This document discusses glucose control in renal transplant patients. It presents a case of new onset diabetes after transplant and reviews the pharmacology of immunosuppressants like calcineurin inhibitors that can cause glucose dysregulation. It also discusses the current recommendations for glucose control during and after transplant, including managing new onset diabetes after transplant through diagnosis and treatment approaches. Risk factors for developing new onset diabetes after transplant are examined, as well as the impacts of hyperglycemia on kidney transplant outcomes.
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
Presentation given to our fellowship program about diabetic kidney disease.
2022 update discussing SGLT2i, MRA (e.g. finerenone), health economics and beyond
- Recorded videos of the lecture:
English Language version of this lecture is available at: https://youtu.be/-Ynxvhbcl7U
Arabic Language version of this lecture is available at: https://youtu.be/QpK_toctVlw
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Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
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New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
Theodoros Katsivas, MD (UC San Diego Owen Clinic), Shira Abeles, MD (UC San Diego Owen Clinic) and Robyn Cunard, MD (UC San Diego) present "Renal Disease in HIV/AIDS"
diabetes was associated with insulin resistant state which affects liver cells.Also fatty liver may be called NAFLA OR NASH may lead to liver cirrhosis and sometimes to hepatocelular carcinoma
New Onset diabetes after kidney transplantation.iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
- Recorded videos of the lecture:
English Language version of this lecture is available at: https://youtu.be/-Ynxvhbcl7U
Arabic Language version of this lecture is available at: https://youtu.be/QpK_toctVlw
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
Diabetes Mellitus Management in CKD (Clinical Tips) - Dr. GawadNephroTube - Dr.Gawad
- Recorded videos of this lecture:
English Language version of this lecture is available at:
https://youtu.be/h3HRvWGUj5A
- Visit our website for more lectures: www.NephroTube.com
- Subscribe to our YouTube channel: www.youtube.com/NephroTube
- Join our facebook group: www.facebook.com/groups/NephroTube
- Like our facebook page: www.facebook.com/NephroTube
- Follow us on twitter: www.twitter.com/NephroTube
New Therapeutics in Diabetic Kidney Disease
Conjoint Meeting of the Iraqi Society of Nephrology and Renal Transplantation and The Iraqi Diabetes Association.
MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of...Dr. Om J Lakhani
Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD).
Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India
Theodoros Katsivas, MD (UC San Diego Owen Clinic), Shira Abeles, MD (UC San Diego Owen Clinic) and Robyn Cunard, MD (UC San Diego) present "Renal Disease in HIV/AIDS"
diabetes was associated with insulin resistant state which affects liver cells.Also fatty liver may be called NAFLA OR NASH may lead to liver cirrhosis and sometimes to hepatocelular carcinoma
New Onset diabetes after kidney transplantation.iosrphr_editor
The IOSR Journal of Pharmacy (IOSRPHR) is an open access online & offline peer reviewed international journal, which publishes innovative research papers, reviews, mini-reviews, short communications and notes dealing with Pharmaceutical Sciences( Pharmaceutical Technology, Pharmaceutics, Biopharmaceutics, Pharmacokinetics, Pharmaceutical/Medicinal Chemistry, Computational Chemistry and Molecular Drug Design, Pharmacognosy & Phytochemistry, Pharmacology, Pharmaceutical Analysis, Pharmacy Practice, Clinical and Hospital Pharmacy, Cell Biology, Genomics and Proteomics, Pharmacogenomics, Bioinformatics and Biotechnology of Pharmaceutical Interest........more details on Aim & Scope).
Copyright 2016 American Medical Association. All rights reserv.docxvanesaburnand
Copyright 2016 American Medical Association. All rights reserved.
Effect of Naltrexone-Bupropion on Major Adverse
Cardiovascular Events in Overweight and Obese Patients
With Cardiovascular Risk Factors
A Randomized Clinical Trial
Steven E. Nissen, MD; Kathy E. Wolski, MPH; Lisa Prcela, RN; Thomas Wadden, PhD; John B. Buse, MD, PhD;
George Bakris, MD; Alfonso Perez, MD; Steven R. Smith, MD
IMPORTANCE Few cardiovascular outcomes trials have been conducted for obesity
treatments. Withdrawal of 2 marketed drugs has resulted in controversy about the
cardiovascular safety of obesity agents.
OBJECTIVE To determine whether the combination of naltrexone and bupropion increases
major adverse cardiovascular events (MACE, defined as cardiovascular death, nonfatal stroke,
or nonfatal myocardial infarction) compared with placebo in overweight and obese patients.
