Apolipoprotein M and Risk of Type 2 Diabetes

2020 ◽  
Vol 105 (9) ◽  
pp. 3046-3057
Author(s):  
Stefan Hajny ◽  
Mette Christoffersen ◽  
Nawar Dalila ◽  
Lars B Nielsen ◽  
Anne Tybjærg-Hansen ◽  
...  

Abstract Context Recent studies have discovered a role of apolipoprotein M (apoM) in energy metabolism, and observational analyses in humans suggest an association with type 2 diabetes. The causal relationship remains however elusive. Objective To investigate whether reduced plasma apoM concentrations are causally linked to increased risk of type 2 diabetes. Design Prospective study design analyzed by Mendelian randomization. Setting and participants Two cohorts reflecting the Danish general population: the Copenhagen City Heart Study (CCHS, n = 8589) and the Copenhagen General Population Study (CGPS; n = 93 857). Observational analyses included a subset of participants from the CCHS with available plasma apoM (n = 725). Genetic analyses included the complete cohorts (n = 102 446). During a median follow-up of 16 years (CCHS) and 8 years (CGPS), 563 and 2132 participants developed type 2 diabetes. Main outcome measures Plasma apoM concentration, genetic variants in APOM, and type 2 diabetes. Results First, we identified an inverse correlation between plasma apoM and risk of type 2 diabetes in a subset of participants from the CCHS (hazard ratio between highest vs lowest quartile (reference) = 0.32; 95% confidence interval = 0.1-1.01; P for trend = .02). Second, genotyping of specific single nucleotide polymorphisms in APOM further revealed a 10.8% (P = 6.2 × 10–5) reduced plasma apoM concentration in participants with variant rs1266078. Third, a meta-analysis including data from 599 451 individuals showed no association between rs1266078 and risk of type 2 diabetes. Conclusions The present study does not appear to support a causal association between plasma apoM and risk of type 2 diabetes.

2020 ◽  
Vol 21 (14) ◽  
pp. 1152-1160
Author(s):  
Imadeldin Elfaki ◽  
Rashid Mir ◽  
Faisel Mohammed Abu-Duhier ◽  
Chandan Kumar Jha ◽  
Adel Ibrahim Ahmad Al-Alawy ◽  
...  

Background:: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations. Objective:: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population. Methods:: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893. Results:: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008. Conclusion:: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.


2018 ◽  
Vol 15 (1) ◽  
pp. 31-43 ◽  
Author(s):  
Sayantan Nath ◽  
Sambuddha Das ◽  
Aditi Bhowmik ◽  
Sankar Kumar Ghosh ◽  
Yashmin Choudhury

Background:Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study.Methods:Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted.Results:Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the risk for T2DM in both Caucasians and Asians, with Asians showing much higher risk of T2DM complications than Caucasians for the same. </P><P> Discussion: GSTM1, GSTT1 and combined GSTM1-GSTT1 null polymorphism may be associated with increased risk for T2DM; while GSTT1 and combined GSTM1-GSTT1 null polymorphism may increase the risk of subsequent development of T2DM complications with Asian population carrying an amplified risk for the polymorphism.Conclusion:Thus GSTM1 and GSTT1 null genotypes increases the risk for Type 2 diabetes mellitus alone, in combination or with regards to ethnicity.


2015 ◽  
Vol 18 (16) ◽  
pp. 3013-3019 ◽  
Author(s):  
Huashan Bi ◽  
Yong Gan ◽  
Chen Yang ◽  
Yawen Chen ◽  
Xinyue Tong ◽  
...  

AbstractObjectiveBreakfast skipping has been reported to be associated with type 2 diabetes (T2D), but the results are inconsistent. No meta-analyses have applied quantitative techniques to compute summary risk estimates. The present study aimed to conduct a meta-analysis of observational studies summarizing the evidence on the association between breakfast skipping and the risk of T2D.DesignSystematic review and meta-analysis.SettingRelevant studies were identified by a search of PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI) and SINOMED up to 9 August 2014. We also reviewed reference lists from retrieved articles. We included studies that reported risk estimates (including relative risks, odds ratios and hazard ratios) with 95 % confidence intervals for the association between breakfast skipping and the risk of T2D.SubjectsEight studies involving 106 935 participants and 7419 patients with T2D were included in the meta-analysis.ResultsA pooled adjusted relative risk for the association between exposure to breakfast skipping and T2D risk was 1·21 (95 % CI 1·12, 1·31; P=0·984; I2=0·0 %) in cohort studies and the pooled OR was 1·15 (95 % CI, 1·05, 1·24; P=0·770; I2=0·0 %) in cross-sectional studies. Visual inspection of a funnel plot and Begg’s test indicated no evidence of publication bias.ConclusionsBreakfast skipping is associated with a significantly increased risk of T2D. Regular breakfast consumption is potentially important for the prevention of T2D.


2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Xiaowen Zhang ◽  
Jie Sun ◽  
Wenqing Han ◽  
Yaqiu Jiang ◽  
Shiqiao Peng ◽  
...  

