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Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes

C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance

  1. Marina Cardellini, MD1,
  2. Lucia Perego, PHD2,
  3. Monica D’Adamo, MD1,
  4. Maria Adelaide Marini, MD1,
  5. Cristina Procopio3,
  6. Marta Letizia Hribal, PHD13,
  7. Francesco Andreozzi, MD3,
  8. Simona Frontoni, MD1,
  9. Maurizio Giacomelli, MD4,
  10. Michele Paganelli, MD4,
  11. Antonio E. Pontiroli, MD5,
  12. Renato Lauro, MD1,
  13. Franco Folli, MD2 and
  14. Giorgio Sesti, MD1
  1. 1Department of Internal Medicine, University of Rome, Rome, Italy
  2. 2Divisione di Medicina Interna, San Raffaele Hospital, Milan, Italy
  3. 3Dipartimento di Medicina Sperimentale e Clinica, Università Magna Græcia di Catanzaro, Catanzaro, Italy
  4. 4Divisione di Chirurgia Generale, San Raffaele Hospital, Milan, Italy
  5. 5Universita di Milano, Cattedra di Medicina Interna, Milan, Italy
  1. Franco Folli, MD, PhD, Department of Internal Medicine, San Raffaele Hospital, Via Olgettina 60, 20132 Milan, Italy. E-mail: folli.franco{at}hsr.it
  2. Address correspondence and reprint requests to Giorgio Sesti, MD, Dipartimento Medicina Sperimentale e Clinica, Università Magna-Græcia di Catanzaro, Via Campanella 115, 88100 Catanzaro, Italy. E-mail: sesti{at}unicz.it
Diabetes Care 2005 Aug; 28(8): 2007-2012. https://doi.org/10.2337/diacare.28.8.2007
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    Figure 1—

    Correlation between log-transformed adipose IL-6 mRNA expression and log-transformed homeostasis model assessment (HOMA) in the cohort of unrelated obese individuals who underwent LAGB (Spearman’s rank correlation coefficient ρ = 0.28, P = 0.014).

Tables

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  • Table 1—

    Clinical and biochemical characteristics according to the C-174G polymorphism of the IL-6 gene in 275 nondiabetic individuals

    IL-6 promoter genotypes
    *P†P (G/G vs. C/G + C/C)
    G/GG/CC/C
    Male/female (n)42/10036/767/140.880.62
    Age (years)39 ± 12 (37)37 ± 11 (37)39 ± 10 (41)0.480.43
    BMI (kg/m2)31.2 ± 8.9 (28)29.4 ± 8.8 (27)28.5 ± 4.5 (28)0.170.13
    Waist-to-hip ratio0.87 ± 0.10 (0.87)0.86 ± 0.09 (0.86)0.85 ± 0.09 (0.85)0.800.80
    Total fat mass (%)37 ± 15 (36)36 ± 14 (35)32 ± 8 (31)0.310.23
    Fasting glucose (mg/dl)95 ± 23 (92)91 ± 12 (91)91 ± 10 (92)0.330.29
    2-h glucose (mg/dl)120 ± 42 (110)110 ± 31 (107)104 ± 26 (105)0.080.09
    Fasting insulin (μU/ml)12 ± 8 (10)11 ± 9 (10)11 ± 7 (10)0.340.09
    2-h insulin (μU/ml)66 ± 55 (47)62 ± 75 (47)64 ± 85 (43)0.270.19
    Total cholesterol (mg/dl)199 ± 42 (197)195 ± 36 (192)196 ± 36 (203)0.730.43
    HDL cholesterol (mg/dl)53 ± 13 (52)53 ± 14 (52)50 ± 13 (49)0.500.57
    Triglycerides (mg/dl)122 ± 83 (94)123 ± 71 (107)116 ± 47 (105)0.840.32
    Fibrinogen (mg/dl)303 ± 83 (294)282 ± 63 (275)‡289 ± 56 (270)0.080.02
    White blood cell count (× 109/ml )7,444 ± 1,998 (7,100)6,872 ± 1,468 (7,020)§6,171 ± 1,457 (6,140)‖0.040.03
    Family history of T2DM (n yes/no)102/3988/2419/20.140.11
    NGT/IGT (n)114/2894/1819/20.220.30
    Glucose disposal (mg · kg–1 · min–1)6.8 ± 2.9 (7.0)7.8 ± 3.3 (7.7)¶8.2 ± 3.3 (7.8)#0.010.004
    Fasting IL-6 (pg/ml)2.5 ± 3.2 (1.7)1.6 ± 1.4 (1.1)**1.5 ± 0.8 (1.4)0.070.02
    • Data are means ± SD (median) unless otherwise indicated.

