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W Kerner

Publications and source records attributed to W Kerner.

At least 19 recordsLinked to original sources
PubMed1999

Protective effect of insulin against hypoglycemia-associated counterregulatory failure.

Antecedent hypoglycemic episodes reduce the counterregulatory neuroendocrine response to hypoglycemia. The role of insulin in the mechanism responsible for the antecedent hypoglycemia causing subsequent counterregulatory failure has not been elucidated. We performed antecedent hypoglycemic clamps (56 mg/dL) lasting 2 h with differing degrees of hyperinsulinemia, which were followed by 6-h stepwise hypoglycemic clamps (76-66-56-46 mg/dL) on the next day. Experiments were carried out in 30 young, healthy men. Fifteen of these subjects were tested on 2 occasions. On 1 occasion the antecedent hypoglycemia was induced by insulin infusion at a rate of 1.5 mU/min x kg (low insulin-ante-hypo); on the other occasion the insulin infusion rate was 15.0 mU/min x kg (high insulin-ante-hypo). Both sessions were separated by at least 4 weeks, and their order was balanced across subjects. The remaining 15 subjects (control group) received the same stepwise hypoglycemic clamp as the other subjects, but without antecedent hypoglycemia. During the stepwise hypoglycemic clamp, the counterregulatory increases in ACTH, cortisol, and norepinephrine were significantly blunted after the low insulin-ante-hypo (P < 0.01, P < 0.05, and P < 0.05, respectively) but not after the high insulin-ante-hypo (P = 0.12, P = 0.92, and P = 0.19, respectively) compared to that in the control group. The cortisol, norepinephrine, and glucagon responses were greater after the high than after the low insulin-ante-hypo (all P < 0.05). In conclusion, the present study clearly demonstrates that even a single episode of mild hypoglycemia reduces neuroendocrine counterregulation 18-24 h later. Insulin has a moderate protective effect on subsequent counterregulation.

Adult↗
PubMed1998

[Hypoglycemia].

Explore the source record for details and available documents.

Adult↗
PubMed1998

Fetal hemoglobin in starvation ketosis of young women.

Ketones can reactivate the production of fetal hemoglobin (HbF) in vitro and in vivo. A reactivation of HbF by ketones, which are generated during starvation, remains largely speculative. Therefore, we investigated HbF in 31 women with anorexia nervosa or bulimia, using both of these as models of intermittent starvation ketosis. For comparison, we also studied 42 female control subjects matched for age. beta-Hydroxybutyrate levels were higher in patients than in controls (460 +/- 90 v 110 +/- 20 mumol/L; P < .0001). We correlated beta-hydroxybutyrate, metabolic, and hematologic parameters with HbF. HbF was measured with high pressure liquid chromatography. The data were analyzed with logistic regression analysis. An elevated HbF fraction (> 0.87%) was observed four times as often in patients than in controls (29% v 7%, P = .01). After adjustment for age, we found HbF elevations associated with beta-hydroxybutyrate levels (P = .005). No other correlations between the various metabolic/ hematologic parameters and HbF were significant. In conclusion, beta-hydroxybutyrate generated in starvation is associated with increased levels of HbF. Thus, unrestrained lipolysis can produce beta-hydroxybutyrate in sufficient quantities to induce a clinically measurable amount of HbF. These findings suggest that intermittent ketosis might also explain some increases of HbF in type 1 diabetes and pregnancy.

Adolescent↗
PubMed1998

A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1alpha (HNF-1alpha) gene.

One form of maturity-onset diabetes of the young, Type 3 (MODY3), results from mutations in the gene coding for hepatocyte nuclear factor-1alpha (HNF-1alpha), a transcription factor first described in the liver. MODY3 is characterized by a defective glucose-stimulated insulin secretion. Earlier observations of glycosuria with normal blood glucose levels in some MODY families suggest an additional renal manifestation of the respective genetic defect. We measured the renal threshold for glucose in five diabetic carriers of a missense mutation (Arg 272 His) in HNF-1alpha and, for comparison, in eight Type 1 diabetic patients, applying a non-invasive protocol of frequent parallel blood and urine sampling during a slow shift in blood glucose levels. We found that the mean renal threshold for glucose was lowered in the HNF-1alpha diabetic patients compared to those with Type 1 diabetes (6.5 +/- 0.9 mmol l(-1) vs 10.7 +/- 0.5 mmol l(-1); p < 0.01). This lowered glucose threshold might be an indication of an extra-pancreatic effect of HNF-1alpha gene mutations in humans. Defects in HNF-1alpha may lead to an altered tubular glucose reabsorption, possibly due to decreased expression of the renal glucose transporter proteins involved in reabsorption of glucose from the urine.

Absorption↗
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↗
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↗