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Biomedical subjects

W Kerner

Publications and source records attributed to W Kerner.

At least 37 records · Page 2Linked to original sources
PubMed1998

Glucose concentration in human subcutaneous adipose tissue: comparison between forearm and abdomen.

There is still controversy about the relation between the glucose concentration in the subcutaneous (sc.) adipose tissue and the blood plasma. Depending on the technique applied, the glucose concentration in sc. tissue varies between 50% and 100% of the plasma glucose concentration. In the present study the sc. glucose concentration of forearm and abdomen in seven healthy volunteers was compared with plasma glucose by applying the microdialysis technique with very low flow rates. A microdialysis probe implanted into the subcutaneous tissue of abdomen and forearm was perfused with a flow rate of 1 microl/4 min. The dialysate was sampled in three 2-h-fractions in the fasting state and in one 2-h-fraction during a hyperglycemic clamp (216.9+/-3.4 mg/dl) (mean +/- SEM). The mean recoveries of the plasma glucose were 91.1+/-4.1% in the forearm and 82.7+/-18.0% in the abdomen. The recoveries in the sc. tissue of abdomen and arm were not significantly different. However, the arm showed significantly (p < 0.014) less interindividual variance (range 73.2- 103.2%) than the abdomen (range 50.6-117.1%) and appears to be the preferable implantation site. The recovery remained constant during the investigation.

Abdomen↗
PubMed1998

Acute stress modulates symptom awareness and hormonal counterregulation during insulin-induced hypoglycemia in healthy individuals.

The purpose of this study was to determine whether the perception of hypoglycemia is reduced during acute stress. In Session I each of our 40 healthy male volunteers received a bolus injection of human insulin (0.05 IU/kg) resulting in plasma glucose nadirs of below 2.8 mmo/L. In Session 2 participants received insulin or saline, with half of each group being stressed by having to prepare and give a speech. Data collection at 5- to 25-min intervals included a symptom checklist, blood pressure, heart rate, and blood sampling for measurement of plasma glucose and counterregulatory hormones. Individuals in the stress + insulin group were less sure of having received insulin and ate fewer cookies compared with controls. They reported lower intensity of the hypoglycemic symptoms of palpitations, tremor, dizziness, and blurred vision, in contrast to the reduced subjective and behavioral reactions, they showed the strongest hormonal counterregulation. We conclude that acute stress during hypoglycemia reduces symptom awareness and the ability to detect hypoglycemia.

Journal Article↗
PubMed1997

Relations between diabetic retinopathy and cardiovascular neuropathy--a cross-sectional study in IDDM and NIDDM patients.

The pathogenetic process of diabetic retinopathy and the role of different systemic risk factors in IDDM and NIDDM is not completely understood. The aim of the present cross-sectional clinical study was (1) to compare the prevalence of systemic risk factors for diabetic retinopathy in IDDM and NIDDM patients, (2) to determine relations between these risk factors and the degree of retinopathy and (3) to evaluate the relationship between retinopathy and neuropathy. The study included 1,218 IDDM and 784 NIDDM patients attending our hospital during 1994. The mean diabetes duration was 15.4 and 13.2 years, respectively. IDDM patients with proliferative retinopathy were characterized by higher mean age of 46.4 +/- 1.08 vs. 21.8 +/- 0.42 years and longer diabetes duration of 30.0 +/- 0.79 vs. 7.7 +/- 0.26 years. Among the NIDDM patients, those ones with proliferative retinopathy had the lowest mean age of 40.5 +/- 1.42 vs. 49.7 +/- 0.61 years (p < 0.01) at diabetes manifestation. There was no statistical difference between mean HbA1c concentrations in relation to retinopathy stages. Albumin excretion was increased in both IDDM and NIDDM patients with proliferative retinopathy (p < 0.01) along with increased BMI of IDDM and increased insulin requirement of NIDDM patients (p < 0.01). Multiple regression analysis showed that proliferative retinopathy with the inclusion of non-proliferative retinopathy of IDDM and NIDDM patients was significantly correlated with diabetes duration, albumin excretion, somatic and autonomic neuropathy (p < 0.01). In NIDDM patients proliferative retinopathy with the inclusion of non-proliferative retinopathy was correlated with the age at diabetes manifestation and with cholesterol levels (p < 0.05). In IDDM and NIDDM patients proliferative retinopathy was found to be correlated with somatic and autonomic neuropathy, albumin excretion (p < 0.01) and hypertension (p < 0.05). The importance of the significant correlation of autonomic neuropathy both with background and proliferative retinopathy in IDDM and NIDDM patients needs to be prospectively investigated.

