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Impact of family history on relations between insulin resistance, LDL cholesterol and carotid IMT in healthy adults
  1. Christian Anderwald1,
  2. Marietta Stadler2,3,
  3. Alain Golay4,
  4. Michael Krebs1,
  5. John Petrie5,
  6. Anton Luger1,
  7. on behalf of the RISC Investigators*
  1. 1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Austria
  2. 23rd Medical Department of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria
  3. 3Karl Landsteiner Institute of Metabolic Diseases and Nephrology, Hietzing Hospital, Vienna, Austria
  4. 4Division of Therapeutical Teaching for Chronic Diseases, University Hospital Geneva, Geneva, Switzerland
  5. 5BHF Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK
  1. Correspondence to Christian Anderwald, Associate Professor of Internal Medicine, Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria; christian-heinz.anderwald{at}


Background Insulin resistance (IR) is implicated as an independent risk factor for vascular disease. The aim of this study was to assess the impact of family history (FH) of type 2 diabetes (T2DM) and/or cardiovascular disease (CVD) on the associations between IR, low-density-lipoprotein cholesterol (LDL-C) and subclinical atherosclerosis (common and internal carotid artery intima media thickness (IMT)) in healthy European adults.

Methods Participants (n=1048) in the Relationship between Insulin Sensitivity and Cardiovascular disease (RISC) study were grouped according to family history of: (i) type 2 diabetes (FH-T2DM); (ii) cardiovascular disease (FH-CVD); (iii) both (FH-BOTH); or (iv) neither (CON). Insulin resistance (M-value, hyperinsulinaemic euglycaemic clamp), LDL-C and IMT were examined in relation to FH in all available participants, and then within subcohorts (highest quintiles) with higher LDL-C (>3.5 mmol/l (>135 mg/dl), n=252) or greater IR (M-value<5 mg/min/kg, n=299).

Results Carotid IMTs were comparable across the four FH groups, but insulin sensitivity (M-value) was lower (p<0.01) in FH-T2DM (6.1±2.6 mg/min/kg than in either CON (6.9±2.9 mg/min/kg) or FH-CVD (7.1±2.7 mg/min/kg). Within the highest LDL-C quintile, those with FH-CVD (or FH-BOTH) had higher common and internal carotid IMT (6–12%, p<0.05 vs CON). In contrast, within the most IR quintile, FH-CVD was not associated with IMT.

Conclusion In this cross-sectional analysis, family history of T2DM (but not of CVD) was associated with IR. In the presence of elevated LDL-C, FH-CVD (but not FH-T2DM) was associated with increased carotid IMT.

  • Insulin resistance
  • vascular disease
  • low-density-lipoprotein cholesterol
  • atherosclerosis
  • metabolic syndrome
  • endocrinology
  • cerebral protection

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  • * RISC Investigators

    RISC recruiting centres

    Amsterdam, The Netherlands: R.J. Heine, J Dekker, S de Rooij, G Nijpels, W Boorsma

    Athens, Greece: A Mitrakou, S Tournis, K Kyriakopoulou, P Thomakos

    Belgrade, Serbia and Montenegro: N Lalic, K Lalic, A Jotic, L Lukic, M Civcic

    Dublin, Ireland: J Nolan, TP Yeow, M Murphy, C DeLong, G Neary, MP Colgan, M Hatunic

    Frankfurt, Germany: T Konrad, H Böhles, S Franke, F Baer, H Zuchhold

    Geneva, Switzerland: A Golay, E. Harsch Bobbioni, V. Barthassat, V. Makoundou, TNO Lehmann, T Merminod

    Glasgow, Scotland: JR Petrie, C Perry, F Neary, C MacDougall, K Shields, L Malcolm

    Kuopio, Finland: M Laakso, U Salmenniemi, A Aura, R Raisanen, U Ruotsalainen, T Sistonen, M Laitinen, H Saloranta

    London, England: SW Coppack, N McIntosh, J Ross, L Pettersson, P Khadobaksh

    Lyon, France: M Laville, F. Bonnet, A Brac de la Perriere, C Louche-Pelissier, C Maitrepierre, J Peyrat, S Beltran, A Serusclat

    Madrid, Spain: R. Gabriel, EM Sánchez, R. Carraro, A Friera, B. Novella

    Malmö, Sweden (1): P Nilsson, M Persson, G Östling, (2): O Melander, P Burri

    Milan, Italy: PM Piatti, LD Monti, E Setola, E Galluccio, F Minicucci, A Colleluori

    Newcastle-upon-Tyne, England: M Walker, IM Ibrahim, M Jayapaul, D Carman, C Ryan, K Short, Y McGrady, D Richardson

    Odense, Denmark: H Beck-Nielsen, P Staehr, K Hojlund, V Vestergaard, C Olsen, L Hansen

    Perugia, Italy: GB Bolli, F Porcellati, C Fanelli, P Lucidi, F Calcinaro, A Saturni

    Pisa, Italy: E Ferrannini, A Natali, E Muscelli, S Pinnola, M Kozakova

    Rome, Italy: G Mingrone, C Guidone, A Favuzzi. P Di Rocco

    Vienna, Austria: C Anderwald, M Bischof, M Promintzer, M Krebs, M Mandl, A Hofer, A Luger, W Waldhäusl, M Roden

    Project Management Board

    B Balkau (Villejuif, France), SW Coppack (London, England), JM Dekker (Amsterdam, The Netherlands), E Ferrannini (Pisa, Italy), A Mari (Padova, Italy), A Natali (Pisa, Italy), M Walker (Newcastle, England)

    Core laboratories and reading centres

    Lipids Dublin, Ireland: P Gaffney, J Nolan, G Boran

    Hormones Odense, Denmark: C Olsen, L Hansen, H Beck-Nielsen

    Albumin:creatinine Amsterdam, The Netherlands: A Kok, J Dekker

    Genetics Newcastle-upon-Tyne, England: S Patel, M Walker

    Stable isotope laboratory Pisa, Italy: A Gastaldelli, D Ciociaro

    Ultrasound reading centre Pisa, Italy: M Kozakova

    ECG reading, Villejuif, France: MT Guillanneuf

    Data Management Villejuif, France: B Balkau, L Mhamdi

    Mathematical modelling and website management Padova, Italy: A Mari, G Pacini, C Cavaggion

    Coordinating office: Pisa, Italy: SA Hills, L Landucci, L Mota

    Further information on the RISC Study and participating centres can be found on

  • Funding Financial support was provided by AstraZeneca (Sweden). The European Group for the Study of Insulin Resistance who carried out the study is supported by Merck Santé, France.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of the local ethics committees from all study centres.

  • Provenance and peer review Not commissioned; externally peer reviewed.