diagnosing diabetes in adults– type 1, lada, or type 2? stanley schwartz md, face, facp affiliate...
TRANSCRIPT
Diagnosing Diabetes In Adultsndash
Type 1 LADA or Type 2
Stanley Schwartz MD FACE FACPStanley Schwartz MD FACE FACPAffiliate Main Line Health
Emeritus Clinical Assoc Prof of MedicinePerlman School of Medicine University of Pennsylvania
Part 4 of 4
Struan FA Grant PhDStruan FA Grant PhD Vanessa GuyVanessa Guy Childrenrsquos Hospital of Philadelphia Childrenrsquos Hospital of Philadelphia Associate Professor University of Pennsylvania Senior Clinical Research Coordinator
Co-Investigators NIH RO-1 Genes in LADA
β-Cell (Islet Cell) Classification Model-Implications for Therapy
(Not Core Defects)-Targets for Therapies
Direct Effect on β-Cells On 1-4 of lsquoEgregious Elevenrsquo
1 β-CELL Incretin Ranolazine
2 α-Cell Glucagon Incretin Pramlintide
3 darrINCRETIN EFFECT Incretin
4 Inflammation Incretin Anti-inflammatory
Egregious Eleven Defect Intervention Therapy
Hierarchy of Medication Choice (a la AACE Guideline)(this and next slide) not just reduction in HgA1c but
1Efficacy2Number of Targets of Therapy each drug addresses3Weight loss4Proven Reduction in CV outcomes
β-Cell (Islet Cell) Classification Model-Implications for Therapy
(Not Core Defects)-Targets for Therapies
In-Direct Effect on β-Cells On 5-11 of lsquoEgregious Elevenrsquo
567 Liver Muscle Fat Insulin Resistance MET TZD Bromocriptine-QR (wt reduction agentsndash GLP-1 RA SGLT-2 Inhibitors)
8 Kidney Renal Threshold for Glucosuria SGLT-2 Inhibitors
9 Brain Appetite IncretinCentrally Controlled Peripheral IR Bromocriptine-QR Sympathetic Tone Bromocriptine-QR
10 StomachIntestine Rate of Appearance of Glucose in the bloodAGI GLP-1 RA Pramlintide
11 ColonBiome Gut Biome Probiotic (may improve IR β-cell function inflam)
Egregious Eleven Target Intervention Therapy
5-11 ALL Decrease Glucose Lipotoxicity
Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1
eg Metformin Colesevalam (TGR-5)] Type 1- minimize brittle dawn unpredictable variability CV benefits Treat those lsquoType 2rsquo Genesrsquo ANTI-INFLAMMATORY LADA = SPIDDM Autoimmune T2DM
Same- Slow stabilize disease process ANTI-INFLAMMATORY Type 2- treats 7 MOArsquos of DeFronzorsquos Octet or 911 EE
Decreases oxidative stress β-cell inflam decreases lipo- and gluco-toxicity preserve mass decreases appetite treats IR via
wt loss MODY 3- recent report
FOR ALL DM ndash potential CV benefit (ANTI-INFLAMMATORY)
Reference list for last slide LADAbull Zhao Yet al Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults one year prospective studyJ Clin Endocrinol Metab 2014 Jan 16jc20133633
TYPE 1Ellis et al Effect of Sitagliptin on glucose control in Adult patients with Type 1 DM Diabetic Medicine DOI 101111j1464-5491201103331Kielgast U et al Treatment of Type Diabetic Patients with GLP-1 and GLP-1 Agonists Current Diabetes Reviews2009 5266-275
TYPE 2bullJu-Young KimExendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis J Pharmacol Sci 118 65 ndash 74 (2012)bullDrucker DJ Rosen CF Glucagon-like peptide-1 (GLP-1) receptor agonists
obesity and psoriasis diabetes meets dermatology Diabetologia 2011542741ndash2744bullChaudhuri A Ghanim H Vora M et al Exenatide exerts a potent antiinflammatory effect J Clin Endocrinol Metab 201297198ndash207bull Makdissi A Ghanim H Vora M et al Sitagliptin exerts an antinflammatory action J Clin Endocrinol Metab 2012973333ndash3341bullDrucker D Incretin Action in the Pancreas Potential Promise Possible Perils and Pathological PitfallsDiabetes 623316ndash3323 2013bullShimoda M Kanda Y Hamamoto S Tawaramoto K Hashiramoto M Matsuki M Kaku KThe human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes
Diabetologia 2011 May54(5)1098-108 doi 101007s00125-011-2069-9 Epub 2011 Feb 22bullKim JY Lim DM Moon CI Jo KJ Lee SK Baik HW Lee KH Lee KW Park KY Kim BJExendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity
