scholarly journals CREBRF missense variant rs373863828 has both direct and indirect effects on type 2 diabetes and fasting glucose in Polynesians living in Samoa and Aotearoa New Zealand

2021 ◽  
Author(s):  
Emily M. Russell ◽  
Jenna C. Carlson ◽  
Mohanraj Krishnan ◽  
Nicola L. Hawley ◽  
Guangyun Sun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
New Zealand ◽  
Path Analysis ◽  
Fasting Glucose ◽  
Missense Variant ◽  
American Samoa ◽  
Minor Allele ◽  
Positive Effects ◽  
Aotearoa New Zealand

AbstractObjectiveThe minor allele of rs373863828 in CREBRF is associated with higher BMI, lower fasting glucose, and lower odds of type 2 diabetes. We examined the associations between BMI and rs373863828 on type 2 diabetes and fasting glucose with a large sample of adult Polynesians from Samoa, American Samoa and Aotearoa New Zealand and estimated direct and indirect (via BMI) effects of rs373863828 on type 2 diabetes and fasting glucose.Research Design and MethodsWe regressed type 2 diabetes and fasting glucose on BMI and rs373863828 stratified by obesity, regressed type 2 diabetes and fasting glucose on BMI stratified by rs373863828 genotype, and assessed the effects of rs373863828 on type 2 diabetes and fasting glucose with path analysis.ResultsAssociation of BMI with fasting glucose was greater in those without obesity than in those with obesity. We did not observe evidence of differences by genotype. In the path analysis, the minor allele has direct negative and indirect positive effects on type 2 diabetes risk and fasting glucose, with the indirect effect mediated through a direct positive effect on BMI.ConclusionsThere may be a stronger effect of BMI on fasting glucose in Polynesians without obesity than in those with obesity. Carrying the rs373863828 minor allele does not decouple higher BMI from odds of type 2 diabetes. Given the current cost of genotyping compared to the accessibility of measuring BMI, including rs373863828 as a clinical predictor of type 2 diabetes may not be indicated.

scholarly journals Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa New Zealand

2017 ◽  
Author(s):  
Mohanraj Krishnan ◽  
Tanya J Major ◽  
Ruth K Topless ◽  
Ofa Dewes ◽  
Lennex Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
New Zealand ◽  
Waist Circumference ◽  
Body Mass ◽  
American Samoa ◽  
Minor Allele ◽  
Association Analyses ◽  
Aotearoa New Zealand

AbstractAim/HypothesesThe minor allele of CREBRF rs373863828 associates with increased body mass index (BMI) and reduced risk of type 2 diabetes (T2D) in the Samoan population of Samoa and American Samoa. Our aim was to test rs373863828 for association with BMI and odds of T2D, gout and chronic kidney disease (CKD) in Māori and Pacific (Polynesian) people living in Aotearoa New Zealand in 2,286 adults.MethodsAssociation analyses were performed by linear and logistic regression with BMI, log-transformed BMI, waist circumference, T2D, gout and CKD. Analyses were adjusted for age, sex, the first four genome-wide principal components, and (when appropriate) BMI, waist circumference and T2D.ResultsFor the minor allele of rs373863828 the effect size for log-transformed BMI was 0.038 (95% CI [0.022-0.055], P=4.8x10−6) and for T2D was OR=0.59 (95% CI [0.47-0.73], P=1.9x10−6). There was no evidence for association of genotype with variance in BMI (P=0.13). Nor was there evidence for association with serum urate (β=0.012 mmol/L, Pc=0.10), gout (OR=1.00, P=0.98) or CKD (OR=0.91, P=0.59).Conclusions/interpretationOur results replicated, with very similar effect sizes, association of the minor allele of rs373863828 with higher BMI but lower odds of T2D among New Zealand Polynesian adults, as in Samoan adults living in Samoa and American Samoa.