Adolescent↗
PubMed1997

Mutations in the hepatocyte nuclear factor-1alpha gene in MODY and early-onset NIDDM: evidence for a mutational hotspot in exon 4.

We have recently shown that mutations in the gene encoding the transcription factor hepatocyte nuclear factor (HNF)-1alpha are the cause of one form of maturity-onset diabetes of the young (MODY3). Here, we report the exon-intron organization and partial sequence of the human HNF-1alpha gene. In addition, we have screened the ten exons and flanking introns of this gene for mutations in a group of 25 unrelated white subjects from Germany who presented with NIDDM before 35 years of age and had a first-degree relative with NIDDM. Mutations were identified in nine of these individuals, suggesting that mutations in the HNF-1alpha gene are a common cause of diabetes in German subjects with early-onset NIDDM and a family history of diabetes. Thus, screening for mutations in this gene may be indicated in subjects with early-onset NIDDM. Interestingly, three of the nine mutations occurred at the same site in exon 4 with insertion of a C in a polyC tract, centered around codon 290 (designated Pro291fsinsC), thereby resulting in a frameshift during translation and premature termination. Analyses of linked DNA polymorphisms in the HNF-1alpha gene indicated that the Pro291fsinsC mutation was present on a different haplotype in each subject, implying that the polyC tract represents a mutational hot spot. We have also identified the mutation in the HNF-1alpha gene in the Jutland pedigree, one of the original MODY pedigrees reported in the literature, as being a T-->G substitution in codon 241, resulting in the replacement of a conserved Cys by Gly (C241G). The information on the sequence of the HNF-1alpha gene and its promoter region will facilitate the search for mutations in other subjects and studies of the role of the gene in determining normal beta-cell functions.

Adolescent↗
PubMed1997

Symptom awareness is affected by the subjects' expectations during insulin-induced hypoglycemia.

OBJECTIVE: To assess how expectations and symptom beliefs based on a previous episode of insulin-induced hypoglycemia influence symptom awareness after a second insulin injection in healthy subjects. RESEARCH DESIGN AND METHODS: After a first episode of insulin-induced hypoglycemia in session 1, half of 40 healthy male subjects were told at the beginning of session 2 that they would receive human insulin (0.05 IU/kg), the other half saline. According to a 2 x 2 balanced placebo design, only half of each group received the announced substance, whereas the other half received the substance contrary to their expectations. Data collection at 10-15 min intervals included a symptom checklist, blood pressure, heart rate, plasma glucose, and counterregulatory hormone levels. RESULTS: The expectation of a repeated hypoglycemia clearly influenced the subjects' psychophysiological responses. Without knowledge about the actual treatment, there was only an average maximum confidence of 65% of having received insulin. Expecting the insulin injection led to an increased sum score of neuroglycopenic symptoms but not of autonomic symptoms. Subjects expecting the insulin injection reported more weakness, blurred vision, and inner restlessness than those subjects expecting the saline injection. Those subjects correctly informed about receiving insulin experienced the most drowsiness, dizziness, and headaches. The expectations of the insulin injection increased the norepinephrine levels and the heart rate. The told insulin/given insulin group showed the highest glucagon levels. CONCLUSIONS: The results support the hypothesis that the subjects' expectations influence their perceived symptoms.

Adrenocorticotropic Hormone↗
PubMed1996

[The therapy of a macroprolactinoma with the intramuscular application of a long-acting bromocriptine preparation].

