losartan-potassium and Hypoglycemia

Topics: Animals; Blood Viscosity; Cardiovascular Diseases; Central Nervous System Diseases; Erythrocyte Deformability; Erythropoietin; Female; Fetal Hypoxia; Fetofetal Transfusion; Fetomaternal Transfusion; Fetus; Follow-Up Studies; Gastrointestinal Diseases; Genital Diseases, Male; Global Health; Growth Disorders; Hematocrit; Humans; Hyperbilirubinemia; Hypocalcemia; Hypoglycemia; Infant, Newborn; Infant, Small for Gestational Age; Kidney Diseases; Male; Mental Disorders; Polycythemia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy in Diabetics; Prognosis; Respiration Disorders; Sheep; Thrombocytopenia

Topics: Adrenocorticotropic Hormone; Calcitonin; Erythropoietin; Gonadotropins; Growth Hormone; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Neoplasms; Neurophysins; Oxytocin; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Peptides; Placental Lactogen; Prolactin; Radioimmunoassay; Receptors, Cell Surface; Thyrotropin; Vasopressins

Topics: Adrenocorticotropic Hormone; Chorionic Gonadotropin; Cushing Syndrome; Erythropoietin; Gastrointestinal Hormones; Hormones, Ectopic; Hypercalcemia; Hypoglycemia; Hyponatremia; Melanocyte-Stimulating Hormones; Neurologic Manifestations; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Polycythemia; Prostaglandins E; Somatomedins; Vasopressins

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Brain Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cerebellar Neoplasms; Child; Child, Preschool; Choriocarcinoma; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Female; Gonadotropins; Hemangiosarcoma; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Infant; Infant, Newborn; Insulin; Insulin Secretion; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms; Parathyroid Hormone; Pheochromocytoma; Polycythemia; Pregnancy; Teratoma; Testicular Neoplasms; Thymus Neoplasms

Topics: Adrenocorticotropic Hormone; Endocrine System Diseases; Erythropoietin; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Hyperthyroidism; Hypoglycemia; Hyponatremia; Insulin; Luteinizing Hormone; Melanocyte-Stimulating Hormones; Neoplasms; Parathyroid Hormone; Polycythemia; Puberty, Precocious; Thyrotropin; Vasopressins

The adrenal gland and its hormones regulate numerous fundamental biological processes; however, the impact of hypoxia signaling on adrenal function remains poorly understood. Here, we reveal that deficiency of HIF (hypoxia inducible factors) prolyl hydroxylase domain protein-2 (PHD2) in the adrenal medulla of mice results in HIF2α-mediated reduction in phenylethanolamine N-methyltransferase (PNMT) expression, and consequent reduction in epinephrine synthesis. Simultaneous loss of PHD2 in renal erythropoietin (EPO)-producing cells (REPCs) stimulated HIF2α-driven EPO overproduction, excessive RBC formation (erythrocytosis), and systemic hypoglycemia, which is necessary and sufficient to enhance exocytosis of epinephrine from the adrenal medulla. Based on these results, we propose that the PHD2-HIF2α axis in the adrenal medulla regulates the synthesis of epinephrine, whereas in REPCs, it indirectly induces the release of this hormone. Our findings are also highly relevant to the testing of small molecule PHD inhibitors in phase III clinical trials for patients with renal anemia. KEY MESSAGES: HIF2α and not HIF1α modulates PNMT during epinephrine synthesis in chromaffin cells. The PHD2-HIF2α-EPO axis induces erythrocytosis and hypoglycemia. Reduced systemic glucose facilitates exocytosis of epinephrine from adrenal gland.

Topics: Adrenal Medulla; Animals; Basic Helix-Loop-Helix Transcription Factors; Calcium; Epinephrine; Erythropoietin; Female; Hypoglycemia; Hypoxia-Inducible Factor-Proline Dioxygenases; Male; Mice, Transgenic; Phenylethanolamine N-Methyltransferase; Polycythemia; Tumor Cells, Cultured

Hypoglycemia is a common complication for insulin treated people with diabetes. Severe hypoglycemia, which occurs in the setting of excess or ill-timed insulin administration, has been shown to cause brain damage. Previous pre-clinical studies have shown that memantine (an N-methyl-d-aspartate receptor antagonist) and erythropoietin can be neuroprotective in other models of brain injury. We hypothesized that these agents might also be neuroprotective in response to severe hypoglycemia-induced brain damage. To test this hypothesis, 9-week old, awake, male Sprague-Dawley rats underwent hyperinsulinemic (0.2 U kg(-1)min(-1)) hypoglycemic clamps to induce severe hypoglycemia (blood glucose 10-15 mg/dl for 90 min). Animals were randomized into control (vehicle) or pharmacological treatments (memantine or erythropoietin). One week after severe hypoglycemia, neuronal damage was assessed by Fluoro-Jade B and hematoxylin and eosin staining of brain sections. Treatment with both memantine and erythropoietin significantly decreased severe hypoglycemia-induced neuronal damage in the cortex by 35% and 39%, respectively (both p<0.05 vs. controls). These findings demonstrate that memantine and erythropoietin provide a protective effect against severe hypoglycemia-induced neuronal damage.

