Quercetin prevents insulin dysfunction in hypertensive animals

Angiotensin II induced increase in hypertension enhances oxidative stress and compromises insulin action and pancreatic function. Quercetin-rich foods are beneficial for hypertensive and diabetic animals owing to their antioxidant function. The aim of this study was to evaluate the antioxidant effects of quercetin in hypertensive rats on insulin action, signaling, and secretion. Wistar rats were randomly divided into three groups: sham, hypertensive rats (H), and hypertensive rats supplemented with quercetin (HQ). After three months of initial hypertension, quercetin was administered at 50 mg/kg/day for 30 days. Our results indicate that hypertension and serum lipid peroxidation levels were reduced by quercetin supplementation. We observed increased insulin sensitivity in adipose tissue, corroborating the insulin tolerance test, HOMA index, and improvements in lipid profile. Despite normal insulin secretion at 2.8 and 20 mM of glucose, animals treated with quercetin exhibited increased number of islets per section; increased protein expression of muscarinic receptor type 3, VEGF, and catalase in islets; and hepatic mRNA levels of Ide were normalized. In conclusion, supplementation with quercetin improved insulin action and prevented pancreatic and metabolic dysfunction.

A Cross-Sectional Study to Evaluate the Safety and Efficacy of the Insulin Tolerance Test

Introduction: The insulin tolerance test (ITT) is the current standard for the diagnosis of pituitary diseases such as growth hormone deficiencies (GHD). Previous reports indicated that the ITT as having a high adverse event profile, and the cosyntropin test as being sensitive enough to diagnose GHD in adults. The purpose of this study is to validate the safety and efficacy of the ITT. Design: Over 400 ITT tests were conducted over the course of 3 years from (2017-2020) at our facility. This study is only focused on adult physiology (Cohort Age 16 - 78) and excludes any pediatric tests. An important measure, time spent in critical state (Tc), is done to know the expected time a patient is to remain hypoglycemic, both for patient expectations and clinician logistics. We did not use a CGM, instead drew blood samples on set intervals for glucose measurements. Since the measurements aren’t continuous, a consistent overestimation is done for all subject encounters to capture the maximum time spent in hypoglycemia. Insulin like growth factor one (IGF-1) was measured before the test was conducted and is listed in the spreadsheet. Growth hormone peaks were and the time to reach that peak (Tp) were also measured. This time is calculated from the listed time of the first dosage of insulin to the time of the GH peak. Other measures listed in the spreadsheet include a brief medical history of the patient, their age, weight, gender, and the blood pressure and heart rate measured at test completion. Any immediate interventions such as intravenous fluid injections were listed. Symptoms of hypoglycemia are excluded as a complication of the test. This is due to the inherent nature of the ITT whose goal is to drop one’s blood sugar past normal ranges. Results: Our results show (0.45%) rate of adverse events. 2 patients in the entire cohort suffered from seizures during their hypoglycemic period. Both of them were successfully aborted with Ativan, and patients were monitored until recovery from post ictal state and discharged home with stable vitals and no acute symptoms. It was later discovered these patients had remote history of epilepsy and should’ve been excluded from this trial. Of the remaining 448 subject encounters, (20%) of them required urgent intervention to BP. Zero of those patients suffered any other symptoms or ongoing adverse effects. 5 patients underwent the ITT twice, again, with no adverse effects. Conclusion: No permanent adverse events or hospitalizations were reported. Based on our findings the clinical safety concerns of the ITT test are minimal compared with the benefit of obtaining an accurate diagnosis in this patient cohort, if done within the correct protocol. Using IGF-1 measures as a determinant of GHD is wildly inaccurate as seen in our results. Combining IGF-1 with the Cosyntropin test is not a good enough measure for diagnosing GHD. The ITT test remains the most accurate and reliable test available today.

Should Pediatric Endocrinologists Consider More Carefully When to Perform a Stimulation Test?

IntroductionPediatric endocrinology rely greatly on hormone stimulation tests which demand time, money and effort. The knowledge of the pattern of pediatric endocrinology stimulation tests is therefore crucial to optimize resources and guide public health interventions. Aim of the study was to investigate the distribution of endocrine stimulation tests and the prevalence of pathological findings over a year and to explore whether single basal hormone concentrations could have saved unnecessary stimulation tests.MethodsRetrospective study with data collection for pediatric endocrine stimulation tests performed in 2019 in a tertiary center.ResultsOverall, 278 tests were performed on 206 patients. The most performed test was arginine tolerance test (34%), followed by LHRH test (24%) and standard dose Synachthen test (19%), while the higher rate of pathological response was found in insulin tolerance test to detect growth hormone deficiency (81%), LHRH test to detect central precocious puberty (50%) and arginine tolerance test (41%). No cases of non-classical-congenital adrenal hyperplasia were diagnosed. While 29% of growth hormone deficient children who performed an insulin tolerance test had a pathological peak cortisol, none of them had central adrenal insufficiency confirmed at low dose Synacthen test. The use of basal hormone determinations could save up to 88% of standard dose Synachthen tests, 82% of arginine tolerance + GHRH test, 61% of LHRH test, 12% of tests for adrenal secretion.ConclusionThe use of single basal hormone concentrations could spare up to half of the tests, saving from 32,000 to 79,000 euros in 1 year. Apart from basal cortisol level <108 nmol/L to detect adrenal insufficiency and IGF-1 <-1.5 SDS to detect growth hormone deficiency, all the other cut-off for basal hormone determinations were found valid in order to spare unnecessary stimulation tests.