HISTORY AND CLINICAL FINDINGS: Three years ago, a now 26-year-old woman with secondary amenorrhoea was found to have a prolactinoma which was treated with bromocriptine. However, because of side effects and psychosocial problems she took the drug only irregularly. There were no neurological symptoms and the visual fields were normal. Her weight was 97 kg and her height 168 cm. INVESTIGATIONS: Without treatment the serum prolactin concentration was 6978 microU/ml, while other endocrine parameters were unremarkable. Cranial computed tomography showed a suprasellar adenoma (craniocaudal diameter 1.0 cm). TREATMENT AND COURSE: Renewed treatment with bromocriptine (5 mg three times daily) brought prolactin concentration to within normal limits, but then rose again to at least 52,600 microU/ml when the patient took the drug irregularly, and the tumour grew to 2.8 cm. As the obesity (her weight now 120 kg) made neurosurgical intervention very risky a treatment trial with long-acting bromocriptine preparation (50 mg bromocriptine every 28 days intramuscularly), was undertaken. Serum prolactin concentration, measured at the end of the 28-day period, rapidly fell (6470 microU/ml after 3 months). Radiological examination indicated significant tumour shrinkage ( < 1.0 cm after 2 years). CONCLUSION: Repeated intramuscular administration of bromocriptine was an effective, well tolerated alternative (but not yet licensed in Germany) to oral dopamine agonists in the treatment of macroprolactinoma.

Adult↗
PubMed1996

Nocturnal blood pressure elevation is related to adrenomedullary hyperactivity, but not to hyperinsulinemia, in nonobese normoalbuminuric type 1 diabetes.

We tested the hypothesis that insulin is an independent risk factor for elevated blood pressure. As our model we selected type 1 diabetes with peripheral circulatory hyperinsulinemia induced by sc insulin treatment. In 15 nonobese normoalbuminuric patients with type 1 diabetes (23.7 +/- 0.8 yr old) and in 15 healthy controls matched for age, sex, and body weight, ambulatory blood pressure was recorded over 24 h. The areas under the curve of free insulin (605 +/- 135 vs. 275 +/- 35 pmol/L.h; P = 0.03) and basal plasma epinephrine concentrations were higher (170 +/- 10 vs. 130 +/- 10 pmol/L; P = 0.02), and the basal aldosterone level was lower (220 +/- 40 vs. 410 +/- 50 pmol/L; P = 0.009) in the patients. The nocturnal decline in systolic blood pressure was less pronounced (13 +/- 1 vs. 19 +/- 2 mm Hg; P = 0.007) in the patients. Multivariate adjustment (r2 = 0.75; P = 0.0002) showed an effect of basal plasma epinephrine and norepinephrine levels and body mass index on the mean nocturnal systolic blood pressure, but showed no effect of age, sex, hemoglobin A1c, aldosterone, or, in particular, insulin. We found a blunted nocturnal fall in blood pressure in nonobese, normoalbuminuric type 1 diabetic patients. These patients showed increased adrenomedullary activity, and this predominantly contributed to the blood pressure alterations. We also found hyperinsulinemia in these patients, but, after controlling for covariates, blood pressure was independent of the insulin level.

Adolescent↗
PubMed1996

[Analytic design and clinical application of an intelligent control system for pharmacotherapy with insulin--2].

To determine whether insulin dosage recommendations provided by a computer system are as effective as those given by human experts, we developed an intelligent control system and prospectively studied its use in 42 type-1 diabetics attending a diabetes education center. Control algorithms were based on blood glucose self-monitoring and included parameter estimations to determine glucose metabolism. The algorithms were implemented in a vest pocket-sized system. Over a period of 32 days, 21 patients used the computer to determine the necessary dose of insulin, while a second group of 21 patients followed the recommendations of the diabetes specialists. Baseline HbA1 levels (9.8 +/- 1.6 vs 9.9 +/- 1.6%) were identical in the two groups. The mean serum glucose over the last two weeks of the study was lower in the computer group (151.3 +/- 25.2 vs 165.7 +/- 36.0 mg/dl; p < 0.01) although the rates of hypoglycaemic episodes were equal (1.7 vs 2.3%). Metabolic control, measured by the day-to-day standard deviation of the serum glucose (46.8 +/- 14.4 vs 50.4 +/- 16.2 mg/dl; p < 0.01), was more stable in the computer group. We conclude that metabolic control and safety were comparable in the two groups, and suggest that such an intelligent control system may be of benefit for use at home, when the help of doctors or diabetes educators is not available.

