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

AbstractObjectiveTo examine the association of erythrocyte n-6 polyunsaturated fatty acid (PUFA) biomarkers with incident type 2 diabetes (T2D) and explore the potential role of gut microbiota in the association.DesignWe evaluated 2,731 non-T2D participants recruited between 2008-2013 in the Guangzhou Nutrition and Health Study, China. T2D 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 T2D, and diversity and composition of gut microbiota.ResultsOver 6.2 years of follow-up, 276 T2D cases were identified (risk=0.10). Higher levels of erythrocyte γ-linolenic acid (GLA), but not linoleic or arachidonic acid, were associated with higher T2D 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 p<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.ConclusionRelative concentrations of erythrocyte GLA were positively associated with incident T2D 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 T2D etiology.

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.

scholarly journals Dietary Inflammatory and Insulinemic Potential and Risk of Type 2 Diabetes: Results from Three Prospective U.S. Cohort Studies

2020 ◽  
Author(s):  
Dong Hoon Lee ◽  
Jun Li ◽  
Yanping Li ◽  
Gang Liu ◽  
Kana Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Repeated Measures ◽  
Hazard Ratio ◽  
Diabetes Risk ◽  
Health Study ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Increased Risk

<b>Objective: </b>To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes. <p><b> </b></p> <p><b>Research Design and Methods: </b>We prospectively followed 74,767 women from the Nurses’ Health Study (1984-2016), 90,786 women from the Nurses’ Health Study 2 (1989-2017), and 39,442 men from the Health Professionals Follow-up Study (1986-2016). Using repeated measures of food frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires. </p> <p><b> </b></p> <p><b>Results: </b>We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI, 2.96-3.27) and 3.40 times (95% CI, 3.23-3.58) higher type 2 diabetes risk, respectively, compared to those in the lowest quintile. Additional adjustment for body mass index (BMI) attenuated the associations (Hazard ratio, 1.95; 95% CI, 1.85-2.05 for EDIP; Hazard ratio, 1.87; 95% CI, 1.78-1.98 for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI, 2.17-2.52), compared to those in both lowest quintiles, after adjustment for BMI.</p> <p> </p> <p><b>Conclusions: </b><a>H</a>igher dietary inflammatory and insulinemic potential were associated with an increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development. </p>

scholarly journals Dietary Inflammatory and Insulinemic Potential and Risk of Type 2 Diabetes: Results from Three Prospective U.S. Cohort Studies

2020 ◽  
Author(s):  
Dong Hoon Lee ◽  
Jun Li ◽  
Yanping Li ◽  
Gang Liu ◽  
Kana Wu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Repeated Measures ◽  
Hazard Ratio ◽  
Diabetes Risk ◽  
Health Study ◽  
Diabetes Incidence ◽  
Incident Type ◽  
Increased Risk

<b>Objective: </b>To examine whether proinflammatory and hyperinsulinemic diets are associated with increased risk of type 2 diabetes. <p><b> </b></p> <p><b>Research Design and Methods: </b>We prospectively followed 74,767 women from the Nurses’ Health Study (1984-2016), 90,786 women from the Nurses’ Health Study 2 (1989-2017), and 39,442 men from the Health Professionals Follow-up Study (1986-2016). Using repeated measures of food frequency questionnaires, we calculated empirical dietary inflammatory pattern (EDIP) and empirical dietary index for hyperinsulinemia (EDIH) scores which are food-based indices that characterize dietary inflammatory or insulinemic potential based on circulating biomarkers of inflammation or C-peptide. Diagnoses of type 2 diabetes were confirmed by validated supplementary questionnaires. </p> <p><b> </b></p> <p><b>Results: </b>We documented 19,666 incident type 2 diabetes cases over 4.9 million person-years of follow-up. In the pooled multivariable-adjusted analyses, individuals in the highest EDIP or EDIH quintile had 3.11 times (95% CI, 2.96-3.27) and 3.40 times (95% CI, 3.23-3.58) higher type 2 diabetes risk, respectively, compared to those in the lowest quintile. Additional adjustment for body mass index (BMI) attenuated the associations (Hazard ratio, 1.95; 95% CI, 1.85-2.05 for EDIP; Hazard ratio, 1.87; 95% CI, 1.78-1.98 for EDIH), suggesting adiposity partly mediates the observed associations. Moreover, individuals in both highest EDIP and EDIH quintiles had 2.34 times higher type 2 diabetes risk (95% CI, 2.17-2.52), compared to those in both lowest quintiles, after adjustment for BMI.</p> <p> </p> <p><b>Conclusions: </b><a>H</a>igher dietary inflammatory and insulinemic potential were associated with an increased type 2 diabetes incidence. Findings suggest that inflammation and hyperinsulinemia are potential mechanisms linking dietary patterns and type 2 diabetes development. </p>

