Diabetes Genetic Predisposition Score and Cardiovascular Complications Among Patients With Type 2 Diabetes

Type 2 diabetes has reached epidemic proportions in the US,1and its prevalence will continue to grow unless contributory factors such as the obesity epidemic and our ever-more sedentary lifestyles are significantly addressed.2These environmental factors, together with genetic predisposition, increase the risk for insulin resistance and the development of diabetes, which in turn is associated with the development of microvascular and cardiovascular complications.

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

Genes & Nutrition ◽

10.1186/s12263-021-00684-6 ◽

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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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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Cardiovascular disease prevalence in type 2 diabetes – an analysis of a large German statutory health insurance database

BMC Public Health ◽

10.1186/s12889-021-10381-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Maximilian Gabler ◽

Silke Geier ◽

Lukas Mayerhoff ◽

Wolfgang Rathmann

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Health System ◽

Cardiovascular Complications ◽

Population Based ◽

Stratified Sample ◽

Icd 10 ◽

Definition Of ◽

Observation Period

Abstract Background The aim of this study was to determine the prevalence of cardiovascular disease in persons with type 2 diabetes mellitus (T2D) in Germany. Methods A claims database with an age- and sex-stratified sample of nearly 4 million individuals insured within the German statutory health system was used. All patients aged ≥18 years with T2D documented between 1 January 2015 and 31 December 2015 and complete retrospective documentation of ≥5 years (continuous enrollment in the German statutory health system) before 2015 were selected based on a validated algorithm. Cardiovascular disease (CVD) events were identified based on ICD-10 and OPS codes according to a previous clinical study (EMPA-REG OUTCOME trial). Results The prevalence of T2D in Germany in 2015 was 9.9% (n = 324,708). Using a narrow definition of CVD, the 6-year observation period prevalence of CVD was estimated as 46.7% [95% CI: 46.52%;46.86%]. Applying a wider CVD definition, the proportion of T2D patients who showed a history of CVD was 57.1% [95% CI: 56.9%;57.24%]. The prevalence of CVD in patients with T2D ranged from 36.3 to 57.1%, depending on the observation period and definition of CVD. Conclusions The results underline the need for a population-based registration of cardiovascular complications in T2D.

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Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702(C/T) Polymorphism of Krüppel-Like Factor 14 Gene

Metabolism ◽

10.1016/j.metabol.2020.154576 ◽

2021 ◽

Vol 116 ◽

pp. 154576

Author(s):

Magellan Guewo-Fokeng ◽

Eugene Sobngwi ◽

Barbara Atogho-Tiedeu ◽

Jean-Claude Mbanya ◽

Wilfred F. Mbacham

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Genetic Predisposition

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Evaluation of glycemic traits in susceptibility to COVID-19 risk: a Mendelian randomization study

BMC Medicine ◽

10.1186/s12916-021-01944-3 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Shiu Lun Au Yeung ◽

Jie V Zhao ◽

C Mary Schooling

Keyword(s):

Type 2 Diabetes ◽

Genetic Predisposition ◽

Mendelian Randomization ◽

Fasting Glucose ◽

Association Studies ◽

Sensitivity Analyses ◽

Genome Wide Association Studies ◽

Inverse Association ◽

Wide Confidence Interval

Abstract Background Observational studies suggest poorer glycemic traits and type 2 diabetes associated with coronavirus disease 2019 (COVID-19) risk although these findings could be confounded by socioeconomic position. We conducted a two-sample Mendelian randomization to clarify their role in COVID-19 risk and specific COVID-19 phenotypes (hospitalized and severe cases). Method We identified genetic instruments for fasting glucose (n = 133,010), 2 h glucose (n = 42,854), glycated hemoglobin (n = 123,665), and type 2 diabetes (74,124 cases and 824,006 controls) from genome wide association studies and applied them to COVID-19 Host Genetics Initiative summary statistics (17,965 COVID-19 cases and 1,370,547 population controls). We used inverse variance weighting to obtain the causal estimates of glycemic traits and genetic predisposition to type 2 diabetes in COVID-19 risk. Sensitivity analyses included MR-Egger and weighted median method. Results We found genetic predisposition to type 2 diabetes was not associated with any COVID-19 phenotype (OR: 1.00 per unit increase in log odds of having diabetes, 95%CI 0.97 to 1.04 for overall COVID-19; OR: 1.02, 95%CI 0.95 to 1.09 for hospitalized COVID-19; and OR: 1.00, 95%CI 0.93 to 1.08 for severe COVID-19). There were no strong evidence for an association of glycemic traits in COVID-19 phenotypes, apart from a potential inverse association for fasting glucose albeit with wide confidence interval. Conclusion We provide some genetic evidence that poorer glycemic traits and predisposition to type 2 diabetes unlikely increase the risk of COVID-19. Although our study did not indicate glycemic traits increase severity of COVID-19, additional studies are needed to verify our findings.

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Glycemic variability and cardiovascular disease in patients with type 2 diabetes

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-002032 ◽

2021 ◽

Vol 9 (1) ◽

pp. e002032

Author(s):

Marcela Martinez ◽

Jimena Santamarina ◽

Adrian Pavesi ◽

Carla Musso ◽

Guillermo E Umpierrez

Keyword(s):

Type 2 Diabetes ◽

Blood Glucose ◽

Glycated Hemoglobin ◽

Glucose Monitoring ◽

Glycemic Variability ◽

Cardiovascular Complications ◽

Glucose Levels ◽

Increased Risk ◽

Patients With Diabetes

Glycated hemoglobin is currently the gold standard for assessment of long-term glycemic control and response to medical treatment in patients with diabetes. Glycated hemoglobin, however, does not address fluctuations in blood glucose. Glycemic variability (GV) refers to fluctuations in blood glucose levels. Recent clinical data indicate that GV is associated with increased risk of hypoglycemia, microvascular and macrovascular complications, and mortality in patients with diabetes, independently of glycated hemoglobin level. The use of continuous glucose monitoring devices has markedly improved the assessment of GV in clinical practice and facilitated the assessment of GV as well as hypoglycemia and hyperglycemia events in patients with diabetes. We review current concepts on the definition and assessment of GV and its association with cardiovascular complications in patients with type 2 diabetes.

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