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Biomedical subjects

W Kerner

Publications and source records attributed to W Kerner.

At least 73 records · Page 4Linked to original sources

In vivo measurement of subcutaneous glucose concentrations with an enzymatic glucose sensor and a wick method.

An amperometric enzyme electrode and a wick technique were used for measurement of glucose in sc. tissue of sheep. When wicks were left implanted long enough to equilibrate with interstitial fluid, sc. glucose could have been reproducibly determined with the necessary accuracy. It was demonstrated that sc. tissue glucose concentrations in sheep are about 30% higher than in whole blood and are on the level of plasma glucose. This allows interpretation of sc. glucose sensor currents since results of in vitro-calibrations cannot be transferred to in vivo conditions. When an enzymatic sensor was implanted in the sc. compartment, the sensor signals were closely related to changes of blood glucose. These in vivo experiments indicate that short term glucose-monitoring with an subcutaneously implantable glucose sensor is feasible and so may provide a possible access to glycemic control. Further experiments will have to show, if glucose-controlled insulin infusions based on the output of a sc. glucose sensor will be able to maintain stable normoglycemia.

Animals↗

Similar effects of pulsatile and constant intravenous insulin delivery.

Effects of constant and pulsatile i.v. insulin delivery were examined in seven healthy subjects by means of euglycemic clamp technique. Each subject received constant insulin infusion (0.175 mU/kg.min) or insulin pulses at 12-min intervals (2.1 mU/kg) in randomized order for 8-h periods (08.00-16.00 h). Endogenous secretion of insulin was inhibited by concomitant administration of somatostatin (300 micrograms/h). Serum insulin concentrations during constant infusion (12 +/- 1 microU/ml) did not differ from basal values (11 +/- 1 microU/ml). Pulsatile insulin delivery resulted in oscillations of mean concentrations between values of about 10 and 20 microU/ml. Mean blood glucose concentrations during experiments were kept at 80 +/- 1 mg/dl, irrespective of the mode of insulin administration. Moreover, dextrose requirements for maintenance of these glucose concentrations did not differ over the hole periods of examination. We conclude that effects of constant and pulsatile delivery of basal amounts of insulin are not different. This at least applies to peripheral, short-term insulin administration in somatostatin-treated normal man, during an euglycemic clamp.

Adult↗

Substitution of basal delivery of insulin by proinsulin in type I diabetic patients under CSII.

In seven C-peptide negative type I diabetic patients conventional insulin therapy was replaced by CSII using biosynthetic human insulin. After a pretest period of 1-3 days duration, the patients received in randomized order basal subcutaneous infusion of either biosynthetic human proinsulin (assumed potency 4 U/mg) or insulin for two days each. For meals, insulin was given throughout the study. Insulin doses were adjusted to the patients requirements during the prephase. Afterwards changes of basal rates were allowed only in case of nocturnal hypoglycemia; bolus doses were modified when premeal glucose concentrations were outside the range from 80 to 120 mg/dl. During the test period with basal proinsulin infusion, plasma glucose control (MBG, MAGE, M-value) was significantly better (P less than 0.05) when compared to periods with basal insulin infusion. Basal rates of insulin and proinsulin as well as bolus doses of insulin were similar at all study periods. It is concluded that subcutaneous basal proinsulin infusion, supplemented by subcutaneous premeal insulin administration, can be used for glucose control of patients with type I diabetes. As basal proinsulin delivery gives significantly better results than basal insulin delivery, the question arises whether the present formulation of proinsulin is equipotent to insulin formulations.

Adult↗

A potentially implantable enzyme electrode for amperometric measurement of glucose.

A membrane limited amperometric enzyme electrode suitable for glucose measurement in biological fluids was developed. The sensor consists of a central platinum wire (0.3 mm) surrounded by a stainless steel tubing (0.8-1.0 mm outer diameter; 2-4 cm length). By successive dipcoating procedures, layers from cellulose acetate, glucose oxidase (crosslinked with glutaraldehyde) and polyurethane are placed on its surface. The platinum is polarized at +700 mV against steel. In vitro results: Electrodes are stable for at least 6 days. They exhibit a linear range extending to 500 mg/dl glucose. Response times are less than 100 sec. The sensors are not dependent on stirring and are relatively insensitive to changes of pH. Dependency of glucose measurement upon dissolved oxygen is negligible at oxygen concentrations above 0.5 mg/l. In vivo results: Preliminary studies in sheep using subcutaneously implanted needles indicate that short term glucose monitoring is feasible.

Animals↗

[Clinical testing of a new blood glucose measuring system. A cooperative study at 8 centers].

The glucometer II system is a small measurement device with built-in batch-specific pressbutton calibration. The corresponding test strip "Glucostix" uses a two-color system. The blood glucose test strip can be evaluated both visually and by instrument. The precision determined in series was between 2.0% and 6.7% using control sera. The day-to-day precision was between 1.5% and 7.9%. Comparison of the methods on the basis of 781 and 109 capillary blood samples respectively revealed a good agreement between the hexokinase method or the glucose oxidase method (Beckman analyser) and the glucometer II values. The precision of measurement by the system was comparable in the two test strip batches employed. Visual reading of the test strips revealed a good agreement with the laboratory method in the hypoglycemic and normoglycemic range; at higher concentrations of blood glucose, a trend to underestimation of the measurement values was shown. The easy handling and small size of the instrument facilitates measurement of blood glucose by the patient under everyday conditions.

