Sökning: WFRF:(Yerges Armstrong Laura M.)
> (2014) >
Genetic evidence fo...
Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease and type 2 diabetes.
-
Yaghootkar, Hanieh (författare)
-
Scott, Robert A (författare)
-
White, Charles C (författare)
-
visa fler...
-
Zhang, Weihua (författare)
-
Speliotes, Elizabeth (författare)
-
Munroe, Patricia B (författare)
-
Ehret, Georg B (författare)
-
Bis, Joshua C (författare)
-
Fox, Caroline S (författare)
-
Walker, Mark (författare)
-
Borecki, Ingrid B (författare)
-
Knowles, Joshua W (författare)
-
Yerges-Armstrong, Laura (författare)
-
- Ohlsson, Claes, 1965 (författare)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Centre for Bone and Arthritis Research,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
-
Perry, John R B (författare)
-
Chambers, John C (författare)
-
Kooner, Jaspal S (författare)
-
Franceschini, Nora (författare)
-
Langenberg, Claudia (författare)
-
Hivert, Marie-France (författare)
-
Dastani, Zari (författare)
-
Richards, J Brent (författare)
-
Semple, Robert K (författare)
-
Frayling, Timothy M (författare)
-
visa färre...
-
(creator_code:org_t)
- 2014-11-13
- 2014
- Engelska.
-
Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 63:12, s. 4369-77
- Relaterad länk:
-
https://diabetes.dia...
-
visa fler...
-
https://gup.ub.gu.se...
-
https://doi.org/10.2...
-
visa färre...
Abstract
Ämnesord
Stäng
- The mechanisms that predispose to hypertension, coronary artery disease (CAD) and type 2 diabetes (T2D) in individuals of normal weight are poorly understood. In contrast, in monogenic primary lipodystrophy - a reduction in subcutaneous adipose tissue - it is clear that it is adipose dysfunction that causes severe insulin resistance (IR), hypertension, coronary artery disease and type 2 diabetes. We aimed to test the hypothesis that common alleles associated with insulin resistance also influence the wider clinical and biochemical profile of monogenic insulin resistance. We selected 19 common genetic variants associated with fasting insulin based measures of insulin resistance. We used hierarchical clustering and results from genome wide association studies of 8 non-disease outcomes of monogenic insulin resistance, to group these variants. We analysed genetic risk scores against disease outcomes including 12,171 T2D cases, 40,365 CAD cases and 69,828 individuals with blood pressure measurements. Hierarchical clustering identified 11 variants associated with a metabolic profile consistent with a common, subtle, form of lipodystrophy. A genetic risk score consisting of these 11 IR risk alleles was associated with higher triglycerides (ß=0.018; p=4x10(-29)), lower HDL cholesterol (ß=-0.020; p=7x10(-37)), greater hepatic steatosis (ß=0.021; p=3x10(-4)) higher alanine transaminase (ß=0.002; p=3x10(-5)), lower SHBG (ß=-0.010; p=9x10(-13)) and lower adiponectin (ß=-0.015; p=2x10(-26)). The same risk alleles were associated with lower BMI (per-allele ß=-0.008; p=7x10(-8)), and increased visceral-to-subcutaneous adipose tissue ratio (ß=-0.015; p=6x10(-7)). Individuals carrying >= 17 fasting insulin raising alleles (5.5% population) were slimmer (0.30 kgm(-2)) but at increased risk of T2D (odds ratio [OR] 1.46, per-allele p=5x10(-13)), CAD (OR 1.12, per-allele p=1x10(-5)), and increased blood pressure (systolic and diastolic blood pressure of 1.21 mmHg (per-allele p=2x10(-5)), and 0.67 mmHg (per-allele p=2x10(-4)), respectively, compared to individuals carrying <=9 risk alleles (5.5% population). Our results provide genetic evidence for a link between the three diseases of the "metabolic syndrome" and point to reduced subcutaneous adiposity as a central mechanism.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
-
Diabetes
(Sök värdpublikationen i LIBRIS)
Till lärosätets databas
- Av författaren/redakt...
-
Yaghootkar, Hani ...
-
Scott, Robert A
-
White, Charles C
-
Zhang, Weihua
-
Speliotes, Eliza ...
-
Munroe, Patricia ...
-
visa fler...
-
Ehret, Georg B
-
Bis, Joshua C
-
Fox, Caroline S
-
Walker, Mark
-
Borecki, Ingrid ...
-
Knowles, Joshua ...
-
Yerges-Armstrong ...
-
Ohlsson, Claes, ...
-
Perry, John R B
-
Chambers, John C
-
Kooner, Jaspal S
-
Franceschini, No ...
-
Langenberg, Clau ...
-
Hivert, Marie-Fr ...
-
Dastani, Zari
-
Richards, J Bren ...
-
Semple, Robert K
-
Frayling, Timoth ...
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Endokrinologi oc ...
- Artiklar i publikationen
-
Diabetes
- Av lärosätet
-
Göteborgs universitet