SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
SGLT2I The paradigm change in diabetes managementPraveen Nagula
Just like ARNI, SGLT2I have changed the face of diabetes management and they have a good profile in multimodality management because of pleiotropic effects
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
Targeting lipids: a primary and secondary care perspectiveInnovation Agency
Presentations by Dr Sue Kemsley and Dr Gavin Galasko from the first webinar of the Mastering Cholesterol webinar series on Thursday 26 January 2023, focusing on lipid management from a primary and secondary care perspective.
Strict Glycemic Control in Critically ill patients: The Demise of another ver...Prof. Mridul Panditrao
Prof. Mridul M. Panditrao tries to explain the pros and cons about the good strategy, whcih became controversial and almost obsolete. He also tries to tract the whole aspect of the phenomenon and reviews/ RCTs/
Strict (Tight) Glycemic control (SGC/TGC), as it is called, was and still is a good strategy. It can be defined as maintenance of the blood glucose level in the range of 80-110 mg /dl. with help of dose variable and intensive insulin therapy (IIT). Since its introduction, there have been conflicting reports of its efficacy and complications. This resulted in slow but steady neglect of this very good idea leading to its almost complete demise.
An effort has been made in this review, to impartially analyze all the available evidence and try to find the reasons for the negative publicity which led to the neglect or worse still, the wrong use of this protocol. Some suggestions for fair and proper implementation of the strategy are put forward.
etc/
Diabetes and heart two sides of the same coinSunil Wadhwa
This ppt presented in a CME of doctors in March 2017 discusses-if all Diabetics should be treated aggressively for prevention of coronary artery disease & SHOULD IT BE PRESUMED AS IF THEY ARE ALREADY PATIENTS OF CAD?
This presentation is updated till March 2017
This Presentation Give You A brief Information About DPP4 And New Recommendations .This Presentation Guide You How To Treat Patients With Safety.
For Further Contact:03354999496
Slide Presentation
Diabetes Melliuts Type 2 management basics are life style modifications followed by use of Metformin
What is the best and safest next pharmacologic choice
Targeting lipids: a primary and secondary care perspectiveInnovation Agency
Presentations by Dr Sue Kemsley and Dr Gavin Galasko from the first webinar of the Mastering Cholesterol webinar series on Thursday 26 January 2023, focusing on lipid management from a primary and secondary care perspective.
Strict Glycemic Control in Critically ill patients: The Demise of another ver...Prof. Mridul Panditrao
Prof. Mridul M. Panditrao tries to explain the pros and cons about the good strategy, whcih became controversial and almost obsolete. He also tries to tract the whole aspect of the phenomenon and reviews/ RCTs/
Strict (Tight) Glycemic control (SGC/TGC), as it is called, was and still is a good strategy. It can be defined as maintenance of the blood glucose level in the range of 80-110 mg /dl. with help of dose variable and intensive insulin therapy (IIT). Since its introduction, there have been conflicting reports of its efficacy and complications. This resulted in slow but steady neglect of this very good idea leading to its almost complete demise.
An effort has been made in this review, to impartially analyze all the available evidence and try to find the reasons for the negative publicity which led to the neglect or worse still, the wrong use of this protocol. Some suggestions for fair and proper implementation of the strategy are put forward.
etc/
Diabetes and heart two sides of the same coinSunil Wadhwa
This ppt presented in a CME of doctors in March 2017 discusses-if all Diabetics should be treated aggressively for prevention of coronary artery disease & SHOULD IT BE PRESUMED AS IF THEY ARE ALREADY PATIENTS OF CAD?
This presentation is updated till March 2017
Achieving Hba1c targets: Strategies For Initiating and Intensifying Diabetes ...Nemencio Jr
This module highlights the appropriate HbA1c targets that reduce microvascular and macrovascular complications in appropriate populations and how to safely achieve them with current anti-hyperglycemic agents
Diabetes Mellitus - An Integrated Approachpgahalya
This Slide contains information about Cause, Symptoms, Prevalence, Pathophysiology, Diagnosis, Complications and Management of Diabetes mellitus. It includes both Conventional and Naturopathic management.
