An atlas on risk factors for type 2 diabetes: a wide-angled Mendelian randomisation study

Abstract Aims/hypothesis The aim of this study was to use Mendelian randomisation (MR) to identify the causal risk factors for type 2 diabetes. Methods We first conducted a review of meta-analyses and review articles to pinpoint possible risk factors for type 2 diabetes. Around 170 possible risk factors were identified of which 97 risk factors with available genetic instrumental variables were included in MR analyses. To reveal more risk factors that were not included in our MR analyses, we conducted a review of published MR studies of type 2 diabetes. For our MR analyses, we used summary-level data from the DIAbetes Genetics Replication And Meta-analysis consortium (74,124 type 2 diabetes cases and 824,006 controls of European ancestry). Potential causal associations were replicated using the FinnGen consortium (11,006 type 2 diabetes cases and 82,655 controls of European ancestry). The inverse-variance weighted method was used as the main analysis. Multivariable MR analysis was used to assess whether the observed associations with type 2 diabetes were mediated by BMI. We used the Benjamini–Hochberg method that controls false discovery rate for multiple testing. Results We found evidence of causal associations between 34 exposures (19 risk factors and 15 protective factors) and type 2 diabetes. Insomnia was identified as a novel risk factor (OR 1.17 [95% CI 1.11, 1.23]). The other 18 risk factors were depression, systolic BP, smoking initiation, lifetime smoking, coffee (caffeine) consumption, plasma isoleucine, valine and leucine, liver alanine aminotransferase, childhood and adulthood BMI, body fat percentage, visceral fat mass, resting heart rate, and four plasma fatty acids. The 15 exposures associated with a decreased risk of type 2 diabetes were plasma alanine, HDL- and total cholesterol, age at menarche, testosterone levels, sex hormone binding globulin levels (adjusted for BMI), birthweight, adulthood height, lean body mass (for women), four plasma fatty acids, circulating 25-hydroxyvitamin D and education years. Eight associations remained after adjustment for adulthood BMI. We additionally identified 21 suggestive risk factors (p < 0.05), such as alcohol consumption, breakfast skipping, daytime napping, short sleep, urinary sodium, and certain amino acids and inflammatory factors. Conclusions/interpretation The present study verified several previously reported risk factors and identified novel potential risk factors for type 2 diabetes. Prevention strategies for type 2 diabetes should be considered from multiple perspectives on obesity, mental health, sleep quality, education level, birthweight and smoking. Graphical abstract

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PLASMA FATTY ACIDS AND THE RISK OF VASCULAR AND MORTALITY OUTCOMES IN INDIVIDUALS WITH TYPE 2 DIABETES: RESULTS FROM THE ADVANCE STUDY

Journal of Hypertension ◽

10.1097/01.hjh.0000744832.31074.90 ◽

2021 ◽

Vol 39 (Supplement 1) ◽

pp. e45

Author(s):

Katie Harris ◽

Megumi Oshima ◽

Naveed Sattar ◽

Peter Wurtz ◽

Min Jun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Advance Study ◽

Plasma Fatty Acids

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Maternal Hypertension Increases Risk of Preeclampsia and Low Fetal Birthweight: Genetic Evidence From a Mendelian Randomization Study

Hypertension ◽

10.1161/hypertensionaha.121.18617 ◽

2022 ◽

Author(s):

Maddalena Ardissino ◽

Eric A.W. Slob ◽

Ophelia Millar ◽

Rohin K. Reddy ◽

Laura Lazzari ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Body Mass Index ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Body Mass ◽

Mendelian Randomization ◽

European Ancestry ◽

Increased Risk

Background: Maternal cardiovascular risk factors have been associated with adverse maternal and fetal outcomes. Given the difficulty in establishing causal relationships using epidemiological data, we applied Mendelian randomization to explore the role of cardiovascular risk factors on risk of developing preeclampsia or eclampsia, and low fetal birthweight. Methods: Uncorrelated single-nucleotide polymorphisms associated systolic blood pressure (SBP), body mass index, type 2 diabetes, LDL (low-density lipoprotein) with cholesterol, smoking, urinary albumin-to-creatinine ratio, and estimated glomerular filtration rate at genome-wide significance in studies of 298 957 to 1 201 909 European ancestry participants were selected as instrumental variables. A 2-sample Mendelian randomization study was performed with primary outcome of preeclampsia or eclampsia (PET). Risk factors associated with PET were further investigated for their association with low birthweight. Results: Higher genetically predicted SBP was associated increased risk of PET (odds ratio [OR] per 1-SD SBP increase 1.90 [95% CI=1.45–2.49]; P =3.23×10 −6 ) and reduced birthweight (OR=0.83 [95% CI=0.79–0.86]; P =3.96×10 −18 ), and this was not mediated by PET. Body mass index and type 2 diabetes were also associated with PET (respectively, OR per 1-SD body mass index increase =1.67 [95% CI=1.44–1.94]; P =7.45×10 −12 ; and OR per logOR increase type 2 diabetes =1.11 [95% CI=1.04–1.19]; P =1.19×10 −3 ), but not with reduced birthweight. Conclusions: Our results provide evidence for causal effects of SBP, body mass index, and type 2 diabetes on PET and identify that SBP is associated with reduced birthweight independently of PET. The results provide insight into the pathophysiological basis of PET and identify hypertension as a potentially modifiable risk factor amenable to therapeutic intervention.

