What is diabetes mellitus, Epidemiology of diabetes, Diabetes diagnosis, Features of diabetes, WHO classification of Diabetes Mellitus, Complications of diabetes, Metabolic alterations of diabetes, Oral glucose tolerance test, WHO criteria of OGTT interpretation, Classification of diabetes mellitus, Gestational diabetes, Pre-diabetes, Insulin, Biosynthesis of insulin, Insulin actions, Hypoglycemia, Impaired fasting glucose, Insulin structure
Advances and Management of Diabetes MellitusPratiksha Doke
Diabetes mellitus is an endocrinological and/or metabolic disorder with an increasing global prevalence and incidence. High blood glucose levels are symptomatic of diabetes mellitus as a consequence of inadequate pancreatic insulin secretion or poor insulin-directed mobilization of glucose by target cells. Diabetes mellitus is aggravated by and associated with metabolic complications that can subsequently lead to premature death. This presentation explores diabetes mellitus in terms of its types, causes and management interventions for improved lifestyle for patient.
Diabetes mellitus is a metabolic disease, characterized by high glucose level in blood (hyperglycaemia).
Insulin-dependent diabetes mellitus (IDDM)
Juvenile-onset diabetes
Type1 diabetes is characterized by the presence of antibodies in blood.
Glutamic Acid Decarboxylase antigen (GAD)
Insulin autoantibodies (IAAs),
Islet cell autoantibodies (ICAs).
These are the markers of the immune destruction of the ß cell.
Therefore, those with more than one autoantibody(i.e., ICA, IAA, GAD etc.) are at high risk.
What is diabetes mellitus, Epidemiology of diabetes, Diabetes diagnosis, Features of diabetes, WHO classification of Diabetes Mellitus, Complications of diabetes, Metabolic alterations of diabetes, Oral glucose tolerance test, WHO criteria of OGTT interpretation, Classification of diabetes mellitus, Gestational diabetes, Pre-diabetes, Insulin, Biosynthesis of insulin, Insulin actions, Hypoglycemia, Impaired fasting glucose, Insulin structure
Advances and Management of Diabetes MellitusPratiksha Doke
Diabetes mellitus is an endocrinological and/or metabolic disorder with an increasing global prevalence and incidence. High blood glucose levels are symptomatic of diabetes mellitus as a consequence of inadequate pancreatic insulin secretion or poor insulin-directed mobilization of glucose by target cells. Diabetes mellitus is aggravated by and associated with metabolic complications that can subsequently lead to premature death. This presentation explores diabetes mellitus in terms of its types, causes and management interventions for improved lifestyle for patient.
Diabetes mellitus is a metabolic disease, characterized by high glucose level in blood (hyperglycaemia).
Insulin-dependent diabetes mellitus (IDDM)
Juvenile-onset diabetes
Type1 diabetes is characterized by the presence of antibodies in blood.
Glutamic Acid Decarboxylase antigen (GAD)
Insulin autoantibodies (IAAs),
Islet cell autoantibodies (ICAs).
These are the markers of the immune destruction of the ß cell.
Therefore, those with more than one autoantibody(i.e., ICA, IAA, GAD etc.) are at high risk.
Diabetes mellitus type 1 (Type 1 diabetes, T1DM, formerly known as insulin dependent or juvenile diabetes) is a form of diabetes mellitus that results a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved. The subsequent lack of insulin leads to increased blood and urine glucose. Eventually, type 1 diabetes is fatal unless treated with insulin.
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine". The first described cases are believed to be of Type 1 Diabetes.
Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants. The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Appollonius of Memphis.
The disease was considered as rare during the time of the Roman Empire, with Galen commenting he had only seen two cases during his career. Galen named the disease "diarrhea of the urine" (diarrhea urinosa). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness.
Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.
The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.
The worldwide explosion of obesity has resulted in an ever-increasing prevalence of type 2 diabetes. The importance of insulin resistance and β-cell dysfunction to the pathogenesis of type 2 diabetes was debated for a long time; many thought that insulin resistance was the main abnormality in type 2 diabetes, and that inability to secrete insulin was a late manifestation. This notion is now challenged. This presentation deals with the important contributing factors in the development of type 2 diabetes mellitus.