Adult↗
PubMed1995

Perioperative management of the diabetic patient.

Patients with diabetes mellitus are at a higher risk to undergo surgical intervention compared with the non-diabetic population, and additionally, they have an increased perioperative morbidity and mortality. Insulin deficiency and insulin resistance are aggravated by surgery and anaesthesia. The consequences of hyperglycemia are glycosuria, volume depletion from osmotic diuresis, impairment of wound healing and leucocyte function and exacerbation of ischemic brain damage. Depending on the extent of hypoinsulinemia, lipolysis and ketogenesis are enhanced which may result in metabolic acidosis with subsequent electrolyte disturbances. Protein catabolism is increased because of increased breakdown and decreased synthesis. Insulin administration reverts or overcomes most of these disturbances. The preoperative assessment includes the diagnoses of the long-term complications to judge the intraoperative risks. Long-acting insulins, such as ultralente of animal origin should be stopped preoperatively and substituted by protamine and lente insulins. In type-2-diabetic patients, long-acting sulfonylurea drugs such as chlorpropamide should be stopped and substituted by short-acting agents. Metformin must always be stopped. Type-2-diabetic patients with marked hyperglycemia under oral treatment should be switched to insulin before operation. The insulin requirements in diabetic patients during surgery vary from 0.25-0.40 U per gram glucose in normal weight patients, 0.4-0.8 U per gram glucose in case of obesity, liver disease, steroid therapy or sepsis, to 0.8-1.2 U per gram glucose in patients undergoing cardiopulmonary bypass surgery. Therefore, the appropriate dose has to be determined individually. The regimen nowadays preferred by most authors is based on variable rate insulin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia↗
PubMed1995

The influence of insulin antibodies on the pharmacokinetics of NPH insulin in patients with type 1 diabetes treated with human insulin.

The influence of insulin binding antibodies on the pharmacokinetics of NPH insulin was studied in Type 1 diabetic patients on human insulin. Insulin-antibody binding (B(o) was measured during a screening procedure in 155 Type 1 diabetic patients. In 36 patients, B(o) was < 1.5%, and in 38 patients B(o) was > 10.0%. Of these, 6 patients, group 1 (B(o) < 1.5%) and 8 patients, group 2 (B(o) > 10.0%), respectively, subsequently participated in a pharmacokinetic study. Free insulin and the glucose infusion rate were measured using a euglycaemic clamp after subcutaneous injection of NPH insulin (0.4 U kg-1). The areas under the curve (AUC) of free insulin concentration were smaller for group 2 (p = 0.01) than for group 1 (212.2 +/- 22.0 vs 316.8 +/- 25.3 mU l-1h). The AUCs of the glucose infusion rate were also smaller for group 2 (p < 0.05) than for group 1 (2.50 +/- 0.32 vs 3.58 +/- 0.36 g kg-1). A significant negative correlation exists between the AUCs for free insulin concentration and insulin-antibody binding B(o) (r = 0.76, p = 0.001). The daily insulin dosage was higher in group 2 (p = 0.02) than in group 1 (0.66 +/- 0.03 vs 0.53 +/- 0.03 U kg-1). We conclude that insulin antibodies influence the pharmacokinetics of NPH human insulin. The demonstrable influence on the kinetics of free insulin and glucose utilization leads to a slight increase in daily total insulin requirements.

Adult↗
PubMed1995

Preserved counterregulatory hormone release and symptoms after short term hypoglycemic episodes in normal men.

