This document summarizes lessons from studies on type 2 diabetes (DM2), including the UK Prospective Diabetes Study (UKPDS). The UKPDS found that intensive glucose control reduced long-term risk of microvascular complications and myocardial infarction compared to conventional treatment. These benefits persisted for over a decade after the trial. The study also found metformin treatment reduced cardiovascular events compared to sulfonylurea/insulin. Overall, the UKPDS provides evidence that earlier and tighter glucose control has long-term benefits in preventing diabetes complications.
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
ADA EASD Management of hyperglycemia in type 2Mgfamiliar Net
Management of Hyperglycemia in Type 2 Diabetes:
A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
Inzucchi SE, Bergenstal RM, Buse JB, et al.
Diabetes Care. 2012 Apr 19.
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
ADA EASD Management of hyperglycemia in type 2Mgfamiliar Net
Management of Hyperglycemia in Type 2 Diabetes:
A Patient-Centered Approach: Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
Inzucchi SE, Bergenstal RM, Buse JB, et al.
Diabetes Care. 2012 Apr 19.
Type 2 diabetes - A 2016 update by Zeena NackerdienZeena Nackerdien
The International Diabetes Federation maintains that one in two adults are undiagnosed for diabetes and that estimates that one in eleven people had diabetes in 2015. If one takes into account that most of the cases involves the preventable condition of Type 2 diabetes, it comes as no surprise that many countries are being hit by staggering socioeconomic costs. Diabetes sites, chat rooms, aps, and ads for ever-evolving and increasingly complex disease management schemes are commonplace on Google. But what does all the information mean? The American Diabetes Association, American Association of Clinical Endocrinologists, The Canadian Diabetes Association, WebMD, and the International Diabetes Federation resources served as the major resources for this accompanying slide deck that tries to unpack some of the major subtopics related to prediabetes and Type 2 diabetes. The slide deck is organized according to disease definition, epidemiology, etiology/pathophysiology, diagnosis, treatment, and prevention. Particular topics such as the early use of insulin could be expanded into several separate slide decks narrating benefits and risks with supporting evidence. However, this deck is meant to provide interested readers with an overview of the Type 2 diabetes literature landscape, with the caveat that specific cases and Type 2 diabetes-related complications should always be discussed with a healthcare provider.
Image credits: slideteam.net; Wikimedia
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.
How to link glucose control to cv outcomesYichi Chen
Outline
1.CV risk of DM patient
2.Glucose to CV outcome - Intensive control vs Conventional control
3.Hypoglycemia
4.Different drugs, different outcomes
5.Expect to Future
Slides to Guide Reducing Cardiovascular Risk in Type 2 Diabetes: What I Do an...hivlifeinfo
Slides to Guide Reducing Cardiovascular Risk in Type 2 Diabetes: What I Do and Why.2018
Zachary T. Bloomgarden, MD, MACE
Program Director
Mikhail N. Kosiborod, MD
Pamela Kushner, MD, FAAFP
Format: Microsoft PowerPoint (.ppt)
File Size: 923 KB
Released: June 29, 2018
Memorias Conferencia Científica Anual sobre Síndrome Metabólico 2017 - Programa Científico
Futuro en el tratamiento de la DM2
Dr. Guillermo E. Umpierrez
Professor of Medicine in the Division of Endocrinology at Emory University School of Medicine, Section Head, Diabetes and Endocrinology. USA. Editor en Jefe del BJM Open Diabetes Research and Care
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
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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.
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
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.
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
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
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.
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
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.
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
2. DM2 … Lessons & Guidance
•The Burden & Barriers
• The lessons : UKPDs Data
• The Guidance : AACE 2016
3.