Objective. Type 2 deiodinase (Dio2) is an enzyme responsible for the conversion of T4 to T3. The Thr92Ala polymorphism has been shown related to an increased risk for developing type 2 diabetes mellitus (T2DM). The aim of this study is to assess the association between this polymorphism and glycemic control in T2DM patients as marked by the HbA1C levels.Design and Methods.The terms “rs225014,” “thr92ala,” “T92A,” or “dio2 a/g” were used to search for eligible studies in the PubMed, Embase, and Cochrane databases and Google Scholar. A systematic review and meta-analysis of studies including both polymorphism testing and glycated hemoglobin (HbA1C) assays were performed.Results. Four studies were selected, totaling 2190 subjects. The pooled mean difference of the studies was 0.48% (95% CI, 0.18–0.77%), indicating that type 2 diabetics homozygous for the Dio2 Thr92Ala polymorphism had higher HbA1C levels.Conclusions. Homozygosity for the Dio2 Thr92Ala polymorphism is associated with higher HbA1C levels in T2DM patients. To confirm this conclusion, more studies of larger populations are needed.


BMJ Open ◽  
2018 ◽  
Vol 8 (11) ◽  
pp. e020062 ◽  
Author(s):  
Xiaosu Bai ◽  
Zhiming Liu ◽  
Zhisen Li ◽  
Dewen Yan

ObjectivesSeveral patients with type 2 diabetes mellitus (T2DM) have depressive disorders. Whether insulin treatment was associated with increased risk of depression remains controversial. We performed a meta-analysis to evaluate the association of insulin therapy and depression.DesignA meta-analysis.MethodsWe conducted a systematic search of PubMed, PsycINFO, Embase and the Cochrane Library from their inception to April 2016. Epidemiological studies comparing the prevalence of depression between insulin users and non-insulin users were included. A random-effects model was used for meta-analysis. The adjusted and crude data were analysed.ResultsTwenty-eight studies were included. Of these, 12 studies presented with adjusted ORs. Insulin therapy was significantly associated with increased risk of depression (OR=1.41, 95% CI 1.13 to 1.76, p=0.003). Twenty-four studies provided crude data. Insulin therapy was also associated with an odds for developing depression (OR=1.59, 95% CI 1.41 to 1.80, p<0.001). When comparing insulin therapy with oral antidiabetic drugs, significant association was observed for adjusted (OR=1.42, 95% CI 1.08 to 1.86, p=0.008) and crude (OR=1.61, 95% CI 1.35 to 1.93, p<0.001) data.ConclusionsOur meta-analysis confirmed that patients on insulin therapy were significantly associated with the risk of depressive symptoms.


2020 ◽  
Vol 52 (05) ◽  
pp. 264-279
Author(s):  
Xiaorong Li ◽  
Juping Liu ◽  
Qianhui Yang ◽  
Yan Zhang ◽  
Xiaomin Zhang

AbstractThe associations between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of type 2 diabetic retinopathy (DR) – proliferative diabetic retinopathy (PDR), and nonproliferative diabetic retinopathy (NPDR) – remain unclear. A systematic search and meta-analysis using odds ratio (OR) with 95% confidence interval (CI) was performed to evaluate the association. Our study concluded 26 studies containing 10 single nucleotide polymorphisms (SNPs). In Asian populations, rs3025039 polymorphism was associated with DR risk, while in overall populations and Caucasians, the DR risk was increased by association with rs2010963. There was a significant association between rs25648 and rs833061 and DR risk in Caucasians. DR risks were found to be significantly associated between rs3025021, rs13207351, and rs2146323 in either overall populations, Caucasians or Asians. Besides, in overall and Asian populations, rs699947 and rs3025039 were associated with PDR risk. rs1570360, rs3025039, and rs833061 played a key role in PDR etiology in Caucasians. rs2010963 was associated with increased risk of PDR in overall populations. A significant association between rs699947, rs3025039, and rs833061 and NPDR risk in overall populations and Asians was found. A significant association was observed between rs2010963 and increased NPDR risk in overall and Caucasian populations. This study provides a new insight into the parthenogenesis of diabetic retinopathy. Targeting VEGF SNPs may be a potential of therapeutic approach for the treatment of DR, PDR, and NPDR.


2019 ◽  
Vol 29 (Supplement_4) ◽  
Author(s):  
A Juul ◽  
C Glümer ◽  
S S Jervelund ◽  
N F Hempler

