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Emerging Trends in Diabetes. Robert Lash, MD Professor of Internal Medicine University of Michigan Health System. 1994. 1995. 1996. 1997. 1998. 1999. 2000. 2001. 2002. 2003. 2004. 2005. 2006. 2007. 2008. 2009. 2010. What’s new in diabetes?.

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Emerging trends in diabetes

Emerging Trends in Diabetes

Robert Lash, MD

Professor of Internal Medicine

University of Michigan Health System



















What s new in diabetes
What’s new in diabetes?

  • Recognizing that diabetes has a variety of ‘causes’, with treatments to match

  • New thinking about endpoints: Is lowering glucose enough?

  • A new medicine that does the wrong thing for the right reason

  • Finally, some real progress on the ‘artificial pancreas’


Sulfonylureas (and insulin)

Metformin

Type 2diabetes

Thiazolidinediones


Lnsulin receptor pathway

Glucose

C

2009

ProteinLounge.com

INSULIN

PIP2

PIP3

Lipid Raft

InsulinReceptor

GLUT4

GLUT4Translocation

lnsulin Receptor Pathway

P

P

SHC

GRB2

PIP2

PI3K

SOS

P

Flotillin

PIP3

IRS1

P

P

Crk

Ras

Nck

P

c-CbI

GTP

CAP

Fyn

ReceptorInternalization

P

Rab4

GRB10

P

P

GLUT4Vesicle

Raf

SHC

IRS1/2

P

P

H+

P

Insulin Degradation& ReceptorDephosphorylation

APS

PPtase1

H+

c-CbI

P

PDK

ATP Citrate lyase

P

PKC

P

P

Rac

P

MEKs

P

AktPKB

EBS

Translation

Insulin

Translation

Anti-apoptosis

Fatty AcidSynthesis

GeneExpression

TRE

Gene Expression

mTOR

Insulin

EAI

ERKs

EAI

GlycogenSynthase

BAD

GSK3

p70S6K

eIF4EBP

FKHRL1

EEF2K

P

BAD

JNK

S6

eIF2B

14-3-3

EEF2

eIF4

Elk

c-Jun

c-Fos


Sulfonylureas (and insulin)

Metformin

Type 2diabetes

Thiazolidinediones

GLP-I analogs & DPP IV inhibitors


GLP-1release

Gosh, I’m full!

DPP-4 inhibitor

DPP-4 enzyme

Increased

insulin secretion

X

Decreased glucagon secretion

Inactive metabolites

GLP-1Mechanisms of Action

Reduced hepatic glucose output


Sulfonylureas (and insulin)

Metformin

Type 2diabetes

Thiazolidinediones

GLP-I analogs & DPP IV inhibitors


What s new in diabetes1
What’s new in diabetes?

  • Recognizing that diabetes has a variety of ‘causes’, with treatments to match

  • New thinking about endpoints: Is lowering glucose enough?

  • A new medicine that does the wrong thing for the right reason

  • Finally, some real progress on the ‘artificial pancreas’


“Diabetes is a remarkable affliction, not very frequent among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts.

“Moreover, life is disgusting and painful; thirst, unquenchable; excessive drinking, which, however, is disproportionate to the large quantity of urine, for more urine is passed; and one cannot stop them either from drinking or making water.”


Chao EC and Herny RR. Nat Rev Drug Discov among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. . 2010;9:551-559.


Cefalu wt leiter la et al lancet 2013 382 941 50

Efficacy and safety of canagliflozin versus glimepiride in among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. patients with type 2 diabetes inadequately controlled withmetformin (CANTATA-SU): 52 week results from arandomised, double-blind, phase 3 non-inferiority trial

Cefalu WT, Leiter LA, et. al.Lancet 2013; 382: 941–50


Percent of patients among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts. with hypoglycemia


Sulfonylureas (and insulin) among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts.

Metformin

Type 2Diabetes

Thiazolidinediones

GLP-I analogs &DPP IV inhibitors

SGLT2 inhibitors


What s new in diabetes2
What’s new in diabetes? among men… The course is the common one, namely, the kidneys and the bladder; for the patients never stop making water, but the flow is incessant, as if from the opening of aqueducts.

  • Recognizing that diabetes has a variety of ‘causes’, with treatments to match

  • New thinking about endpoints: Is lowering glucose enough?

  • A new medicine that does the wrong thing for the right reason

  • Finally, some tangible progress on the ‘artificial pancreas’


Threshold based insulin pump interruption for reduction of hypoglycemia

Threshold-Based Insulin-Pump Interruption for Reduction of Hypoglycemia

Bergenstal RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.


Bergenstal Hypoglycemia RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.


Frequency and severity of hypoglycemia Hypoglycemia

‘Duration’ of hypoglycemic events

Bergenstal RM, Klonoff DC, et. al.N Engl J Med 2013;369:224-32.


What s new in diabetes3
What’s new in diabetes? Hypoglycemia

  • Recognizing that diabetes has a variety of ‘causes’, with treatments to match

  • New thinking about endpoints: Is lowering glucose enough?

  • A new medicine that does the wrong thing for the right reason

  • Finally, some tangible progress on the ‘artificial pancreas’


Questions
Questions? Hypoglycemia


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