To test the hypothesis that subsequent neuroendocrine and symptomatic responses are sustained after short term hypoglycemic episodes of less than 1-h duration, we studied hypoglycemia on 4 consecutive days and after an 8-day pause in 10 nondiabetic men. Highly reproducible decreases in plasma glucose (< 2.8 mmol/L) occurred on study days 1, 2, 3, 4, and 12 after iv insulin boluses (0.04 U/kg). Levels of the counterregulatory hormones rose during the hypoglycemic episodes in all instances, but maximal concentrations on study day 4 were not attenuated: glucagon (peaks on day 1 vs. day 4), 150 +/- 10 vs. 180 +/- 20 ng/L; cortisol, 400 +/- 30 vs. 420 +/- 40 nmol/L; ACTH, 12 +/- 2 vs. 13 +/- 2 pmol/L; GH, 11.1 +/- 1.8 vs. 12.5 +/- 2.2 micrograms/L; norepinephrine, 1.68 +/- 0.17 vs. 1.65 +/- 0.13 nmol/L; and epinephrine, 1370 +/- 440 vs. 1520 +/- 480 pmol. On each study day, symptoms of hypoglycemia were produced after induction of hypoglycemia, and there was no decrease in the degree of symptomatology on subsequent days. The multivariate analysis of variance showed no day to day differences in plasma glucose, counterregulatory hormones, or hypoglycemic symptoms. We conclude, firstly, that after short term hypoglycemic episodes, the neuroendocrine and symptomatic responses remain completely intact in normal individuals and, secondly, that short term periods of hypoglycemia are fundamentally different from prolonged periods, as described previously.

Adrenocorticotropic Hormone↗
PubMed1994

Amperometric biosensor for in vivo glucose sensing based on glucose oxidase immobilized in a redox hydrogel.

A potentially implantable glucose sensor, based on glucose oxidase immobilized in a redox hydrogel, is considered. The redox hydrogel consisted of glucose oxidase immobilized in a cross-linkable poly(vinylpyridine) complex of [Os(bis-bipyridine)2Cl]+1/+2 that communicates electrically with the flavin adenine dinucleotide (FADH2) redox centres of the glucose oxidase. The implantable electrode consisted of a Teflon insulated platinum wire (0.25 mm diameter) which was coated at the tip with a cross-linked redox polymer/glucose oxidase film and covered with a thin layer of polycarbonate. In a three-electrode system at +400 mV (Ag/AgCl) the response to increasing glucose concentrations in isotonic phosphate buffer and human plasma was approximately 0.2-0.3 nA/mM, linear in the range between 0 and 15 mM glucose. No oxygen dependence was observed. To determine the in vivo performance, the electrode was implanted into the subcutaneous tissue of a dog. The sensor currents after an oral glucose load paralleled the plasma glucose measurements, with a time lag of 10 min. Three-day implantations in cultured cells showed that the electrode did not affect the growth and differentiation of cell monolayers.

Animals↗
PubMed1994

Effects of insulin and hypoglycemia on the auditory brain stem response in humans.

1. This study aimed to differentiate effects of insulin and hypoglycemia on sensory brain stem functions in humans. Auditory brain stem responses (ABR) were examined in 30 healthy men during euglycemia and after 20 and 50 min of steady-state hypoglycemia of 2.6 mM induced with human insulin (HI) in one session and porcine insulin (PI) in another session. 2. Levels of blood glucose and serum insulin were identical in both sessions during HI and PI infusion. 3. Hypoglycemia increased interpeak latencies III-V (+71 microseconds; P < 0.001) and I-V (+123 microseconds; P < 0.001), whereas changes in the latency of wave I were not significant. 4. After 20 min of constant hypoglycemia, increases in the interpeak latencies I-V and III-V were significantly more pronounced during infusion of PI than HI. These differences disappeared with time spent in hypoglycemia, i.e., after 50 min of hypoglycemia. 5. Apart from the delaying effect of hypoglycemia on neuronal transmission within the sensory brain stem, the results provide evidence for a separate influence of insulin on these functions.

Adolescent↗