scholarly journals Deciphering the Plasma Proteome of Type 2 Diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Elhadad ◽  
Christian Jonasson ◽  
Cornelia Huth ◽  
Rory Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Hormone Receptor ◽  
Smoking Status ◽  
Underlying Disease ◽  
Sex Hormone Binding Globulin ◽  
Health Study ◽  
Study Cohort ◽  
Incident Type ◽  
Incident Type 2 Diabetes

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1000 plasma proteins in the KORA (Cooperative health research in the Region of Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the HUNT3 (Third wave of the Nord-Trøndelag Health Study) cohort (n=940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bi-directional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which eight are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding protein-2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations, and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.

scholarly journals Deciphering the Plasma Proteome of Type 2 Diabetes

2020 ◽  
Author(s):  
Ada Admin ◽  
Mohamed A. Elhadad ◽  
Christian Jonasson ◽  
Cornelia Huth ◽  
Rory Wilson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Growth Hormone Receptor ◽  
Smoking Status ◽  
Underlying Disease ◽  
Sex Hormone Binding Globulin ◽  
Health Study ◽  
Study Cohort ◽  
Incident Type ◽  
Incident Type 2 Diabetes

With an estimated prevalence of 463 million affected, type 2 diabetes represents a major challenge to health care systems worldwide. Analyzing the plasma proteomes of individuals with type 2 diabetes may illuminate hitherto unknown functional mechanisms underlying disease pathology. We assessed the associations between type 2 diabetes and >1000 plasma proteins in the KORA (Cooperative health research in the Region of Augsburg) F4 cohort (n=993, 110 cases), with subsequent replication in the HUNT3 (Third wave of the Nord-Trøndelag Health Study) cohort (n=940, 149 cases). We computed logistic regression models adjusted for age, sex, BMI, smoking status and hypertension. Additionally, we investigated associations with incident type 2 diabetes and performed two-sample bi-directional Mendelian randomization (MR) analysis to prioritize our results. Association analysis of prevalent type 2 diabetes revealed 24 replicated proteins, of which eight are novel. Proteins showing association with incident type 2 diabetes were aminoacylase-1, growth hormone receptor, and insulin-like growth factor binding protein-2. Aminoacylase-1 was associated with both prevalent and incident type 2 diabetes. MR analysis yielded nominally significant causal effects of type 2 diabetes on cathepsin Z and rennin, both known to have roles in the pathophysiological pathways of cardiovascular disease, and of sex hormone-binding globulin on type 2 diabetes. In conclusion, our high-throughput proteomics study replicated previously reported type 2 diabetes-protein associations, and identified new candidate proteins possibly involved in the pathogenesis of type 2 diabetes.

Abstract MP05: Leisure-Time Running and Incident Type 2 Diabetes

Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duck-chul Lee ◽  
Carl J. Lavie ◽  
Timothy S. Church ◽  
Xuemei Sui ◽  
Steven N. Blair
Keyword(s):  
Type 2 Diabetes ◽  
Lower Risk ◽  
Leisure Time ◽  
Cox Regression ◽  
Smoking Status ◽  
Physical Activities ◽  
Incident Type ◽  
Incident Type 2 Diabetes

Introduction: There is still little evidence on the dose-response relation between leisure-time running and incident type 2 diabetes (T2D). Hypothesis: We examined the hypothesis that running reduces the risk of developing T2D. Methods: Participants were 19,347 adults aged 18 to 100 years (mean age, 44) who received an extensive preventive medical examination during 1974-2006 in the Aerobics Center Longitudinal Study. Participants were free of cardiovascular disease, cancer, and T2D at baseline. Running and other physical activities were assessed on the medical history questionnaire by self-reported leisure-time activities during the past 3 months. We defined T2D as fasting glucose ≥126 mg/dl, insulin use, or physician-diagnosis during follow-up medical examinations. Cox regression was used to quantify the association between running and T2D after adjusting for baseline age, sex, examination year, body mass index, smoking status, heavy alcohol drinking, abnormal electrocardiogram, hypertension, hypercholesterolemia, and levels of other physical activities. Results: During an average follow-up of 6.5 years, 1,015 adults developed T2D. Approximately 30% of adults participated in leisure-time running. Runners had a 29% lower risk of developing T2D compared with non-runners. The hazard ratios (95% confidence intervals) of T2D were 0.97 (0.74-1.27), 0.66 (0.49-0.89), 0.62 (0.45-0.85), 0.78 (0.58-1.03), and 0.57 (0.42-0.79) across quintiles (Q) of running time (minutes/week); 0.99 (0.76-1.30), 0.60 (0.44-0.82), 0.72 (0.55-0.94), 0.65 (0.47-0.90), and 0.63 (0.47-0.86) across Q of running distance (miles/week); 1.08 (0.83-1.40), 0.67 (0.50-0.90), 0.70 (0.53-0.93), 0.61 (0.45-0.83), and 0.53 (0.36-0.76) across Q of running frequency (times/week); 0.95 (0.73-1.24), 0.70 (0.52-0.94), 0.62 (0.45-0.84), 0.73 (0.55-0.97), and 0.58 (0.42-0.80) across Q of total amount of running (MET-minutes/week); and 0.95 (0.71-1.28), 0.76 (0.59-0.99), 0.59 (0.42-0.83), 0.66 (0.51-0.85), and 0.62 (0.43-0.90) across Q of running speed (mph), respectively, compared with no running after adjusting for confounders including levels of other physical activities. Conclusions: Participating in leisure-time running is associated with markedly lower risk of developing T2D in adults. Except for those in the very lowest Q for running doses, even relatively low running doses (starting with Q 2) were associated with marked reductions in T2D risk over time, supporting the prescription of running to reduce T2D.