J Korean Med Sci 2010 Nov25(11)1626-32 doi 103346jkms201025111626 Epub 2010 Oct 26bullLiu Z Stanojevic V Brindamour LJ Habener GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β- cells
from glucolipotoxicity J Endocrinol 2012 May213(2)143-54 doi 101530JOE-11-0328 Epub 2012 Mar 13bullGlucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus Diabetologia - Clinical and Experimental Diabetes and Metabolism 03042014 Hogan AE
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
β-Cell (Islet Cell) Classification Model-Implications for Therapy
(Not Core Defects)-Targets for Therapies
Direct Effect on β-Cells On 1-4 of lsquoEgregious Elevenrsquo
1 β-CELL Incretin Ranolazine
2 α-Cell Glucagon Incretin Pramlintide
3 darrINCRETIN EFFECT Incretin
4 Inflammation Incretin Anti-inflammatory
Egregious Eleven Defect Intervention Therapy
Hierarchy of Medication Choice (a la AACE Guideline)(this and next slide) not just reduction in HgA1c but
1Efficacy2Number of Targets of Therapy each drug addresses3Weight loss4Proven Reduction in CV outcomes
β-Cell (Islet Cell) Classification Model-Implications for Therapy
(Not Core Defects)-Targets for Therapies
In-Direct Effect on β-Cells On 5-11 of lsquoEgregious Elevenrsquo
567 Liver Muscle Fat Insulin Resistance MET TZD Bromocriptine-QR (wt reduction agentsndash GLP-1 RA SGLT-2 Inhibitors)
8 Kidney Renal Threshold for Glucosuria SGLT-2 Inhibitors
9 Brain Appetite IncretinCentrally Controlled Peripheral IR Bromocriptine-QR Sympathetic Tone Bromocriptine-QR
10 StomachIntestine Rate of Appearance of Glucose in the bloodAGI GLP-1 RA Pramlintide
11 ColonBiome Gut Biome Probiotic (may improve IR β-cell function inflam)
Egregious Eleven Target Intervention Therapy
5-11 ALL Decrease Glucose Lipotoxicity
Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1
eg Metformin Colesevalam (TGR-5)] Type 1- minimize brittle dawn unpredictable variability CV benefits Treat those lsquoType 2rsquo Genesrsquo ANTI-INFLAMMATORY LADA = SPIDDM Autoimmune T2DM
Same- Slow stabilize disease process ANTI-INFLAMMATORY Type 2- treats 7 MOArsquos of DeFronzorsquos Octet or 911 EE
Decreases oxidative stress β-cell inflam decreases lipo- and gluco-toxicity preserve mass decreases appetite treats IR via
wt loss MODY 3- recent report
FOR ALL DM ndash potential CV benefit (ANTI-INFLAMMATORY)
Reference list for last slide LADAbull Zhao Yet al Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults one year prospective studyJ Clin Endocrinol Metab 2014 Jan 16jc20133633
TYPE 1Ellis et al Effect of Sitagliptin on glucose control in Adult patients with Type 1 DM Diabetic Medicine DOI 101111j1464-5491201103331Kielgast U et al Treatment of Type Diabetic Patients with GLP-1 and GLP-1 Agonists Current Diabetes Reviews2009 5266-275
TYPE 2bullJu-Young KimExendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis J Pharmacol Sci 118 65 ndash 74 (2012)bullDrucker DJ Rosen CF Glucagon-like peptide-1 (GLP-1) receptor agonists
obesity and psoriasis diabetes meets dermatology Diabetologia 2011542741ndash2744bullChaudhuri A Ghanim H Vora M et al Exenatide exerts a potent antiinflammatory effect J Clin Endocrinol Metab 201297198ndash207bull Makdissi A Ghanim H Vora M et al Sitagliptin exerts an antinflammatory action J Clin Endocrinol Metab 2012973333ndash3341bullDrucker D Incretin Action in the Pancreas Potential Promise Possible Perils and Pathological PitfallsDiabetes 623316ndash3323 2013bullShimoda M Kanda Y Hamamoto S Tawaramoto K Hashiramoto M Matsuki M Kaku KThe human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes
Diabetologia 2011 May54(5)1098-108 doi 101007s00125-011-2069-9 Epub 2011 Feb 22bullKim JY Lim DM Moon CI Jo KJ Lee SK Baik HW Lee KH Lee KW Park KY Kim BJExendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity
