to medical trials with man as the subject. 2) Their emphasis on informed consent. 3) Their attitudes to inclusion of patients not being able to give informed consent. 4) Their attitudes to tentative participation in 4 concrete projects. In all, 98% considered doctors' and patients' collaboration on new therapeutical methods both necessary and desirable. Eighty-eight per cent considered information of patients participating in trials a prerequisite. Eighty-six per cent accepted participation in scientific trials based on the guarantee of the doctors responsible. Of these 86%, 58% felt that a scientific-ethical committee's accept of the project implied an extra element of security. Seventy-five per cent replied that patients not being able to give informed consent themselves could be included in scientific trials. The majority, 77%, added that patients' relatives would then have to accept, 20% that such trials could be based on the participating doctors' responsibility, and only 2% that such a responsibility was to place on scientific-ethical committees. In the 4 concrete projects, answers followed a uniform trend: full information of patients was demanded by approximately 80%, and acceptance of participation resting with responsible doctors in more than 80%. Less than half of these 80% felt that evaluation by a scientific-ethical committee would add to patients' security.

Smoking habits and maternal serum alpha-fetoprotein levels during the second trimester of pregnancy.

In a prospective study the influence of cigarette smoking on maternal serum alpha-fetoprotein levels at 16 weeks gestation was examined. Significantly higher levels were found in 120 smokers compared with 138 non-smokers (median 54.0 and 44.3 micrograms/1 respectively, P less than 0.001). No difference in maternal body weight between the two groups could account for the results. The possibility of smoking-induced increased permeability of the placental barrier is discussed.

PIP: This work tested the hypothesis that during pregnancy cigarette smokers would exhibit elevated levels of alpha-fetoproteins (AFP), reflecting leakage of an albumin-sized molecule across the placenta or through the membranes. Maternal serum AFP levels of 258 patients at 16 weeks gestation were prospectively studied in a prenatal clinic. Patients of uncertain gestational age, with threatened abortion, fetal death, suspected twins, previous birth of a child with neural-tube defect or maternal diabetes were excluded. Notes were taken on smoking habits and preconception body weight. Maternal AFP levels in 120 smokers were about 20% higher than those of the 138 nonsmokers (median 54.0 and 44.3 mcg/1 respectively, P0.001). There was no difference between the median pregestational weights. Although the results are not proof of a causal association, they are consistent with the hypothesis that maternal smoking in early pregnancy leads to increased leakage of fetal proteins across the placental barrier.

Effect of strict metabolic control on regulation of subcutaneous blood flow in insulin-dependent diabetic patients.

The effect of 10 weeks of improved metabolic control on the impaired autoregulation of the subcutaneous blood flow was studied at the level of the lateral malleolus in eight long-term insulin-dependent diabetic patients with clinical microangiopathy. Blood flow was measured by the local 133-Xenon washout technique. Mean arterial blood pressure was reduced by a maximum of 23 mmHg by elevating the limb above heart level and elevated to a maximum of 65 mmHg by head-up tilt; in the latter position venous pressure was kept constantly low by activation of the leg muscle vein pump (heel raising). Improved metabolic control was achieved using either continuous subcutaneous insulin infusion or multiple insulin injections. The blood glucose concentration declined from (median) 12.7 to 6.8 mmol/l and the HbA1C level from 10.1 to 7.5% during strict metabolic control (p less than 0.01 and p less than 0.01, respectively). The slope of the subcutaneous blood flow autoregulation curves during poor metabolic control (median: 11.6% per 10 mmHg, range: 8.0-30.5% per 10 mmHg) was not significantly different from the slope values during improved metabolic control (13.4% per mmHg, 10.1-24.4% per mmHG). No association was demonstrated between the impaired autoregulation of subcutaneous blood flow and the metabolic parameters. Our results indicate that improved metabolic control for 10 weeks has no effect on the impaired autoregulation of subcutaneous blood flow in long-term insulin-dependent diabetic patients with clinical microangiopathy.