This document provides information on Maturity Onset Diabetes of the Young (MODY), including its history, classification, types, clinical presentation, diagnosis, and management. Specifically, it discusses MODY type 3, which is caused by mutations in the HNF1A gene and is characterized by early-onset diabetes diagnosed before age 25, autosomal dominant inheritance, lack of obesity, and primary defect in insulin secretion. The diagnosis of MODY3 can be made through genetic testing for HNF1A mutations after considering clinical criteria. Treatment primarily involves use of sulfonylureas due to the effectiveness of these drugs for HNF1A mutations.
MODY is the name given to a collection of different types of inherited forms of diabetes that usually develop in adolescence or early adulthood.
MODY stands for “Maturity-onset diabetes of the young” and was given that name in the past because it acted more like the adult type of diabetes (Type 2 Diabetes) but was found in young people.
MODY limits the body’s ability to produce insulin, but is different than the juvenile type of diabetes (Type 1 Diabetes).
When our bodies don’t produce enough insulin, it can increase blood glucose levels. High blood glucose levels lead to diabetes.
MODY is the name given to a collection of different types of inherited forms of diabetes that usually develop in adolescence or early adulthood.
MODY stands for “Maturity-onset diabetes of the young” and was given that name in the past because it acted more like the adult type of diabetes (Type 2 Diabetes) but was found in young people.
MODY limits the body’s ability to produce insulin, but is different than the juvenile type of diabetes (Type 1 Diabetes).
When our bodies don’t produce enough insulin, it can increase blood glucose levels. High blood glucose levels lead to diabetes.
John B. Buse, MD, PhD, discusses type 2 diabetes in this CME activity titled "Exploring the Science and Practice of GLP-1 Receptor Agonists: An Update on Current and Emerging Evidence." For the full presentation, downloadable infographics, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2oL19BK. CME credit will be available until October 21, 2020.
John B. Buse, MD, PhD, discusses type 2 diabetes in this CME activity titled "Exploring the Science and Practice of GLP-1 Receptor Agonists: An Update on Current and Emerging Evidence." For the full presentation, downloadable infographics, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2oL19BK. CME credit will be available until October 21, 2020.
DIABETES MELLITUS. Homoeopathic approach to diabetes mellitusDrswetha Bp
DIABETES - EMPOWERING GLOBAL HEALTH. Every year, Nov 14th is celebrated as World Diabetes Day.
My approach of todays topic is “Access to Diabetes care”, and slogan is “Know your risk, Know your response”.
DEFINITION OF DIABETES MELLITUS :
It is the group of metabolic disorders which characterised by hyperglycemia and abnormalities of carbohydrate, fat and protein metabolism. resulting from defects in insulin secretion, insulin action, or. Both .
Causes:-
Life style
Genetics factor
Obesity
Diet time variation
Etiological Classification of Diabetes:
Type :-1 Diabetes (insulin dependent)
Type :-2 Diabetes (non insulin dependent)
Gestational diabetes
DEFINTION OF TYPE 1 DIABETES :
Type 1 diabetes, once known as juvenile diabetes or insulin-dependent diabetes, is a chronic condition by the beta cells in islets of Langerhans in the pancreas in which the pancreas produces little or no insulin, due to the autoimmune destruction of the beta cells in the pancreas. Although onset frequently occurs in childhood, the disease can also develop in adults.
DEFINITION OF TYPE 2 DIABETES :
known as adult-onset diabetes, is a form of diabetes that is characterized by high blood sugar, due to body cells don’t respond normally to insulin; this is called insulin resistance.
DEFINITION OF GESTATIONAL DIABETES :
Gestational Diabetes: Is the increasing of blood sugar levels for Some women tend to experience high levels of blood glucose as during pregnancy due to reduced sensitivity of insulin receptors.
CAUSES :
The exact cause of type 1 diabetes is unknown. Usually, the body's own immune system — which normally fights harmful bacteria and viruses — mistakenly destroys cells which the insulin-producing (islets of Langerhans) cells in the pancreas. Other possible causes include:
Genetics
Exposure to viruses and other environmental factors
Endocrine disorders such as acromegaly , Cushing's syndrome
Endocrine disorders e.g. Pancreatitis .
Medications e.g. glucocorticoids , niacin , pentamine alpha- interferons .