DESIGN, SETTING, AND PARTICIPANTS Randomized, multicenter, placebo-controlled,
double-blind noninferiority trial enrolling 8910 overweight or obese patients at increased
cardiovascular risk from June 13, 2012, to January 21, 2013, at 266 US centers. After public
release of confidential interim data by the sponsor, the academic leadership of the study
recommended termination of the trial and the sponsor agreed.
INTERVENTIONS An Internet-based weight management program was provided to all
participants. Participants were randomized to receive placebo (n=4454) or naltrexone,
32 mg/d, and bupropion, 360 mg/d (n=4456).
MAIN OUTCOMES AND MEASURES Time from randomization to first confirmed occurrence of a
MACE. The primary analysis planned to assess a noninferiority hazard ratio (HR) of 1.4 after
378 expected events, with a confidential interim analysis after approximately 87 events (25%
interim analysis) to assess a noninferiority HR of 2.0 for consideration of regulatory approval.
RESULTS Among the 8910 participants randomized, mean age was 61.0 years (SD, 7.3 years),
54.5% were female, 32.1% had a history of cardiovascular disease, and 85.2% had diabetes,
with a median body mass index of 36.6 (interquartile range, 33.1-40.9). For the 25% interim
analysis, MACE occurred in 59 placebo-treated patients (1.3%) and 35 naltrexone-bupropion–
treated patients (0.8%; HR, 0.59; 95% CI, 0.39-0.90). After 50% of planned events, MACE
occurred in 102 patients (2.3%) in the placebo group and 90 patients (2.0%) in the
naltrexone-bupropion group (HR, 0.88; adjusted 99.7% CI, 0.57-1.34). Adverse effects were
more common in the naltrexone-bupropion group, including gastrointestinal events in 14.2%
vs 1.9% (P < .001) and central nervous system symptoms in 5.1% vs 1.2% (P < .001).
CONCLUSIONS AND RELEVANCE Among overweight or obese patients at increased
cardiovascular risk, based on the interim analyses performed after 25% and 50% of planned
events, the upper limit of the 95% CI of the HR for MACE for naltrexone-bupropion
treatment, compared with placebo, did not exceed 2.0. However, because of the
unanticipated ear.
NKTI Renal Capsule 2021 - 4th Quarter
Dear NKTI family,
We are pleased to send you the latest issue of the NKTI Renal Capsule (October to December 2021).
What's Inside?
COVID-19 booster shots for NKTI employees
NKTI holds best practice sharing contest
Launching of NHIMS project
From Nursing attendant To Union President
Annual Physical Exam for Employees
Virtual Research Forum
Attaching also the link for the magazine format. Click on full screen to enlarge.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
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We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
2. Objectives
To present a case of post transplant Diabetes Mellitus
To review the pharmacology of immunosuppressants
that cause glucose dysreguation
To discuss the current recommendations on glucose
control during and post transplant
To Discuss New onset diabetes after transplant, its
diagnosis and approach to management
3. TAKE OFF CASE
PATHOPHYSIOLOGY OF NODAT
PHARMACOLOGY OF CALCINEURIN
INHIBITORS
IMPACT OF HYPERGLYCEMIA IN
KIDNEY TRANSPLANTATION
MANAGEMENT
SUMMARY
O
U
T
L
I
N
E
INTRODUCTION
4. M.M.
47,male, married
BMI 28
Works as policeman Angeles city, Pampanga
30 pack year smoker and an alcoholic drinker
Chronic kidney disease secondary to obstructive uropathy s/p kidney transplant LNRD June 17,
2009
4 ABDR MM , 0 DR match, blood type O+, crossmatch negative
induction: simulect/ tacrolimus /MMF/ prednisone
Immediate graft function
discharge Creatinine 1.4
Admitted July 2009 (1 month post KT) due to elevated creatinine at 2.5,proteinuria +2, renal graft
biopsy showed suspicious of acute rejection on renal graft biopsy, underwent MPPT pulsing
6. Tissues involved in Glucose Balance
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
7. Stress hyperglycemia
during the early post-
transplant period is a
common phenomenon
and can affect up to 70–90
% of patients
new-onset diabetes
(NODA T) itself can affect
around 40 % long term
Pre transplant Diabetes
Transient post transplant
hyperglycemia
Medication induced hyperglycemia
New onset Diabetes After
Transplantation
Post transplantation Diabetes
Mellitus
Rodolfo J. Galindo 1 & Amisha Wallia, Hyperglycemia and Diabetes Mellitus Following Organ Transplantation, Curr Diab
Rep (2016) 16:14 DOI 10.1007/s11892-015-0707-1
8.
