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W Kerner

Publications and source records attributed to W Kerner.

At least 19 recordsLinked to original sources
PubMed2000

Excess triiodothyronine as a risk factor of coronary events.

BACKGROUND: Abnormalities in cardiac function, eg, arrhythmias and congestive heart failure, often accompany thyrotoxicosis. A relationship between thyroid hormone excess and the cardiac complications of angina pectoris and myocardial infarction (MI) remains largely speculative. METHODS: The results of thyroid function studies on blood samples drawn from a total of 1049 patients (aged 40 years or older) immediately on emergency medical admission were related to frequencies of angina pectoris and myocardial infarction as determined according to current diagnostic algorithms. After 3 years, those patients who had initially presented with angina pectoris or acute MI were observed for subsequent coronary events; of these (n=185), 98% of the subjects (n=181) could be reevaluated. RESULTS: On hospital admission, the relative rate of angina pectoris and MI was markedly high (odds ratio, 2.6; 95% confidence interval, 1.3-5.2; P=.007) in patients with elevated serum free and total triiodothyronine (T(3)) levels. An initially elevated free T(3) level was a risk factor for subsequent coronary events during the 3-year follow-up (adjusted odds ratio, 4.8; 95% confidence interval, 1.3-17.4; P=.02). CONCLUSIONS: An elevation of serum free T(3) levels at hospital admission is associated with a 2.6-fold greater likelihood of the presence of a coronary event. Moreover, an initially elevated T(3) level is associated with a 3-fold higher risk of developing a subsequent coronary event during the next 3 years. Excess T(3) seemed to be a factor associated with the development and progression of acute myocardial ischemia.

Adult↗
PubMed2000

Increase in systolic blood pressure and catecholamine level during hyperinsulinemia in a placebo-controlled euglycemic clamp in healthy subjects.

Hyperinsulinemia has been shown to induce vasodilation and activation of the sympathetic nervous system. Whether these effects result in changes in blood pressure (BP) is discussed controversially. We measured BP and catecholamine levels in 50 healthy subjects during a 40-min baseline phase and during a 100-min euglycemic clamp phase. In a double-blind, between-subject comparison, 30 subjects were infused with 1.5mU insulin/kg x min, 20subjects were infused with saline solution. Insulin levels increased during insulin infusion from (mean+/-SE) 23.7 0.6 pmol/l to 406.2+/-3.0 pmol/l, but remained unchanged during placebo infusion. Blood glucose levels were identical during both conditions. Systolic BP increased from 116.6+/-1.5 mmHg to 119.8+/-1.8 mmHg during insulin infusion and decreased from 116.6+/-2.3 mmHg to 114.0+/-2.4 mmHg during placebo infusion (p<0.001, for the difference between the effects of insulin vs. placebo). Heart rate was higher during insulin infusion as compared to placebo infusion (63.8+/-1.9 vs. 60.9+/-2.4 beats/min, p<0.05). Norepinephrine levels increased from 1.25+/-0.09 to 1.58+/-0.12 nmol/l during insulin infusion and remained unchanged during placebo infusion (1.24+/-0.09 vs. 1.29+/-0.11 pmol/l; p<0.001). Epinephrine levels were also higher during insulin as compared to placebo infusion (249.8+/-17.4 vs. 212.8+/-21.1 pmol/l, p<0.001). The changes did not depend on whether the subject experienced his first or second clamp. Data demonstrate reproducable increasing effects of hyperinsulinemia within the normal physiological range on catecholamine release and systolic BP in healthy humans.

Adolescent↗
PubMed2000

Maculopathy in patients with diabetes mellitus type 1 and type 2: associations with risk factors.