Micro vascular complications (zeroplateas , neutrophils , eosinophil's )
Macro vascular complications (CHF , stroke , peripheral vascular disease)
SYMPTOMS :
Type 1 diabetes signs and symptoms can appear relatively suddenly and may include:
Increased thirst
Frequent urination
Bed-wetting in children who previously didn't wet the bed during the night
Extreme hunger
Unintended weight loss
Irritability and other mood changes
Fatigue and weakness
Blurred vision
PHARMACOLOGICAL TREATMENT :
Insulin:
People with type 1 diabetes must take insulin every day. You usually take the insulin through an injection.
Metformin :
Metformin is a type of oral diabetes medication. For many years, it was only used in people with type 2 diabetes. However, some people with type 1 diabetes can develop insulin resistance. That means the insulin they get from injections doesn’t work as well as it should.
Metformin helps lower sugar in the blood by reducing sugar production in the liver. Your doctor may advise you to take Metformin in addition to insulin.
B) NON- PHARMACOLOGICAL TREATMENT :
CONTROL THE SYMPTOMS .
EXERCISES
MONITORING THE SUGAR LEVELS
HEALTHY FOODS .
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
This presentation will surely help the general physicians and paediatricians to understand the symptoms of cystic fibrosis and will educate regarding various diagnostic modalities in cystic fibrosis
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
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!
CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
3. HISTORY
• ELLIOT JOSLIN OBSERVED BEFORE THE DISCOVERY OF INSULIN THAT SOME
YOUNG PATIENTS WITH DIABETES AND A STRONG FAMILY HISTORY OF THE
CONDITION SURVIVED MUCH LONGER THAN EXPECTED.
• SIMILAR CLINICAL REPORTS MAY BE TRACED IN THE SUBSEQUENT
LITERATURE, BUT THE HISTORY OF MODY REALLY BEGAN IN 1974 WHEN
TATTERSALL AND PYKE DESCRIBED THREE FAMILIES WITH EARLY ONSET
DIABETES TRANSMITTED AS AN AUTOSOMAL DOMINANT TRAIT,
RESPONSIVE TO SULPHONYLUREAS, AND WITH A RELATIVELY BENIGN
PROGNOSIS.
• FAJANS HAD INDEPENDENTLY DESCRIBED A GROUP OF PATIENTS
DIAGNOSED WITH DIABETES UNDER THE AGE 25 YEARS WHO HAD NOT
PROGRESSED TO INSULIN AFTER MANY YEARS ON SULPHONYLUREAS.
• TATTERSALL AND FAJANS JOINED FORCES TO COIN THE SOMEWHAT
UNFORTUNATE TERM MATURITY ONSET DIABETES OF THE YOUNG (MODY),
WHICH THEY DEFINED AS 'FASTING HYPERGLYCAEMIA DIAGNOSED UNDER
AGE 25 WHICH COULD BE TREATED WITHOUT INSULIN FOR MORE THAN
TWO YEARS'.
4. • MATURITY ONSET DIABETES OF THE YOUNG (MODY) IS A
CLINICALLY GROUP OF HETEROGENEOUS DISORDER
CHARACTERIZED BY NON-INSULIN DEPENDENT DIABETES
DIAGNOSED AT A YOUNG AGE (<25 YEARS) WITH AUTOSOMAL
DOMINANT TRANSMISSION AND LACK OF AUTOANTIBODIES
4
DEFINITION-MODY
5. • EARLY ONSET DIABETES (<25 years)
• NON-INSULIN DEPENDENT
• AUTOSOMAL DOMINANT INHERITANCE
• CAUSED BY A SINGLE GENE DEFECT ALTERING BETA
CELL FUNCTION
• OBESITY UNUSUAL
• PRIMARY DEFECT IN INSULIN SECRETION
BACKGROUND
8. • COMMONEST CAUSE
OF MODY
• MAY BE
MISDIAGNOSED AS
TYPE 1
• TYPICALLY DEVELOPS
BEFORE 25 YEARS
• FBG MAYBE NORMAL
INITIALLY
• LARGE RISE (>5MMOL/L) IN
OGTT
WORSENING GLYCAEMIA
WITH AGE
• LOW RENAL THRESHOLD
(GLYCOSURIA)
• NOT OBESE (USUALLY)
• PARENTS AND
GRANDPARENTS
USUALLY DIABETIC
INTRODUCTION
9. • HNF1 HOMEOBOX A (HEPATOCYTE NUCLEAR FACTOR 1 HOMEOBOX A), ALSO
KNOWN AS HNF1A, IS A HUMAN GENE WHICH IS LOCATED ON
CHROMOSOME 12Q24.2
• THE PROTEIN ENCODED BY THIS GENE IS A TRANSCRIPTION FACTOR THAT IS
HIGHLY EXPRESSED IN THE PANCREAS.