Osteoporosis is a poorly recognized entity in India, especially among the non-endocrine physicians. Talk given to chest physicians focusing on glucocorticoid induced osteoporosis
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.
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.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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.
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
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
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
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.
1. Insulin should be the
first drug in type 2
diabetes
Against the motion …..
Dr Mathew John, MD, DM, DNB
Consultant Endocrinologist
Providence Endocrine & Diabetes Specialty Centre
Trivandrum
www.providence.co.in
2. How will you treat your newly diagnosed
patient with type 2 diabetes ?
A. Insulin
B. Oral hypoglycemic agents
4. Why insulin is not the choice ?
From a pathophysiological perspective ?
From an evidence perspective ?
From an outcome
From the adverse event ?
From a guideline perspective ?
5. Ominous Octet
The pathophysiology of type 2 diabetes
Ralph A. DeFronzo From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment
of Type 2 Diabetes Mellitus DIABETES, VOL. 58, APRIL 2009
SGLT 2
blockers
TZD
Insulin
SU
GLP-1 GLP-1
GLP-1
GRA
GLP-1
Metformin
Cabergoline
TZD
7. 0%
20%
40%
60%
0 3 6 9 12 15
Proportionofpatientswithevent
Years from randomization
Conventional (n=411)
Intensive (n=951)
Metformin (n=342)
UKPDS: Any Diabetes-Related
Endpoint in Metformin Study
M vs I
P=0.0034
M vs C
P=0.0023
UKPDS Group. Lancet. 1998;352:854-865.
8. 0%
10%
20%
30%
35%
0 3 6 9 12 15
Proportionofpatientswithevents
Years from randomization
Conventional (n=411)
Intensive (n=951)
Metformin (n=342)
UKPDS: Diabetes-Related Deaths
in Metformin Study
M vs I
P=0.11
M vs C
P=0.017
UKPDS Group. Lancet. 1998;352:854-865.
9. 0%
10%
20%
25%
0 3 6 9 12 15
Proportionofpatientswithevents
Years from randomization
Conventional (n=411)
Intensive (n=951)
Metformin (n=342)
UKPDS: Microvascular Endpoints
in Metformin Study
M vs I
P=0.39
M vs C
P=0.19
UKPDS Group. Lancet. 1998;352:854-865.
10. M vs. I
P=0.12
0%
10%
20%
30%
35%
0 3 6 9 12 15
Proportionofpatientswithevents
Years from randomization
Conventional (n=411)
Intensive (n=951)
Metformin (n=342)
M vs. C
P=0.01
UKPDS: Myocardial Infarction
in Metformin Study
UKPDS Group. Lancet. 1998;352:854-865.
11. UKPDS: Comparison of Metformin
vs. Intensive Therapy Results
Favors
conventional
0.2 1 5
Reduced
risk
Increased
risk
M vs Int RR P value*
Any diabetes-related endpoint
Metformin
Intensive
P =0.0034
0.68
0.93
0.0023
0.46
Diabetes-related deaths
Metformin
Intensive
P =0.11
0.58
0.80
0.017
0.19
All-cause mortality
Metformin
Intensive
P =0.021
0.64
0.92
0.011
0.49
Myocardial infarction
Metformin
Intensive
P =0.12
0.61
0.79
0.01
0.11
Relative risk* (95% CI)
Favors
metformin
*Vs conventional policy.
UKPDS Group. Lancet. 1998;352:854-865.
13. Any episode
Major episodes
UKPDS: Hypoglycemic Episodes
in Metformin Study
Actual Therapy Analysis
0
10
20
30
40
50
0 2 4 6 8 10
Proportionofpatients(%)
Years from randomization
0
2
4
6
8
0 2 4 6 8 10
UKPDS Group. Lancet. 1998;352:854-865.