Shashikiran Umakanth made this presentation at the "First Endocrine Update Program” – ENDO EGYPT 2015, from 17-20 December 2015 in the Historic City of Luxor, Egypt. This endocrine update was organised by the Egyptian Association of Endocrinology , Diabetes and Atherosclerosis (EAEDA) in collaboration with the Endocrine Society, USA.
Diabetes and various types have been discussed in detail as regard for Pg entrance and with various images, tables .....
Topics discussed: 1) introduction
2) types of diabetes
3) comp0lication of diabetes
4) DKA
5) NKHOC
6) Diabetic nephropathy
7) skin diseases in diabetes
Diabetes mellitus type 1 (Type 1 diabetes, T1DM, formerly known as insulin dependent or juvenile diabetes) is a form of diabetes mellitus that results a progressive autoimmune disease, in which the beta cells that produce insulin are slowly destroyed by the body's own immune system. It is unknown what first starts this cascade of immune events, but evidence suggests that both a genetic predisposition and environmental factors, such as a viral infection, are involved. The subsequent lack of insulin leads to increased blood and urine glucose. Eventually, type 1 diabetes is fatal unless treated with insulin.
Diabetes was one of the first diseases described, with an Egyptian manuscript from c. 1500 BCE mentioning "too great emptying of the urine". The first described cases are believed to be of Type 1 Diabetes.
Indian physicians around the same time identified the disease and classified it as madhumeha or "honey urine", noting the urine would attract ants. The term "diabetes" or "to pass through" was first used in 230 BCE by the Greek Appollonius of Memphis.
The disease was considered as rare during the time of the Roman Empire, with Galen commenting he had only seen two cases during his career. Galen named the disease "diarrhea of the urine" (diarrhea urinosa). He described the symptoms and the course of the disease, which he attributed to the moisture and coldness.
Diabetes mellitus (DM) is a group of diseases characterized by high levels of blood glucose resulting from defects in insulin production, insulin action, or both.
The term diabetes mellitus describes a metabolic disorder of multiple aetiology characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both.
The effects of diabetes mellitus include long–term damage, dysfunction and failure of various organs.
The worldwide explosion of obesity has resulted in an ever-increasing prevalence of type 2 diabetes. The importance of insulin resistance and β-cell dysfunction to the pathogenesis of type 2 diabetes was debated for a long time; many thought that insulin resistance was the main abnormality in type 2 diabetes, and that inability to secrete insulin was a late manifestation. This notion is now challenged. This presentation deals with the important contributing factors in the development of type 2 diabetes mellitus.
Shashikiran Umakanth made this presentation at the "First Endocrine Update Program” – ENDO EGYPT 2015, from 17-20 December 2015 in the Historic City of Luxor, Egypt. This endocrine update was organised by the Egyptian Association of Endocrinology , Diabetes and Atherosclerosis (EAEDA) in collaboration with the Endocrine Society, USA.
Diabetes and various types have been discussed in detail as regard for Pg entrance and with various images, tables .....
Topics discussed: 1) introduction
2) types of diabetes
3) comp0lication of diabetes
4) DKA
5) NKHOC
6) Diabetic nephropathy
7) skin diseases in diabetes
Screening for diabetes and its complications as part of the Alberta Diabetes ...Kelli Buckreus
2004 (Jan) 3rd National Conference on Diabetes and Aboriginal Peoples, National Aboriginal Diabetes Association (NADA), poster presentation by BRAID Research
All what you have to know about Diabetes MellitusYapa
All what you have to know about Diabetes Mellitus is here.Introduction of Diabetes,Regulation of blood glucose,Predisposing factors of DM,Clinical presentation,DM and pregnancy ,Diabetes ketoacidosis ,Complications of DM ,Diagnosis ,Dietary management of DM & Prevention of DM.
Student seminar on Diabetes Mellitus presented by 2007/2008 Batch students of Faculty of Medicine,University of Peradeniya,Sri Lanka.
Buy Accu chek active glucometer,test strips and other branded glucose meter in Diabeticpick.com. Shop for best diabetic products online, get free shipping.