• IT REGULATES EXPRESSION OF THE INSULIN GENE AND OTHER GENES
ENCODING PROTEINS INVOLVED IN GLUCOSE TRANSPORT AND METABOLISM.
• HNF1 A MUTATIONS MAY CONTRIBUTE TO ABNORMAL PANCREATIC ISLET CELL
DEVELOPMENT DURING FETAL LIFE, AS WELL AS IMPAIRED TRANSCRIPTIONAL
REGULATION OF GENES INVOLVED IN NORMAL ISLET CELL FUNCTION
• ITS MUTATIONS ALSO INFLUENCE EXPRESSION OF HNF4A(MODY1). THIS
SUGGESTS THAT THE MODY TRANSCRIPTION FACTORS FORM A REGULATOR
NETWORK THAT IS NECESSARY TO MAINTAIN GLUCOSE HOMOSTASIS.
HNF1A
10. PATHOPHYSIOLOGY
• MODY3 is caused by mutation in the hepatic transcription factor-
1 gene (TCF1) on chromosome 12q24.2.
11. CLINICAL PRESENTATION
• MILD TO MODERATE HYPERGLYCEMIA (TYPICALLY 130–250 MG/DL, OR 7–
14 MMOL/L) DISCOVERED BEFORE 25 YEARS OF AGE. HOWEVER, ANYONE UNDER
50 CAN DEVELOP MODY.
• A FIRST-DEGREE RELATIVE WITH A SIMILAR DEGREE OF DIABETES.
• USUAL DIABETIC SYMPTOMS LIKE POLYUREA, POLYDYPSIA & POLYPHAGIA.
• ABSENCE OF POSITIVE ANTIBODIES OR OTHER AUTOIMMUNITY (E.G., THYROIDITIS)
IN PATIENT AND FAMILY.
• PERSISTENCE OF A LOW INSULIN REQUIREMENT (E.G., LESS THAN 0.5 U/KG/DAY)
PAST THE USUAL "HONEYMOON" PERIOD.
12. • ABSENCE OF OBESITY (ALTHOUGH OVERWEIGHT OR OBESE PEOPLE CAN
GET MODY) OR METABOLIC
SYNDROME (E.G.,HYPERTENSION, HYPERLIPIDEMIA, POLYCYSTIC OVARY
SYNDROME).
• INSULIN RESISTANCE VERY RARELY HAPPENS.
• CYSTIC KIDNEY DISEASE IN PATIENT OR CLOSE RELATIVES.
• ON-TRANSIENT NEONATAL DIABETES, OR APPARENT TYPE 1 DIABETES WITH
ONSET BEFORE SIX MONTHS OF AGE.
• LIVER ADENOMA OR HEPATOCELLULAR CARCINOMA IN MODY TYPE 3
• THE DIAGNOSIS OF MODY IS CONFIRMED BY SPECIFIC GENE TESTING
AVAILABLE THROUGH COMMERCIAL LABORATORIES.
CLINICAL PRESENTATION
13. • THE MAJORITY OF PATIENTS WITH GENETICALLY PROVEN MONOGENIC
DIABETES ARE INITIALLY INCORRECTLY DIAGNOSED AS TYPE 1 OR TYPE 2
DIABETES.
• IT IS IMPORTANT TO CORRECTLY DIAGNOSE MONOGENIC DIABETES AS IT
CAN PREDICT THE CLINICAL COURSE OF THE PATIENT, EXPLAIN OTHER
ASSOCIATED CLINICAL FEATURES AND MOST IMPORTANTLY GUIDE THE
MOST APPROPRIATE TREATMENT.
• IN ADDITION, MAKING A DIAGNOSIS WILL HAVE IMPLICATIONS FOR
OTHER FAMILY MEMBERS OFTEN CORRECTING THE DIAGNOSIS AND
TREATMENT FOR OTHER DIABETIC FAMILY MEMBERS AS WELL AS
ALLOWING APPROPRIATE GENETIC COUNSELING
WHY DIAGNOSE MODY?
