| 1. |
- Ji, Yingjie, et al.
(författare)
-
Genome-wide and abdominal MRI data provide evidence that a genetically determined favorable adiposity phenotype is characterized by lower ectopic liver fat and lower risk of type 2 diabetes, heart disease, and hypertension
- 2019
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 68:1, s. 207-219
-
Tidskriftsartikel (refereegranskat)abstract
- Recent genetic studies have identified alleles associated with opposite effects on adiposity and risk of type 2 diabetes. We aimed to identify more of these variants and test the hypothesis that such favorable adiposity alleles are associated with higher subcutaneous fat and lower ectopic fat. We combined MRI data with genome-wide association studies of body fat percentage (%) and metabolic traits. We report 14 alleles, including 7 newly characterized alleles, associated with higher adiposity but a favorable metabolic profile. Consistent with previous studies, individuals carrying more favorable adiposity alleles had higher body fat % and higher BMI but lower risk of type 2 diabetes, heart disease, and hypertension. These individuals also had higher subcutaneous fat but lower liver fat and a lower visceral-to-subcutaneous adipose tissue ratio. Individual alleles associated with higher body fat % but lower liver fat and lower risk of type 2 diabetes included those in PPARG, GRB14, and IRS1, whereas the allele in ANKRD55 was paradoxically associated with higher visceral fat but lower risk of type 2 diabetes. Most identified favorable adiposity alleles are associated with higher subcutaneous and lower liver fat, a mechanism consistent with the beneficial effects of storing excess triglycerides in metabolically low-risk depots.
|
|
| 2. |
|
|
| 3. |
- Wagner, Róbert, et al.
(författare)
-
Nonsuppressed glucagon after glucose challenge as a potential predictor for glucose tolerance
- 2017
-
Ingår i: Diabetes. - : American Diabetes Association. - 0012-1797 .- 1939-327X. ; 66:5, s. 1373-1379
-
Tidskriftsartikel (refereegranskat)abstract
- Glucagon levels are classically suppressed after glucose challenge. It is still not clear as to whether a lack of suppression contributes to hyperglycemia and thus to the development of diabetes. We investigated the association of postchallenge change in glucagon during oral glucose tolerance tests (OGTTs), hypothesizing that higher postchallenge glucagon levels are observed in subjects with impaired glucose tolerance (IGT). Glucagon levels were measured during OGTT in a total of 4,194 individuals without diabetes in three large European cohorts. Longitudinal changes in glucagon suppression were investigated in 50 participants undergoing a lifestyle intervention. Only 66-79% of participants showed suppression of glucagon at 120 min (fold change glucagon120/0 <1) during OGTT, whereas 21-34% presented with increasing glucagon levels (fold change glucagon120/0 ≥1). Participants with nonsuppressed glucagon120 had a lower risk of IGT in all cohorts (odds ratio 0.44-0.53, P < 0.01). They were also leaner and more insulin sensitive and had lower liver fat contents. In the longitudinal study, an increase of fold change glucagon120/0 was associated with an improvement in insulin sensitivity (P = 0.003). We characterize nonsuppressed glucagon120 during the OGTT. Lower glucagon suppression after oral glucose administration is associated with a metabolically healthier phenotype, suggesting that it is not an adverse phenomenon.
|
|
| 4. |
- Wu, Chuanyan, et al.
(författare)
-
Elevated circulating follistatin associates with an increased risk of type 2 diabetes
- 2021
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12, s. 1-10
-
Tidskriftsartikel (refereegranskat)abstract
- The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04-1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09-1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
|
|