Life Style and Nutritional profile of NIDDM patients.Runa La-Ela
Life Style and Nutritional profile of NIDDM patients.
Diabetes mellitus is one of the most burdensome chronic diseases that are increasing in epidemic proportion throughout the world.
Obesity and physical inactivity constitute part of the risk for NIDDM because of their propensity to induce insulin resistance.
Food and dietary pattern of an individual have an important role to play in the development, treatment or prevention of NIDDM
Diabetes mellitus, its types and compicationsMohit Adhikary
Diabetes mellitus and the different types of it. The classification of the diabetes, description and the complications of diabetes. Spectrum and the Epidemiology.
Definition of diabetes - introduction - classification of diabetes - etiology of diabetes type 1 and type 2- risk factors for diabetes - diagnosis of diabetes - clinical manifestations of diabetes type 1 and type 2- investigations for diabetes - treatment of diabetes - non-pharmacological treatment and pharmacological treatment - pharmacotherapy of type 1 and type 2 - acute complications of diabetes and treatment
Diabetes is a serious condition where your blood glucose level is too high. It can happen when your body doesn't produce enough insulin or the insulin it produces isn't effective. Or, when your body can't produce any insulin at all.
B12 metabolism..................................... and role of various proteins in b12 metabolism..... necessity of supplementation..........................................
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.
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
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.
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!
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
Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
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Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
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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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
3. Diabetes is a group of Metabolic Disorders
characterized by Hyperglycemia resulting from defects
in insulin secretion, insulin action, or both.
-Diabetes Care Volume 37, Supplement 1, January 2014, S81
4. Etiological Classification of DM
i
Type 1 Diabetes
Immune mediated β cell destruction,
idiopathic
ii
Type 2 Diabetes
Insulin resistance
iii
Genetic defect of β cell function
MODY
Genetic defect in insulin processing Defect in proinsulin conversion, insulinor action
gene & receptor mutation etc.
Exocrine pancreatic defect
Other endocrinopathies
Glucagonoma, hyperthyroidism, cushing
syndrome etc.
infections
CMV, Coxsackie B etc.
Drugs
Steroids, thyroxin, β adrenergic etc.
Genetic syndromes
iv
Pancreatitis, cystic fibrosis etc.
Down, turner etc.
Gestational Diabetes Mellitus
Diabetic care 25, 2003
6. Genetics
•
•
•
•
•
•
•
•
Susceptibility of type1 DM is inherited.
Mode of inheritance is complex.
Concordance rate between identical twins is 30%.
MHC on chromosome 6
Multigenic trait
INS gene on chr 11
other loci on chr 9
HLA – DQ & DR are most important determinant.
HLA – DQB1*0602 allele significantly reduces the risk of type1
DM.
INS VNTR also increases the risk.
Routine assessment of genetic markers is not recommended for
Δx and Mx.
7. Environmental factors
• Viruses such as rubella, mumps and coxsackie B have been
implicated.
• Autoimmunity to β cell is initiated by viral proteins.
• Genetic susceptibility determines the progression of β cell
destruction.
8. Autoimmunity
• Type1 DM results from cell mediated autoimmune destruction
of pancreatic β cell.
• 80-90% destruction of β cell is required to induce
symptomatic diabetes.
• Marker of β cell autoimmunity are circulating antibodies.
• They are present in the serum years before the onset of
hyperglycemia.
9. •
•
•
-
Islet cell cytoplasmic antibodies (ICAs):
Against sialoglycoconjugate antigen present in the cytoplasm of all
endocrine cells of the pancreatic islets.
Detectable in 75-80% of newly diagnosed DM type1 and 0.5% of
normal subjects.
Insulin autoantibody: detectable in
>90% of type1 DM developing before age 5.
<40% of type1 DM developing after age 12.
0.5 % of normal subjects.
Antibodies to glutamic acid decarboxylase 65KDa isoform:
60% of newly diagnosed type1 DM.
May be used to identify patients with apparent type2 DM who will
subsequently progress to type1.
10. • Insulinoma associated antigen (IA-2A & IA-2βA):
- Directed against tyrosin phosphatases
- Detected in >50% of newly diagnosed type1 DM.