14. Diabetes in Young Adults (15-30 years)
Age of diagnosis
5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90
Type 2
Type 1
MODY
MIDD
15. • FEATURES IN CHILDREN INITIALLY THOUGHT TO HAVE TYPE 1 DIABETES THAT
SHOULD SUGGEST A POSSIBLE DIAGNOSIS OF MONOGENIC DIABETES ARE SHOWN
BELOW. NONE OF THESE ARE ABSOLUTE AND SHOULD BE CONSIDERED AS
TOGETHER RATHER THAN IN ISOLATION(C) 3. THE APPROXIMATE PERCENTAGE OF
PATIENTS WITH TYPE 1 DIABETES IS GIVEN IN BRACKETS
• A DIAGNOSIS OF DIABETES BEFORE 6 MONTHS (B) (<1% TYPE 1 IAFUSCO, 2002
#2514 )
• FAMILY HISTORY OF DIABETES WITH A PARENT AFFECTED (C) (2-4%4)
WHEN TO SUSPECT A DIAGNOSIS OF TYPE 1 DIABETES IN
CHILDREN MAY NOT BE CORRECT?
16. • EVIDENCE OF ENDOGENOUS INSULIN PRODUCTION OUTSIDE THE
‘HONEYMOON’ PHASE (AFTER 3 YEARS OF DIABETES) WITH DETECTABLE C
PEPTIDE (>200NMOL/L) WHEN GLUCOSE > 8 MMOL/L. (1-5% TYPE 1).
• WHEN PANCREATIC ISLET AUTOANTIBODIES ARE ABSENT, ESPECIALLY IF
MEASURED AT DIAGNOSIS (3-30% TYPE 1 PATIENTS.
WHEN TO SUSPECT A DIAGNOSIS OF TYPE 1 DIABETES IN
CHILDREN MAY NOT BE CORRECT?
17. WHEN TO SUSPECT A DIAGNOSIS OF TYPE 2 DIABETES IN
CHILDREN MAY NOT BE CORRECT?
• NOT MARKEDLY OBESE OR DIABETIC FAMILY MEMBERS WHO ARE NORMAL
WEIGHT (20%)
• ACANTHOSIS NIGRICANS NOT DETECTED (10%)
• ETHNIC BACKGROUND FROM A LOW PREVALENCE TYPE 2 DIABETES RACE
E.G. EUROPEAN CAUCASIAN (0-45%)
• NO EVIDENCE OF INSULIN RESISTANCE WITH FASTING C PEPTIDE WITHIN
THE NORMAL RANGE (0-20%8-11)
19. Tattersall (QJM 1974)
•Early-onset diabetes
•Not insulin-dependent
diabetes
•Autosomal dominant inheritance
Caused by a single gene defect
altering beta-cell function, obesity
unusual
Diagnosis of diabetes before
25 years in at least 1 & ideally
2 family members
Must be diabetes in one
parent (2 generations) and
ideally a grandparent or child
( 3 generations)
ON CLINICAL
BASIS
Off insulin treatment or measurable C-
peptide at least 3 (ideally 5) years after
diagnosis
20. WHEN THERE IS A HIGH INDEX OF SUSPICION I.E.
1. FAMILIAL DIABETES WITH AUTOSOMAL DOMINANT PATTERN OF
INHERITANCE (>2 GENERATIONS),
2. ONSET <25 YEARS,
3. NON-OBESE,
4. NEGATIVE ISLET AUTOANTIBODIES
GENETIC TESTING
22. Diagnostic Testing : why do
it?
HNF1a:very sensitive to sulphonylureas
4
6
8
10
12
8 9 10 11 12 13
Glibenclamide stopped
Metformin started
Glibenclamide started
Metformin stopped
HbA1c
(%)
Years since diagnosis(Pearson et al Diab Med 2000)
23. • RECENT WORK DONE BY TIM J, MCDONALD… SHOWED THAT HIGH SENSITIVITY C-
REACTIVITY LEVELS ARE LOWER IN HNFA1 THAN TYPE 1, TYPE 2 SIABETES OR
GLUCOKINASE (GCK) – MODY (DIABETES CARE JOURNAL)
• METHOD : HS-CRP LEVELS WERE ASSESSED IN 750 PATIENTS (220
HNF1A, 245 GCK, 54 HNF4A, 21 HNF1B, 53 TYPE 1 AND 157 TYPE 2
DIABETES.