Topics: Animals; Cell Count; Cerebral Cortex; Erythropoietin; Hippocampus; Hypoglycemia; Insulin; Male; Memantine; Nerve Degeneration; Neurons; Neuroprotective Agents; Rats; Rats, Sprague-Dawley

Circulating erythropoietin (EPO) and vascular endothelial growth factor (VEGF) increase during hypoglycaemia and may represent protective hormonal counter-regulatory responses. We tested the hypothesis that low levels of EPO and VEGF are associated with a higher frequency of severe hypoglycaemia in a cohort of patients with type 1 diabetes.. Prospective observational follow-up study.. Totally 219 patients with type 1 diabetes (41% females, age 46+/-13 years (mean+/-s.d.), duration of diabetes 21+/-12 years, and HbAlc 8.5+/-1.1%) were followed in a 1-year observational study. Plasma EPO and serum VEGF levels were measured at baseline with ELISA. Events of severe hypoglycaemia defined by third party assistance were recorded and validated in telephone interviews within 24 h.. Totally 235 episodes of severe hypoglycaemia (1.1 episodes per patient-year) were reported by 82 patients (37%). At baseline, plasma EPO was 8.6 (3.1-34.3) U/l (median (range)), and serum VEGF was 52.2 (6.6-337) pg/ml. The levels of EPO and VEGF were not associated with frequency of severe and mild hypoglycaemia. The levels of EPO were not associated with age, sex, duration of diabetes, body mass index, HbAlc, C-peptide level or hypoglycaemia awareness status. The levels of VEGF were positively associated with age and female sex.. Although several studies suggest that VEGF and EPO may affect brain function during hypoglycaemia, this study does not support random VEGF or EPO levels to determine future risk of severe hypoglycaemia in people with type 1 diabetes.

Topics: Adult; Age Factors; Biomarkers; Diabetes Mellitus, Type 1; Erythropoietin; Female; Follow-Up Studies; Humans; Hypoglycemia; Male; Middle Aged; Prospective Studies; Risk Factors; Severity of Illness Index; Sex Factors; Vascular Endothelial Growth Factor A

Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function.. We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1 diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion.. Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia.. Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia.

Topics: Adult; Blood Glucose; C-Peptide; Cognition; Creatinine; Cross-Over Studies; Diabetes Mellitus, Type 1; Erythropoietin; Female; Glomerular Filtration Rate; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Male; Middle Aged; Renin-Angiotensin System; Single-Blind Method

Topics: Aged; Anemia; Arteriovenous Shunt, Surgical; Disorders of Excessive Somnolence; Erythropoietin; Female; Hemoglobins; Humans; Hypoglycemia; Iatrogenic Disease; Kidney Failure, Chronic; Polycythemia; Recombinant Proteins; Renal Dialysis

To examine whether perinatal hypoxia increases the risk of occurrence of hypoglycaemia--between first and second hour of life--in newborn of the diabetic mother.. The study material consisted of 151 newborns born to 58 pregestational and 93 gestational diabetes mothers. The occurrence of hypoglycaemia was examined in accordance with some perinatal hypoxia indicators such as: 1 and 5 minutes Apgar scores, umbilical arterial blood gas analysis and cord blood erythropoietin (EPO) level.. Newborns of the diabetic mothers in whom hypoglycaemia was recognised had lower 1 minutes Apgar scores, lower pH values, higher pCO2 values and higher EPO levels than those, in whom normoglycaemia was recognised.. Low 1 minutes Apgar scores and occurrence of even mild perinatal hypoxia are factors increasing the risk of hypoglycaemia in the group of newborns of the diabetic mothers in the time between first and second hour of life.