J Korean Med Sci 2010 Nov25(11)1626-32 doi 103346jkms201025111626 Epub 2010 Oct 26bullLiu Z Stanojevic V Brindamour LJ Habener GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β- cells
from glucolipotoxicity J Endocrinol 2012 May213(2)143-54 doi 101530JOE-11-0328 Epub 2012 Mar 13bullGlucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus Diabetologia - Clinical and Experimental Diabetes and Metabolism 03042014 Hogan AE
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
β-Cell (Islet Cell) Classification Model-Implications for Therapy
(Not Core Defects)-Targets for Therapies
In-Direct Effect on β-Cells On 5-11 of lsquoEgregious Elevenrsquo
567 Liver Muscle Fat Insulin Resistance MET TZD Bromocriptine-QR (wt reduction agentsndash GLP-1 RA SGLT-2 Inhibitors)
8 Kidney Renal Threshold for Glucosuria SGLT-2 Inhibitors
9 Brain Appetite IncretinCentrally Controlled Peripheral IR Bromocriptine-QR Sympathetic Tone Bromocriptine-QR
10 StomachIntestine Rate of Appearance of Glucose in the bloodAGI GLP-1 RA Pramlintide
11 ColonBiome Gut Biome Probiotic (may improve IR β-cell function inflam)
Egregious Eleven Target Intervention Therapy
5-11 ALL Decrease Glucose Lipotoxicity
Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1
eg Metformin Colesevalam (TGR-5)] Type 1- minimize brittle dawn unpredictable variability CV benefits Treat those lsquoType 2rsquo Genesrsquo ANTI-INFLAMMATORY LADA = SPIDDM Autoimmune T2DM
Same- Slow stabilize disease process ANTI-INFLAMMATORY Type 2- treats 7 MOArsquos of DeFronzorsquos Octet or 911 EE
Decreases oxidative stress β-cell inflam decreases lipo- and gluco-toxicity preserve mass decreases appetite treats IR via
wt loss MODY 3- recent report
FOR ALL DM ndash potential CV benefit (ANTI-INFLAMMATORY)
Reference list for last slide LADAbull Zhao Yet al Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults one year prospective studyJ Clin Endocrinol Metab 2014 Jan 16jc20133633
TYPE 1Ellis et al Effect of Sitagliptin on glucose control in Adult patients with Type 1 DM Diabetic Medicine DOI 101111j1464-5491201103331Kielgast U et al Treatment of Type Diabetic Patients with GLP-1 and GLP-1 Agonists Current Diabetes Reviews2009 5266-275
TYPE 2bullJu-Young KimExendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis J Pharmacol Sci 118 65 ndash 74 (2012)bullDrucker DJ Rosen CF Glucagon-like peptide-1 (GLP-1) receptor agonists
obesity and psoriasis diabetes meets dermatology Diabetologia 2011542741ndash2744bullChaudhuri A Ghanim H Vora M et al Exenatide exerts a potent antiinflammatory effect J Clin Endocrinol Metab 201297198ndash207bull Makdissi A Ghanim H Vora M et al Sitagliptin exerts an antinflammatory action J Clin Endocrinol Metab 2012973333ndash3341bullDrucker D Incretin Action in the Pancreas Potential Promise Possible Perils and Pathological PitfallsDiabetes 623316ndash3323 2013bullShimoda M Kanda Y Hamamoto S Tawaramoto K Hashiramoto M Matsuki M Kaku KThe human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes
Diabetologia 2011 May54(5)1098-108 doi 101007s00125-011-2069-9 Epub 2011 Feb 22bullKim JY Lim DM Moon CI Jo KJ Lee SK Baik HW Lee KH Lee KW Park KY Kim BJExendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity
J Korean Med Sci 2010 Nov25(11)1626-32 doi 103346jkms201025111626 Epub 2010 Oct 26bullLiu Z Stanojevic V Brindamour LJ Habener GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β- cells
from glucolipotoxicity J Endocrinol 2012 May213(2)143-54 doi 101530JOE-11-0328 Epub 2012 Mar 13bullGlucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus Diabetologia - Clinical and Experimental Diabetes and Metabolism 03042014 Hogan AE
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1
