Therapy of Type 2 Diabetes Mellitus: UPDATE

Glycemic Goals in the Care of Patients with Type Glycemic Goals in the Care of Patients with Type 2 Diabetes- 2013 ADA and AACE Guidelines:2 Diabetes- 2013 ADA and AACE Guidelines:

Room For Improvement Room For Improvement (Be HAPPY/ Avoid Burnout, While Caring for Patients with DM)(Be HAPPY/ Avoid Burnout, While Caring for Patients with DM)

Stan Schwartz MD, FACP, FACEAffiliate, Main Line Health System

Clinical Associate Professor of Medicine, Emeritus, U of Pa.

Part 3

Treatment of Type 2 Diabetes:

PathophysiologicApproaches

Prevention

IR phenotypeAtherosclerosisobesityhypertensionHDL,TG,

HYPERINSULINEMIA

Endothelial dysfunctionPCO,ED

Envir.+ Other Disease

Obesity (visceral)

Poor Diet Inactivity

Insulin Resistance

Risk of Dev. Complications

ETOHBPSmoking

EyeNerveKidney

Beta Cell Secretion

Genes

BlindnessAmputationCRF

Disability

Disability

MICVAAmp

Age 0-15 15-40+ 15-50+25-70+

Macrovascular Complications

IGT – OMINOUS OCTET Type II DM8 mechanisms of hyperglycemia

Microvascular Complications

DEATHpp>7.8

Treat Pre-Diabetes to Prevent DM:Delay/ Prevent/ Reverse Beta-Cell Dysfunction

FINNISH=Tuomilehto J, et al. N Engl J Med 2001; 344: 1343-50DA QING=Pan XR, et al. Diabetes Care. 1997; 20: 537-44DPP=Diabetes Prevention Program. Nathan DM, et al. N Engl J Med 2002; 346:393-403STOP-NIDDM=Study TO Prevent Non-Insulin-Dependent Diabetes Mellitus. Chiasson JL, et al. Lancet 2002; 359:2072–77TRIPOD=Troglitazone in the Prevention of Diabetes. Buchanan T, et al. Diabetes 2002; 51(9): 2796-2803XENDOS=XEnical in the Prevention of Diabetes in Obese Subjects. Torgerson JS, et al. Diabetes Care 2004; 27 (1): 155-61DREAM=Diabetes Reduction Assessment with Ramipril & Rosiglitazone Medication. Gerstein H, et al. Lancet 2006; 368:1096-1105

0

10

20

30

40

50

60

70

Diabetes Prevention Clinical Trials

Finnish-Diet+ ExerciseDa Qing – Diet + ExerciseDPP-LifestyleDPP-MetforminSTOP-NIDDMTRIPODXENDOS

Dia

bete

s M

ellit

us R

educ

tion

(%)

DREAM

41%

25%

42%

58% 58%

31%

55%

62%

PIOPOD

55%

80

ActNOW

72%

Prevention Increased with Use of Incretin

9 m, 105 pts

7

IN DPP TRIAL- if Achieve Normal Glucose Tolerance--Markedly Delay Future Overt Diabetes

10 % / YEAR PROGRESS TO DMIF NO TREATMENT

~50% reduction in risk = 5%/ YEAR IF DON’T REACH NGT

BUT Only ~18% risk6 years after studyie: only 3%/yr incidence IF GET TO NORMAL GLUCOSE TOLERANCE

Clinical Consequences of Abnormal First- phase Secretion and Elevated Post-Prandial Sugars, ie: treat PPG PPG increases

– Variability– Microvasular disease and adverse pregnancy outcomes– ASVD risk factors – adverse CV outcomes

Treating elevated PPG leads to– Reduce Pregnancy Outcomes– Reduce micro/macrovascular risk// CV Outcomes– Prevent Diabetes

Alter the Natural History of Diabetes

IR PhenotypeIR PhenotypeAtherosclerosisAtherosclerosisObesityObesityHypertensionHypertensionHDL,HDL,TG,TG,

HYPERINSULINEMIAHYPERINSULINEMIA

Endothelial DysfunctionEndothelial DysfunctionPCO,EDPCO,ED

Envir.+ Envir.+ Other Other DiseaseDisease

Obesity(visceral)Obesity(visceral)

Poor Diet Poor Diet InactivityInactivity

Insulin Insulin ResistanceResistance

Risk of Risk of ComplicationsComplications

ETOHETOHBPBPSmokingSmoking

EyeEyeNerveNerveKidneyKidney

-Cell Secretion-Cell Secretion

GenesGenes

BlindnessBlindnessAmputationAmputationCRFCRF

DisabilityDisability

DisabilityDisability

MIMICVACVAAmpAmp

Age Age 0-150-15 15-40+15-40+ 15-50+15-50+25-70+25-70+

Macrovascular ComplicationsMacrovascular Complications

IGT Type 2 DMIGT Type 2 DM

Microvascular ComplicationsMicrovascular Complications

DEATHDEATHpp>7.8pp>7.8

ADOPT: Treatment effect on primary outcome

Kahn SE et al. N Engl J Med. 2006;355:2427-43.

40

30

20

10

0

Glyburide

Metformin

Rosiglitazone

0 1 2 3 4 5Years

Cumulative incidence of

mono-therapy failure*

(%)

Hazard ratio (95% CI) Rosiglitazone vs metformin, 0.68 (0.55–0.85), P < 0.001 Rosiglitazone vs glyburide, 0.37 (0.30–0.45), P < 0.001

N = 4351

*Time to FPG >180mg/dL

Natural History of Type 2 DiabetesInsulin Resistance

IR phenotypeAtherosclerosisobesityhypertensionHDL,TG,

HYPERINSULINEMIA

Endothelial dysfunctionPCO,ED

Envir.+ Other Disease

Obesity (visceral)

Poor Diet Inactivity

Insulin Resistance

Risk of Dev. Complications

ETOHBPSmoking

EyeNerveKidney

Beta Cell Secretion

Genes

BlindnessAmputationCRF

Disability

Disability

MICVAAmp

Age 0-15 15-40+ 15-50+25-70+

Macrovascular Complications

IGT – OMINOUS OCTET Type II DM8 mechanisms of hyperglycemia

Microvascular Complications

DEATHpp>7.8