Conventional InsulinChlorpropamide Glibenclamide Metformin
14. Insulin and hypoglycemia
Wrighta AD. Hypoglycemia in Type 2 diabetic patients randomized to and maintained on monotherapy with diet,
sulfonylurea, Metformin, or insulin for 6 years from diagnosis: UKPDS73 Journal of Diabetes and Its Complications 20
(2006) 395– 401
Grade 1-4 hypoglycemia Grade 2-4 hypoglycemia
15. Years from randomization
UKPDS: Change in Weight
With Sulfonylureas vs. Insulin
Cohort, Mean Data
0.0
2.5
5.0
7.5
10.0
0 2 4 6 8 10
Meanchangeinweight(kg)
Conventional Insulin Chlorpropamide
Glibenclamide
UKPDS Group. Lancet. 1998;352:837-853.
16. The graph illustrates that the QALY decrement associated with an increase in weight and hypoglycaemia by
approximately 3 kg and 30%, respectively, will offset the QALY gain associated with a 1% reduction in HbA1c
(McEwan, Evans. Diab, Obesity and Metab; In Press)
Relationship between weight gain,
hypoglycaemia and quality of life
QALY gain associated with 1 % improvement
in HbA1c is offset by a 3 kg increase in weight
17. Diabetes therapies and cancer
Kaplan–Meier curves adjusted for confounding factors (age, sex, smoking
status and prior cancer) using a Cox proportional hazards model
Currie CJ, Poole CD, Gale EAM The influence of glucose-lowering therapies on cancer risk in type 2 diabetes
Diabetologia (2009) 52:1766–1777
Metformin
No treatment
Sulphonylurea
Insulin
18. Risk of cancer and duration of
insulin
0
1
2
3
4
5
<3 yrs 3-5 yrs > 5 yrs
The risk of CRC was found to increase with duration of exposure to
insulin use, the odds ratio increasing by 1.21 for each additional
year of insulin use (95% CI, 1.03 - 1.42; P = .02).
Gastroenterology 2004;127:1044-1050
22. The argument always is
Newer insulin analogs reduce risk of
hypoglycemia……….
• Evidence : “ Benefits in terms of reduced
hypoglycaemia were inconsistent”
Newer methods of insulin delivery reduce
further risk
“ I am waiting for close loop CSII”
Singh SR . Efficacy and safety of insulin analogues for the management of diabetes
mellitus: a meta-analysis CMAJ 2009;180(4):385-97
23. Trials looking at “ Insulin as first
drug in type 2 diabetes”
• Weng J, Li Y et al. Effect of intensive insulin therapy on beta-
cell function and glycaemic control in patients with newly
diagnosed type 2 diabetes: a multicentre randomized parallel-
group trial. Lancet. 2008 May 24;371(9626):1753-60.
• Li Y, Xu W et al. Induction of long-term glycemic control in
newly diagnosed type 2 diabetic patients is associated with
improvement of beta-cell function. Diabetes Care. 2004
Nov;27(11):2597-602.
• Park S, Choi SB. Induction of long-term normoglycemia
without medication in Korean type 2 diabetes patients after
continuous subcutaneous insulin infusion therapy. Diabetes
Metab Res Rev. 2003 Mar-Apr;19(2):124-30
24. Summary of trials
• Short duration of intervention ( normoglycemia
for 2 weeks)
• Follow up period : 1 year
• Not blinded
• Used CSII in significant number of patients
25. Why insulin is not the first drug in
type 2 diabetes ?
• Pathophysiology
• Evidence from trials
• Adverse events
• Guidelines
• Why “ insulin first“ trials are not that great
27. Effect of intensive insulin therapy on beta-cell function
and glycaemic control in patients with newly diagnosed
type 2 diabetes
• More patients achieved target control in insulin group
( 97.1% , 95.2 % , 83.5 % CSII, MDI, OHA)
• The control was achieved in less time ( 4 days, 5.6 days, 9.3 days )
• Remission rates were significantly higher in the insulin group
(51.1 % in CSII, 44.9 % in MDI, 26.7 % in OHA p: 0.0012)
• Beta cell function as represented by HOMA B and acute insulin
response improved after intensive interventions
• Acute insulin response was sustained in the insulin group but
reduced in the OHA group at 1 year.