Blood Glucose↗

Characterization of insulin resistance in type I diabetes.

Insulin sensitivity was assessed using the euglycaemic clamp technique in eight type I diabetic patients (after overnight blood glucose normalization with an artificial pancreas) and in six healthy subjects. Basal insulin concentrations were higher in diabetic patients (25 +/- 4 microU/ml) than in control subjects (17 +/- 1 microU/ml; P less than 0.05). Insulin infusion of 0.5, 1.0, 2.0 and 5.0 mU/kg per min during subsequent 2-h periods resulted in similar mean steady-state insulin concentrations in both groups. The mean dextrose requirements during the last 40 min of each period were nevertheless decreased in diabetic patients (1.6 +/- 0.5, 3.5 +/- 0.8, 6.5 +/- 0.7, 10.2 +/- 0.7 mg/kg per min) as compared with control subjects (4.7 +/- 0.3, 8.2 +/- 0.9, 10.2 +/- 0.9, 12.4 +/- 0.9 mg/kg per min). At low insulin concentrations dextrose requirements were diminished in all diabetic subjects. At the highest insulin levels, individual dose-response curves from only four patients were within the normal range. Under basal conditions, the monocyte receptor number was significantly reduced in diabetic patients (17,500 +/- 2,800 sites/cell) as compared with control subjects (26,700 +/- 2,500 sites/cell; P less than 0.05), whereas there were no differences regarding empty site affinities. Receptor data did not differ in patients with normal and decreased maximal dextrose requirements. Insulin resistance is apparently a common feature of type I diabetes at serum insulin concentrations of approximately 100 microU/ml. Normalization of the insulin effect by higher insulin concentrations is not possible in all patients. Insulin antibodies at concentrations observed in this study (less than 0.16 mU/ml) do not contribute significantly to insulin resistance; receptor and postreceptor defects are possibly more important.

Adolescent↗

Use of artificial pancreas and portable insulin infusion pumps in diabetes therapy: past, present, and future.

The development of the artificial pancreas (AP) was an important contribution to modern diabetology. The practical and theoretical findings obtained by its application in type I diabetic patients gave rise to new forms of treatment, i.e., portable insulin pumps and intensified conventional insulin therapy. Although these therapies lead to better results than conventional insulin administration, there is no doubt that the problems of diabetes therapy can be solved only by an implantable AP or pancreas transplantation.

Adult↗

Semisynthetic human insulin and purified pork insulin do not differ in their biological potency.

The biological potency of semisynthetic human insulin (Actrapid HM, Novo) and purified pork insulin (Actrapid MC, Novo) was assessed in normal and diabetic subjects. The blood glucose lowering effect and the related counter-regulatory response were initially tested in six healthy subjects who received an i.v. injection of 0.15 U/kg body weight of either insulin preparation. The attained insulin levels were very similar (peak at 15 min: HM 139 +/- 7, MC 129 +/- 7 microU/ml), as well as the resulting blood glucose curves. A prolonged suppression of C-peptide values was observed after injecting both preparations. The evoked counter-regulatory response [glucagon, growth hormone (GH), cortisol and catecholamines] showed minimal differences. Prolactin secretion was almost identical after HM and MC injection. A glucose clamp study was subsequently performed in six insulin-dependent diabetic (IDD) patients. Blood glucose levels were maintained at 80 mg/dl by the artificial pancreas during a 180 min infusion of MC or HM insulin (30 mU/kg/h). The amounts of dextrose infused during the last 60 min of the study were not significantly different (121 +/- 14 vs 137 +/- 11 mg/kg/h for MC and HM, respectively). It is clear from our results that at the dose levels used in this study, the biological potency of i.v. injected HM is very similar to that of MC.

Adult↗

Importance of early postprandial insulin delivery in insulin-dependent diabetics.

In nine insulin-dependent diabetics postprandial glucose control under closed loop insulin infusion by an artificial endocrine pancreas was compared with that obtained under open loop infusion employing identical infusion profiles which were advanced 20 min by time in the case of open loop infusion. The earlier increase of insulin infusion rates in the latter case resulted in lower postprandial glucose concentrations during the first 90 min after meal intake. Incremental areas under the blood glucose curves during this time were significantly lower when insulin infusion rates rose earlier (4.5 X 10(3) +/- 0.5 X 10(3) vs 2.1 X 10(3) +/- 0.6 X 10(3) mg/dl X min; p less than 0.02). Insulin was administered at maximum rates 45-50 min after the start of the meal during closed loop infusion (196 +/- 38 mU/min) and 25-30 min after the meal during open loop infusion (192 +/- 35 mU/min). Correspondingly, mean free insulin concentrations which are available from six patients rose to 135 +/- 47 (40 min) or 141 +/- 50 muU/ml (20 min). Glucagon levels did not differ between both parts of the study. It is concluded that increases of postprandial insulin infusion rates occurring earlier than increases of blood glucose levels are important for optimizing glucose profiles and possibly reflect physiologic conditions.