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Plasma fatty acids and the risk of vascular disease and mortality outcomes in individuals with type 2 diabetes: results from the ADVANCE study

Diabetologia ◽

10.1007/s00125-020-05162-z ◽

2020 ◽

Vol 63 (8) ◽

pp. 1637-1647 ◽

Cited By ~ 1

Author(s):

Katie Harris ◽

Megumi Oshima ◽

Naveed Sattar ◽

Peter Würtz ◽

Min Jun ◽

...

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Vascular Disease ◽

Advance Study ◽

Plasma Fatty Acids

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Plasma Free Fatty Acids Metabolic Profile Among Uyghurs and Kazaks With or Without Type 2 Diabetes Based on GC-MS

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/s-0043-121263 ◽

2017 ◽

Vol 126 (10) ◽

pp. 604-611 ◽

Cited By ~ 4

Author(s):

Xiao-li Ma ◽

Lei Meng ◽

Lin-lin Li ◽

Li-na Ma ◽

Xin-min Mao

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Free Fatty Acids ◽

Metabolic Profile ◽

Gas Chromatography Mass Spectrometry ◽

Traditional Risk Factors ◽

A Prospective Study ◽

Medical University

AbstractFree fatty acids (FFAs) participate in a variety of physiological functions. FFAs are associated with the development of type 2 diabetes mellitus (T2DM). Uyghurs and Kazaks have a different prevalence of T2DM, which cannot be explained by traditional risk factors. This study aimed to examine FFAs as potential biomarkers to distinguish between healthy and T2DM Uyghurs and Kazaks. This was a prospective study conducted at the Xianjiang Medical University from 01/2007 to 06/2010 in Uyghurs and Kazaks. The subjects were grouped as T2DM patients (Uyghurs: n=39; Kazaks, n=21) and controls (Uyghurs: n=35; Kazaks, n=40). Gas chromatography-mass spectrometry (GC-MS) and partial least squares discriminant analysis (PLS-DA) models were used to study the FFA profiles between Uyghurs and Kazaks with T2DM. PLS-DA analysis showed that among Kazaks, T2DM patients had lower C22:6, C18:3 n-6, and C20:3 n-6, but higher C22:0 levels compared with controls. Among Uyghurs, the most important variables to discriminate T2DM patients from controls were higher C22:6 and C20:4 n-6, and lower C22:0, C14:1, C18:3 n6, and C20:3 n6. Kazaks and Uyghurs displayed different FFA profiles between patients with T2DM and controls. These results suggest different risk factors and pathogenesis of T2DM between Kazaks and Uyghurs.

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Erythrocyte trans-fatty acids, type 2 diabetes and cardiovascular risk factors in middle-aged and older Chinese individuals

Diabetologia ◽

10.1007/s00125-012-2674-2 ◽

2012 ◽

Vol 55 (11) ◽

pp. 2954-2962 ◽

Cited By ~ 26

Author(s):

D. X. Yu ◽

Q. Sun ◽

X. W. Ye ◽

A. Pan ◽

G. Zong ◽

...

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Cardiovascular Risk ◽

Cardiovascular Risk Factors ◽

Trans Fatty Acids ◽

Middle Aged ◽

Older Chinese

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P298 DISTINCT PLASMA FATTY ACIDS ASSOCIATE WITH COMPONENTS OF THE METABOLIC SYNDROME IN HEALTHY OFFSPRING OF TYPE 2 DIABETES PATIENTS

Atherosclerosis Supplements ◽

10.1016/s1567-5688(10)70365-2 ◽

2010 ◽

Vol 11 (2) ◽

pp. 80

Author(s):

L. Scheja ◽

M. Vossen ◽

K. Toedter ◽

U. Beisiegel

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Fatty Acids ◽

Plasma Fatty Acids ◽

The Metabolic Syndrome ◽

Diabetes Patients

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The association between plasma fatty acid and cognitive function mediated by inflammation in patients with type 2 diabetes mellitus

10.21203/rs.3.rs-577863/v3 ◽

2021 ◽

Author(s):