• Zinc transporter (ZnT8):
- It is recently identified major autoantigen in type1 DM
- 60-80% of type1DM, <3% of type2 DM and <2% of controls.
11. Role of antibodies in Mx of Diabetes
Initial fasting hyperglycemia
detected
Presence of multiple
antibodies
85-90% of type1
DM
5-10% of type2
DM
1-2% of healthy subjects
have single autoantibody
Known as latent
autoimmune diabetes of
adulthood (LADA)
No acceptable T/t available to prevent the clinical onset of diabetes
in autoantibody +ve individuals.
Immunosuppresant therapy under development to prevent auotoimmunity
12. Pathogenesis of type2 DM
Genetic
susceptibility
Environmental
factors
Insulin
Resistance
Loss of
β cell function
13. Genetic Susceptibility
• Susceptibility of type2 DM is inherited.
• Mode of inheritance is complex.
• Concordance rate between identical twins
• Multigenic trait.
insulin receptor gene
• Mutation in
GLUT 4 genes
glycogen synthase gene
is ~100%.
14. • Genome
wide association studies – 17 genetic loci for type2
diabetes identified.
• Most of them are related to insulin secretion pathway and not the
insulin resistance.
• Despite the well known fact that type 2 DM has strong genetic
association, only 5% of patients can be pinpointed with a genetic
defect with available information on gene association studies.
• So,
genes causing common forms of type2 DM are still
unknown.
15. Environmental factors
• Diet : high fat diet, excessive intake of free sugars
specially fructose.
• Exercise : Sedentary life style increases the risk of
diabetes.
In a age, gender, BMI and family history matched study it
is observed that for every 500 Kcal increase in energy
expenditure there is 6% decrease in risk of type 2 DM.
• BMI :
BMI
Relative risk of developing
DM type2
30-34.9
20
23>
35≤
38
16. Insulin resistance
•
•
Insulin resistance is decreased biological response to normal
concentration of Insulin.
It is present in type2 DM and virtually all obese individuals.
17.
18. Factors causing insulin resistance
Pre-receptor
Insulin autoantibodies
Primary defect in insulin signaling
Insulin receptor mutations
Leprechaunism (complete)
Ataxia telangectasia syndrome
Secondary to other endocrine disorders
Cushing syndrome
Acromegaly
Pheochromocytoma
Glucagonoma
Hyperthyroidism
Secondary to other disorders
Visceral obesity
Stress (infection, surgery, etc)
Cytogenetic disorders (Down,Turner,
Klinefelter)
Secondary to normal physiologic states
Puberty
Pregnancy
Starvation
Secondary to medications
Glucocorticoids
Thiazide diuretics
Oral contraceptive
Progesterone
blockers
19. • The insulin resistance syndrome (aka Syndrome X or
metabolic syndrome) is a constellation of clinical and lab
findings including hyperinsulinemia, insulin resistance,
dyslipidemia, obesity and hypertension.
• WHO criteria for diagnosis of metabolic syndrome isAny one of the following
Any two of the following
DM
Blood pressure: ≥ 140/90
Impaired fasting glucose
TG >150 and HDL <35 M & < 40F
Impaired glucose tolerance
WHR >0.9 M & >0.85 F or BMI >30
Insulin resistance
urinary albumin excretion ≥ 20 µg/min
or albumin : creatinine ratio ≥ 30 mg/g
20. Type1
Normal or increased
No (if +ve LADA)
Ketoacidosis is common
Hyperosmolar state common
30% concordance in twins
~100%
HLA linked
Not linked
Autoimmunity
Insulin resistance
Severe insulin deficiency
Islet cell histology
Obese mostly
Autoantibodies +ve
pathogenesis
>30 years
↓ blood insulin levels
Genetics
Onset < 20 year
Normal or underweight
Clinical
Type2
Relative insulin deficiency
Insulitis
NO
Marked atrophy and
fibrosis
Focal atrophy with amyloidosis
Severe beta cell depletion
Mild beta cell depletion
Dr. Prabhash
22. Effect of insulin on metabolism
• Carbohydrate metabolism:
- ↑ glucose uptake in muscle and adipose tissues
- In liver : ↑ glycogenesis ↓ glycogenolysis & gluconeogenesis
• Fat metabolism:
- ↓ TG degradation by inhibiting lipoprotein lipase
- ↑ TAG synthesis in adipose tissues.