    • *

      ↵* P values for comparisons of differences of continuous variables between the three genotypes using ANOVA.

    • †

      ↵† P values for comparisons of differences of continuous variables between two genotypes using unpaired Student’s t or Mann-Whitney U test. Categorical variables were compared by χ2 test.

    • ‡

      ↵‡ P = 0.03 vs. G/G,

    • §

      ↵§ P = 0.05 vs. G/G,

    • ‖

      ↵‖ P = 0.03 vs. G/G,

    • ¶

      ↵¶ P= 0.01 vs. G/G,

    • #

      ↵# P = 0.05 vs. G/G,

    • **

      ↵** P = 0.03 vs. G/G genotype after least significant difference correction for multiple comparisons. IGT, impaired glucose tolerance; NGT, normal glucose tolerance; T2DM, type 2 diabetes.

  • Table 2—

    Clinical and biochemical characteristics according to the C-174G polymorphism of the IL-6 gene in 77 obese subjects who underwent LAGB

    IL-6 promoter genotypes
    *P†P (G/G vs. G/C + C/C)
    G/GG/CC/C
    Male/female (n)4/334/302/40.300.58
    Age (years)39 ± 9 (39)39 ± 10 (38)44 ± 10 (41)0.560.60
    Weight (kg)116 ± 17 (113)127 ± 24 (124)‡119 ± 10 (122)0.080.04
    BMI (kg/m2)43.6 ± 5.3 (44.0)47.5 ± 8.1 (45.6)‡42.8 ± 4.0 (43.1)0.040.09
    Waist-to-hip ratio0.86 ± 0.07 (0.85)0.87 ± 0.07 (0.86)0.89 ± 0.1 (0.87)0.680.26
    Ultrasound thickness of VAT (mm)84.3 ± 23.3 (79)89.3 ± 26.9 (88)95.3 ± 30.1 (108)0.710.46
    Ultrasound thickness of SAT (mm)46.0 ± 8.7 (46)48.9 ± 8.7 (51)44.3 ± 15.5 (38)0.560.50
    CT scan area of VAT (mm2)170 ± 26 (126)203 ± 55 (162)215 ± 60 (188)0.660.74
    CT scan area of SAT (mm2)493 ± 83 (480)503 ± 80 (452)523 ± 90 (497)0.790.81
    VAT-to-SAT ratio0.55 ± 0.45 (0.23)0.44 ± 0.51 (0.32)0.41 ± 0.70 (0.25)0.820.58
    Fasting glucose (mg/dl)110 ± 26 (102)113 ± 36 (102)113 ± 36 (105)0.960.82
    2-h glucose (mg/dl)143 ± 50 (137)174 ± 90 (155)174 ± 90 (156)0.140.11
    Fasting insulin (μU/ml)21 ± 9 (17)17 ± 7 (15)‡11 ± 3 (10)§0.020.04
    2-h insulin (μU/ml)78 ± 50 (75)88 ± 75 (65)81 ± 95 (54)0.850.55
    A1C (%)6.0 ± 1.3 (5.7)6.4 ± 1.4 (6.2)5.9 ± 1.4 (5.8)0.450.23
    Total cholesterol (mg/dl)189 ± 41 (182)220 ± 39 (210)‖204 ± 19 (198)0.0060.007
    HDL cholesterol (mg/dl)47 ± 12 (46)51 ± 22 (46)37 ± 7 (40)0.250.90
    Triglycerides (mg/dl)135 ± 69 (124)179 ± 139 (148)¶179 ± 139 (123)#0.0060.04
    HOMA6.4 ± 5.9 (4.5)4.5 ± 2.1 (4.1)3.0 ± 0.5 (3.1)**0.080.07
    NGT/IGT/IFG/T2DM (n)24/7/2/418/8/1/73/2/0/10.990.79
    IL-6 mRNA levels (arbitrary units)21 ± 19 (13.3)10 ± 12 (7.0)††13 ± 20 (2.4)0.0590.04
    • Data are means ± SD (median) unless otherwise indicated.