4. Over time, glycaemic control deteriorates (progression)
*Diet initially then sulphonylureas, insulin and/or metformin if FPG>15 mmol/L
†ADA clinical practice recommendations. UKPDS 34, n=1704
UKPDS 34. Lancet 1998:352:854–65; Kahn et al. (ADOPT). N Engl J Med 2006;355:2427–43
6.2% – upper limit of normal range
Conventional*
Glibenclamide
Metformin
Insulin
UKPDS
MedianHbA1c(%)
6.0
7.0
8.0
9.0
Years from randomisation
2 4 6 8 100
7.5
8.5
6.5
Recommended
treatment
target <7.0%†
ADOPT Glibenclamide
Metformin
Rosiglitazone
8.0
6.0
7.5
7.0
6.5
Time (years)
0 2 3 4 51
5. Beta-cell function progressively declines
Lebovitz. Diabetes Rev 1999;7:139–53 (data are from the UKPDS population: UKPDS 16. Diabetes 1995;44:1249–58); Wright et al. Diabetes Care
2002;25:330–6
FPG, fasting plasma glucose; HOMA, homeostasis model assessment
Beta-cellfunction(%,HOMA)
Extrapolation of
beta-cell function
prior to diagnosis
0
20
40
100
–4 6–10 –8 –6 –2 0 2 4
80
60
–12 8
Diabetes
diagnosis
Time from diagnosis (years)
UKPDS: at 6 years, more than 50% of
patients need insulin to reach target
(FPG ≤108 mg/dL [≤6.0 mmol/L])
6. Type 2 diabetes and the need for insulin
Wright et al. Diabetes Care 2002;25:330–6
20
40
60
0
Patientsrequiringinsulin
(%)
1 2 4 5
Time from randomisation (years)
3 6
UKPDS: at 6 years, more than 50% of
patients need insulin to reach target
(FPG ≤108mg/dL [≤6.0 mmol/L])
8. Too Late
Understanding the pathophysiology
Late in Screening & Dx
Risk Reduction: Far From Ideal
LDL ,BP,HbA1c
Residual Risk…Yes
Room to improve
9. Type 2 Diabetes Prevalence
MI, myocardial infarction.
1. IDF Diabetes Atlas 6th Edition 2014 http://www.idf.org/diabetesatlas; 2. The Emerging Risk Factors Collaboration.
JAMA. 2015;314(1):52-60.
9
This will rise to
592 million by 20351
Disease status
at baseline
Hazard ratio
(95% Cl)a
Diabetes, stroke, and
MI
6.9 (5.7, 8.3)
Stroke and MI 3.5 (3.1, 4.0)
Diabetes and stroke 3.8 (3.5, 4.2)
Diabetes and MI 3.7 (3.3, 4.1)
MI 2.0 (1.9, 2.2)
Stroke 2.1 (2.0, 2.2)
Diabetes 1.9 (1.8, 2.0)
None 1.0 (Ref)
Globally, 387 million people are
living with diabetes1
All-cause mortality by disease status of
participants at baseline2
Hazard ratio
(95% CI)
1.0 2.0 4.0 8.0 16.0
Type 2 Diabetes is a CVD
10. DM is Not a Number
DM= A Cardiovascular Disease
Complications : Micro / Macro
Hidden faces of :
Organic : Sexual dysfunction
Diabetic foot
Psychiatric ; Depression
11. DM is Not a Number
Economic Burden
-Complications management : CVD , CKD …
-Admissions for metabolic derangement
(Hypo /Hyper )
-Cost of Rx
16. A retrospective cohort study –UK Clinical Practice Research Data link
81, 573 T2D patients; (2004-2011)
Time to intensify Rx;Years
Groups One OAD Two OAD Three OAD
HbA1c ≥ 7.0%, 2.9 1.9 1.6
HbA1c ≥ 7.5 %, 7.2 7.2 6.9
HbA1c ≥ 8 .0%, 7.2 7.2 7.1
Mean HbA1c
@ Rx Intensification
8.7% 9.1% 9.7%
Khunti K, Wolden ML,Thorsted BL, et al. Diabetes Care. 2013 : 36:3411-3417
17. DM2 … Lessons & Guidance
• The Burden & Barriers
•The lessons : UKPDs Data
• The Guidance : AACE 2016
18. UKPDS 80. N Eng J Med 2008; 359:
UK Prospective Diabetes Study
20-year Interventional Trial from 1977 to 1997
5,102 patients with newly-diagnosed type 2 diabetes recruited
between 1977 and 1991
Median follow-up 10.0 years, range 6 to 20 years
Results presented at the 1998 EASD Barcelona meeting
10-year Post-Trial Monitoring from 1997 to 2007
Annual follow-up of the survivor cohort
Clinic-based for first five years