GROWTH HORMONE LEVELS AT INDUCED HYPOGLYCEMIA; AN EFFECTIVE WAY OF DIAGNOSING GROWTH HORMONE DEFICIENCY

Objective: To introduce a relatively convenient and effective way of conducting Insulin Tolerance Test for diagnosis of Growth Hormone deficiency in children with short stature. Study Design: Cross sectional analytical study. Place and Duration of Study: Conducted at Department of Chemical Pathology and Endocrinology, Armed Forces Institute of Pathology, Rawalpindi, from May 2017 to Jul 2018. Methodology: A total of 185 cases were included. Sample selection was done by non-probability consecutive sampling technique. Insulin tolerance test was performed by taking basal sample for serum growth hormone and plasma glucose levels before giving intravenous insulin bolus according to dose of 0.15 IU/kg. Samples for Growth Hormone level were repeated at time of induced hypoglycemia (defined as plasma glucose level of <2.8 mmol/L), 30 minutes and 60 minutes post induction. Results: Mean age of the patients was 10 ± 4 years, majority 120 (65%) were males. In the study population, 41 (22%) patients showed adequate response to insulin tolerance test while 144 (78%) showed inadequate response. At level of induction, mean growth hormone levels were 31.9 ± 18.8 mIU/l and 4.7 ± 4.4 mIU/l in patients showing adequate and inadequate response respectively (p-value <0.05). Majority 32 (78%) of the patients showing adequate response had peak growth hormone response (>20 mIU/l) at induction alone, followed by 30 minutes post induction; reflecting the significance of these two samples in diagnosis of growth hormone deficiency. Conclusion: We concluded that there is a simpler ...........

MORNING SERUM CORTISOL LEVEL PREDICTS CENTRAL ADRENAL INSUFFICIENCY DIAGNOSED BY INSULIN TOLERANCE TEST

Introduction According to guidelines, a morning serum cortisol level <83 nmol/L is diagnostic for central adrenal insufficiency (CAI), a value >414 nmol/L excludes CAI, while values between 83 and 414 nmol/L require stimulation tests. However, there are no currently reliable data on morning serum cortisol for prediction of cortisol response to insulin tolerance test (ITT). Objective Using the receiver operating characteristic curve analysis, the purpose of this study was to detect the morning serum cortisol cut-off with a specificity (SP) or a sensitivity (SE) above 95% that identify those patients who should not be tested with ITT. Methods We included 141 adult patients (83 males) aged 42.7+/-12.3 (mean +/- SD) years old. Based on serum cortisol response to ITT, patients have been divided in two groups: subjects with CAI (peak serum cortisol <500 nmol/L; 65 patients) and subjects with preserved adrenocortical function (peak cortisol >500 nmol/L; 76 patients). Results The best morning cortisol cut-off, in terms of SE (87.7%) and SP (46.1%), was ≤323.3 nmol/L. The cut-off of morning serum cortisol concentration that best predicted a deficient response to ITT was ≤126.4 nmol/L (SE 13.8%, SP 98.7%). The cut-off of morning serum cortisol concentration that best predicted a normal response to ITT was >444.7 nmol/L (SE 96.9%, SP 14.5%). Conclusions This is the first study that identifies a morning serum cortisol cut-off that best predict the response to ITT in order to simplify the diagnostic process in patients with suspected CAI. A new diagnostic flow chart for CAI is proposed.

Insulin Resistance in Apolipoprotein M Knockout Mice is Mediated by the Protein Kinase Akt Signaling Pathway

Background: Previous clinical studies have suggested that apolipoprotein M (apoM) is involved in glucose metabolism and plays a causative role in insulin sensitivity. Objective: The potential mechanism of apoM on modulating glucose homeostasis is explored and differentially expressed genes are analyzed by employing ApoM deficient (ApoM-/- ) and wild type (WT) mice. Methods: The metabolism of glucose in the hepatic tissues of high-fat diet ApoM-/- and WT mice was measured by a glycomics approach. Bioinformatic analysis was applied for analyzing the levels of differentially expressed mRNAs in the liver tissues of these mice. The insulin sensitivity of ApoM-/- and WT mice was compared using the insulin tolerance test and the phosphorylation levels of protein kinase Akt (AKT) and insulin stimulation in different tissues were examined by Western blot. Results: The majority of the hepatic glucose metabolites exhibited lower concentration levels in the ApoM-/- mice compared with those of the WT mice. Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicated that ApoM deficiency affected the genes associated with the metabolism of glucose. The insulin tolerance test suggested that insulin sensitivity was impaired in ApoM-/- mice. The phosphorylation levels of AKT in muscle and adipose tissues of ApoM-/- mice were significantly diminished in response to insulin stimulation compared with those noted in WT mice. Conclusion: : ApoM deficiency led to the disorders of glucose metabolism and altered genes related to glucose metabolism in mice liver. In vivo data indicated that apoM might augment insulin sensitivity by AKT-dependent mechanism.