Early-phase insulin secretion during mixed-meal tolerance testing predicts β-cell function and secretory capacity in cystic fibrosis.

Unlabelled: Insulin secretion within 30 minutes of nutrient ingestion is reduced in people with cystic fibrosis (PwCF) and pancreatic insufficiency and declines with worsening glucose tolerance. The glucose potentiated arginine (GPA) test is validated for quantifying β-cell secretory capacity as an estimate of functional β-cell mass but requires technical expertise and is burdensome. This study sought to compare insulin secretion during mixed-meal tolerance testing (MMTT) to GPA-derived parameters in PwCF.

Preservation of β-cell Function in Pancreatic Insufficient Cystic Fibrosis With Highly Effective CFTR Modulator Therapy.

Context: Elexacaftor/tezacaftor/ivacaftor (ETI; Trikafta) enhances aberrant cystic fibrosis transmembrane conductance regulator function and may improve the insulin secretory defects associated with a deterioration in clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF).

Objective: This longitudinal case-control study assessed changes in β-cell function and secretory capacity measures over 2 visits in individuals with PI-CF who were initiated on ETI after the baseline visit (2012-2018) and (1) restudied between 2019 and 2021 (ETI group) vs (2) those restudied between 2015 and 2018 and not yet treated with cystic fibrosis transmembrane conductance regulator modulator therapy (controls).

Methods: Nine ETI participants (mean ± SD age, 25 ± 5 years) and 8 matched controls were followed up after a median (interquartile range) 5 (4-7) and 3 (2-3) years, respectively (P < .

Bone metabolism and incretin hormones following glucose ingestion in young adults with pancreatic insufficient cystic fibrosis.

Background: Gut-derived incretin hormones, including glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide 1 (GLP-1), regulate post-prandial glucose metabolism by promoting insulin production. GIP, GLP-1, and insulin contribute to the acute bone anti-resorptive effect of macronutrient ingestion by modifying bone turnover. Cystic fibrosis (CF) is associated with exocrine pancreatic insufficiency (PI), which perturbs the incretin response.

Effects of GLP-1 and GIP on Islet Function in Glucose-Intolerant, Pancreatic-Insufficient Cystic Fibrosis.

Impaired insulin and incretin secretion underlie abnormal glucose tolerance (AGT) in pancreatic insufficient cystic fibrosis (PI-CF). Whether the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) can enhance pancreatic islet function in cystic fibrosis (CF) is not known. We studied 32 adults with PI-CF and AGT randomized to receive either GLP-1 (n = 16) or GIP (n = 16) during glucose-potentiated arginine (GPA) testing of islet function on two occasions, with either incretin or placebo infused, in a randomized, double-blind, cross-over fashion.

Utilization of the Healthy Eating Index in Cystic Fibrosis.

(1) Background: Malnutrition has been a hallmark of cystic fibrosis (CF) for some time, and improved nutritional status is associated with improved outcomes. While individuals with CF historically required higher caloric intake than the general population, new CF therapies and improved health in this population suggest decreased metabolic demand and prevalence of overweight and obesity have increased. This study aimed to (a) examine diet quality in a population of young adults with CF using the Healthy Eating Index, a measure of diet quality in accordance with the U.

Infant Body Mass Index or Weight-for-Length and Risk of Undernutrition in Childhood Among Children with Cystic Fibrosis.

Objectives: To compare performance of weight-for-length and body mass index as estimators of undernutrition in children with cystic fibrosis (CF).

Study Design: We analyzed pediatric anthropometric data from the Cystic Fibrosis Foundation Patient Registry. Undernutrition was defined by weight-for-length z score (WFLZ) or body mass index z score (BMIZ) ≤-1 (15th-percentile).

Effect of Sitagliptin on Islet Function in Pancreatic Insufficient Cystic Fibrosis With Abnormal Glucose Tolerance.

Purpose: Impaired incretin secretion may contribute to the defective insulin secretion and abnormal glucose tolerance (AGT) that associate with worse clinical outcomes in pancreatic insufficient cystic fibrosis (PI-CF). The study objective was to test the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitor-induced increases in intact incretin hormone [glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)] concentrations augment insulin secretion and glucagon suppression and lower postprandial glycemia in PI-CF with AGT.

Methods: 26 adults from Children's Hospital of Philadelphia and University of Pennsylvania CF Center with PI-CF and AGT [defined by oral glucose tolerance test glucose (mg/dL): early glucose intolerance (1-h ≥ 155 and 2-h < 140), impaired glucose tolerance (2-h ≥ 140 and < 200 mg/dL), or diabetes (2-h ≥ 200)] were randomized to a 6-month double-blind trial of DPP-4 inhibitor sitagliptin 100 mg daily or matched placebo; 24 completed the trial (n = 12 sitagliptin; n = 12 placebo).

Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis.

Context: Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established.

Objective: To delineate the mechanism(s) underlying OGTT-related hypoglycemia.

Design And Setting: We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group.

Genetic potential and height velocity during childhood and adolescence do not fully account for shorter stature in cystic fibrosis.

Background: Despite improved health, shorter stature is common in cystic fibrosis (CF). We aimed to describe height velocity (HV) and contribution of height-related genetic variants to height (HT) in CF.

Methods: HV cohort: standard deviation scores (-Z) for HT, mid-parental height-adjusted HT (MPAH), and HV were generated using our Pediatric Center's CF Foundation registry data.