Questionnaire-based for last five years
Median overall follow-up 17.0 years, range 16 to 30 years
19. UKPDS 80. N Eng J Med 2008; 359:
Glucose Interventional Trial
Intensive
Conventional
Intensive
2,729
Intensive
with sulfonylurea/insulin
1,138 (411 overweight)
Conventional
with diet
342 (all overweight)
Intensive
with metformin
P
Trial end
1997
P
5,102
Newly-diagnosed
type 2 diabetes
744
Diet failure
FPG >15 mmol/l
149
Diet satisfactory
FPG <6 mmol/l
Dietary
Run-in
4209
Randomisation
1977-1991
Mean age 54 years
(IQR 48–60)
20. UKPDS 80. N Eng J Med 2008; 359:
Post-Trial Monitoring: Aims
To observe HbA1c levels after cessation of the
intervention trial
To observe glucose therapy regimens after
cessation of the intervention trial
To determine the longer-term impact of earlier
improved glucose control on microvascular
and on macrovascular outcomes
To evaluate the health economic implications with a
projected 50% mortality at ten years post trial
21. UKPDS 80. N Eng J Med 2008; 359:
Post-Trial Monitoring: Protocol
At trial end, patients were returned to usual physician care
for their diabetes management
No attempt was made to maintain them in randomised
groups, or to influence their therapy
All endpoints were adjudicated in an identical manner
by the same Adjudication Committee as during the trial
From 1997 to 2002:
Patients were seen annually in UKPDS clinics for
standardised collection of clinical and biochemical data
From 2002 to 2007:
Clinical outcomes were ascertained remotely by
questionnaires sent to patients and GPs
22. UKPDS 80. N Eng J Med 2008; 359:
Post-Trial Monitoring: Patients
880
Conventional
2,118
Sulfonylurea/Insulin
279
Metformin
1997
# in survivor cohort
2002
Clinic
Clinic
Clinic
Questionnaire
Questionnaire
Questionnaire
2007
# with final year data
379
Conventional
1,010
Sulfonylurea/Insulin
136
Metformin
P
P
Mortality 44% (1,852)
Lost-to-follow-up 3.5% (146)
Mean age
62±8 years
23. UKPDS 80. N Eng J Med 2008; 359:
Post-Trial Changes in HbA1c
UKPDS results
presented
Mean (95%CI)
24. UKPDS 80. N Eng J Med 2008; 359:
Post-Trial Changes in HbA1c
UKPDS results
presented Mean (95%CI)
25. UKPDS 80. N Eng J Med 2008; 359:
Any Diabetes Related Endpoint Hazard Ratio
Intensive (SU/Ins) vs. Conventional glucose control
HR (95%CI)
26. UKPDS 80. N Eng J Med 2008; 359:
Microvascular Disease Hazard Ratio
Intensive (SU/Ins) vs. Conventional glucose control
(photocoagulation, vitreous haemorrhage, renal failure)
HR (95%CI)
27. UKPDS 80. N Eng J Med 2008; 359:
Myocardial Infarction Hazard Ratio
(fatal or non-fatal myocardial infarction or sudden death)
Intensive (SU/Ins) vs. Conventional glucose control
HR (95%CI)
28. UKPDS 80. N Eng J Med 2008; 359:
All-cause Mortality Hazard Ratio
Intensive (SU/Ins) vs. Conventional glucose control
HR (95%CI)
29. UKPDS 80. N Eng J Med 2008; 359:
Any Diabetes Related Endpoint Hazard Ratio
Intensive (Metformin) vs. Conventional glucose control
HR (95%CI)
30. UKPDS 80. N Eng J Med 2008; 359:
Microvascular Disease Hazard Ratio
(photocoagulation, vitreous haemorrhage, renal failure)
Intensive (Metformin) vs. Conventional glucose control
HR (95%CI)
31. UKPDS 80. N Eng J Med 2008; 359:
Myocardial Infarction Hazard Ratio
(fatal or non-fatal myocardial infarction or sudden death)
Intensive (Metformin) vs. Conventional glucose control
HR (95%CI)
32. UKPDS 80. N Eng J Med 2008; 359:
All-cause Mortality Hazard Ratio
Intensive (Metformin) vs. Conventional glucose control
HR (95%CI)
33.