• RESULTS : HS-CRP WAS LOWER IN HNF1A-MODY (MEDIAN 0.3 [0.1-0.6])
THAN TYPE 2 DIABETES ( MEDIAN 1.40 [ 0.60-3.45] MG/L) THAN TYPE 1
(1.10 [0.50-1.85] MG/DL) THAN HNF1B-MODY (0.60 [0.10-2.8] MG/DL)
THAN GCK-MODY(0.60 [0.30-1.8]MG/DL)
• CONCLUSION: HS-CRP LEVELS ARE LOWER IN HNF1A-MODY THAN OTHER
FORMS OF DIABETES AND MAY BE USED A S A BIOMARKER TO SELECT
PATIENTS FOR DIAGNOSTIC HNF1A GENETIC TESTING.
HIGH SENSITIVE CRP
24. • RECENT WORK DONE S. A. MUGHAL, R. PARK… SHOWED THAT SERUM APOM
LEVELS ARE LOWER IN HNFA1 THAN TYPE 1. (DIABETES MED JOURNAL)
• METHOD : APO M LEVELS WERE ASSESSED IN 69 HNF1A, 50 TYPE 1, 120
TYPE 2 DIABETES AND 100 HEALTHY CONTROL.
• RESULTS : MEAN SERUM APO M CONCENTRATION WAS SIGNIFICANTLY
LOWER FOR SUBJECTS WITH HNF1A-MODY [0.86(0.29)] THAN THOSE WITH
TYPE 1 AND CONTROL SUBJECTS [1.34(0.22)
• CONCLUSION: APO M LEVELS ARE LOWER IN HNF1A-MODY THAN IN
CONTROLS. ALSO IT PROVIDES A GOOD DISCRIMINATION BETWEEN HNF1A
MODY AND TYPE 1 DIABETIC PATIENTS.
APOLIPOPROTEIN M
25. • USE BOTH DIAGNOSTIC CRITERIA AND CLINICAL INFORMATION AND
NON-GENETIC INVESTIGATION TO SUGGEST A DIAGNOSIS
• GENETIC TESTING MAKES DIAGNOSIS : DEFINES MODY, DEFINES
SUBTYPE HELPS WITH COUNSELLING, PROGNOSIS AND TREATMENT
• BUT ….EXPENSIVE - ONLY DO IF ALTER MANAGEMENT
• TEST ORDERED GUIDED BY CLINICAL CRITERIA AS TO LIKELY GENE.
DISCUSS EACH CASE BEFORE TESTING
DIAGNOSIS CONCLUSION
26. MANAGEMENT
• Unfortunately, chronic hyperglycemia of any cause can
eventually cause blood vessel damage and the microvascular
complications of diabetes.
• The principal treatment goals for people with MODY — keeping
the blood sugars as close to normal as possible ("good glycemic
control"), while minimizing other vascular risk factors — are the
same for all known forms of diabetes.
27. PRIMARY MANAGEMENT
• PATIENTS WITH HNF-1a GENE MUTATIONS CAN INITIALLY BE TREATED WITH
DIET AND EXERCISE ALTHOUGH THEY WILL HAVE MARKED POST PRANDIAL
HYPERGLYCAEMIA HIGH CARBOHYDRATE FOOD AS THE BETA-CELL DEFECT
RESULTS IN INSUFFICIENT INCREASE IN INSULIN SECRETION WITH
HYPERGLYCAEMIA.
• MOST PATIENTS WILL NEED PHARMACOLOGICAL TREATMENT AS THEY
SHOW PROGRESSIVE DETERIORATION IN GLYCAEMIC CONTROL
THROUGHOUT LIFE AND ARE AT RISK OF CONSIDERABLE MICRO-VASCULAR
AND MACRO-VASCULAR COMPLICATIONS.
28. • THE CURRENT INTERNATIONAL SOCIETY FOR PEDIATRIC AND
ADOLESCENT DIABETES/INTERNATIONAL DIABETES
FEDERATION (ISPAD/IDF) GUIDELINES PUBLISHED IN 2009
SUGGEST SWITCHING PATIENTS WITH PROFEN HNF1A
MUTATION (HNF1A–MODY) FROM INSULIN TO
SULFONYLUREA.
• DESPITE THIS, 40% OF HNF1A PATIENTS WITH PAEDIATRIC
AND ADOLESCENT-ONSET DIABETES CONTINUED TO RECEIVE
INSULIN TREATMENT.
• INSULIN TREATMENT WAS ASSOCIATED WITH HIGHER HBA1C
AND A HIGHER RISK OF HYPOGLYCAEMIA.
