AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic-hyperinsulinaemic (240 pmol min(-1) m(-2)) clamp technique] in 1,296 non-diabetic (on a 75 g OGTT) individuals [716 women and 579 men, mean age 44 years, BMI 26 kg/m(2) (range 18-44 kg/m(2))] recruited at 19 centres in 14 European countries. IR was related to fasting proinsulin or pancreatic glucagon concentrations in univariate and multivariate analyses. Given its known relationship to IR, serum adiponectin was used as a positive control. RESULTS: In either sex, both glucagon and proinsulin were directly related to IR, while adiponectin was negatively associated with it (all p < 0.0001). In multivariate models, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR. Finally, when these associations were tested as the probability that individuals in the top IR quartile would have hormone levels in the top quartile of their distribution independently of covariates, the odds ratio was approximately 2 for both glucagon (p = 0.05) and proinsulin (p = 0.02) and 0.36 for adiponectin (p < 0.0001). CONCLUSIONS/ INTERPRETATION: Whole-body IR is independently associated with raised fasting plasma glucagon and proinsulin concentrations, possibly as a result of IR at the level of alpha cells and beta cells in pancreatic islets.
AIMS/HYPOTHESIS: Hyperproinsulinaemia and relative hyperglucagonaemia are features of type 2 diabetes. We hypothesised that raised fasting glucagon and proinsulin concentrations may be associated with insulin resistance (IR) in non-diabetic individuals. METHODS: We measured IR [by a euglycaemic-hyperinsulinaemic (240 pmol min(-1) m(-2)) clamp technique] in 1,296 non-diabetic (on a 75 g OGTT) individuals [716 women and 579 men, mean age 44 years, BMI 26 kg/m(2) (range 18-44 kg/m(2))] recruited at 19 centres in 14 European countries. IR was related to fasting proinsulin or pancreatic glucagon concentrations in univariate and multivariate analyses. Given its known relationship to IR, serum adiponectin was used as a positive control. RESULTS: In either sex, both glucagon and proinsulin were directly related to IR, while adiponectin was negatively associated with it (all p < 0.0001). In multivariate models, controlling for known determinants of insulin sensitivity (i.e. sex, age, BMI and glucose tolerance) as well as factors potentially affecting glucagon and proinsulin (i.e. fasting plasma glucose and C-peptide concentrations), glucagon and proinsulin were still positively associated, and adiponectin was negatively associated, with IR. Finally, when these associations were tested as the probability that individuals in the top IR quartile would have hormone levels in the top quartile of their distribution independently of covariates, the odds ratio was approximately 2 for both glucagon (p = 0.05) and proinsulin (p = 0.02) and 0.36 for adiponectin (p < 0.0001). CONCLUSIONS/ INTERPRETATION: Whole-body IR is independently associated with raised fasting plasma glucagon and proinsulin concentrations, possibly as a result of IR at the level of alpha cells and beta cells in pancreatic islets.
Authors: Kohjiro Ueki; Terumasa Okada; Jiang Hu; Chong Wee Liew; Anke Assmann; Gabriella M Dahlgren; Jennifer L Peters; Jonathan G Shackman; Min Zhang; Isabella Artner; Leslie S Satin; Roland Stein; Martin Holzenberger; Robert T Kennedy; C Ronald Kahn; Rohit N Kulkarni Journal: Nat Genet Date: 2006-04-23 Impact factor: 38.330
Authors: Aruna D Pradhan; JoAnn E Manson; James B Meigs; Nader Rifai; Julie E Buring; Simin Liu; Paul M Ridker Journal: Am J Med Date: 2003-04-15 Impact factor: 4.965
Authors: S A Hills; B Balkau; S W Coppack; J M Dekker; A Mari; A Natali; M Walker; E Ferrannini Journal: Diabetologia Date: 2004-02-14 Impact factor: 10.122
Authors: E Ferrannini; A Natali; E Muscelli; P M Nilsson; A Golay; M Laakso; H Beck-Nielsen; A Mari Journal: Diabetologia Date: 2011-03-22 Impact factor: 10.122
Authors: Jon D Adams; Aoife M Egan; Marcello C Laurenti; Daniel Schembri Wismayer; Kent R Bailey; Claudio Cobelli; Chiara Dalla Man; Adrian Vella Journal: Am J Physiol Endocrinol Metab Date: 2021-10-18 Impact factor: 4.310
Authors: Jon D Adams; Chiara Dalla Man; Marcello C Laurenti; M Daniela Hurtado Andrade; Claudio Cobelli; Robert A Rizza; Kent R Bailey; Adrian Vella Journal: Metabolism Date: 2020-02-08 Impact factor: 8.694
Authors: Helga Ellingsgaard; Jan A Ehses; Eva B Hammar; Leentje Van Lommel; Roel Quintens; Geert Martens; Julie Kerr-Conte; Francois Pattou; Thierry Berney; Daniel Pipeleers; Philippe A Halban; Frans C Schuit; Marc Y Donath Journal: Proc Natl Acad Sci U S A Date: 2008-08-21 Impact factor: 11.205