Weng J, Li Y et al Lancet. 2008 May 24;371(9626):1753-60
28. Other studies supporting use of insulin as
initial therapy in type 2 diabetes
• 138 treatment naïve patients with type 2 diabetes
• FPG > 200 mg/dl
• CSII for 2 weeks
• 126 achieved normoglycemia ( FPG < 110 mg/dl, PPG < 144 mg/dl)
within 6.3 days
• % of patients maintaining euglycemia at 3, 6, 12 and 24 months
were 72.6 % , 67 % , 47.1% and 42.3 %
• Patients who maintained normoglycemia > 12 months showed
significant improvement in beta cell function especially FPIR
Li Y, Xu W Diabetes Care. 2004 Nov;27(11):2597-602
29. How does this work ?
• Beta cell rest
• Reversing glucotoxicity
• Reversing lipotoxicity
• Ant apoptotic effect /anti inflammatory effect
• Improved GLP –1 effect
Vinik A: benefits of early initiation of insulin , Insulin 2006;1: 2-12
Weng J, Li Y et al Lancet. 2008 May 24;371(9626):1753-60
30. Intensive blood-glucose control with sulphonylureas or insulin
compared with conventional treatment and risk of complications in
patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes
Study (UKPDS) Group.
• 3867 newly diagnosed patients with type 2 diabetes, median age 54
years (IQR 48-60 years),
• Randomised to SU vs. Insulin vs. diet
• Target FPG < 6 mmol/L
• There was no difference in HbA1c among agents in the intensive
group.
• Was no difference for any of the three aggregate endpoints
between the three intensive agents ( any diabetes related end
point, diabetes related death, all cause mortality )
• Weight gain was more with insulin
Lancet. 1998 Sep 12;352(9131):837-53.
31. Ominous Octet
The pathophysiology of type 2 diabetes
Ralph A. DeFronzo From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment
of Type 2 Diabetes Mellitus DIABETES, VOL. 58, APRIL 2009
SGLT 2
blockers
TZD
Insulin
SU
GLP-1
GLP-1
GLP-1
GRA
GLP-1
Metformin
Cabergoline
TZD
32. Disclaimer
The material for these slides were derived from various sources
including pictures and cartoons from the world wide web. I have
tried my best to acknowledge all possible sources and references.
However, if I have overlooked any particular reference, it is not done
intentionally. Anyone reproducing materials from this presentations
should acknowledge the author of the original work.
Cartoons are made to simplify certain concepts. The presenter
should attach explanations to all cartoons or else it will appear quite
amateurish.
Editor's Notes
This Kaplan-Meier plot shows the proportion of diabetes-related endpoints in patients assigned to conventional, intensive (a sulfonylurea or insulin), or metformin treatment. These diabetes-related endpoints include microvascular and macrovascular complications.2
Patients assigned to intensive blood glucose control with metformin had a significant 32% lower risk of developing any diabetes-related endpoint than patients assigned to conventional treatment (P=0.0023). The metformin group also had significantly greater risk reduction than the group assigned to intensive therapy with a sulfonylurea or insulin (P=0.0034).2
This Kaplan-Meier plot shows that patients treated with metformin had a 42% lower risk of diabetes-related death (P=0.017) than patients assigned to conventional treatment. There were no significant differences in the risk of diabetes-related deaths between those assigned to intensive therapy with metformin and those given sulfonylureas or insulin.2
Metformin-treated patients also had a 36% lower risk of all-cause mortality compared with patients assigned to conventional treatment (P=0.011). This risk reduction with metformin treatment was also greater than in patients treated with a sulfonylurea or insulin (P=0.021).2
This Kaplan-Meier plot shows microvascular endpoints in patients assigned to conventional treatment, intensive treatment with a sulfonylurea or insulin, or intensive treatment with metformin. Microvascular endpoints included retinopathy events and renal failure.2
Microvascular endpoints decreased 29% in overweight patients assigned to metformin therapy (P=0.19). Overweight patients treated with sulfonylureas and insulin exhibited a 16% decrease in microvascular complications (P=0.38).2
Patients assigned metformin treatment had a lower rate of progression to retinopathy at 9 years (P=0.44) than patients assigned conventional treatment. This result was similar to that in the sulfonylurea/insulin intensive therapy group. The proportion of patients with urinary albumin >50 mg/L did not differ among the intensive, metformin, or conventional-treatment groups.2
This Kaplan-Meier plot shows the proportion of patients experiencing myocardial infarction. Cardiovascular disease accounted for 62% of the mortality in overweight patients assigned to conventional treatment.