Abstract Background Immigrants from non-Western countries have a higher prevalence of type 2 diabetes. In addition, immigrants have an increased risk of developing diabetes complications, compared with the general population. Diabetes education programmes facilitate essential knowledge and skills that enable people to manage their condition in daily life. However, fewer immigrants attend and complete diabetes education compared with the general population. The aim of this study is to explore what characterises those who decline and accept participation in diabetes education in relation to ethnicity, household composition and diabetes burden in the family. Methods The study population consisted of adults with type 2 diabetes referred to a municipal diabetes centre (n = 1819). Individual medical record data was linked to national registry data. Descriptive statistics and logistic regression models were applied. Results Preliminary results showed that 23% of individuals from the study population participated in diabetes education. We found no overall differences in participation rates between the general population and non-Western immigrants (24% vs. 18%, P = 0.12). However, when examining the immigrant groups by language (Arabic, Urdu and Turkish), the results indicated a non-significant tendency: Urdu speaking groups’ participation was similar to the general population (24%), whereas Arabic and Turkish speaking groups had lower participation rates (17% and 11%, P = 0.25/0.40). Conclusions The results suggest that there are differences in participation between some immigrant groups and the general population. Increased knowledge about which mechanisms affecting participation in diabetes education programme is required to ensure equal access. Further studies and analyses will explore how immigrants’ social relations enable and/or hamper participation in diabetes education and investigate which factors can be changed to improve participation rates. Key messages There are differences in participation in diabetes education programmes across different ethnic groups, which suggests a need for in-depth analysis into which mechanisms that affect participation. The results will be used to give input for future practices that can increase immigrant’s participation and retention in diabetes education programmes.


Author(s):  
Bert B. Little ◽  
Robert Reilly ◽  
Brad Walsh ◽  
Giang T. Vu

Objective: To test the hypothesis that cadmium (Cd) exposure is associated with type 2 diabetes mellitus (T2DM). Materials and Methods: A two-phase health screening (physical examination and laboratory tests) was conducted in a lead smelter community following a Superfund Cleanup. Participants were African Americans aged >19 years to <89 years. Multiple logistic regression was used to analyze T2DM regressed on blood Cd level and covariates: body mass index (BMI), heavy metals (Ar, Cd, Hg, Pb), duration of residence, age, smoking status, and sex. Results: Of 875 subjects environmentally exposed to Cd, 55 were occupationally exposed to by-products of lead smelting and 820 were community residents. In addition, 109 T2DM individuals lived in the community for an average of 21.0 years, and 766 non-T2DM individuals for 19.0 years. T2DM individuals (70.3%) were >50 years old. Blood Cd levels were higher among T2DM subjects (p < 0.006) compared to non-T2DM individuals. Logistic regression of T2DM status identified significant predictors: Cd level (OR = 1.85; 95% CI: 1.14–2.99, p < 0.01), age >50 years (OR = 3.10; 95% CI: 1.91–5.02, p < 0.0001), and BMI (OR = 1.07; CI: 1.04–1.09, 0.0001). In meta-analysis of 12 prior studies and this one, T2DM risk was OR = 1.09 (95% CI: 1.03–1.15, p < 0.004) fixed effects and 1.22 (95% CI: 1.04–1.44, p < 0.02) random effects. Discussion: Chronic environmental Cd exposure was associated with T2DM in a smelter community, controlling for covariates. T2DM onset <50 years was significantly associated with Cd exposure, but >50 years was not. Meta-analysis suggests that Cd exposure is associated with a small, but significant increased risk for T2DM. Available data suggest Cd exposure is associated with an increased propensity to increased insulin resistance.


2010 ◽  
Vol 163 (3) ◽  
pp. 427-434 ◽  
Author(s):  
José Miguel Dora ◽  
Walter Escouto Machado ◽  
Jakeline Rheinheimer ◽  
Daisy Crispim ◽  
Ana Luiza Maia

ObjectiveThe type 2 deiodinase (D2) is a key enzyme for intracellular triiodothyronine (T3) generation. A single-nucleotide polymorphism in D2 (Thr92Ala) has been associated with increased insulin resistance in nondiabetic and type 2 diabetes (DM2) subjects. Our aim was to evaluate whether the D2 Thr92Ala polymorphism is associated with increased risk for DM2.Design and methodsA case–control study with 1057 DM2 and 516 nondiabetic subjects was performed. All participants underwent genotyping of the D2 Thr92Ala polymorphism. Additionally, systematic review and meta-analysis of the literature for genetic association studies of D2 Thr92Ala polymorphism and DM2 were performed in Medline, Embase, LiLacs, and SciELO, and major meeting databases using the terms ‘rs225014’ odds ratio (OR) ‘thr92ala’ OR ‘T92A’ OR ‘dio2 a/g’.ResultsIn the case–control study, the frequencies of D2 Ala92Ala homozygous were 16.4% (n=173) versus 12.0% (n=62) in DM2 versus controls respectively resulting in an adjusted OR of 1.41 (95% confidence intervals (CI) 1.03–1.94, P=0.03). The literature search identified three studies that analyzed the association of the D2 Thr92Ala polymorphism with DM2, with the following effect estimates: Mentuccia (OR 1.40 (95% CI 0.78–2.51)), Grarup (OR 1.09 (95% CI 0.92–1.29)), and Maia (OR 1.22 (95% CI 0.78–1.92)). The pooled effect of the four studies resulted in an OR 1.18 (95% CI 1.03–1.36, P=0.02).ConclusionsOur results indicate that in a case–control study, the homozygosity for D2 Thr92Ala polymorphism is associated with increased risk for DM2. These results were confirmed by a meta-analysis including 11 033 individuals, and support a role for intracellular T3 concentration in skeletal muscle on DM2 pathogenesis.


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