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Pathophysiology

The Concurrent Accumulation of Intra-Abdominal and Subcutaneous Fat Explains the Association Between Insulin Resistance and Plasma Leptin Concentrations

Distinct Metabolic Effects of Two Fat Compartments

  1. Miriam Cnop1,
  2. Melinda J. Landchild1,
  3. Josep Vidal1,
  4. Peter J. Havel3,
  5. Negar G. Knowles1,
  6. Darcy R. Carr2,
  7. Feng Wang1,
  8. Rebecca L. Hull1,
  9. Edward J. Boyko1,
  10. Barbara M. Retzlaff1,
  11. Carolyn E. Walden4,
  12. Robert H. Knopp1 and
  13. Steven E. Kahn1
  1. 1Division of Metabolism, Endocrinology, and Nutrition, Department of Medicine, VA Puget Sound Health Care System, and Harborview Medical Center, Seattle, Washington
  2. 2Department of Obstetrics and Gynecology, University of Washington, Seattle, Washington
  3. 3Department of Nutrition, University of California, Davis, California
  4. 4College of Medicine Research Office, University of Arizona, Tucson, Arizona
    Diabetes 2002 Apr; 51(4): 1005-1015. https://doi.org/10.2337/diabetes.51.4.1005
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    • FIG. 1.
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      FIG. 1.

      BMI (A), SI (B), total abdominal fat area (C), SCF area (D), IAF area (E), and fasting plasma leptin levels (F) in 56 LIS (□), 61 LIR ([cjs2108]), and 57 OIR (▪) subjects. *P < 0.001 vs. LIS; ∧P < 0.001 vs. LIR. SI, fat areas, and leptin levels were log-transformed before ANOVA because they were not normally distributed.

    • FIG. 2.
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      FIG. 2.

      Relationships between the SI and BMI (A) and measures of body fat distribution:waist-to-hip ratio (C), SCF area (E), and IAF area (G) in 174 subjects classified as LIS (▪), LIR (▵), or OIR (•). B, D, F, and H display the correlations between SI and adiposity measures after loge transformation of non–normally distributed variables. P < 0.001 for all correlations.

    • FIG. 3.
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      FIG. 3.

      Relationships between fasting plasma leptin levels and measures of body fat distribution in 174 subjects classified as LIS (▪), LIR (▵), or OIR (•). Correlation coefficients were determined for men (⧫) and women (+). P < 0.001 for all correlations.

    Tables

    • Figures
    • TABLE 1

      Age, BMI, and metabolic characteristics of LIS, LIR, and OIR subjects subdivided by gender

      LISLIROIR
      Men
       n192727
       Age (years)46.6 ± 7.355.7 ± 11.5†53.9 ± 10.1
       BMI (kg/m2)24.1 ± 2.324.8 ± 1.430.5 ± 2.7‡¶
       SI (× 10−5 min−1 · [pmol/l]−1)11.3 ± 5.24.3 ± 0.5‡3.3 ± 1.3‡‖
       Glucose (mmol/l)5.36 ± 0.425.59 ± 0.395.77 ± 0.47†
       Insulin (pmol/l)45.0 ± 19.263.6 ± 25.2*88.2 ± 69.6‡
      Women
       n373430
       Age (years)51.0 ± 8.653.0 ± 11.553.3 ± 9.5
       BMI (kg/m2)23.0 ± 2.223.8 ± 1.8#31.5 ± 3.9‡¶
       SI (× 10−5 min−1 · [pmol/l]−1)10.7 ± 3.75.2 ± 1.2‡#3.7 ± 1.7‡¶
       Glucose (mmol/l)5.14 ± 0.33#5.28 ± 0.33**5.52 ± 0.48‡§
       Insulin (pmol/l)39.6 ± 16.257.0 ± 29.4†93.6 ± 48.6‡¶
      • Data are means ± SD.

      • *

        * P < 0.05,

      • †

        † P < 0.01,

      • ‡

        ‡ P < 0.001 vs. LIS;

      • §

        § P < 0.05,

      • ‖

        ‖ P < 0.01,

      • ¶

        ¶ P < 0.001 vs. LIR;

      • #

        # P < 0.05,

      • **

        ** P < 0.01 for women vs. men within the group. SI and insulin were log-transformed to obtain normal distribution of the variable before ANOVA.

