Reducing the Risk of T2DM: What Works? Alice YY Cheng.

Reducing the Risk of T2DM:What Works?

Alice YY Cheng

Presenter Disclosure

• Faculty: Alice Cheng

• Relationships with commercial interests:– Grants/Research Support: None– Speakers Honoraria: Abbott, AZ, BI, BD, BMS, Eli Lilly,

Lifescan, Merck, Novo Nordisk, Sanofi, Servier, Valeant– Consulting Fees: Merck, Novo Nordisk, Sanofi, Takeda,

Janssen– Other: none

CFPC CoI Templates: Slide 1

Disclosure of Commercial Support

• This program has received financial support from the following companies in the form of an educational grant:• AZ/BMS, Eli Lilly, BI, Novo Nordisk, Sanofi, Merck,

Janssen, Takeda, Amgen, Paladin, Servier, Valeant, Abbott

• Potential for conflict(s) of interest:– Alice Cheng has received honorarium from “CVH

Endocrine Day”– The companies listed above benefit from the sale of

product(s) that will be discussed in this program: all diabetes, hypertension and androgen related products

Mitigating Potential Bias• All content based on peer-reviewed publications or the 2013

Canadian Diabetes Association clinical practice guidelines

CFPC CoI Templates: Slide 3

Learning Objectives

At the completion of this program, participants will be able to:

1. Define prediabetes

2. Discuss the strategies that have worked to reduce the risk of diabetes

3. Apply the strategies to their own clinical practice

guidelines.diabetes.ca | 1-800-BANTING (226-8464) | diabetes.caCopyright © 2013 Canadian Diabetes Association

guidelines.diabetes.ca


FPG ≥7.0 mmol/LFasting = no caloric intake for at least 8 hours

or

A1C ≥6.5% (in adults)Using a standardized, validated assay, in the absence of factors that affect the

accuracy of the A1C and not for suspected type 1 diabetesor

2hPG in a 75-g OGTT ≥11.1 mmol/Lor

Random PG ≥11.1 mmol/L Random= any time of the day, without regard to the interval since the last meal

2hPG = 2-hour plasma glucose; FPG = fasting plasma glucose; OGTT = oral glucose tolerance test; PG = plasma glucose

Diagnosis of Diabetes 2013


Pima Indians

Egyptians

NHANES III

Glycemia and Retinopathy Thresholds

The International Expert Committee. Diabetes Care 2009; 32:1327-1334.

Threshold levels for the development of

retinopathy are similar in all 3 populations: FPG ≥7.0 mmol/L

2hPG ≥11.1 mmol/L A1C ≥6.5%

FPG2hPGHbA1c

70- 89- 93- 97- 100- 105- 116-109- 136- 226-364-244-185-156-138-126-116-106-94-38-

3.4- 4.8- 5.0- 5.2- 5.3- 5.5- 5.7- 6.0- 6.7-HbA1c (%)2hPG (mg/dl)

FPG (mg/dl)Re

tinop

athy

(%)

9.5-

15

10

5

0

FPG2hPGHbA1c

57- 79- 84- 89- 93- 99- 130-108- 178- 258-386-304-218-155-125-110-99-90-80-39-

2.2- 4.7- 4.9- 5.1- 5.4- 5.6- 6.0- 6.9- 8.5-HbA1c (%)2hPG (mg/dl)

FPG (mg/dl)

Retin

opat

hy (%

)

10.3-

50

20

10

0

40

30

FPG2hPGHbA1c

42- 87- 90- 93- 96- 98- 104-101- 109- 120-195-154-133-120-112-102-94-86-75-34-

3.3- 4.9- 5.1- 5.2- 5.4- 5.5- 5.6- 5.7- 5.9-HbA1c (%)2hPG (mg/dl)

FPG (mg/dl)

Retin

opat

hy (%

)

6.2-

15

10

5

0


Diagnosis of Prediabetes*

Test Result Prediabetes Category

Fasting Plasma Glucose(mmol/L)

6.1 - 6.9

Impaired fasting glucose (IFG)

2-hr Plasma Glucose in a 75-g Oral Glucose Tolerance Test (mmol/L)

7.8 – 11.0 Impaired glucose tolerance (IGT)

GlycatedHemoglobin(A1C) (%)

6.0 - 6.4 Prediabetes

* Prediabetes = IFG, IGT or A1C 6.0 - 6.4% high risk of developing T2DM

2013


A1C Level and Future Risk of Diabetes: Systematic Review

A1C Category (%)5-year incidence of

diabetes

5.0-5.4 <5 to 9%

5.5-6.0 9 to 25%

6.0-6.4 25 to 50%

Zhang X et al. Diabetes Care. 2010;33:1665-1673.