    • *

      ↵* P values for comparisons of differences of continuous variables between the three genotypes using ANOVA.

    • †

      ↵† P values for comparisons of differences of continuous variables between two genotypes using unpaired Student’s t or Mann-Whitney U test. Categorical variables were compared by χ2 test.

    • ‡

      ↵‡ P = 0.05 vs. G/G,

    • §

      ↵§ P = 0.05 vs. G/G,

    • ‖

      ↵‖ P = 0.002 vs. G/G,

    • ¶

      ↵¶ P = 0.007 vs. G/G,

    • #

      ↵# P = 0.002 vs. G/G,

    • **

      ↵** P = 0.05 vs. G/G, genotype after least significant difference correction for multiple comparisons,

    • ††

      ↵†† P = 0.02 vs. G/G. IFG, impaired fasting glucose; IGT, impaired glucose tolerance; NGT, normal glucose tolerance; SAT, subcutaneous adipose tissue; T2DM, type 2 diabetes; VAT, visceral adipose tissue.

  • Table 3—

    Independent predictors of insulin sensitivity after forward stepwise linear regression analysis

    Partial r2 (%)Total r2 (%)P (ANOVA)
    Model A*
        BMI (kg/m2)45.845.80.0001
        Triglyceride (mg/dl)3.249.00.0001
        C-174G polymorphism2.051.00.0001
        Age (years)0.951.90.0001
        Fasting plasma glucose (mg/dl)1.753.60.0001
    Model B†
        BMI (kg/m2)49.849.80.0001
        Triglyceride (mg/dl)3.953.70.0001
        Waist-to-hip ratio1.855.50.0001
        Fasting IL-6 concentration (pg/ml)1.657.10.0001
    • *

      ↵* Model A includes C-174G polymorphism, sex, age, BMI, waist-to-hip ratio, fasting plasma glucose, HDL cholesterol, and triglycerides levels.

    • †

      ↵† Model B includes C-174G polymorphism, plasma IL-6 concentrations, sex, age, BMI, waist-to-hip ratio, fasting plasma glucose, HDL cholesterol, and triglycerides levels.

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C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance
Marina Cardellini, Lucia Perego, Monica D’Adamo, Maria Adelaide Marini, Cristina Procopio, Marta Letizia Hribal, Francesco Andreozzi, Simona Frontoni, Maurizio Giacomelli, Michele Paganelli, Antonio E. Pontiroli, Renato Lauro, Franco Folli, Giorgio Sesti
Diabetes Care Aug 2005, 28 (8) 2007-2012; DOI: 10.2337/diacare.28.8.2007

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C-174G Polymorphism in the Promoter of the Interleukin-6 Gene Is Associated With Insulin Resistance
Marina Cardellini, Lucia Perego, Monica D’Adamo, Maria Adelaide Marini, Cristina Procopio, Marta Letizia Hribal, Francesco Andreozzi, Simona Frontoni, Maurizio Giacomelli, Michele Paganelli, Antonio E. Pontiroli, Renato Lauro, Franco Folli, Giorgio Sesti
Diabetes Care Aug 2005, 28 (8) 2007-2012; DOI: 10.2337/diacare.28.8.2007
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