eg Metformin Colesevalam (TGR-5)] Type 1- minimize brittle dawn unpredictable variability CV benefits Treat those lsquoType 2rsquo Genesrsquo ANTI-INFLAMMATORY LADA = SPIDDM Autoimmune T2DM
Same- Slow stabilize disease process ANTI-INFLAMMATORY Type 2- treats 7 MOArsquos of DeFronzorsquos Octet or 911 EE
Decreases oxidative stress β-cell inflam decreases lipo- and gluco-toxicity preserve mass decreases appetite treats IR via
wt loss MODY 3- recent report
FOR ALL DM ndash potential CV benefit (ANTI-INFLAMMATORY)
Reference list for last slide LADAbull Zhao Yet al Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults one year prospective studyJ Clin Endocrinol Metab 2014 Jan 16jc20133633
TYPE 1Ellis et al Effect of Sitagliptin on glucose control in Adult patients with Type 1 DM Diabetic Medicine DOI 101111j1464-5491201103331Kielgast U et al Treatment of Type Diabetic Patients with GLP-1 and GLP-1 Agonists Current Diabetes Reviews2009 5266-275
TYPE 2bullJu-Young KimExendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis J Pharmacol Sci 118 65 ndash 74 (2012)bullDrucker DJ Rosen CF Glucagon-like peptide-1 (GLP-1) receptor agonists
obesity and psoriasis diabetes meets dermatology Diabetologia 2011542741ndash2744bullChaudhuri A Ghanim H Vora M et al Exenatide exerts a potent antiinflammatory effect J Clin Endocrinol Metab 201297198ndash207bull Makdissi A Ghanim H Vora M et al Sitagliptin exerts an antinflammatory action J Clin Endocrinol Metab 2012973333ndash3341bullDrucker D Incretin Action in the Pancreas Potential Promise Possible Perils and Pathological PitfallsDiabetes 623316ndash3323 2013bullShimoda M Kanda Y Hamamoto S Tawaramoto K Hashiramoto M Matsuki M Kaku KThe human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes
Diabetologia 2011 May54(5)1098-108 doi 101007s00125-011-2069-9 Epub 2011 Feb 22bullKim JY Lim DM Moon CI Jo KJ Lee SK Baik HW Lee KH Lee KW Park KY Kim BJExendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity
J Korean Med Sci 2010 Nov25(11)1626-32 doi 103346jkms201025111626 Epub 2010 Oct 26bullLiu Z Stanojevic V Brindamour LJ Habener GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β- cells
from glucolipotoxicity J Endocrinol 2012 May213(2)143-54 doi 101530JOE-11-0328 Epub 2012 Mar 13bullGlucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus Diabetologia - Clinical and Experimental Diabetes and Metabolism 03042014 Hogan AE
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Reference list for last slide LADAbull Zhao Yet al Dipeptidyl peptidase 4 inhibitor sitagliptin maintains β-cell function in patients with recent-onset latent autoimmune diabetes in adults one year prospective studyJ Clin Endocrinol Metab 2014 Jan 16jc20133633
TYPE 1Ellis et al Effect of Sitagliptin on glucose control in Adult patients with Type 1 DM Diabetic Medicine DOI 101111j1464-5491201103331Kielgast U et al Treatment of Type Diabetic Patients with GLP-1 and GLP-1 Agonists Current Diabetes Reviews2009 5266-275
TYPE 2bullJu-Young KimExendin-4 Protects Against Sulfonylurea-Induced β-Cell Apoptosis J Pharmacol Sci 118 65 ndash 74 (2012)bullDrucker DJ Rosen CF Glucagon-like peptide-1 (GLP-1) receptor agonists
obesity and psoriasis diabetes meets dermatology Diabetologia 2011542741ndash2744bullChaudhuri A Ghanim H Vora M et al Exenatide exerts a potent antiinflammatory effect J Clin Endocrinol Metab 201297198ndash207bull Makdissi A Ghanim H Vora M et al Sitagliptin exerts an antinflammatory action J Clin Endocrinol Metab 2012973333ndash3341bullDrucker D Incretin Action in the Pancreas Potential Promise Possible Perils and Pathological PitfallsDiabetes 623316ndash3323 2013bullShimoda M Kanda Y Hamamoto S Tawaramoto K Hashiramoto M Matsuki M Kaku KThe human glucagon-like peptide-1 analogue liraglutide preserves pancreatic beta cells via regulation of cell kinetics and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes
Diabetologia 2011 May54(5)1098-108 doi 101007s00125-011-2069-9 Epub 2011 Feb 22bullKim JY Lim DM Moon CI Jo KJ Lee SK Baik HW Lee KH Lee KW Park KY Kim BJExendin-4 protects oxidative stress-induced β-cell apoptosis through reduced JNK and GSK3β activity
J Korean Med Sci 2010 Nov25(11)1626-32 doi 103346jkms201025111626 Epub 2010 Oct 26bullLiu Z Stanojevic V Brindamour LJ Habener GLP1-derived nonapeptide GLP1(28-36)amide protects pancreatic β- cells
from glucolipotoxicity J Endocrinol 2012 May213(2)143-54 doi 101530JOE-11-0328 Epub 2012 Mar 13bullGlucagon-like peptide 1 analogue therapy directly modulates innate immune-mediated inflammation in individuals with type 2 diabetes mellitus Diabetologia - Clinical and Experimental Diabetes and Metabolism 03042014 Hogan AE
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Follow current AACE GUIDELINE PRINCIPLES
Treat as many of the Egregious 11 Targets as needed with least of agents to get lowest sugarsHgA1c as possible without undue weight gain or hypoglycemia
Early Combination TherapyFirst Tier- Efficacy (my add- CV event reduction Weight Loss)
Treat with agents that address FBS AND PPG Ideally agents will stabilize preserve β-cells the CORE
DEFECT ( NO SUGLINIDES) Ideally agents will have potential to synergistically
decrease in CV risk factors outcomes
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Summary What do we do for Treatment
Which therapies to use will be based on New research as available New guidelines to be developed Each physicians assessment comfort with
modalities at hand in anhellip Evidence-Based PRACTICE approach
eg I give incretins to (nearly) all (my) patients with diabetes now (whenever possible) even lsquooff-labelrsquo lsquoPatient-centric approachrsquo
PICK RIGHT DRUG FOR THE RIGHT PATIENT AND VICE-VERSA
bullEg no hesitation to use for example TZD SGLT-2 Incretins in lsquousualrsquo T1DM
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Patient-Centric Diagnosis and CareTherapy
Diabetes Rxbull B = β-cell- Incretin suppressing glucagon agents SGLT-2
bull Br = Brain- Bromo-QR stomach R
bull I = Inflam- Incretin (New)
bull R = Resistance- MET Pio (New)
bull E = Environment- diet exercise
bull Biome-( Effects on IR β-cell Inflam)
( ) = Not provenTempered by DATA- focus for future Research
Traditional LabsTestingFBS RBS HgA1c
Etiologic Diagnostic Markersβ-Cell IR Inflam Environment Genes
Specific TherapyAt Risk
Individuals
Genes
Pre-Diabetes RxB = β-cell- (Incretin)Br= Brain- (Bromo-QR)I = Inflam- (Incretin new)R = Resistance- MET Pio-E = Environment- diet exercise
Biome- ( Effects on IR β-cell Inflam)
( Multiple- a la DeFronzo pilot)
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
Based on lsquoNewrsquo ClassificationRecommended Process For Prevention Diagnosis
and Therapy 2014 Convene ADAEASDWHOAACE Committee Revising Classification of Diabetes Mellitus
Set Processes in PlaceIncrease current repositories- JAEB JDRI to include LADA patients (but all lsquokinds of
hyperglycemic patient types) HDLI Large Health Systems ( K-P)
Research- into these ideas approaches
EDUCATE MDs re issues
bullAllan D Sniderman et al The Necessity for Clinical Reasoning in the Era of Evidence-Based MedicineMayo Clin Proc 201388(10)1108-1114
THEN use Evidence-Based Practice Approaches to DX amp provide Therapy Where evidence incomplete But logic exists to help patients apply appropriate
Clinical Reasoning= Evidence Based Practice
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
So For Now with Current Terminology Cost- Driven
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
So For Now with Current Terminology Cost- DrivenDiagnosis of Diabetes in Adults Dagger
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW-genotype all
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
So For Now with Current Terminology Cost- Driven