• Protein metabolism:
- ↑ AA entry into the cells
- ↑ protein synthesis by activating translational factors
23. Meal absorbed
Plasma glucose
Plasma fatty acid
Plasma amino acid
No insulin released
Fat
breakdown
Fat
storage
Plasma
fatty acid
Glucose
uptake
Glucose
utilization
Aminoacid
uptake
Plasma
amino acid
Liver
Ketones glycogenolysis
gluconeogenesis
Tissue
loss
Brain interpret
as starvation
ventilation
Metabolic
acidosis
Protein
breakdown
Tissue
loss
hyperglycemia
polyphagia
Osmotic diuresis
Lactic
acidosis
Anaerobic
metabolism
thirst
Coma
and
death
dehydration
Hypovolemia & Hypotension
Circulatory failure
polydipsia
26. Diagnostic criteria for DM
Any one of the following is diagnostic
A. Glucose
1. Fasting plasma glucose ≥126 mg% or
2. Symptoms of hyperglycemia and
casual plasma glucose ≥200mg%
or
3. During an OGTT 2 hour plasma glucose ≥ 200mg%
B.
HbA1c ≥
6.5 mg%
Point of care assay should not be used for diagnosis.
27. Pre clinical screening of DM
•
Type1 DM:
-
Screening is not recommended other than clinical studies.
-
Islet cell autoantibody detection may be useful in- (1) identifying
LADA (2) to screen non diabetic family member who wish to donate
kidney or part of pancreas fir transplantation (3) screening of women
with GDM to identify those at high risk of progression to type1 DM
(4) distinguishing type1 from type2 in children to institute insulin at
the time of diagnosis.
-
HLA typing is not recommended.
-
Glucose induced insulin secretion test is also not recommended for
routine clinical use.
28. •
Type 2 DM
-
All asymptomatic individuals over 45 years of age
-
Overweight children with any of the two following risk factors- (i)
type2 DM in of 1st or 2nd degree relative (ii) high risk race/ethnic group
(iii) have conditions associated with insulin resistance (iv) maternal
history of GDM……. Testing should be done every 3 years starting at
the age of 10.
-
Screening can be done using fasting glucose, 2 hour OGTT or HbA1c.
29. Monitoring of blood glucose
•
SMBG:
-
With glucometer
-
Indications
(1) patient under intense insulin therapy- 4-5 times a day.
(2) prevention and detection of hypoglycemia, especially in those who are
not able to recognize the early warning signs.
(3) avoidance of severe hyperglycemia especially when having medication
that alter insulin secretion and action
(4) adjusting the dose in response to life style modification, exercise, food
taken etc.
(5) determination of necessity for initiating insulin therapy in GDM
-
Should not be used for diagnosis.
30. Minimally invasive monitoring of blood glucose:
• Implanted sensors:
- CGMS- needle type of sensor, monitors glucose 1 to 5
minute from interstitial tissue fluid.
- Glucoday- microdialysis, every second
• Gluco watch biographer:
- Low level electric current moves glucose across the skin by
electroosmosis where measured by GOD
31. Noninvasive glucose monitoring
• Glucose has specific absorption at 1035nm
- Near infrared spectroscopy
- Raman scattering spectroscopy
- Photoacoustic spectroscopy
• All under active investigation and considerable success
has been achieved but none is FDA approved for clinical
use.
32. Monitoring long term glucose control
•
•
-
Glycated hemoglobin
Gives an idea of glucose control over past 3 months
Goal is to keep it below 7%.
Should be repeated every 6 months in patients meeting the treatment
goal
Estimated average glucose mg% = 28.7*HbA1c – 46.7
Altered life span of RBCs affect the result significantly.
Fructosamine
Proteins (other than Hb) with nonenzymatic attachment of glucose are
known as fructosamine.
Reflect glucose control over past 2-3 weeks.
Should not be done in patients with hypoalbuminemia.