9. Incidence
Diabetes is the primary cause of renal disease
in up to 28.4 % of adults on the waiting list
for a kidney transplant in 2002, rising to 34.2
% by 2012
NODAT incidence: 24 to 37 % (12–36 months)
in kidney transplantation
Matas AJ, Smith JM, Skeans MA, et al. OPTN/SRTR 2012 annual data report: kidney. Am J Transplant. 2014;14 Suppl 1:11–44
Rodolfo J. Galindo 1 & Amisha Wallia, Hyperglycemia and Diabetes Mellitus Following Organ Transplantation, Curr Diab
Rep (2016) 16:14 DOI 10.1007/s11892-015-0707-1
10. PATHOPHYSIOLOGY OF NODAT
Steroids
insulin resistance
increased liver
gluconeogenesis
decreased insulin
secretion
Sirolimus
islet cell toxicity
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
Pancreatic B cell
dysfunction
11. Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes,
Metabolic Syndrome and Obesity: Targets and Therapy 2011:4 175–186
12. Non modifiable risk factors
AGE
Cosio et al,
transplant recipients older than 45 years of age were 2.2 times more likely to
develop NODAT than those younger at the time of transplantation (P , 0.0001).
USRDS: In 11,000 Medicare beneficiaries who received primary KT 1996 - 2000
Kasiske et al:
strong association between older age and NODAT. Compared to a reference
range of 18–44 years of age transplant recipients
age of 45–59 years= relative risk for NODAT of 1.9 (P = 0.0001)
60 years of age= relative risk of 2.09 (P , 0.0001)
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic Syndrome
and Obesity: Targets and Therapy 2011:4 175–186
13. Non modifiable risk factors
RACE/ ETHNICITY
USRDS : NODAT was more common among African
Americans (RR = 1.68, P , 0.0001) and Hispanics (RR =
1.35, P , 0.0001) compared with Caucasians
FAMILY HISTORY OF DIABETES
The increased prevalence of NODAT associated with a
family history of diabetes has been documented across
all types of solid organ transplantation.
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes,
Metabolic Syndrome and Obesity: Targets and Therapy 2011:4 175–186
14. Modifiable risk factors:
CORTICOSTEROIDS
Midtvedt and colleagues:
prednisolone dose reduction from a mean of 16 mg daily (range 10 to 30) to 9 mg daily
(range 5 to 12.5) resulted in an average increase in insulin sensitivity index of 24 %
complete withdrawal of 5 mg/day of prednisolone did not influence insulin sensitivity
significantly.
OPTN/SRTR database: retrospective analysis consisting of 25,000 KT recipients January
2004 to December 2006
Luan et al,
steroid-free immunosuppression was associated with a significant reduction in the
likelihood of developing NODAT compared with steroid-containing regimens
cumulative incidence of NODAT within three years post KT 12.3% in steroid-free
versus 17.7% in steroid-containing regimens, P , 0.001.
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
15. Modifiable risk factors:
CALCINEURIN INHIBITOR
The DIRECT Study: first multi-center open label, randomized trial
assess glucose abnormalities in de novo kidney transplant patients
who were randomized to cyclosporine microemulsion- (CSA-ME)
or tacrolimus-based immunosuppression.
The incidence of NODAT or IFG at 6-month post-transplant was
significantly lower in CSA-ME (26%) vs tacrolimus- treated
patients (33.6%) P = 0.046
lower proportion of CSA-ME patients with NODAT required
hypoglycemic medication or dual therapy with insulin and oral
hypoglycemic agents compared with their tacrolimus-treated
counterparts.
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
16. Modifiable risk factors:
SIROLIMUS
USRDS database : > 20,000 primary KT recipients receiving sirolimus
or CNI (CsA or Tac) or both in various combination therapies with an
antimetabolite [MMF or AZA]
Johnston et aL,
patients treated with sirolimus in combination with a CNI (CsA or
Tac) had the highest incidence of NODAT.
(Sir + Tac) combination therapy: hazard ratio of 1.9 for developing
NODAT compared with those receiving (Tac + MMF/AZA)
sirolimus was associated with an increased risk for NODAT
independent of any effect of tacrolimus.