Topics: Adult; Blood Gas Analysis; Diabetes, Gestational; Erythropoietin; Female; Fetal Blood; Humans; Hypoglycemia; Hypoxia; Infant, Newborn; Mothers; Pregnancy; Risk Factors

Correction of anemia with recombinant human erythropoietin (rHuEPO) in patients with end-stage renal disease (ESRD) has been associated with improvement of several endocrine abnormalities. However, long-term effects of this therapy on pituitary secretion in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The aim of the present work was to assess the growth hormone (GH) and cortisol responses to insulin-induced hypoglycemia before and after the correction of anemia with rHuEPO therapy in CAPD patients. Five well-nourished and clinically stable patients were studied before and after 12-24 weeks of rHuEPO treatment. Seven normal volunteers were studied as controls. Insulin-induced hypoglycemia tests were performed prior to starting rHuEPO therapy and again after partial correction of anemia. Blood samples for GH, cortisol, and glucose were collected between -30 and 120 min after insulin (0.1 U/kg bw) administration. GH responses to hypoglycemic stress were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (10.6 +/- 4.8 micrograms/L and 15.4 +/- 6.1 micrograms h/L, respectively) did not differ from those obtained in control subjects (14.3 +/- 4.1 micrograms/L and 19.4 +/- 3.5 micrograms h/L, respectively). The study, after correction of anemia, showed an evident decrease of GH values at each time point on the response curve in 4 patients, and no modification in 1 patient. Mean values of GH peak and AUC were 8.8 +/- 2.8 micrograms/L and 9.6 +/- 2.3 micrograms h/L.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Anemia; Blood Glucose; Erythropoietin; Female; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory

The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on pituitary-adrenal axis responses to stress in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the influence of rHuEPO treatment on corticotropin (ACTH) levels and cortisol responses to insulin-induced hypoglycemia in CAPD patients. Nine clinically stable and well-nourished patients (age 19-59 years) treated with subcutaneous rHuEPO, 34-208 U/kg BW/week, during 6-25 months were studied. Nine patients matched for age, sex, and duration of CAPD and not previously treated with rHuEPO were studied as the control group. Crystalline insulin (0.1 U/kg BW) was injected IV to the fasting subjects. Blood samples were collected before and 15, 30, 60, 90, and 120 minutes after insulin administration. In all blood samples serum cortisol and glucose concentrations were assessed. There were no statistically significant differences between both groups in hematocrit values and blood hemoglobin concentrations. Insulin administration induced a decrease in glucose levels that reached a nadir at 30 minutes in both groups (1.8 +/- 0.1 mmol/L in the rHuEPO group vs 2.1 +/- 0.2 mmol/L in the control group). After hypoglycemic stimuli cortisol levels clearly rose in rHuEPO-treated patients reaching a peak of 720 +/- 71 nmol/L at 60 minutes. However, in the control group the cortisol peak, which was not different from that observed in the rHuEPO group (676 +/- 44 nmol/L), occurred at 90 minutes. The areas under the secretory curve of cortisol did not differ between groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adrenocorticotropic Hormone; Adult; Anemia; Blood Glucose; Erythropoietin; Female; Humans; Hydrocortisone; Hypoglycemia; Insulin; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Recombinant Proteins

Several alterations of growth hormone (GH) secretion have been described in patients with chronic renal failure. The effect of chronic treatment with recombinant human erythropoietin (rHuEPO) on GH secretion in uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. The purpose of this study was to assess the GH responses to both direct and hypothalamic stimuli in CAPD patients chronically treated with rHuEPO. Eight clinically stable and well-nourished patients (age 19-59 yr) treated with subcutaneous rHuEPO, 96.5 +/- 72.1 U/kg/week, during 6-25 months were tested with GH-releasing hormone (GHRH, 100 micrograms iv in bolus). Insulin-induced hypoglycemia (0.1 U/kg iv in bolus) and clonidine (0.15 mg/m2 po) were used as indirect stimuli for GH release. Baseline concentrations of insulin-like growth factor I (IGF I) concentration was also determined. Five CAPD patients matched for age and sex and not previously treated with EPO were studied as a control group. There was no statistically significant difference in baseline IGF I concentrations in EPO treated patients in comparison with control group (2.6 +/- 0.7 vs 0.9 +/- 0.3 U/ml). GHRH administration was followed by a GH release in the treated group that did not differ significantly from that obtained in controls (peak: 10.6 +/- 3.7 vs 15.2 +/- 7.8 micrograms l, area under the curve [AUC]: 16.3 +/- 5.6 vs 24.0 +/- 11.4 micrograms.h/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Clonidine; Erythropoietin; Female; Growth Hormone; Growth Hormone-Releasing Hormone; Humans; Hypoglycemia; Hypothalamus; Insulin; Insulin-Like Growth Factor I; Kidney Failure, Chronic; Male; Middle Aged; Peritoneal Dialysis, Continuous Ambulatory; Pituitary Function Tests; Recombinant Proteins