29. 1. SULPHONYLYUREAS
• THE FIRST TREATMENT TO BE USED IN CHILDREN WHO ARE NOT
CONTROLLED ON INSULIN SHOULD BE LOW DOSE SULPHONYLUREAS
WHICH RESULTS IN A 4 FOLD GREATER LOWERING OF GLUCOSE THAN
METFORMIN.
• THESE PATIENTS ARE EXTREMELY SENSITIVE TO SULPHONYLUREAS AND AS
LONG AS THEY DO NOT HAVE PROBLEMS WITH HYPOGLYCAEMIA CAN BE
MAINTAINED ON THESE FOR MANY DECADES .
• GLYCAEMIC CONTROL IN SULPHONYLUREAS IS OFTEN BETTER THAN THAT
ACHIEVED ON INSULIN ESPECIALLY IN CHILDREN AND YOUNG ADULTS.
• THE DOSE OF SULPHONYLUREAS SHOULD INITIALLY BE LOW (¼ - OF THE
NORMAL STARTING DOSE IN ADULTS) TO AVOID HYPOGLYCAEMIA .
• IF THERE IS HYPOGLYCAEMIA DESPITE DOSE TITRATION OF A ONCE OR
TWICE DAILY SULPHONYLUREA PREPARATION SUCH AS GLICLAZIDE A SLOW
RELEASE PREPARATION OR MEAL TIME DOSES WITH A SHORT ACTING
AGENTS LIKE NATEGLINIDE MAY BE CONSIDERED.
PHARMACOLOGICAL RX
30.
31. 2. MEGLITINIDE ANALOGUES
• MARIANNE BECKER, ANGELA GALLER AND KLEMENS RAILE HAD PUBLISHED
CASE REPORTS SUGGESTING THAT MEGLITINIDES CAN BE USED AS SINGLE OR
COMBINED BASED THERAPY FOR MODY 3 PATIENTS.
• The Hba1c with the use of meglitinide was 51 mmol/mol , 6.8% whereas with
insulin was 58 mmol/mol, 7.5%.
• In combination with Insulin Hba1c was 55 mmol/ml and 7.2%
PHARMACOLOGICAL RX
32. 3. GLUCAGON LIKE PEPTIDE – 1 RECEPTOR AGONIST THERAPY
• Maricor, Charles, Christine, kevin published a Case study report of three
patients saying that GLP-1 receptor agonist therapy may be of value in
managing glycemia in patients with MODY 3
• In all 3 patients C-peptide levels went 3-fold after 3 days of liraglutide.
• They also experienced significant weight loss (10-15%)
• Hb1ac was 7.4%, 6.4 % and 6.8 % respectively.
• With the help of GLP 1, they were able to discontinue Insulin.
33. 1. UPTODATE
2. YAMAGATA, K; ODA, N; KAISAKI, PJ; MENZEL, S; FURUTA, H; VAXILLAIRE, M;
SOUTHAM, L; COX, RD; LATHROP, GM; BORIRAJ, VV; CHEN, XN; COX, NJ; ODA, Y;
YANO, H; LEBEAU, MM; YAMADA, S; NISHIGORI, H; TAKEDA, J; FAJANS, SS;
HATTERSLEY, AT; IWASAKI, N; HANSEN, T; PEDERSEN, O; POLONSKY, KS; TURNER, RC;
VELHO, G; CHEVRE, JC; FROGUEL, P; BELL, GI. (1996) "MUTATIONS IN THE
HEPATOCYTE NUCLEAR FACTOR-1 ALPHA GENE IN MATURITY-ONSET DIABETES OF
THE YOUNG (MODY3)." NATURE 384(6608): 455-458.
3. MARIANNE BECKER, MD, ANGELA GALLER, MD, AND KLEMENS RAILE, MD
“MEGLITINIDE ANALOGUES IN ADOLESCENT PATIENTS WITH HNF1A-MODY (MODY
3)” PEDIATRICS VOLUME NO. 133 NO.3 MARCH 1, 2014. PP. E775-E779
4. MCDONALD TJ, SHIELDS BM, LAWRY J, ET AL. HIGH-SENSITIVITY CRP DISCRIMINATES
HNF1A-MODY FROM OTHER SUBTYPES OF DIABETES. DIABETES
CARE2011;34(8):1860-1862. DOI:10.2337/DC11-0323.
REFERENCES