Glucose-Dependent Insulinotropic Polypeptide Is Associated With Lower Low-Density Lipoprotein But Unhealthy Fat Distribution, Independent of Insulin: The ADDITION-PRO Study.
BACKGROUND
Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, given that GIP promotes release of insulin by the pancreas and insulin is anti-lipolytic, the effect may be indirect.


OBJECTIVE
In this study we examined the association between GIP and lipid metabolism in individuals with low to high risk of type 2 diabetes and assessed whether the associations were modified by or mediated through insulin.


METHODS
Analyses were based on the Danish cross-sectional ADDITION-PRO study (n = 1405). Lipid metabolism was measured by fasting plasma lipids and obesity including abdominal fat distribution assessed by ultrasonography. GIP and insulin were measured during an oral glucose tolerance test (0, 30 and 120 min). Linear regression analysis was used to study the associations between GIP, plasma lipids, and obesity measures.


RESULTS
A doubling in fasting GIP levels was associated with lower low-density lipoprotein in both men (mean [95% CI] -0.10 mmol/l [-0.18--0.03]) and women (-0.14 mmol/l [-0.23--0.04]) and with higher high-density lipoprotein in women (0.06 mmol/l [-0.02-0.10]). In men, a doubling in stimulated GIP was associated with 0.13 cm less 0.01-0.25 sc fat but with more visceral abdominal fat (0.45 cm [0.12-0.78]) and higher waist-hip ratio (0.011 [0.004-0.019]).


CONCLUSIONS
Contrary to what was previously thought, GIP may be associated with improved low-density lipoprotein clearance but with an unhealthy fat distribution independent of insulin. The effect of GIP on obesity measures was substantially different between men and women. The potential effect of GIP on visceral and sc adipose tissue physiology warrants further examination.
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Cathrine Laustrup
CL
Møller
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Dorte
D
Vistisen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Kristine
K
Færch
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Nanna Borup
NB
Johansen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Daniel R
DR
Witte
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Anna
A
Jonsson
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Oluf
O
Pedersen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Torben
T
Hansen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Torsten
T
Lauritzen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Marit E
ME
Jørgensen
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Signe S
SS
Torekov
Steno Diabetes Center (C.L.M., D.V., K.F., N.B.J., M.E.J.), 2820 Gentofte, Denmark; The Danish Diabetes Academy (N.B.J., D.R.W.), 5000 Odense, Denmark; Department of Public Health, Section for General Practice (D.R.W., T.L.), Aarhus University, 8000 Aarhus, Denmark; NNF Center for Basic Metabolic Research (A.J., O.P., T.H., S.S.T., J.J.H.), University of Copenhagen, 2200 Copenhagen, Denmark; and Department of Biomedical Sciences (S.S.T., J.J.H.), Public Health, University of Copenhagen, 1014 Copenhagen, Denmark.
Jens Juul
JJ
Holst
D050153:Abdominal Fat / Q000000981:diagnostic imaging; D050154:Adiposity / Q000235:genetics*; D000368:Aged; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000235:genetics* / Q000378:metabolism*; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D050356:Lipid Metabolism / Q000235:genetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D012306:Risk; D012727:Sex Characteristics; D014463:Ultrasonography
D007328:Insulin; D008077:Lipoproteins, LDL; D005749:Gastric Inhibitory Polypeptide