The South Asian Indian The South Asian Indian WomenWomen’’s Weight Loss Studys Weight Loss Study

Latha Palaniappan, MD, MSBIRCWH ScholarOctober 20, 2005

South AsianSouth Asian

Emigrants and second generation from• India• Bhutan • Bangladesh• Maldives• Nepal • Pakistan• Sri Lanka

Women Age 25-84

0

100

200

CHD

PMR

totalWhiteHispanicBlackChineseJapaneseIndian

Palaniappan, et al. Annals of Epidemiology. 2004 August;14(7):495-506

Obesity+

Genetic Susceptibility

Insulin Resistance

Type 2 Diabetes

Pancreatic Insufficiency

Insulin

Glucose

Role of Insulin ResistanceRole of Insulin Resistance

Insulin

Normal Glucose

Metabolic Syndrome

Coronary Heart Disease

Ethnicity modifies the interaction Ethnicity modifies the interaction between insulin and BMIbetween insulin and BMI

Palaniappan, et al., AJC, 2001

2030405060708090

100110120

< 22 22 - 24 25 - 27 28 - 30 31 - 33 > 34BMI Categories

Insu

lin

BlackWhiteMA

Insulin by Ethnicity Insulin by Ethnicity -- WomenWomen

Palaniappan et al, Diabetes Care. 2002 August;25(8):1351-1357.

Does Obesity operate Does Obesity operate differently in different differently in different

ethnic groups?ethnic groups?

Fasting insulin higher among ethnic minority women than white women at a lower body massDifferences not as apparent among menFasting insulin is a strong predictor of diabetes among non-obese (BMI < 30) womenAre South Asian Indian women more insulin resistant at lower BMI, and does insulin resistance improve with weight loss?

Work to dateWork to date

Relationship Between Insulin Resistance (SSPG Relationship Between Insulin Resistance (SSPG Concentration) and Fasting Insulin Levels in 490 Concentration) and Fasting Insulin Levels in 490

Nondiabetic SubjectsNondiabetic Subjects

Yeni-Komshian H. Diabetes Care. 2000;23:171-175

0

10

20

30

40

50

60

70

0 100 200 300 400

SSPG (mg/dL)

Fasting Insulin (μIU/mL) r=0.61 

P<0.001

HypothesesHypotheses

1. Insulin sensitivity will improve with weight loss in South Asian Indian women.2. Among overweight and obese subjects, the prevalence of insulin resistance will be higher in South Asian Indian women than whites.3. At lower levels of body mass index, South Asian Indian women will be more likely to have insulin resistance

Steady State Plasma Glucose Steady State Plasma Glucose (SSPG)(SSPG)

180 min infusion with octreotide (0.27 ug/m2.min), insulin (32 mU/m2·min), and glucose (237 mg/m2·min)Suppresses endogenous insulin and every subject receives same insulin concentration based on body surface areaBlood drawn at 10 min intervals between 150 and 180 min for steady state glucoseHigher glucose concentration indicates resistance to insulin-mediated glucose disposal

Weight Loss ProtocolWeight Loss ProtocolBaseline metabolic measurements

– SSPG and Meal Profile (hourly blood draws 8am to 4pm with administration of two standardized test meals

– Dietary intervention40% CHO, 45% fat, 15% protein, - 750 kcal/d

Weight Loss Protocol ContWeight Loss Protocol Cont’’dd

3 mo of hypocaloric ethnicity specific diet followed by 2 wks eucaloric diet (same macronutrient composition) followed by metabolic testing (SSPG and Meal Profile)Compliance monitored with food diaries/weekly visit with dietitianNo change in baseline exercise

Patient Recruitment and Patient Recruitment and RetentionRetention

150 screened

75 SSPG

41 IR 34 IS

41 Enrolled

2 ongoing 17 Dropped Out22 completed

0.400.4068 68 ++ 1.61.667 67 ++ 1.51.5PulsePulse

0.14 0.14 0.070.07

112 112 ++ 2.92.968 68 ++ 1.81.8

117 117 ++ 3.33.372 72 ++ 1.61.6

Systolic BP (mm Hg)Systolic BP (mm Hg)Diastolic BP (mm Hg)Diastolic BP (mm Hg)

0.0090.00929 29 ++ 0.80.827 27 ++ 0.60.6BMI (kg/m2)BMI (kg/m2)

0.0080.00874 74 ++ 1.51.568 68 ++ 1.81.8Weight (kg)Weight (kg)

0.300.3042 42 ++ 1.91.944 44 ++ 1.81.8Age (yrs)Age (yrs)

PP--valuevalueInsulin Insulin ResistantResistant

SSPG >=150SSPG >=150(n=24)(n=24)

Insulin Insulin SensitiveSensitive

SSPG < 150SSPG < 150(n= 29)(n= 29)