Adult↗

Impaired blood pressure response to norepinephrine in a case of insulin-dependent diabetes mellitus--improvement with a beta-adrenergic antagonist.

A case of juvenile-onset insulin-dependent diabetes mellitus in a 30-year-old male patient is reported. He was admitted to the hospital because of severe diabetic neuropathy, predominantly in the lower extremities. Signs of autonomic neuropathy were not evident but the patient had severe orthostatic hypotension. Circulating catecholamine concentrations were normal; however, the blood pressure response to infused norepinephrine was reduced ten-fold compared to a group of normals. An improvement of the blood pressure response to sympathomimetic drugs was accomplished during the simultaneous administration of propranolol, a beta-receptor blocking agent. The present data suggest a possible defect of the adrenergic receptor system in response to sympathomimetic drugs while the release of catecholamines and the function of the parasympathetic nervous system appears to be intact. Treatment with beta-blocking agents such as propranolol as an adjunct to sympathomimetics seems to be a promising approach which might deserve further consideration in similar cases.

Adrenergic beta-Antagonists↗

Studies on the pathogenesis of the dawn phenomenon in insulin-dependent diabetic patients.

To assess the role of hormonal factors in the pathogenesis of the dawn phenomenon, nocturnal (9:00 PM to 9 AM) concentrations of blood glucose, free insulin, and counterregulatory hormones were determined in eight insulin-dependent diabetic patients under feedback-controlled and continuous insulin infusions after previous blood glucose normalization. Under feedback control, mean insulin requirements, necessary for maintenance of euglycemia rose significantly in the early morning (11:00 PM to 3 AM: 8.4 +/- 1.4; 5 AM to 9 AM: 12.6 +/- 1.5 mU/kg/h; P less than 0.01). Mean free-insulin concentrations did not increase simultaneously. Correspondingly, mean insulin-clearance rates under continuous insulin infusion were higher in the morning (11:00 AM to 3 AM: 359 +/- 58; 5 AM to 9 AM: 459 +/- 72 mL/min/m2; P less than 0.05). Increases of insulin clearance rates were most marked (greater than 15%) in patients whose blood glucose rose during continuous insulin administration. Glucagon and norepinephrine concentrations were stable throughout both parts of the study. Cortisol and growth hormone exhibited the known nocturnal rhythms. Epinephrine levels were at the lower limit of detection at night and rose to normal basal concentrations at 9:00 AM. We conclude that increases of insulin clearance rates may be an important factor for the development of the dawn phenomenon while the role of most counter-regulatory hormones is still uncertain.

Adult↗

Abnormal growth hormone levels in insulin-dependent diabetic patients under continuous subcutaneous insulin infusion and intensified conventional treatment.

The present study was developed to assess the influence of prolonged blood glucose near normalization, achieved by means of continuous sc insulin infusion (CSII) or intensified conventional therapy (ICT) upon growth hormone (GH) secretion in insulin-dependent diabetes (IDD). Sixteen IDD patients (8 CSII-treated for 3-20 months and 8 under ICT) and 8 healthy control subjects were connected for 24 h to a newly developed, battery-powered glucose monitor. Diabetic patients received their usual food intake and insulin doses. During the second hour after meals moderate exercise, walking at 1.5 km/h, was performed by all subjects. Blood samples for insulin and GH determination were taken before and 60, 120 and 180 min after meal ingestion. Despite a similar degree of previous blood regulation, near normal glucose levels were attained only by the CSII group. Both ICT and CSII patients presented a marked postprandial hyperinsulinaemia. Abnormal GH levels were consistently registered in 4 CSII and 6 ICT patients 120 min after meal initiation. In consequence, both groups showed significantly elevated mean diurnal GH levels (controls: 1.1 +/- 0.3, ICT: 5.2 +/- 0.9, CSII: 4.1 +/- 1.1 ng/ml; P less than 0.05). According to these results, the pathologic GH secretion found in diabetic subjects is not fully normalized by tight control of blood glucose values.

Adolescent↗

[A new test-strip for checking blood-sugar levels].

Blood sugar levels in 228 EDTA-treated venous blood samples were measured in the laboratory by a new test-strip (Visidex) and the hexokinase reference method. There was good agreement between the two, with a linear correlation of r = 0.92 and a regression line with a slope of 0.98. 97.8% of all values deviated by less than one concentration range from the reference values. At low glucose concentrations the median of the absolute differences between the two methods was 9.5 mg/dl. Over the whole concentration range of 20-800 mg/dl the mean deviation from the reference values was between 14.4 and 32.6 mg/dl. The results indicate that the Visidex test-strip method is suitable for the visual estimation of blood sugar values.

Blood Glucose↗