In five hemodialyzed patients the influence of erythropoietin (EPO) treatment for 3 months on function of the pituitary-adrenal feedback and STH secretion was studied. Results were compared with those obtained in 6 hemodialyzed patients (No-EPO group) showing a comparable Hb concentration and Hct value as patients in the EPO group post-treatment and in 15 healthy subjects. EPO treatment was followed by a significant (ACTH and STH) or moderate (cortisol) suppression of basal plasma levels of ACTH, STH and cortisol respectively, and by a significant reduction of the response of plasma concentrations of these hormones to insulin-induced hypoglycemia. As the response of plasma levels of ACTH, STH and cortisol respectively in patients of the EPO group post-treatment differed markedly from that of the No-EPO group with similar Hb and Hct values, it seems that the EPO-induced endocrine alterations are not, at least not exclusively, a consequence of the improvement of anemia. Results presented in this study suggest that EPO treatment influences directly or indirectly the function of endocrine organs.

Topics: Adrenocorticotropic Hormone; Adult; Erythropoietin; Growth Hormone; Humans; Hydrocortisone; Hypoglycemia; Hypothalamo-Hypophyseal System; Kidney Failure, Chronic; Middle Aged; Pituitary-Adrenal System; Renal Dialysis

Topics: Adrenocorticotropic Hormone; Cushing Syndrome; Erythropoietin; Gonadotropins; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Hyponatremia; Insulin; Melanocyte-Stimulating Hormones; Paraneoplastic Endocrine Syndromes; Parathyroid Hormone; Pigmentation Disorders; Vasopressins

Topics: Adrenocorticotropic Hormone; Bartter Syndrome; Calcitonin; Choriocarcinoma; Corticotropin-Releasing Hormone; Erythropoietin; Female; Gonadotropins; Humans; Hypercalcemia; Hypoglycemia; Male; Paraneoplastic Endocrine Syndromes; Paraneoplastic Syndromes; Pregnancy; Prolactin; Renin; Repressor Proteins; Teratoma; Testicular Neoplasms; Thyrotropin

Topics: Adrenal Gland Neoplasms; Adult; alpha-Fetoproteins; Carcinoma, Hepatocellular; Erythropoietin; Heart Neoplasms; Hemochromatosis; Humans; Hypoglycemia; Iron; Liver; Liver Neoplasms; Lung Neoplasms; Male; Neoplasm Metastasis; Polycythemia; Precancerous Conditions

Among the malignant tumors of nonendocrine origin that are capable of producing polypeptide hormones and of manifesting as different endocrine syndromes discussed here are ectopic ACTH syndrome, SIADH, and ectopic gonadotropin-producing tumors.

Topics: Adrenocorticotropic Hormone; Carcinoma, Hepatocellular; Carcinoma, Small Cell; Chorionic Gonadotropin; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Follicle Stimulating Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hyperthyroidism; Hypoglycemia; Hyponatremia; Liver Neoplasms; Lung Neoplasms; Luteinizing Hormone; Male; Paraneoplastic Endocrine Syndromes; Polycythemia; Puberty, Precocious; Thyrotropin; Vasopressins; Water Intoxication

The exact prevalence of the humoral syndromes associated with neoplasm is not known but it seems clear that they exist more commonly than is realized. Hormonal syndromes are very often seen in patients with carcinoma of the lung. Awareness of the large number of ectopic hormonal syndromes in patients with tumors can lead to early diagnosis, treatment, and herald recurrence. They may be responsible for new signs and symptoms which can be life-shortening. Hormonal causes of clinical deterioration must be considered before concluding that symptoms are due to metastases in patients with neoplastic disease. Tumors are chemically active and the important concept which has had great impact on the diagnosis, treatment, and basic understanding of mechanisms, which are important to endocrinologists and oncologists has been stated by Liddle: "Certain tumors of nonendocrine tissue can produce hormones that are similar to normal hormones except that their production is not appropriately controlled by normal physiologic mechanisms." Survival and quality of life can be reduced in patients with the metabolic complications of these humors. The list of humoral substances released by tumors is growing as technologic advances lead to their detection. Other chemical substances produced by neoplastic tissue may have biologic activity which impacts on the patient's clinical condition and which we cannot recognize, at this time, because the techniques to detect them have not been developed. If there are signs or symptoms of overproduction of a hormone, search for a tumor; if a patient has a tumor, search for biologically active substances.

Topics: Cushing Syndrome; Erythropoietin; Hormones; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Neoplasms; Paraneoplastic Endocrine Syndromes; Vasopressins