VariableVariable

Screening VisitScreening Visit

Baseline Laboratory Characteristics*Baseline Laboratory Characteristics*

* Mean + SEM

Baseline Laboratory Characteristics*Baseline Laboratory Characteristics*

0.360.36104 104 ++ 4.64.6107 107 ++ 4.84.8LDLLDL--CC

0.00030.000343 43 ++ 1.81.852 52 ++ 1.91.9HDLHDL--CC

0.0590.059131 131 ++ 11.511.5104 104 ++ 12.412.4TriglyceridesTriglycerides

0.370.37171 171 ++ 4.94.9174 174 ++ 6.56.5CholesterolCholesterol

0.090.0995 95 ++ 2.32.392 92 ++ 1.51.5Glucose(mg/dLGlucose(mg/dL))

3.6 E 3.6 E --1212211 211 ++ 10.610.6105 105 ++ 6.36.3SSPG (mg/SSPG (mg/dLdL))

PP--valuevalueInsulin ResistantInsulin ResistantSSPG >=150SSPG >=150

(n=24)(n=24)

InsulinInsulinSensitiveSensitive

SSPG < 150SSPG < 150(n=29 )(n=29 )

VariableVariable

* Mean + SEM

Typical South Asian DietTypical South Asian Diet

Breakfast4 idlis1 cup sambar (dhal)Tea with half cup full fat milkLunch4 rotishalf cup mateer panner (peas and cheese)half cup full fat yogurt1 glass juice

Snack2 gulab jamuns

Dinner1 cup cooked ricehalf cup full fat yogurtDhal1 cup potato curry1 cup malai kofta korma~2600 kcals

12% Protein56% Carbohydrate 32% fat

Study South Asian DietStudy South Asian Diet40% CHO, Lacto40% CHO, Lacto--OvoOvo VegVeg

Breakfast2 slices whole grain bread ½ banana1 cup milk (skim or lowfat)12 almondsLunch2/3 cup cooked basmati rice 1/3 cup dal1-2 cup vegetables ½ cup yogurt or Raitha

Snack½ mango 20 peanuts

Dinner1 small Roti plus 1/3 cup cooked Rice1 egg1.5 cups vegetables ½ cup yogurt-1% lowfator nonfat2-3 teaspoons olive oil orcanola oil

1400 Kcal , 40% CHO, 30% fat, 30% protein

Actual Macronutrient Actual Macronutrient CompositionComposition

Food Diary Data Analyzed with USDA Nutrient Database

17*14Monounsaturated %

15*7Polyunsaturated %

8*8Saturated Fat %

3935Total Fat %

1816Protein %

4148CHO %

CaucasianN=27

South Asian Indian N=15

*data missing for remaining 7% of kcals from fat

Change in Weight (kg)Change in Weight (kg)

P < 0.0001, N=22

687072747678

Weight

PrePost

Change in SSPG (mg/Change in SSPG (mg/dLdL))

P < 0.0001, N=22

0

50100

150200

250

SSPG

PrePost

Change in Fasting GlucoseChange in Fasting Glucose

P = 0.004, N=22

85

90

95

100

Fasting Glucose

(mg/dL)

PrePost

Change in CholesterolChange in Cholesterol

P = 0.2, N=22

160165170175180

Cholesterol

mg/dl

PrePost

Change in LDLChange in LDL--CC

P = 0.37, N=22

100102104106108110112

LDL-C

mg/dl

PrePost

Change in Triglycerides Change in Triglycerides

P = 0.003, N=22

050

100150200

Triglycerides

mg/dl

Change in HDLChange in HDL--CC

P = 0.36, N=22

38404244464850

HDL-C

mg/dl

PrePost

-100-50

050

100150

-5 0 5 10 15

Weight Loss in Kilograms Pre - Post

Cha

nge

in S

SPG

Pre

- Pos

t SSP

G

N = 22r = 0.24

Correlation of Weight Loss and Change in SSPG

-15

-10

-5

0

5

10

15

-5 0 5 10 15

Weight Loss in KilogramsPre - Post

Cha

nge

in H

DL-

C

(Pre

- Po

st)

N = 22r = -0.08

Correlation of Weight Loss and Correlation of Weight Loss and Change in HDLChange in HDL--CC

-100

-50

0

50

100

150

200

-5 0 5 10 15

Weight Loss in Kilograms Pre - Post

Cha

nge

in T

rigly

cerid

esPr

e - P

ost

N = 22r = 0.38

Correlation in Weight Loss and Correlation in Weight Loss and Change in TriglyceridesChange in Triglycerides

-2-10123456

-5 0 5 10 15

Weight Loss in KilogramsPre - Post

Cha

nge

in T

G:H

DL

Rat

io

N = 22r = 0.5

Correlation of Weight Loss and Correlation of Weight Loss and Change in TG:HDL RatioChange in TG:HDL Ratio

Thanks!Thanks!

Dr. Gerald ReavenDr. Tracey McLaughlinCindy Lamendola, NP & Dr. Fahim Abbassi

GCRC Nurses and StaffDr. Marcia Stefanick for support and mentorship