scholarly journals The minor allele of the CREBRF rs373863828 p.R457Q coding variant is associated with reduced levels of myostatin in males: Implications for body composition

2021 ◽  
Author(s):  
Kate Lee ◽  
Sanaz Vakili ◽  
Hannah J Burden ◽  
Shannon Adams ◽  
Greg C Smith ◽  
...  
Keyword(s):  
Body Composition ◽  
New Zealand ◽  
Lean Mass ◽  
Pacific Islands ◽  
Minor Allele ◽  
Composition Analysis ◽  
Aotearoa New Zealand ◽  
The Pacific ◽  
New Evidence

The minor allele (A) of the rs373863828 variant (p.Arg457Gln) in CREBRF is restricted to indigenous peoples of the Pacific islands (including New Zealand Māori and peoples of Polynesia), with a frequency up to 25% in these populations. This allele associates with a large increase in body mass index (BMI) but with significantly lower risk of type-2 diabetes (T2D). It is unclear whether the increased BMI is driven by increased adiposity or by increased lean mass. Hence, we undertook body composition analysis using DXA in 189 young men of Māori and Pacific descent living in Aotearoa New Zealand. The rs373863828 A allele was associated with a trend toward increased relative lean mass although this was not statistically significant (p=0.06). Notably though this allele was associated with significantly lower circulating levels of the muscle inhibitory hormone myostatin (p<0.05). This was further investigated in two Arg458Gln knockin mouse models on FVB/Nj and C57Bl/6j backgrounds. Supporting the human data, significant increases in relative lean mass were observed in male knockin mice. This was more significant in older mice (p<0.01) where it was associated with increased grip strength (p<0.01) and lower levels of myostatin (p <0.05). Overall these results provide new evidence that the rs373863828 A-allele is associated with a reduction of myostatin levels which likely contributes to increased lean muscle mass component of BMI, at least in males.

scholarly journals Discordant association of the CREBRF rs373863828 A allele with increased BMI and protection from type 2 diabetes in Māori and Pacific (Polynesian) people living in Aotearoa/New Zealand

Diabetologia ◽  
2018 ◽  
Vol 61 (7) ◽  
pp. 1603-1613 ◽  
Author(s):  
Mohanraj Krishnan ◽  
Tanya J. Major ◽  
Ruth K. Topless ◽  
Ofa Dewes ◽  
Lennex Yu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
New Zealand ◽  
Aotearoa New Zealand

Circulating Netrin-1 as a Novel Biomarker for Impaired Fasting Glucose and Newly Diagnosed Type 2 Diabetes Mellitus

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1535-P ◽  
Author(s):  
HYE-IN JUNG ◽  
JAEHYUN BAE ◽  
EUGENE HAN ◽  
GYURI KIM ◽  
JI-YEON LEE ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Impaired Fasting Glucose ◽  
Fasting Glucose ◽  
Newly Diagnosed

1476-P: Progression to Type 2 Diabetes from Normal or Impaired Fasting Glucose

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1476-P
Author(s):  
AOIFE M. EGAN ◽  
CHRISTINA WOOD-WENTZ ◽  
KENT R. BAILEY ◽  
ADRIAN VELLA
Keyword(s):  
Type 2 Diabetes ◽  
Impaired Fasting Glucose ◽  
Fasting Glucose

Fasting Glucose-to-HbA1c Ratio Is a Good Indicator of G6PD Deficiency in Patients with Type 2 Diabetes

2019 ◽  
Author(s):  
Ya-Sian Chang ◽  
Li-Yun Hsiao ◽  
Chien-Yu Lin ◽  
Mu-Chin Shih ◽  
Ming-Chia Hsieh ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
G6pd Deficiency ◽  
Fasting Glucose