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
So For Now with Current Terminology Cost- Driven
FH +(-) Ketosis prone
Younger
BMI gt30
Type 2
Older
(-) Ketosis proneFH+
BMI gt30
Type 2
Genome to Clarify
lt30 BMI
MODY
lsquoLADArsquo
SPIDDM Autoimmune Type2
BMI lt30
Antibody HLA to Verify
FH -( +) ketosis prone
Younger
Type 1
lsquoLADArsquo
SPIDDM Autoimmune Type2
Antibody HLA to Verify
BMI gt30
Diagnosis of Diabetes in Adults Dagger
Dagger BASED ON FAMILY HX (GENES) AGE KETOSIS PRONE BMI ANTIBODIES
If cost lsquoless of an Issuersquo- antibodies in allStanford Antibody Chip- fraction of cost of RAI
At some point NOW- genotype all
VOILA et MERCI
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
In Summarybull Current Classification of Diabetes Types are unable to differentiate
patients inhibit appropriate use of all therapies that are available to us now and in near future
bull New Classification that recognizes the Beta-cell as THE CORE DEFECT in ALL Diabetes and describes the multiple causes for their dysfunction offers wonderful opportunities for Prevention Therapy Research and Education
bull In particular we must recognize that multiple types of therapy are and will be available to be used in any patient with diabetes based on the causes of their dysfunction- genes inflammation insulin resistance gut biome central (brain) mechanisms
bull defining markers and processes of care in using them will then allow appropriate patient-centric approaches- whether we choose to use old ie current nomenclature or develop a new nomenclature Eg even at present it allows us to use for example incretins insulin sensitivity agents SGLT-2 inhibitors in T1DM LADA patients etc
bull More research always needed but in an evidence-based PRACTICE approach to care we can START NOW
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
With Great Thanks
Dr Richard Aguilar- Clinician Educator CollaboratorA Best Friend
Our Mentors bull Arthur Rubenstein David Rabin Jesse Roth Al Weingrad Oscar Crawford John Williamson Barabara Corkey Lester Baker Charles Stanley bull Hakon Hankerson
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-
AcknowledgementsOur NIH Grant Collaborators
Action LADA Consortium T1D Exchange Institut de Biologie de LilleDavid Leslie Carla Greenbaum Philippe Froguel
Mohammed Hawa Asa Davis Veacuteronique Dhennin
Bernhard Boehm Kristen Kuhns Marianne Deweirder
Knud Yderstraeligde T1D Exchange Biobank Operations Center
Didac Mauricio Puente
Alberto Deleiva Geisinger Clinic Mayo ClinicCharles Thivolet Ronald Harris Adrian Vella
Werner Scherbaum John Kennedy Paula Giesler
Nanette Schloot Rosemarie Delucca Jeanette Laugen
Mary Ann Ngoc Dang
National Disease Research Interchange University of Leicester Adventist Health SystemSunbeltJohn Lonsdale Kamlesh Khunti Richard Pratley
Lee Ducat Melanie Davies Julie Clyatt
Stephanie Goldby
University of Alabama at Birmingham Sian Hill University of PennsylvaniaFernando Ovalle Michael Rickels
Kentress Davison Nora Rosenfeld
University of Washington Weill Cornell Medical College Health Diagnostic Laboratory IncSantica Marcovina David Brillon Steven Varvel
Jessica Harting Karen Hyams Joe McConnell
- Diagnosing Diabetes In Adultsndash Type 1 LADA or Type 2
- PowerPoint Presentation
- Slide 3
- Hedge your Bets All get Incretins DPP_4 Inh GLP-1 RAs [ or agents that increase GLP-1 eg Metformin Colesevalam (TGR-5)]
- Reference list for last slide
- Follow current AACE GUIDELINE PRINCIPLES
- Summary What do we do for Treatment
- Patient-Centric Diagnosis and CareTherapy
- Based on lsquoNewrsquo Classification Recommended Process For Prevention Diagnosis and Therapy 2014
- So For Now with Current Terminology Cost- Driven
- Slide 11
- Slide 12
- Slide 13
- In Summary
- With Great Thanks
- Acknowledgements Our NIH Grant Collaborators
-