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

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

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

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

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

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