Metformin: Up to Date

2020 ◽  
Vol 20 (2) ◽  
pp. 172-181 ◽  
Author(s):  
Silvia Sciannimanico ◽  
Franco Grimaldi ◽  
Fabio Vescini ◽  
Giovanni De Pergola ◽  
Massimo Iacoviello ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Current Literature ◽  
Weight Control ◽  
Low Cost ◽  
Hepatic Glucose Production ◽  
Metabolic Effects ◽  
Hypoglycemic Agents ◽  
Positive Effects ◽  
Mesh Terms

Background: Metformin is an oral hypoglycemic agent extensively used as first-line therapy for type 2 diabetes. It improves hyperglycemia by suppressing hepatic glucose production and increasing glucose uptake in muscles. Metformin improves insulin sensitivity and shows a beneficial effect on weight control. Besides its metabolic positive effects, Metformin has direct effects on inflammation and can have immunomodulatory and antineoplastic properties. Aim: The aim of this narrative review was to summarize the up-to-date evidence from the current literature about the metabolic and non-metabolic effects of Metformin. Methods: We reviewed the current literature dealing with different effects and properties of Metformin and current recommendations about the use of this drug. We identified keywords and MeSH terms in Pubmed and the terms Metformin and type 2 diabetes, type 1 diabetes, pregnancy, heart failure, PCOS, etc, were searched, selecting only significant original articles and review in English, in particular of the last five years. Conclusion: Even if many new effective hypoglycemic agents have been launched in the market in the last few years, Metformin would always keep a place in the treatment of type 2 diabetes and its comorbidities because of its multiple positive effects and low cost.

scholarly journals Interaction between dietary branched-chain amino acids and genetic risk score on the risk of type 2 diabetes in Chinese

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Weiqi Wang ◽  
Haiyang Jiang ◽  
Ziwei Zhang ◽  
Wei Duan ◽  
Tianshu Han ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Predisposition ◽  
Genetic Risk ◽  
Odds Ratio ◽  
Regression Models ◽  
Fasting Glucose ◽  
Genetic Risk Score ◽  
Branched Chain Amino Acids ◽  
Branched Chain

Abstract Background and objectives Previous studies have found the important gene-diet interactions on type 2 diabetes (T2D) incident but have not followed branched-chain amino acids (BCAAs), even though they have shown heterogeneous effectiveness in diabetes-related factors. So in this study, we aim to investigate whether dietary BCAAs interact with the genetic predisposition in relation to T2D risk and fasting glucose in Chinese adults. Methods In a case-control study nested in the Harbin Cohort Study on Diet, Nutrition and Chronic Non-Communicable Diseases, we obtained data for 434 incident T2D cases and 434 controls matched by age and sex. An unweighted genetic risk score (GRS) was calculated for 25 T2D-related single nucleotide polymorphisms by summation of the number of risk alleles for T2D. Multivariate logistic regression models and general linear regression models were used to assess the interaction between dietary BCAAs and GRS on T2D risk and fasting glucose. Results Significant interactions were found between GRS and dietary BCAAs on T2D risk and fasting glucose (p for interaction = 0.001 and 0.004, respectively). Comparing with low GRS, the odds ratio of T2D in high GRS were 2.98 (95% CI 1.54–5.76) among those with the highest tertile of total BCAA intake but were non-significant among those with the lowest intake, corresponding to 0.39 (0.12) mmol/L versus − 0.07 (0.10) mmol/L fasting glucose elevation per tertile. Viewed differently, comparing extreme tertiles of dietary BCAAs, the odds ratio (95% CIs) of T2D risk were 0.46 (0.22–0.95), 2.22 (1.15–4.31), and 2.90 (1.54–5.47) (fasting glucose elevation per tertile: − 0.23 (0.10), 0.18 (0.10), and 0.26 (0.13) mmol/L) among participants with low, intermediate, and high genetic risk, respectively. Conclusions This study indicated that dietary BCAAs could amplify the genetic association with T2D risk and fasting glucose. Moreover, higher BCAA intake showed positive association with T2D when genetic predisposition was also high but changed to negative when genetic predisposition was low.

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