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.

scholarly journals Association of Alcohol Drinking With Incident Type 2 Diabetes and Pre-diabetes: the Guangzhou Biobank Cohort Study

2021 ◽  
Author(s):  
Mei Jiao Li ◽  
Jing Ren ◽  
Wei Sen Zhang ◽  
Chao Qiang Jiang ◽  
Ya Li Jin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Genetic Polymorphisms ◽  
Impaired Fasting Glucose ◽  
Alcohol Drinking ◽  
Fasting Glucose ◽  
Heavy Alcohol ◽  
Incident Type ◽  
Incident Type 2 Diabetes

Abstract Background To examine associations of baseline alcohol drinking with incident type 2 diabetes or impaired fasting glucose, and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B).Methods Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident type 2 diabetes was defined as fasting glucose ≥7.0 mmol/l or post-load glucose ≥11.1 mmol/l at follow-up examination (2008-2012), self-reported type 2 diabetes and/or initiation of hypoglycemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6 mmol/l and <7 mmol/l. Results Of 15,716 participants without diabetes and 11,232 participants without diabetes and impaired fasting glucose at baseline, 1,624 (10.33%) developed incident type 2 diabetes, and 1,004 (8.94%) developed incident impaired fasting glucose during average 4 years of follow-up. After adjusting for sex, age, education, occupation, personal annual income, smoking, physical activity, body mass index, waist/hip ratio, health status, family history of diabetes, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident type 2 diabetes+impaired fasting glucose (odds ratio (OR) 1.08, 95% confidence interval (CI) 0.94-1.25, and 0.89 (0.68-1.16), respectively), but heavy alcohol drinking was associated with a higher risk of incident type 2 diabetes+impaired fasting glucose (1.83, 1.25-2.69). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B or ALDH2 genes with alcohol drinking on incident type 2 diabetes and/or impaired fasting glucose were found (p for interaction from 0.12 to 0.81). Conclusions Our results support a detrimental effect of heavy alcohol use on impaired fasting glucose and type 2 diabetes. No protective effect was found for those carrying lower risk alleles for ADH1B and ALDH2 genes.

scholarly journals Natriuretic peptides and risk of type 2 diabetes: Results from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium

2021 ◽  
Author(s):  
Chaterina Sujana ◽  
Veikko Salomaa ◽  
Frank Kee ◽  
Simona Costanzo ◽  
Stefan Söderberg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Risk Assessment ◽  
Cardiovascular Risk ◽  
Inverse Association ◽  
Cardiovascular Risk Assessment ◽  
Multiplicative Interaction ◽  
Incident Type ◽  
Incident Type 2 Diabetes

<p><b>Objective: </b>Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVD) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and mid-regional pro-atrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD. </p> <p><b> </b></p> <p><b>Research Design and Methods:</b> Based on the Biomarkers for Cardiovascular Risk Assessment in Europe-(BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models. </p> <p> </p> <p><b>Results: </b>Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95%CI] per 1-standard deviation increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without, but not in individuals with CVD (0.81 [0.76; 0.86] vs 1.04 [0.90; 1.19]; <i>P</i>-multiplicative interaction= 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs 0.81 [0.66; 0.99]; <i>P</i>-multiplicative interaction= 0.236). </p> <p> </p> <p><b>Conclusions:</b> NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.</p>

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.

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