Ernst F Pfeiffer

Subcutaneous Glucose Concentration in Humans: Real estimation and continuous monitoring

OBJECTIVE To determine the real subcutaneous glucose concentration in healthy volunteers to help in the development of new calibration methods for subcutaneous glucosensors. RESEARCH DESIGN AND METHODS We developed a new method to estimate the real subcutaneous glucose concentration based on the recirculation of phosphate-buffered saline (PBS) in a microdialysis probe inserted into the subcutaneous tissue. Tissue glucose diffuses into the probe until complete equilibration between the glucose concentration outside and inside the microdialysis probe is achieved. Later, the glucose content of the recirculated PBS is assessed in vitro. We applied the method in 10 healthy volunteers under fasting state and during a hyperglycemic clamp. In addition, we monitored the subcutaneous glucose with an enzymatic-amperometric glucosensor combined with a microdialysis probe. RESULTS The subcutaneous glucose concentration measured by the recirculation method was 72 ± 6 and 78 ± 6% of the blood glucose measured in the fasting state and during the hyperglycemic clamps, respectively. On the other hand, the glucosensors signal correlated significantly with the blood glucose. CONCLUSION The recirculation method estimated the real subcutaneous glucose concentration, opening the way to develop new calibration procedures for subcutaneous glucosensors. However, a suitable calibration procedure is still lacking.

Paradoxical ACTH Response to Glucocorticoids in Cushing's Disease

To define further the defect in the steroid feedback mechanism in Cushings disease, we studied the acute effects of intravenous administration of glucorticoids on plasma ACTH levels in seven patients with this disease after total adrenalectomy. In seven other patients with hypoadrenocorticism ACTH was readily suppressed; a significant decrease (72.5+/-5 per cent, mean +/- S.E.M., P less than 0.002) occurred within 15 minutes of the start of an infusion of 50 mg per hour of cortisol. In contrast, in the seven adrenalectomized patients with Cushings disease, cortisol induced a transient paradoxical rise in ACTH levels, with a maximum at 15 minutes (347+/-99 per cent,, P less than 0.05). A similar ACTH response was observed with dexamethasone. Cushings disease is characterized by a paradoxical transient rise in ACTH after glucocorticoid administration. This effect was more pronounced in adrenalectomized than in nonadrenalectomized patients.

Incidence of Hypoglycemic Episodes in Diabetic Patients Under Continuous Subcutaneous Insulin Infusion and Intensified Conventional Insulin Treatment: Assessment by Means of Semiambulatory 24-hour Continuous Blood Glucose Monitoring

The incidence and magnitude of hypoglycemia (i.e., blood glucose values < 50 mg/dl) were assessed by continuous blood glucose monitoring over 24 h in 10 insulin-dependent diabetic (IDD) patients treated with continuous subcutaneous insulin infusion (CSII) and 9 IDD patients under intensified conventional treatment (ICT). A newly developed, battery-powered blood glucose monitor was employed. Patients were thus enabled to move freely in the hospital premises. Despite similar quality of previous blood glucose control (HbA1: 8.0 ± 0.05% CSII versus 8.0 ± 0.3% ICT, x¯ ± SEM), the obtained profiles showed better regulation under CSII treatment (mean blood glucose [MBG], 99.6 ± 10.0 versus 133.1 ± 7.4 mg/dl; M-value, 12.3 ± 3.5 versus 26.2 ± 4.1; mean amplitude of glycemic excursion [MAGE], 71.9 ± 8.7 versus 132.9 ± 14.2 mg/dl; CSII versus ICT, x¯ ± SEM). The incidence of blood glucose values < 50 mg/dl was 9/10 patients (CSII) and 5/9 patients (ICT). In both groups, hypoglycemia was most frequent at noon and was related to elevated pre- and postprandial free insulin levels. Patients became aware of hypoglycemia only in 6/23 episodes (CSII) and 6/8 episodes (ICT). Our data indicate that CSII as well as ICT may result in postprandial hyperinsulinemia leading to frequent hypoglycemic episodes of variable length, reassessing the traditional experience of close correlation between aggressive insulin therapy and enhanced hypoglycemic risk.

Differences in insulin, growth hormone and pancreatic enzyme secretion after intravenous and intraduodenal administration of mixed amino acids in man.

Abstract To determine whether intestinal hormones have a physiologic role in amino-acid-induced secretion of insulin, growth hormone and pancreatic enzymes, 42 metabolically normal human subjects were studied. An amino acid mixture (30 g) was administered intravenously and intraduodenally. A higher rise in serum insulin occurred after the intraduodenal application, and took place before the maximum blood concentration of amino acids was reached. Blood sugar, nonesterified fatty acids and free glycerol concentrations fell more clearly after intraduodenal administration. The route of administration did not significantly affect blood concentrations of growth hormone. After intraduodenal amino acids, the volume and bicarbonate contents of the duodenal juice rose slightly, whereas trypsin and bilirubin content increased considerably. These results suggest that, after oral administration of amino acids in man, only the secretion of insulin is clearly influenced by intestinal factors. Much evidence suggests that...

Hypoglycaemia Detection by Ulm Sugar Watch System Indicating On-Line s.c. Glucose in Type-1 Diabetic Patients under Intensive Insulin Therapy

This chapter discusses a study focusing on hypoglycaemia detection by Ulm Sugar watch system indicating on-line s.c. glucose in type-1 diabetic patients under intensive insulin therapy. The Ulm Sugar Watch System consists of: (1) microdialysis probe inserted in the s.c. tissue, (2) Glucosensor Unitec Ulm, (3) sensor signal telemetrically transmitted to a wrist watch, (4) optic and acoustic alarm indicating provoked or spontaneous hypoglycaemia, and (5) minutely storage of s.c. glucose concentration for later evaluation before PC. The tissue glucose (T.G.) of patients under intensive-insulin treatment was on-line continuously monitored with glucosensor during hypoglycaemic clamps and under daily therapy. The blood glucose was clamped at 52 ± 4 mg/dl by means of the Bilostator. After clamping, blood glucose was conventionally assessed every 60 or 120 min. Calibration of the glucosensor was achieved by applying a one-point in-vitro , one-point in-vivo method. A further two-point in-vivo calibration and a simple mathematical algorithm a posteriori , yield the smoothing of the sensors signal. The results showed that the blood glucose levels fluctuated between 40 and 400 mg/dl. The sensor signal correlated significantly with the correspondent blood glucose profiles. A delay of 5 to 10 min was determined.