34.
35. Reductions in MI (15% Su/ InsulinVs 33% MFN)
All-cause mortality (13% and 27%, respectively)
N Engl J Med 2008;359:1577–1589
36. UKPDS 80. N Eng J Med 2008; 359:
After median 8.5 years post-trial follow-up
Aggregate Endpoint 1997 2007
Any diabetes related endpoint RRR: 12% 9%
P: 0.029 0.040
Microvascular disease RRR: 25% 24%
P: 0.0099 0.001
Myocardial infarction RRR: 16% 15%
P: 0.052 0.014
All-cause mortality RRR: 6% 13%
P: 0.44 0.007
RRR = Relative Risk Reduction, P = Log Rank
Legacy Effect of Earlier Glucose Control
37. UKPDS 80. N Eng J Med 2008; 359:
After median 8.8 years post-trial follow-up
Aggregate Endpoint 1997 2007
Any diabetes related endpoint RRR: 32% 21%
P: 0.0023 0.013
Microvascular disease RRR: 29% 16%
P: 0.19 0.31
Myocardial infarction RRR: 39% 33%
P: 0.010 0.005
All-cause mortality RRR: 36% 27%
P: 0.011 0.002
RRR = Relative Risk Reduction, P = Log Rank
Legacy Effect of Earlier Metformin Therapy
38. Does a intensive therapy targeting HbA1c
< 6.0% versus 7.0–7.9% reduce CVD risk in
middle-aged/older patients with high CV risk?
Complex relationship between hyperglycaemia and CV risk
Current evidence does not support intensive glycaemic control for reducing CV risk
YES – early intensive glycaemic control in newly
diagnosed patients reduces long-term CV risk
(myocardial infarction, RR = 0.85, p = 0.014)
NO – intensive glycaemic control had non-
significant reduction in CV events (HR = 0.9,
p = 0.16); may increase mortality (HR = 1.22,
p = 0.04); increased risk of hypoglycaemia
NO – intensive control has no impact on CV
events (HR = 0.88, p = 0.14). Increased risk
of hypoglycaemia
Study Conclusion
UKPDS
ACCORD
ADVANCE
VADT
NO – intensive glycaemic control had no effect
on CV events (HR = 0.94, p = 0.32), but did
reduce microvascular events (HR = 0.86,
p < 0.01); increased risk of hypoglycaemia
Question
Does intensive glucose control with SU
or insulin in newly diagnosed patients with
T2D provide any benefit?
Are micro- and macrovascular events
reduced by intensive glucose control (HbA1c
6.5%) compared with standard therapy?
Does intensive glycaemic control affect CVD
risk compared with standard therapy in older
male patients with T2D?
ACCORD Study Group. N Engl J Med. 2008;358:2545–2559; ADVANCE Collaborative Group.
N Engl J Med. 2008;358:2560–2572; Duckworth W, et al. N Engl J Med. 2009;360:129–139;
Holman RR, et al. N Engl J Med. 2008;359:1577–1589.
39. UKPDS 80. N Eng J Med 2008; 359:
• Despite an early loss of glycemic differences, a continued reduction in
microvascular risk and emergent risk reductions for MI and death from
any cause were observed during 10 years of post-trial follow-up
• A continued benefit after metformin therapy was evident among
overweight patients.
UKPDs … Conclusions
40. DM2 … Lessons & Guidance
• The Burden & Barriers
• The lessons : UKPDs Data
•The Guidance : AACE 2016
41.
42.
43.
44.