AIM: To examine possible relation between diabetic maculopathy and various risk factors for diabetic complications in patients with diabetes mellitus type 1 and type 2. METHODS: Cross sectional study of two cohorts of diabetic patients, comprising 1796 patients with type 1 diabetes (mean age 47 years, mean duration of diabetes 24 years) and 1563 patients with type 2 diabetes (mean age 62 years, mean duration of diabetes 16 years). Retinopathy levels (R0-RV) and maculopathy were assessed by fluorescence angiography and fundus photography and binocular biomicroscopy. Diabetic neuropathy was assessed by means of computer assisted electrocardiography and by thermal and vibratory sensory examination. Patients were classified as normoalbuminuric (<20 microg/min) or microalbuminuric (20-200 microg/min) according to their albumin excretion rates measured in urine collected overnight. Using univariate analyses, the effects of selected patient characteristics on the presence of maculopathy were evaluated. Multiple logistic regression analyses were performed to determine independent effects of risk variables on diabetic maculopathy. RESULTS: Background retinopathy (RII) was found to be present in 28% of type 1 diabetic patients and in 38% of type 2 diabetic patients. The prevalence of maculopathy in these patients was remarkably high (42% in type 1 and 53% in type 2 diabetic patients). Patients with maculopathy had significantly impaired visual acuity. Multiple logistic correlation analysis revealed that in both types of diabetes maculopathy exhibited independent associations with duration of diabetes and with neuropathy (p <0. 01); in type 1 diabetic patients there were significant associations with age at diabetes onset, serum triglyceride and total cholesterol levels (p <0.05); in type 2 diabetes with serum creatinine levels and with hypertension (p <0.05). CONCLUSIONS: Irrespective of the type of diabetes, diabetic patients with long standing diabetes have a high risk for the development of diabetic maculopathy. Diabetic maculopathy is closely associated with diabetic nephropathy and neuropathy and with several atherosclerotic risk factors which suggests that these factors might have an important role in the pathogenesis of maculopathy. However, prospective trials are necessary to evaluate the predictive value of such factors. The findings of the present cross sectional study reinforce the arguments of previous studies by others for tight control of hypertension and hyperglycaemia.

Adult↗
PubMed2000

Glucose metabolism rather than insulin is a main determinant of leptin secretion in humans.

Circulating plasma insulin and glucose levels are thought to be major regulators of leptin secretion. There is evidence from in vitro and animal experiments that glucose metabolism rather than insulin alone is a main determinant of leptin expression. Here, we tested the hypothesis that in humans also leptin secretion is primarily regulated by glucose uptake and only secondarily by plasma insulin and glucose. In 30 lean and healthy men we induced 4 experimental conditions by using the blood glucose clamp technique. A total of 60 hypoglycemic and euglycemic clamps, lasting 6 h each, were performed. During these clamps insulin was infused at either high (15.0 mU/min x kg) or low (1.5 mU/min x kg) rates, resulting in low-insulin-hypo, high-insulin-hypo, low-insulin-eu, and high-insulin-eu conditions. Serum leptin increased from 0-360 min by 20.5 +/- 4.1% in the low-insulin-hypo, 33.6 +/- 7.6% in the high-insulin-hypo, 39.6 +/- 6.0% in the low-insulin-eu, and 60.4 +/- 7.6% in the high-insulin-eu condition. Multiple regression analysis revealed a significant effect of circulating insulin (low vs. high insulin; P = 0.001) and blood glucose (hypoglycemia vs. euglycemia; P = 0.001) on the rise of serum leptin. However, when the total amount of dextrose infused during the clamp (grams of dextrose per kg BW) was included into the regression model, this variable was significantly related to the changes in serum leptin (P = 0.001), whereas circulating insulin and glucose had no additional effect. These findings in humans support previous in vitro data that leptin secretion is mainly related to glucose metabolism.

Adult↗
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↗
PubMed1999

Supraphysiological hyperinsulinemia acutely increases hypothalamic-pituitary-adrenal secretory activity in humans.

Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in association with hyperinsulinemia is frequently found in patients with type 1 and type 2 diabetes mellitus and in subjects with abdominal adiposity. We questioned whether insulin could cause HPA axis activation and, if so, whether this insulin action may arise at the adrenal level or at a central (i.e. hypothalamic-pituitary) level. Experiments lasting for 6 h each were done in 30 lean healthy men. In 15 men, insulin was infused at a rate of 1.5 mU min(-1) kg(-1). Plasma glucose concentration was held constant during an euglycemic clamp session and was decreased stepwise in a hypoglycemic clamp session. The sequence of the 2 clamp sessions was random, and a 4-weeks recovery period was allowed between the two sessions. The protocol was essentially the same in another 15 men, with the exception that insulin was infused at a rate of 15.0 mU min(-1) kg(-1). During the euglycemic clamp sessions, we found plasma ACTH levels to increase only in the high-, but not in the low-insulin group (group by time interaction, P < 0.01); serum cortisol levels were greater in the high than in the low-insulin group (P < 0.02). In the hypoglycemic clamp sessions, plasma ACTH levels increased in the same pattern in the 2 groups; serum cortisol was greater in the high than in the low-insulin group at the beginning of the clamp (plasma glucose approximately 4.1 mmol/L; P < 0.05). Our results demonstrate that insulin acutely stimulates the HPA secretory activity in humans. The pattern suggests an effect of insulin at both peripheral and central levels of the HPA axis.

Adrenal Glands↗
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↗