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
- metabolic syndrome
- 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 http://www.egir.org/
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.