Abstract MP037: Plasma Organochlorine Concentration and Risk of Diabetes: the Nurses' Health Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Hongyu Wu ◽  
Kimberly A Bertrand ◽  
Anna L Choi ◽  
Frank B Hu ◽  
Francine Laden ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Polychlorinated Biphenyl ◽  
Plasma Concentrations ◽  
Diabetes Risk ◽  
Health Study ◽  
Blood Draw ◽  
Incident Type ◽  
Increased Risk ◽  
Incident Type 2 Diabetes

Background: Animal experiments have suggested that exposure to persistent organic pollutants (POPs) may lead to increased risk of type 2 diabetes. Although recent human studies supported this hypothesis, evidence from prospective investigations is sparse. Objective: To examine the associations of plasma POP concentrations with risk of incident type 2 diabetes in a prospective setting among US women. Methods: Study population was comprised of participants from two independent nested case-control studies in the Nurses’ Health Study, in which major polychlorinated biphenyl (PCB 118, 138, 153, and 180), p-p'- dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyltrichloroethane (DDT), and hexachlorobenzene (HCB) were measured. A non-parametric approach was used to derive standardized scores for plasma concentrations of lipid-adjusted POPs within each study to minimize between-study variation of the POP measurements. Risk of incident type 2 diabetes during the follow-up period (1990-2008) across the tertiles of the scores was examined. Results: Of 1,120 participants, we identified 48 incident type 2 diabetes cases. After adjusting for covariates assessed at blood draw in 1990, including smoking status, body mass index, and total fish intake, plasma HCB concentration was positively associated with type 2 diabetes risk: odds ratio (OR) (95% confidence interval [CI]) was 2.77 (1.17, 6.55, P for trend =0.022) comparing the highest vs. lowest tertile. Other POPs were not significantly associated with diabetes: the ORs (95% CI) were 1.10 (0.51, 2.34, P for trend =0.81) for p-p'-DDE, 0.93 (0.44, 1.95, P for trend =0.86) for DDT, and 0.88 (0.39, 1.97, P for trend =0.76) for sum of the 4 major PCBs, comparing the extreme tertiles. Conclusion: The significant association of plasma HCB concentration with diabetes risk supports a role of POP exposure in the etiology of type 2 diabetes. More prospective data are warranted to confirm these findings.

scholarly journals Islet amyloid polypeptide gene variation (IAPP) and the risk of incident type 2 diabetes mellitus: The women's genome health study

2011 ◽  
Vol 412 (9-10) ◽  
pp. 785-787 ◽  
Author(s):  
Robert Y.L. Zee ◽  
Patricia Pulido-Perez ◽  
Ricardo Perez-Fuentes ◽  
Paul M Ridker ◽  
Daniel I. Chasman ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Islet Amyloid Polypeptide ◽  
Health Study ◽  
Islet Amyloid ◽  
Incident Type ◽  
Gene Variation ◽  
Incident Type 2 Diabetes

scholarly journals Dietary Patterns and Incident Type 2 Diabetes in Chinese Men and Women: The Singapore Chinese Health Study

Diabetes Care ◽  
2011 ◽  
Vol 34 (4) ◽  
pp. 880-885 ◽  
Author(s):  
A. O. Odegaard ◽  
W.-P. Koh ◽  
L. M. Butler ◽  
S. Duval ◽  
M. D. Gross ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Dietary Patterns ◽  
Health Study ◽  
Men And Women ◽  
Chinese Men ◽  
Incident Type ◽  
Incident Type 2 Diabetes ◽  
Singapore Chinese

scholarly journals Erythrocyte n-6 polyunsaturated fatty acids, gut microbiota and incident type 2 diabetes: a prospective cohort study