    • TABLE 2

      Body fat distribution and fasting plasma leptin concentrations in LIS, LIR, and OIR subjects subdivided by gender

      LISLIROIR
      Men
       n192727
       Waist-to-hip ratio0.87 ± 0.060.90 ± 0.050.96 ± 0.05†‡
       Total fat area (cm2)175 ± 64264 ± 85†431 ± 100†‡
       SCF area (cm2)110 ± 51166 ± 64†248 ± 87†‡
       IAF area (cm2)65 ± 2898 ± 38*183 ± 62†‡
       Leptin (ng/ml)3.1 ± 1.06.0 ± 3.9†10.1 ± 6.2†‡
      Women
       n373430
       Waist-to-hip ratio0.75 ± 0.06¶0.77 ± 0.05¶0.83 ± 0.05†‡¶
       Total fat area (cm2)185 ± 75283 ± 99†517 ± 160†‡§
       SCF area (cm2)143 ± 61208 ± 72†§381 ± 124†‡¶
       IAF area (cm2)42 ± 23‖75 ± 42†§136 ± 59†‡¶
       Leptin (ng/ml)10.7 ± 6.6¶14.6 ± 6.8*¶32.5 ± 13.6†‡¶
      • Data are means ± SD.

      • *

        * P < 0.01,

      • †

        † P < 0.001 vs. LIS;

      • ‡

        ‡ P < 0.001 vs. LIR;

      • §

        § P < 0.05,

      • ‖

        ‖ P < 0.01,

      • ¶

        ¶ P < 0.001 for women vs. men within the group. Fat areas and leptin levels were log-transformed to obtain normal distribution of the variable before ANOVA.

    • TABLE 3

      Multiple linear regression analysis of the relationship between insulin sensitivity and age, gender, and measures of body fat distribution

      Independent variablesCoefficientSEP
      Age−0.0020.0040.67
      Gender0.0020.1290.99
      BMI−0.0210.0160.19
      Waist-to-hip ratio−0.6270.7900.43
      SCF area−0.0010.0010.06
      IAF area−0.0040.001<0.001
      Intercept2.9560.702<0.001
      • The dependent variable is loge SI. The model r2 is 0.544. Sex was coded (0, 1) with the higher number indicating female sex. SE is the standard error for the regression coefficient.

    • TABLE 4

      Body fat distribution and fasting plasma leptin concentrations in a subgroup of LIS and LIR subjects matched for SCF area and gender (14 men/24 women)

      LISLIR
      n3838
      Age (years)49.6 ± 8.553.2 ± 12.0
      BMI (kg/m2)24.1 ± 1.723.6 ± 1.7
      SI (× 10−5 min−1 · [pmol/l]−1)10.5 ± 3.85.2 ± 1.3*
      SCF area (cm2)157 ± 52160 ± 52
      Waist-to-hip ratio0.79 ± 0.080.80 ± 0.09
      IAF area (cm2)56 ± 2973 ± 39†
      Insulin (pmol/l)42.6 ± 19.253.4 ± 24.6†
      Leptin (ng/ml)8.8 ± 7.19.2 ± 5.9
      • Data are means ± SD.

      • *

        * P < 0.001;

      • †

        † P < 0.05.

    • TABLE 5

      Multiple regression analysis of the association between fasting plasma leptin levels and measures of body fat distribution and insulin sensitivity

      Independent variablesMen
      Women
      CoefficientSEPCoefficientSEP
      Age0.0050.0050.31−0.0120.0050.03
      BMI−0.0200.0210.330.0100.0210.64
      Waist-to-hip ratio−0.7881.0330.45−0.8061.0350.44
      SCF area0.0050.001<0.0010.0020.0010.002
      IAF area0.0020.0010.0460.0030.0020.07
      SI−0.0300.0200.14−0.0620.0250.02
      Insulin0.0150.0060.02−1 × 10−50.0111.0
      Intercept1.4600.9320.123.1180.812<0.001
      • The dependent variable is loge leptin. The model r2 is 0.764 for men and 0.620 for women. SE is the standard error for the regression coefficient.

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    The Concurrent Accumulation of Intra-Abdominal and Subcutaneous Fat Explains the Association Between Insulin Resistance and Plasma Leptin Concentrations
    Miriam Cnop, Melinda J. Landchild, Josep Vidal, Peter J. Havel, Negar G. Knowles, Darcy R. Carr, Feng Wang, Rebecca L. Hull, Edward J. Boyko, Barbara M. Retzlaff, Carolyn E. Walden, Robert H. Knopp, Steven E. Kahn
    Diabetes Apr 2002, 51 (4) 1005-1015; DOI: 10.2337/diabetes.51.4.1005

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    The Concurrent Accumulation of Intra-Abdominal and Subcutaneous Fat Explains the Association Between Insulin Resistance and Plasma Leptin Concentrations
    Miriam Cnop, Melinda J. Landchild, Josep Vidal, Peter J. Havel, Negar G. Knowles, Darcy R. Carr, Feng Wang, Rebecca L. Hull, Edward J. Boyko, Barbara M. Retzlaff, Carolyn E. Walden, Robert H. Knopp, Steven E. Kahn
    Diabetes Apr 2002, 51 (4) 1005-1015; DOI: 10.2337/diabetes.51.4.1005
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