Type 2 Diabetes – A Global Epidemic

Arya M Sharma, MD, FRCP(C)Professor of Medicine

Research Chair for Obesity Research & ManagementUniversity of Alberta

Medical DirectorEdmonton Weight Wise Program

Edmonton, AB, Canadawww.drsharma.ca

An estimated 285 million people worldwide are affected

by diabetes.

With a further 7 million people developing diabetes each

year, this number is expected to hit 438 million by 2030.

More than 3 million Canadians have diabetes and this number

is expected to reach 3.7 million by 2020.

Diabetes is a contributing factor in the deaths of approximately 41,500 Canadians each year.

50% of Canadians diagnosed with type 2 diabetes do not achieve the CDA Guidelines target level of blood glucose.

DICE Study

Abdominal obesity increases the risk of developing type 2 diabetes

<71 71–75.9 76–81 81.1–86 86.1–91 91.1–96.3 >96.3

24

20

16

12

8

4

0

Rel

ativ

e ri

sk

Waist circumference (cm)

Carey V, 1997

Conventional treatment (n = 411)*

UKPDS 34. Lancet 1998:352:854; Kahn SE, et al. N Engl J Med 2006;355:2427

The Double-Edged Sword: Weight Gain With Diabetes Treatment

*Diet initially then sulphonylureas, insulin, and/or metformin if FPG > 15 mmol/LFPG = fasting plasma glucose

Ch

an

ge in

weig

ht

(kg

)

Years from randomization

0

1

5

0 3 6 9 12

8

7

6

4

3

2

Insulin (n = 409)Glyburide (n = 277)Metformin (n = 342)

UKPDSWeight gain up to 8 kg

over 12 years

DepressionPseudotumor cerebri

Obstructive sleep apnea

Coronary artery diseaseHeart failure

Fatty liver

Thrombosis

Osteoarthritis

Intertrigo

Incontinence

Gallbladder disease

Infertility

GE-Reflux disease

Hypertension

Diabetes

Gout

Cancer

Sharma 2006

Health Consequences of Obesity

Obesity Treatment Pyramid

DietDiet Physical ActivityPhysical Activity

Lifestyle ModificationLifestyle Modification

PharmacotherapyPharmacotherapy

SurgerySurgery

Placebo

Metformin

Lifestyle

Diabetes Prevention StudyMean Weight Change

The DPP Research Group, NEJM 346:393-403, 2002

0 1 2 3 4

0

10

20

30

40Placebo (n=1082)Metformin (n=1073, p<0.001 vs. Plac)Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )

Percent developing diabetes

All participants

All participants

Years from randomization

Cum

ulat

ive

inci

denc

e (%

)

Placebo (n=1082)

Metformin (n=1073, p<0.001 vs. Placebo)

Lifestyle (n=1079, p<0.001 vs. Metformin , p<0.001 vs. Placebo)

Diabetes Prevention StudyDiabetes Prevention StudyIncidence of Diabetes Incidence of Diabetes

Risk reductionRisk reduction31% by metformin31% by metformin58% by lifestyle58% by lifestyle

The DPP Research Group, NEJM 346:393-403, 2002

The Dilemma

Kg

decades

Weight Curves in Obese and Never-Obese Rats

MacLean PS et al. Am J Physiol 2004

Isn’t Obesity Simple?

EnergyIn

EnergyOut

+/- +/-

Energy Regulation is Complex!

EnvironmentalDeterminants

EnvironmentalDeterminants

Sharma AM 2007

Genetics

Central Control of Energy Metabolism

Principal Sites of Synthesis of GI Peptides Implicated in the Regulation of Food Intake

Cummings & Overduin J Clin Invest. 2007;117:13

Phases of Obesity Treatment

Phase I(Weight Loss)

3-6 months

Phase II(Weight-Loss Maintenance)

Indefinitely

When you stop treatment,the disease comes back!

We

igh

t

Treatment SuccessC

han g

e in

We i

g ht

Years

Lifestyle (LS) ~ 3-5%

LS+Surgery ~ 20-30%

LS+Pharmacotherapy ~ 5-15%

Randomized Controlled Trial of Weight-Loss Maintenance

Svetky LP et al., JAMA 2008;299:1139

STORMSTORM Mean bodyweight changes duringMean bodyweight changes duringweight loss and weight maintenanceweight loss and weight maintenancephases over 2 yearsphases over 2 years

104

102

100

98

96

94

92

90

880 122 4 6 8 10 14 16 18 20 22 24

Month

Bod

yw

eig

ht

(kg

) Control

Sibutramine

Weight loss Weight maintenance

Same diet and exercise for both sibutramine and control

James WPT, Lancet 2001

Bariatric Surgery Reduces Mortality in Swedish Obese Subjects

(n=2010 vs. 2037)

Sjostrom L et al. NEJM 2007;357:741-52

30% Reduction in All Cause Mortality

Bariatric SurgeryEffect on Cardiovascular Risk

A Systematic Review and Meta-Analysis of 22,090 Patients

% r

eso

lved

62%70%

77%86%

Hypertension Dyslipidemia Diabetes Sleepapnea

Buchwald H, et al. JAMA 2004;292:1724

, 2004

Key Points

We currently have a “diabesity” epidemic in Canada

Conventional treatment of “diabesity” is limited and expensive

New thinking is required to better manage this epidemic

My Obesity Blog: www.drsharma.ca