Abnormal glucose tolerance and the 50-gram glucose challenge test in Cystic fibrosis.

Diabetes has emerged as a major co-morbidity in cystic fibrosis (CF). The 75 g oral glucose tolerance test (OGTT) is used to screen for CF-related diabetes (CFRD) but is inconvenient, and adherence to screening is poor. The 50 g glucose challenge test (GCT) is shorter, performed non-fasting, and may serve to pre-screen the subset of individuals requiring confirmatory OGTT.

Advanced glycation end products (AGEs), protein aggregation and their cross talk: new insight in tumorigenesis.

Protein glycation and protein aggregation are two distinct phenomena being observed in cancer cells as factors promoting cancer cell viability. Protein aggregation is an abnormal interaction between proteins caused as a result of structural changes in them after any mutation or environmental assault. Protein aggregation is usually associated with neurodegenerative diseases like Alzheimer's and Parkinson's, but of late, research findings have shown its association with the development of different cancers like lung, breast and ovarian cancer.

Dysregulated insulin in pancreatic insufficient cystic fibrosis with post-prandial hypoglycemia.

Background: Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear.

Methods: To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF).

Results: Hypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion.

Higher Physician Body Mass Index is Associated with Increased Weight Bias in an Arab Country with High Prevalence of Obesity.

Background: Obesity is a worldwide problem. The Arab world, and particularly the Middle East, has witnessed a recent dramatic rise in obesity and obesity-related diseases. Yet, little is known about physician attitudes toward or management of obesity in this region of the world.

Islet Hormone and Incretin Secretion in Cystic Fibrosis after Four Months of Ivacaftor Therapy.

Rationale: Diabetes is associated with worse cystic fibrosis (CF) outcomes. The CFTR potentiator ivacaftor is suggested to improve glucose homeostasis in individuals with CF.

Objectives: To test the hypothesis that clinically indicated ivacaftor would be associated with improvements in glucose tolerance and insulin and incretin secretion.

Is Educating Girls the Best Investment for South Asia? Association Between Female Education and Fertility Choices in South Asia: A Systematic Review of the Literature.

Universal education is a key strategy to enhance the well-being of individuals and improve the economic and social development of societies. A large proportion of school-aged girls in developing countries are not attending schools. Approximately one-third of South Asian girls do not attend school and in some regions only one in four girls attend primary school.

β-Cell secretory defects are present in pancreatic insufficient cystic fibrosis with 1-hour oral glucose tolerance test glucose ≥155 mg/dL.

Background: Patients with pancreatic insufficient cystic fibrosis (PI-CF) meeting standard criteria for normal glucose tolerance display impaired β-cell secretory capacity and early-phase insulin secretion defects. We sought evidence of impaired β-cell secretory capacity, a measure of functional β-cell mass, among those with early glucose intolerance (EGI), defined as 1-hour oral glucose tolerance test (OGTT) glucose ≥155 mg/dL (8.6 mmol/L).

Blocking mutation independent p53 aggregation by emodin modulates autophagic cell death pathway in lung cancer.

Loss of p53 function via mutation is a very common cause of human cancers. Recent studies have provided evidence on presence of self aggregated p53 in cancer cells leading to its altered functions towards cause of cancer. The general notion has been that mutated p53 exposes adhesive sites that promote self aggregation, however a complete mechanistic understanding to this has been lacking.

ER chaperone GRP78 regulates autophagy by modulation of p53 localization.

GRP78 (glucose regulated protein 78) is a major Endoplasmic Reticulum (ER) chaperone that plays a pivotal role in normal ER functioning. Its increased expression also works as an indicator of ER stress. Its anti-apoptotic and pro-autophagic activity makes it an intriguing target to study the relationship between GRP78 and p53, which is also a major regulator of apoptosis and autophagy.

Reduced β-Cell Secretory Capacity in Pancreatic-Insufficient, but Not Pancreatic-Sufficient, Cystic Fibrosis Despite Normal Glucose Tolerance.

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions.

Cissus quadrangularis Linn. Stem Ethanolic Extract Liberates Reactive Oxygen Species and Induces Mitochondria Mediated Apoptosis in KB Cells.

Background: Cissus quadrangularis Linn. (CQ) commonly known as Hadjod (Family: Vitaceae) is usually distributed in India and Sri Lanka and contains several bioactive compounds responsible for various metabolic and physiologic effects.

Objective: In this study, the biological effects of CQ ethanolic extract were evaluated by in vitro and supported by in silico analysis on KB oral epidermoid cancer cell line.

The Female Sexual Function Index (FSFI): Translation, Validation, and Cross-Cultural Adaptation of an Urdu Version "FSFI-U".

Introduction: Female sexual dysfunction (FSD) is a common problem, and many self-report questionnaires are available for its evaluation. Pakistani women with sexual problems feel shy to consult with their physician. A validated self-report questionnaire, in the local language with modest expressions is required for these women.

The Chromone Alkaloid, Rohitukine, Affords Anti-Cancer Activity via Modulating Apoptosis Pathways in A549 Cell Line and Yeast Mitogen Activated Protein Kinase (MAPK) Pathway.

The field of cancer research and treatment has made significant progress, yet we are far from having completely safe, efficient and specific therapies that target cancer cells and spare the healthy tissues. Natural compounds may reduce the problems related to cancer treatment. Currently, many plant products are being used to treat cancer.