45. 17%
In the 6-year Da Qing study, intervention led to
lower incidence of type 2 DM
0
20
40
60
80
100
2 4 6 8 10 12 14 16 18 20
Follow-up (years)
6-year intervention hazard ratio: 0.49 (95% CI: 0.33;0.73)
20-year follow-up hazard ratio: 0.57 (95% CI: 0.41;0.81)
Cumulativeincidenceof
type2diabetes(%)
0
Lifestyle intervention (diet + exercise)Control
Intervention Follow-up
n=530 overweight Chinese men and women with IGT;
mean BMI=26
Li et al. Lancet 2008;371:1783–9
BMI, body mass index; CI, confidence interval
46. Reduction in the incidence of type 2 DM
with lifestyle intervention or metformin
20
25
30
35
15
10
5
1 42 3
Time (years)
Placebo
Lifestyle intervention
Metformin
0
Cumulativeincidenceof
type2diabetes(%)
3234 participants
2.8 years’ duration
Risk reduction:
58% lifestyle intervention
31% metformin
Knowler et al. N Engl J Med 2002;346:393–403
48. SU TZD DPP-4i GLP-1RA
Insulin
(Basal)
Physiological
action(s)
↑ Insulin
secretion
↑ Insulin
sensitivity
↑ Insulin
secretion†
↓ Glucagon
secretion†
↑ Insulin
secretion†
↓ Glucagon
secretion†
Slows gastric
emptying
↑ satiety
↑ Glucose
disposal
↓ Hepatic
glucose
production
Efficacy
(↓HbA1c) High High Intermediate High Highest
Hypoglycaemia
risk
Moderate Low Low Low High
Weight effect ↑ ↑ ↔ ↓ ↑
Major side
effects
Hypoglycaemia
Oedema
Heart failure
Bone fractures
Rare GI Hypoglycaemia
Beyond Metformin: Pros/Cons
*Limited comparative data are available; †Glucose dependent.
DPP-4i, dipeptidyl peptidase-4 inhibitor; GI, gastrointestinal; GLP-1RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycosylated haemoglobin; SU, sulphonylurea; TZD, thiazolidinedione; ↑,
increase; ↓, decrease; ↔, neutral.
Adapted from Inzucchi SE et al. Diabetologia 2012;55:1577–1596.
49.
50. Healthy eating, weight control, increased physical activity & diabetes education
Metformin
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
high
low risk
gain
edema, HF, fxs
low
Thiazolidine-
dione
intermediate
low risk
neutral
rare
high
DPP-4
inhibitor
highest
high risk
gain
hypoglycemia
variable
Insulin (basal)
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Metformin
+
Basal Insulin +
Sulfonylurea
+
TZD
DPP-4-i
GLP-1-RA
Insulin§
or
or
or
or
Thiazolidine-
dione
+
SU
DPP-4-i
GLP-1-RA
Insulin§
TZD
DPP-4-ior
or
or GLP-1-RA
high
low risk
loss
GI
high
GLP-1 receptor
agonist
Sulfonylurea
high
moderate risk
gain
hypoglycemia
low
SGLT2
inhibitor
intermediate
low risk
loss
GU, dehydration
high
SU
TZD
Insulin§
GLP-1 receptor
agonist
+
SGLT-2
Inhibitor
+
SU
TZD
Insulin§
Metformin
+
Metformin
+
or
or
or
or
SGLT2-i
or
or
or
SGLT2-i
Mono-
therapy
Efficacy*
Hypo risk
Weight
Side effects
Costs
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
Triple
therapy
or
or
DPP-4
Inhibitor
+
SU
TZD
Insulin§
SGLT2-i
or
or
or
SGLT2-i
or
DPP-4-i
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
+
Combination
injectable
therapy‡
GLP-1-RAMealtime Insulin
Insulin (basal)
+
Diabetes Care 2015;38:140-149; Diabetologia 2015;58:429-
ADA 2015
51.
52.
53.
54.
55.
56. Lixi- Lan :
1 mcg Lixi /
2 or 4 u Glargine
Lira- Deg
3.6 mg Lira /
100 u Degludec
59. Conclusions
HbA1c doesn’t tell the whole story
Rx other CVD risk factors simultaneously
We are too late on many fronts of management
Barriers : Therapeutics (ex: adverse reactions)
Physicians (Inertia) and
Patients (ex: Adherence /Compliance)
60. Conclusions
• TLC modifications and DM Rx can delay DM-2
• Individualize … Individualize
• Achieve Targets ; Safely
As early as possible ;Legacy effect
• Insulin is inevitable for many DM patients