17. Other Risk factors for NODAT
OBESITY = BMI >30 kg/m2
Hypertriglyceridemia/ hypertension
Bayer et al: prevalence of NODAT at 1 year
increased with increasing number of
metabolic syndrome score P = 0.001
0: 0%, 1: 24%, 2: 29%, 3: 31%, 4: 35%, 5: 74%
low-density lipoprotein was independently
associated with the development of NODAT
HYPOMAGNESEMIA
Van Laecke et al: hypomagnesemia during
the first-month posttransplantation was
associated with the development of NODAT,
independent of the immunosuppressive
regimen used
CMV
Hjelmesaeth and colleagues: asymptomatic
CMV infection was associated with a 4x
increased risk of new-onset diabetes
(adjusted RR = 4.00; P = 0.025)
CMV-induced release of proinflammatory
cytokines may lead to apoptosis and
functional disturbances of pancreatic β-cells
resulting to decreased insulin release
HCV
insulin resistance; decreased hepatic
glucose uptake and glycogenesis; and
direct cytopathic effect of the virus on
pancreatic β cells
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
18. Calcineurin
Harini A. Chakkera, et al, Calcineurin Inhibition and New-Onset Diabetes Mellitus After
Transplantation, NIH Public Access, 2012
20. Calcineurin inhibition on insulin secretion
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
21. Calcineurin inhibitors and effect on adipocytes
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
22. Calcineurin inhibitors and effect
on skeletal muscles
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
23. Tacrolimus vs. Cyclosporine and
Glucose Homeostasis
Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
24. Harini A. Chakkera, MD, MPH, Calcineurin Inhibitors: Pharmacologic mechanisms impacting both insulin resistance and insulin
secretion leading to glucose dysregulation and diabetes mellitus, 2016 Mayo Foundation for Medical Education and Research
25. Impact of hyperglycemia on
Kidney Transplantation
Early perioperative hyperglycemia in
patients without pre transplant DM
increased acute rejection episodes at BG
> 145 mg/dl
increased post-operative infections at
BG > 200 mg/dl
IFG (>100 mg/dl) or NODA T (FBG > 126
md/dl) was associated with increased risk up
to 40 months:
coronary artery disease (CAD)
peripheral vascular disease (PVD)
cerebrovascular accidents (CVA)
Rodolfo J. Galindo 1 & Amisha Wallia, Hyperglycemia and Diabetes Mellitus Following Organ Transplantation, Curr Diab Rep (2016)
16:14 DOI 10.1007/s11892-015-0707-1
More rapid DM-related complications in
NODAT (mean 500 days)
renal (31.3 %)
neurologic complications (16.2 %)
ketoacidosis (8.1 %)
ophthalmic complications (8.3 %)
hypoglycemia/shock (7.3 %)
peripheral circulatory disorders (4.1
%)
hyperosmolarity (3.2 %)
26. Impact of NODAT on allograft
outcomes
United Renal Data System data:
over 11,000 Medicare beneficiaries who received primary KT
from 1996 to 2000
NODAT was associated with:
63% increased risk of graft failure (P , 0.0001)
46% increased risk of death-censored graft failure (P , 0.0001)
87% increased risk of mortality (P , 0.0001)
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
27.
28.
29. P: patients undergoing renal transplantation
I: 3-day postrenal transplant group treated with intensive
iv insulin [blood glucose (BG) 70–110 mg/dl] or a control
group treated with sc insulin (BG 70–180mg/dl)
O: primary endpoint: delayed graft function. Secondary
endpoints: glycemic control, graft survival, and acute
rejection episodes
M: randomized controlled trial
Hermayer et al. Glycemic Control on Renal Transplantation J Clin Endocrinol Metab, December 2012,
97(12):4399–4406
30.