Patients assigned to the metformin group had a significant 39% lower risk of myocardial infarction than patients assigned to conventional treatment (P=0.01), but this risk reduction was not significantly different from that of the intensive-treatment group.2
For all macrovascular diseases together (myocardial infarction, sudden death, angina, stroke, peripheral vascular disease), metformin-treated patients had a 30% lower risk (P=0.020) than the conventional-treatment group.2
Assigning treatment with metformin to overweight patients significantly reduced the risk of developing any diabetes-related endpoint, experiencing a myocardial infarction, diabetes-related death, and death from any cause. When compared with intensive treatment (sulfonylurea or insulin), metformin significantly reduced the risk of developing any diabetes-related endpoint and all-cause mortality.2
Overweight patients allocated to metformin had a risk reduction in any diabetes-related endpoint of 32% compared with a 7% reduction for patients assigned to intensive therapy with sulfonylureas or insulin (P=0.0034). Patients treated with metformin had a 42% lower risk of diabetes-related death. There were no significant differences in diabetes-related death between those assigned to intensive therapy with metformin and those assigned to other intensive therapy (P=0.11).2
The reduction in risk for all-cause mortality was significant between groups (P=0.021), with a risk reduction vs conventional therapy of 36% for the metformin group and 8% for the intensive-therapy group (P=0.021). The risk of myocardial infarction was reduced by 39% in the group assigned to metformin therapy and by 21% in the group assigned to other intensive therapies (P=0.12).2
This slide shows the proportion of patients experiencing one or more major hypoglycemic episodes (ie, requiring third-party assistance or medical intervention) and those with any hypoglycemic episode, as based on actual therapy analysis rather than intention-to-treat analysis. All hypoglycemic episodes were most common in patients on insulin therapy; during the first few years of therapy, hypoglycemic episodes were also frequent in patients on chlorpropamide or glibenclamide but the number of episodes fell as FPG increased. The proportion of patients experiencing episodes of hypoglycemia was generally similar in patients on metformin and conventional treatments. There were fewer episodes of hypoglycemia with metformin than with any other intensive therapy.2
Over 10 years of follow-up, the proportions of patients per year taking the allocated treatment who had at least one major hypoglycemic episode were 0.7%, 0.6%, 2.5%, 0.3%, and 0% for patients on conventional, chlorpropamide, glibenclamide, insulin, and metformin therapy, respectively. The corresponding proportions for any hypoglycemic episode were 0.9%, 12.1%, 17.5%, 34.0%, and 4.2%, respectively.2
Patients on intensive therapy gained more weight than those on conventional therapy (white), with insulin therapy resulting in the greatest weight gain. Significantly, at 11 years, those on chlorpropamide gained about 2.6 kg (5.7 lb), those on glibenclamide gained about 1.7 kg (3.8 lb), and those on insulin gained about 4.0 kg (8.8 lb) more than those patients on conventional therapy.1
Rate of progression of solid tumour cancers in people with diabetes receiving alternative glucose-lowering therapies (metformin monotherapy, black lines; sulfonylurea monotherapy, green lines; sulfonylurea plus metformin, blue lines; insulin-based therapy, red lines) and a group with no diabetes treatment exposure (grey lines). a
Unadjusted (Kaplan–Meier curve). b Adjusted for confounding factors (age, sex, smoking status and prior cancer) using a Cox proportional hazards model
The risk of CRC was found to increase with duration of exposure to insulin use, the odds ratio increasing by 1.21 for each additional year of insulin use (95% CI, 1.03 - 1.42; P = .02). Those with fewer than three years of insulin therapy had an adjusted OR for CRC of 1.4 (95% CI, 0.6 - 2.9; P = 0.5), while those with three to five years of insulin exposure were at significantly higher risk (OR, 2.9; 95% CI, 1.1 - 7.7; P = .03). Those with more than five years of insulin use were at the greatest risk of developing CRC (OR, 4.7; 95% CI, 1.3 - 16.7; P = .02).
