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Leveraging Weight Loss in the Treatment of Type 2 Diabetes
Part 1 of 4
Overview• Overweight/obesity health risks associated with type 2
diabetes• American Diabetes Association (ADA) guidelines for
medical nutrition therapy (MNT) and lifestyle changes• Glycemic benefits and additional advantages of weight loss
in type 2 diabetes• Application to clinical practice
Bo
dy
We
igh
t (l
b)
200
220
240
260
280
300
320
Adapted from Kendall DM, et al. © 2004 International Diabetes Center, Minneapolis, MN. All rights reserved.
Years
DiabetesDiagnosis
Onset
Prediabetes (IFG, IGT)Metabolic Syndrome
Fasting Glucose
Postmeal Glucose
Glu
co
se
(m
g/d
L)
50
100
150
200
250
300
350
Obesity, Inactivity,Genetics
Re
lati
ve
Fu
nc
tio
n
-10 -5 0 5 10 15 20 25 30
Insulin Resistance
Insulin Response
0
50
100
150
200
250
-15
Progressive -Cell Defect (glucose specific)
Amylin Response
Oral Agents/Incretin Enhancers
Basal Insulin
Basal/Bolus Insulin
Amylin Replacement
Natural History of Type 2 Diabetes and Obesity
Prevalence of Overweight and Obesity Among Adults Diagnosed With Diabetes
BMI = body mass index.
Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 2004;53:1066-1068.www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm. Accessed April 9,2008.
20-64 ≥650
20
40
60
80
100
Age (years)
%
Obese (BMI ≥30)
Overweight or Obese (BMI ≥25)
Health Risks of Obesity • Increased morbidity
– Hypertension– Dyslipidemia – Coronary heart disease– Type 2 diabetes– Stroke– Cancer (endometrial, breast, colon)– Impairments in health-related quality of life and
psychosocial well-being– Sleep apnea– Osteoarthritis
• Increased mortality
NIH-NHLBI. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults. 1998.
Excess Weight in Individuals With Type 2 Diabetes Increases Mortality Risk
Comorbidities of Obesity
TC = total cholesterol; Ref category = normal weight without the risk factor.
Wei M, et al. JAMA. 1999;282:1547-1553.
Relative Risk of All-Cause Death by BMI Categories for Selected Mortality Predictors
Ref Category Normal Overweight Obese
Rel
ativ
e R
isk
Ad
just
ed
for
Ag
e an
d E
xam
Yea
r
0
0.5
1
1.5
2
2.5
3
3.5
TC >239 Diabetes Hypertension Smoker
Additional Problems Associated With Obesity in Individuals With Type 2 Diabetes
• Exacerbation of metabolic risk factors– Hyperglycemia– Dyslipidemia– Increased thrombogenic risk (eg, increased PAI-1)
• Increased insulin resistance and glucose intolerance• Increased risk of hypertension and cardiovascular disease• Increased mortality
– Mortality ratio for individuals with diabetes whose body weights are 20% to 30% above ideal is 2.5 to 3.3 times higher than those of normal body weight
PAI-1 = Plasminogen activator inhibitor-1.
Maggio CA, et al. Diabetes Care. 1997;20:1744-1766.
Additional Problems Associated With Obesity in Individuals With Type 2 Diabetes
• Exacerbation of metabolic risk factors– Hyperglycemia– Dyslipidemia– Increased thrombogenic risk (eg, increased PAI-1)
• Increased insulin resistance and glucose intolerance• Increased risk of hypertension and cardiovascular disease• Increased mortality
– Mortality ratio for individuals with diabetes whose body weights are 20% to 30% above ideal is 2.5 to 3.3 times higher than those of normal body weight
PAI-1 = Plasminogen activator inhibitor-1.
Maggio CA, et al. Diabetes Care. 1997;20:1744-1766.
Standards of Medical Care in Type 2 Diabetes: 2008 ADA Glycemic Goals
• A1C <7.0%– Preprandial glucose 70-130 mg/dL– Postprandial glucose (PPG) <180 mg/dL
• At diagnosis: Metformin (MET) and lifestylechanges (MNT)– Add therapy to reach A1C of <7%– Add therapy to maintain an A1C of <7%
• Target PPG if A1C goals are unmet, despite reaching preprandial glucose
American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12-S54.
Standards of Medical Care in Type 2 Diabetes: 2008 ADA Weight Recommendations
• Weight loss is an important therapeutic objective1
– 85% of individuals with type 2 diabetes are obese/overweight2 • Physical activity and behavior modification are important1
• Moderate weight loss (5% in short-term studies)1
– Decreased insulin resistance– Improved measures of glycemia and lipemia– Reduced blood pressure
• “The importance of controlling body weight in reducing risks related to diabetes is of great importance…” but sustaining weight loss is difficult1
1. American Diabetes Association. Diabetes Care. 2008;31(suppl 1):S12-S78.2. www.cdc.gov/mmwr/preview/mmwrhtml/mm5345a2.htm. Accessed April 9,2008.
Modest Weight Loss Can Drastically Reduce Abdominal Visceral Fat
Before Weight Loss
(95 kg, BMI 32)After 10% Weight Loss
(85 kg, BMI 29)
Després J-P. Baillière’s Clin Endocrinol Metab. 1994;8:629-660.
Weight Loss in Type 2 Diabetes:Study Objective and Design
• Objective: Determine if modest weight loss would provide a long-term benefit
Weight Control Program• Group treatment• Individualized treatment goals to produce
a 1-kg/wk weight loss• Calorie/food restriction with focus on reduced
fat intake• Gradual increase of exercise goals with final
goal of 3.2 km/d, 5 days per week• Behavior-modification strategies
1-Year Follow-up Physical
Wing RR, et al. Arch Intern Med. 1987;147:1749-1753.
N=114
Type 2 diabetes treated with insulin, orals, diet only, or insulin plus oral
medications
Weight Loss in T2DM Dramatically Improves Glycemia and Metabolic Risk Factors
Δ Body Weight (%)
Δ A1C
Δ Body Weight (kg)
-2 to
-4.9
-5 to
-9.9
0
-0.4
0.4
0.8
00
to -1
.9
> -1
0
-0.8
-1.2
-1.6
-20
-40
0
Δ Triglycerides (mg/dL)
0
0 to
-2.3
-2.4
to -6
.8-6
.9 t
o -1
3.6
> -1
3.6
-60
-80
-100
Δ HDL-C (mg/dL)
8
6
10
12
4
2
0
00
to -2
.3-2
.4 to
-6.8
-6.9
to
-13.
6>
-13.
6
Δ Body Weight (kg)
Wing RR, et al. Arch Intern Med. 1987;147:1749-1753.
Hamdy O, et al. Diabetes Care. 2003;26:2119-2125.Monzillo LU. Obes Res. 2003;11:1048-1054.
Ch
ang
e F
rom
Bas
elin
e (%
) IL-6 TNF- hCRP PAI-1 Leptin
P<.05 NS NS P<.001 P<.01 NS
Adiponectin
-16.3 -17.4-18.7
-25.5
-15.7
4.3
-30
-25
-20
-15
-10
-5
0
5
Benefits of Weight Reduction on Cytokines in Type 2 Diabetes and Prediabetes