31. Glycemic Targets During
Hospitalization: AACE and ADA
IV infusion for BG ≥
180 mg/dl
target: BG of 140–
180 mg/dl
lower targets: 110–
140 mg/dl in
selected patients
Rodolfo J. Galindo 1 & Amisha Wallia, Hyperglycemia and Diabetes Mellitus Following Organ Transplantation, Curr Diab
Rep (2016) 16:14 DOI 10.1007/s11892-015-0707-1
target pre-meal BG:
<140 mg/dl
random BG:
< 180 mg/dl
SQ basal-bolus
regimen preferred
NON CRITICALLY ILLCRITICALLY ILL
32. Subcutaneous insulin regimen
Baldwin, et al
two basal-bolus (glargine-glulisine) insulin-
dosing regimens in hospitalized patients with
DM and CKD (eGFR < 45)
half-dose weight-based insulin regimen (TDD of
0.25 units/kg/day) was associated with 50 % less
hypoglycemia (15.8 vs 30 %, p = 0.08) and similar
glycemic control
Baldwin D, Zander J, Munoz C, et al. A randomized trial of two weight-based doses of insulin glargine and glulisine in
hospitalized subjects with type 2 diabetes and renal insufficiency. Diabetes Care. 2012;35:1970–4
33. Non insulin agents in inpatient setting
Umpierrez,et al, RCT
noncritical ill patients with DM treated with sitagliptin
alone or in combination with basal insulin may
achieve glycemic targets with minimal hypoglycemia,
particularly if admission blood glucose <180 mg/dl
the use of oral hypoglycemic agents (OHAs) is not
currently recommended for routine inpatient glycemic
management
Umpierrez GE, Gianchandani R, Smiley D, et al. Safety and efficacy of sitagliptin therapy for the inpatient management of general
medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013;36:3430–5
34. Discharge Recommendations
insulin therapy for patients with immediate post-transplant
hyperglycemia with the introduction of OHAs later
HbA1c in all inpatients with known diabetes or with hyperglycemia,
unless it was performed within the preceeding 2–3 months
If the insulin dose discharge:
>0.25 units/kg (on stable steroids): BASAL BOLUS INSULIN
<0.25 units/ kg: BASAL INSULIN WITH CORRECTIONAL SCALE
OR OHA
diabetes education is a key for a safe discharge and should start as early
as possible
Rodolfo J. Galindo 1 & Amisha Wallia, Hyperglycemia and Diabetes Mellitus Following Organ Transplantation,
Curr Diab Rep (2016) 16:14 DOI 10.1007/s11892-015-0707-1
35. MANAGEMENT
NODAT
Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
36.
37. Phuong-Thu T Pham, et al, New onset diabetes after transplantation (NODAT): an overview, Diabetes, Metabolic
Syndrome and Obesity: Targets and Therapy 2011:4 175–186
38. Comorbid conditions
DYSLIPIDEMIA
Pravastatin and fluvastatin are used preferentially in transplant patients
with dyslipidemia
Sirolimus and glucocorticoids are associated with hypertriglyceridemia that
may require treatment with fibrates, fish oil can be used as an alternative
BLOOD PRESSURE
The National Kidney Foundation: blood pressure control be maintained at
below 130/80 mm Hg in renal transplant recipients
ACE INHIBITORS AND ARBS are associated with decreases in GFR and
hyperkalemia and should be used with caution in renal transplant recipients
James T. Lane and Samuel Dagogo-Jack,Approach to the Patient with New-Onset Diabetes after Transplant (NODAT), J Clin
Endocrinol Metab, November 2011, 96(11):3289–3297
39. Comorbid conditions
MICROALBUMINEMIA
ominous finding that is associated with glomerular injury and systemic
inflammation from diverse causes
no longer merely a marker of diabetic nephrop-athy
predictor of renal al-lograft loss and increased mortality
HYPERURICEMIA
associated with cardiovascular disease, inflammation, insulin resistance, and
decreased renal graft survival
Herna ´ndez-Molina et al: recommended that interventions be targeted at
patients with the highest pretransplant uric acid levels who are also receiving
cyclosporine
James T. Lane and Samuel Dagogo-Jack,Approach to the Patient with New-Onset Diabetes after Transplant (NODAT), J Clin
Endocrinol Metab, November 2011, 96(11):3289–3297
40. SUMMARY
NODAT can affect up to 40% of patients long term
The non modifiable risk factors should be known to identify high risk individuals
And the modifiable and potentially modifiable risk factors are identified to optimize the
management of NODAT
The central pathophysiologic defect is pancreatic B-cell dysfunction in the context of insulin
resistance
Cyclosporine A and TACROLIMUS form complexes with the immunophilins cyclophilin A and
FKBP12 (FK506-binding protein), respectively, and inhibit calcineurin phosphatase activity
NODAT is associated with increased risk of graft failure and mortality
Insulin is the preferred agent in the management of inpatient hyper-glycemia
Management of NODAT is comprised of dietary and lifestyle modification, modification of
immunosupprssive agents and and adequate monitoring of patients