2020 ◽  
Author(s):  
Zelei Miao ◽  
Jie-sheng Lin ◽  
Yingying Mao ◽  
Geng-dong Chen ◽  
Fang-fang Zeng ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Health Study ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Β Diversity ◽  
Α Diversity ◽  
Incident Type 2 Diabetes

<b>OBJECTIVE </b>To examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes and explore the potential role of gut microbiota in the association. <p><b>RESEARCH DESIGN AND METHODS </b>We evaluated 2,731 participants without type 2 diabetes recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. Type 2 diabetes cases were identified with clinical and biochemical information collected at follow-up visits. Using stool samples collected during the follow-up in the subset (n=1,591), 16S rRNA profiling was conducted. Using multivariable-adjusted Poisson or linear regression, we examined associations of erythrocyte n-6 PUFA biomarkers with incident type 2 diabetes, and diversity and composition of gut microbiota.</p> <p><b>RESULTS </b>Over<b> </b>6.2 years of follow-up, 276 type 2 diabetes cases were identified (risk=0.10). Higher levels of erythrocyte <a>γ-linolenic acid</a> (GLA), but not linoleic or arachidonic acid, were associated with higher type 2 diabetes incidence. Comparing the top to the bottom quartile groups of GLA levels, relative risk was 1.72 (95% confidence intervals: 1.21, 2.44) adjusted for potential confounders. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both <i>p</i><0.05) during follow-up, and significantly associated with microbiota β-diversity (<i>p</i>=0.002). α-diversity acted as a potential mediator in the association between GLA and type 2 diabetes (<i>p</i><0.05). Seven genera (<i>Butyrivibrio</i>,<i> Blautia</i>,<i> Oscillospira</i>,<i> Odoribacter</i>,<i> S24-7 other</i>, <i>Rikenellaceae other</i>,<i> </i>and <i>Clostridiales other</i>) were enriched in quartile 1 of GLA, and in participants without type 2 diabetes.</p> <p><b>CONCLUSIONS </b>Relative concentrations of erythrocyte GLA were positively associated with incident type 2 diabetes in a Chinese population and also with gut microbial profiles. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and type 2 diabetes etiology.</p>

scholarly journals Erythrocyte n-6 Polyunsaturated Fatty Acids, Gut Microbiota and Incident Type 2 Diabetes: A Prospective Cohort Study

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1452-1452
Author(s):  
Ze-Lei Miao ◽  
Ju-Sheng Zheng ◽  
Yu-Ming Chen
Keyword(s):  
Type 2 Diabetes ◽  
Gut Microbiota ◽  
Health Study ◽  
Incident Type ◽  
Α Diversity ◽  
Increased Risk ◽  
Incident Type 2 Diabetes ◽  
Prospective Association

Abstract Objectives To examine the prospective association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D), and the potential role of gut microbiota. Methods 2731 non-T2D participants recruited between 2008–2013 in the Guangzhou Nutrition and Health Study were included in the present study. 276 incident T2D was ascertained after a median follow-up of 6.2 years, and 16S rRNA profiling was conducted using stool samples collected during follow-up. We examined the prospective association of erythrocyte n-6 PUFA biomarkers with incident T2D, and with diversity and composition of gut microbiota. Results Higher levels of erythrocyte γ-linolenic acid (GLA) were associated with higher T2D risk, with relative risk (quartile 4 versus 1) 1.72 (95% confidence intervals: 1.21, 2.44), adjusting for potential confounders. No association with T2D was found for erythrocyte linoleic acid or arachidonic acid. Baseline GLA was inversely associated with gut microbial richness and diversity (α-diversity, both P &lt; 0.05) during follow-up, and significantly associated with microbiota β-diversity (P = 0.002). Seven genera (Butyrivibrio, Blautia, Oscillospira, Odoribacter, S24–7 other, Rikenellaceae other, and Clostridiales other) were enriched in quartile 1 of GLA, and in participants without T2D. Conclusions The present study suggests that erythrocyte GLA biomarker is positively associated with incident T2D in a Chinese population. High GLA status is associated with unfavorable gut microbial profiles, which may contribute to the increased risk of T2D. These results highlight that gut microbiota may play an important role linking n-6 PUFA metabolism and T2D etiology. Funding Sources This study was funded by the National Natural Science Foundation of China, Westlake University and the 5010 Program for Clinical Researches of the Sun Yat-sen University.

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