Jingyi Shen ◽

Kaifeng Li ◽

Huiyan Yu ◽

Bingjie Ding ◽

Rong Xiao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Type 2 Diabetes Mellitus ◽

Cognitive Function ◽

Chinese Patients ◽

Cognitive Test ◽

Enzyme Linked Immunosorbent Assay ◽

Plasma Fatty Acids

Abstract In this study, we evaluated the cognitive function of 372 Chinese patients (214 males and 158 females; the average age was 57.09 ± 9.00 years) with type 2 diabetes mellitus (T2DM) by using the mini-mental state examination (MMSE) and the Montreal cognitive assessment (MoCA), with Plasma fatty acids measured by gas chromatography analysis and inflammatory cytokines determined by immune turbidimetric analysis and enzyme-linked immunosorbent assay (ELISA) to investigate whether there was a correlation between the plasma fatty acids, plasma inflammatory cytokine levels and cognitive test scores in Chinese patients with T2DM. We found the increasing of body mass index (BMI) might lead to cognitive impairment and induce inflammatory response. Higher saturated fatty acids (SFAs) levels in plasma were linked to cognitive decline, while higher monounsaturated fatty acids (MUFAs) intake might be a protective factor for cognitive function. In addition, most polyunsaturated fatty acids (PUFAs) levels stood out as having increasing trends that were positively correlated to cognitive function scores. In our study, we found higher SFAs led to higher proinflammatory factor levels. Apart from that, MUFAs and stearoyl-CoA desaturase-18 (SCD-18) were positively related to hypersensitive C-reactive protein (hs-CRP) (P<0.05; P<0.05; P<0.05). Meanwhile, our result also indicated that the increasing of C18:0 might reduce MoCA language skill scores by regulating plasma IL-10 levels. Plasma fatty acids could improve or damage cognitive function by regulating IL-10, which suggested plasma fatty acids could be evaluated as a potential indicator of cognitive function decline in T2DM.

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The association between plasma fatty acid and cognitive function mediated by inflammation in patients with type 2 diabetes mellitus

10.21203/rs.3.rs-577863/v2 ◽

2021 ◽

Author(s):

Jingyi Shen ◽

Kaifeng Li ◽

Huiyan Yu ◽

Bingjie Ding ◽

Rong Xiao ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Fatty Acids ◽

Type 2 Diabetes Mellitus ◽

Cognitive Function ◽

Chinese Patients ◽

Cognitive Test ◽

Enzyme Linked Immunosorbent Assay ◽

Plasma Fatty Acids

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Impact of lung function on cardiovascular diseases and cardiovascular risk factors: a two sample bidirectional Mendelian randomisation study

Thorax ◽

10.1136/thoraxjnl-2020-215600 ◽

2021 ◽

pp. thoraxjnl-2020-215600

Author(s):

Shiu Lun Au Yeung ◽

Maria Carolina Borges ◽

Debbie A Lawlor ◽

C Mary Schooling

Keyword(s):

Risk Factors ◽

Type 2 Diabetes ◽

Cardiovascular Risk ◽

Lung Function ◽

Sensitivity Analyses ◽

Mendelian Randomisation ◽

Summary Statistics ◽

Reverse Causation

IntroductionObservational studies suggested lung function is inversely associated with cardiovascular disease (CVD) although these studies could be confounded. We conducted a two sample Mendelian randomisation study using summary statistics from genome-wide association studies (GWAS) to clarify the role of lung function in CVD and its risk factors, and conversely the role of CVD in lung function.MethodsWe obtained genetic instruments for forced expiratory volume in 1 s (FEV1: 260) and forced vital capacity (FVC: 320) from publicly available UK Biobank summary statistics (n=421 986) and applied to GWAS summary statistics for coronary artery disease (CAD) (n=184 305), stroke (n=446 696), atrial fibrillation (n=1 030 836) and heart failure (n=977 320) and cardiovascular risk factors. Inverse variance weighting was used to assess the impact of lung function on these outcomes, with various sensitivity analyses. Bidirectional Mendelian randomisation was used to assess reverse causation.ResultsFEV1 and FVC were inversely associated with CAD (OR per SD increase, 0.72 (95% CI 0.63 to 0.82) and 0.70 (95%CI 0.62 to 0.78)), overall stroke (0.87 (95%CI 0.77 to 0.97), 0.90 (95% CI 0.82 to 1.00)) and some stroke subtypes. FEV1 and FVC were inversely associated with type 2 diabetes and systolic blood pressure. Sensitivity analyses produced similar findings although the association with CAD was attenuated after adjusting for height (eg, OR for 1SD FEV10.95 (0.75 to 1.19), but not for stroke or type 2 diabetes. There was no strong evidence for reverse causation.ConclusionHigher lung function likely protect against CAD and stroke.

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