TY - JOUR

T1 - Glucose-dependent insulinotropic polypeptide (GIP) is associated with lower LDL but unhealthy fat distribution, independent of insulin

T2 - The ADDITION-PRO study

AU - Møller, Cathrine Laustrup

AU - Vistisen, Dorte

AU - Færch, Kristine

AU - Johansen, Nanna Borup

AU - Witte, Daniel R.

AU - Jonsson, Anna

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Lauritzen, Torsten

AU - Jørgensen, Marit E

AU - Torekov, Signe S

AU - Juul Holst, Jens

PY - 2016/2

Y1 - 2016/2

N2 - CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, as 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.DESIGN, SETTING AND PARTICIPANTS: Analyses were based on the Danish cross-sectional ADDITION-PRO study (n=1,405). 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 minutes). 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 (-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) subcutaneous 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 LDL 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 subcutaneous adipose tissue physiology warrants further examination.

AB - CONTEXT: Glucose-dependent insulinotropic polypeptide (GIP) may increase lipid clearance by stimulating lipid uptake. However, as 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.DESIGN, SETTING AND PARTICIPANTS: Analyses were based on the Danish cross-sectional ADDITION-PRO study (n=1,405). 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 minutes). 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 (-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) subcutaneous 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 LDL 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 subcutaneous adipose tissue physiology warrants further examination.

U2 - 10.1210/jc.2015-3133

DO - 10.1210/jc.2015-3133

M3 - Journal article

C2 - 26505824

VL - 101

SP - 485

EP - 493

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 2

ER -