Risk of diabetes in the next 5 years…

IFG + A1C (6.0-6.4%) = 100%

Heianza Y et al. Diabetic Med 2012;29:e279-85.

Lifestyle


Da Qing – 20 yrs follow up of IGT population

Annual incidence of DM: 7% intervention vs 11% control

Li G, et al. Lancet 2008-371:1783-89.

HR 0.49 (0.33-0.73)

HR 0.57(0.41-0.81)


Diabetes Prevention Program (DPP)

Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:393-403.

Years

• Benefit of diet and exercise on diabetes prevention in at-risk patients• N = 3234 with IFG and IGT, without diabetes

00

10

20

30

40

1.0 2.0 3.0 4.0

Placebo

Lifestyle

Cumulativeincidence of diabetes(%)

58%< 0.001

*vs placeboIFG = impaired fasting glucose, IGT = impaired glucose tolerance


DPP – 10 years follow up

Placebo

Lifestyle

34%

DPP investigators. Lancet 2009;374:1677-86.

Systematic review of lifestyle for IGT showing incidence of diabetes

Yoon U et al. Metab Clin Exp 2013;62:303-314

Yoon U et al. Metab Clin Exp 2013;62:303-314

Pharmacologic


Diabetes Prevention Program (DPP)

Diabetes Prevention Program (DPP) Research Group. N Engl J Med 2002;346:393-403.

Years

• Benefit of diet and exercise or Metformin on diabetes prevention in at-risk patients

• N = 3234 with IFG and IGT, without diabetes

00

10

20

30

40

1.0 2.0 3.0 4.0

Placebo

Metformin

Lifestyle

Cumulativeincidence of diabetes(%)

31%

58%

P*< 0.001

< 0.001

*vs placeboIFG = impaired fasting glucose, IGT = impaired glucose tolerance


STOP-NIDDM Study Effects of Acarbose on the risk of T2DM

Chiasson JL, et al. Lancet 2002;359:2072-77.

N = 1429 people with IGT, BMI 25-40, 40-70 yrs, 3.3 years follow up

Days after randomization

Cum

ulat

ive

prob

abili

ty

P = 0.0022

0

AcarbosePlacebo

100200

300400

500600

700800

9001000

1100

12001300

1.00

0.95

0.90

0.50

0.45

0.40

0.65

0.60

0.55

0.80

0.75

0.70

0.85

Acarbose25%


Intervention Studies for Diabetes Prevention: Risk Reduction and Number Needed To Treat

Study Intervention RRR (%) NNT for 3y

DPP1

(n = 3234 IFG+IGT)Lifestyle interventionMetformin

5831

7 14

STOP-NIDDM2

(n = 1429 IGT)Acarbose 25 11

DREAM 3 (n = 5269 IFG / IGT)

Rosiglitazone 62 7

ACT NOW4

(n = 602 IGT or both)Pioglitazone 62 8.5

CANOE5

(n = 207 IGT)Rosiglitazone + metformin

66 3.8

XENDOS 6

(n = 694 IGT)Orlistat + lifestyle 45 10

1. Knowler WC, et al. N Engl J Med 2002;346:393-403. 2. Chiasson JL, et al. Lancet 2002;359:2072-7; 3.The DREAM Trial Investigators. Lancet 2006;368:1096-105. 4. Defronzo RA, et al. N Engl J Med 2011;364:1104-15. 5. Zinman B et al. Lancet Jul 10;376(9735):103-11. doi: 10.1016/S0140-6736(10)60746-5. Epub 2010 Jun 3. 6. Torgorsen JS et al. Diabetes Care 2004;27:155-67.


Recommendation 1 and 2

1. A structured program of lifestyle modification that

includes moderate weight loss and regular

physical activity should be implemented to reduce

risk of T2DM in individuals with IGT [Grade A, Level 1A] or

IFG [Grade B, Level 2] or A1C 6.0-6.4% [Grade D, consensus].

2. In individuals with IGT, pharmacologic therapy with

Metformin [Grade A, Level 1A] or Acarbose [Grade A, level 1A]

may be used to reduce the risk of T2DM.

2013


THEREFORE …

• LIFESTYLE, LIFESTYLE, LIFESTYLE– Low calorie, low fat– Moderate activity ≥ 150 minutes per week– Increase fibre intake– Goal of 5-10% weight loss

• PHARMACOLOGIC– Metformin 850 mg BID– Acarbose 100 mg TID

Reducing the Risk of T2DM: What Works? Alice YY Cheng.

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