scholarly journals Purine Metabolites and Carnitine Biosynthesis Intermediates Are Biomarkers for Incident Type 2 Diabetes

2019 ◽  
Vol 104 (10) ◽  
pp. 4921-4930 ◽  
Author(s):  
Filip Ottosson ◽  
Einar Smith ◽  
Widet Gallo ◽  
Céline Fernandez ◽  
Olle Melander

Abstract Context Metabolomics has the potential to generate biomarkers that can facilitate understanding relevant pathways in the pathophysiology of type 2 diabetes (T2DM). Methods Nontargeted metabolomics was performed, via liquid chromatography–mass spectrometry, in a discovery case-cohort study from the Malmö Preventive Project (MPP), which consisted of 698 metabolically healthy participants, of whom 202 developed T2DM within a follow-up time of 6.3 years. Metabolites that were significantly associated with T2DM were replicated in the population-based Malmö Diet and Cancer–Cardiovascular Cohort (MDC-CC) (N = 3423), of whom 402 participants developed T2DM within a follow-up time of 18.2 years. Results Using nontargeted metabolomics, we observed alterations in nine metabolite classes to be related to incident T2DM, including 11 identified metabolites. N2,N2-dimethylguanosine (DMGU) (OR = 1.94; P = 4.9e-10; 95% CI, 1.57 to 2.39) was the metabolite most strongly associated with an increased risk, and beta-carotene (OR = 0.60; P = 1.8e-4; 95% CI, 0.45 to 0.78) was the metabolite most strongly associated with a decreased risk. Identified T2DM-associated metabolites were replicated in MDC-CC. Four metabolites were significantly associated with incident T2DM in both the MPP and the replication cohort MDC-CC, after adjustments for traditional diabetes risk factors. These included associations between three metabolites, DMGU, 7-methylguanine (7MG), and 3-hydroxytrimethyllysine (HTML), and incident T2DM. Conclusions We used nontargeted metabolomics in two Swedish prospective cohorts comprising >4000 study participants and identified independent, replicable associations between three metabolites, DMGU, 7MG, and HTML, and future risk of T2DM. These findings warrant additional studies to investigate a potential functional connection between these metabolites and the onset of T2DM.

2018 ◽  
Vol 6 (1) ◽  
pp. e000492 ◽  
Author(s):  
Mamoru Takeuchi ◽  
Hironori Imano ◽  
Isao Muraki ◽  
Yuji Shimizu ◽  
Mina Hayama-Terada ◽  
...  

ObjectiveTo assess the association between low serum creatinine levels and an increased risk of type 2 diabetes mellitus and dysglycemia.Research design and methodsWe conducted a retrospective cohort study of 3313 Japanese male workers aged 30–55 years, who underwent annual health check-ups during 2001–2008 and showed no type 2 diabetes mellitus, and underwent follow-up examinations until March 2013. Dysglycemia was defined as a fasting plasma glucose concentration of ≥110 mg/dL (6.1 mmol/L), or a non-fasting plasma glucose concentration of ≥140 mg/dL (7.8 mmol/L). A Cox proportional model was used to calculate HRs and 95% CIs for developing type 2 diabetes mellitus or dysglycemia.ResultsDuring the median 6.7-year follow-up, there were 207 cases of incident type 2 diabetes mellitus and 596 cases of incident dysglycemia, including 115 cases of type 2 diabetes mellitus among the subjects with normal glucose concentrations at baseline. After adjustment for age, body mass index and known diabetes risk factors, the multivariable HR of type 2 diabetes mellitus for the lowest category of serum creatinine (<0.7 mg/dL) vs the highest category (0.9–1.1 mg/dL) was 1.9 (95% CI 1.2 to 2.9; P for trend 0.03). The multivariable HRs of dysglycemia for the lowest category of serum creatinine versus the highest category was 1.5 (95% CI 1.1 to 1.9; P for trend 0.01).ConclusionsLow serum creatinine levels were associated with an increased risk of type 2 diabetes mellitus and dysglycemia.


2012 ◽  
Vol 109 (6) ◽  
pp. 1143-1153 ◽  
Author(s):  
Ulrika Ericson ◽  
Emily Sonestedt ◽  
Bo Gullberg ◽  
Sophie Hellstrand ◽  
George Hindy ◽  
...  

Diets high in protein have shown positive effects on short-term weight reduction and glycaemic control. However, the understanding of how dietary macronutrient composition relates to long-term risk of type 2 diabetes is limited. The aim of the present study was to examine intakes of macronutrients, fibre and protein sources in relation to incident type 2 diabetes. In total, 27 140 individuals, aged 45–74 years, from the population-based Malmö Diet and Cancer cohort, were included. Dietary data were collected with a modified diet history method, including registration of cooked meals. During 12 years of follow-up, 1709 incident type 2 diabetes cases were identified. High protein intake was associated with increased risk of type 2 diabetes (hazard ratio (HR) 1·27 for highest compared with lowest quintile; 95 % CI 1·08, 1·49; P for trend = 0·01). When protein consumption increased by 5 % of energy at the expense of carbohydrates (HR 1·20; 95 % CI 1·09, 1·33) or fat (HR 1·21; 95 % CI 1·09, 1·33), increased diabetes risk was observed. Intakes in the highest quintiles of processed meat (HR 1·16; 95 % CI 1·00, 1·36; P for trend = 0·01) and eggs (HR 1·21; 95 % CI 1·04, 1·41; P for trend = 0·02) were associated with increased risk. Intake of fibre-rich bread and cereals was inversely associated with type 2 diabetes (HR 0·84; 95 % CI 0·73, 0·98; P for trend = 0·004). In conclusion, results from the present large population-based prospective study indicate that high protein intake is associated with increased risk of type 2 diabetes. Replacing protein with carbohydrates may be favourable, especially if fibre-rich breads and cereals are chosen as carbohydrate sources.


Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3249
Author(s):  
Andrés Díaz-López ◽  
Lucía Iglesias-Vázquez ◽  
Meritxell Pallejà-Millán ◽  
Cristina Rey Reñones ◽  
Gemma Flores Mateo ◽  
...  

Type 2 diabetes poses a major public health challenge. Here, we conducted a cohort study with a large sample size to determine the association of baseline serum ferritin (SF), a marker of iron status, with incident type 2 diabetes in primary healthcare patients in Catalonia, a western Mediterranean region. A total of 206,115 patients aged 35–75 years without diabetes and with available baseline SF measurements were eligible. The variables analyzed included sociodemographic characteristics, anthropometry, lifestyle, morbidity and iron status (SF, serum iron and hemoglobin). Incident type 2 diabetes during follow-up (2006–2016) was ascertained using the International Classification of Diseases, 10th edition. Cox proportional-hazards models adjusted for multiple baseline confounders/mediators were used to estimate hazard ratios (HRs). Over a median follow-up of 8.4 years, 12,371 new cases of type 2 diabetes were diagnosed, representing an incidence rate of 7.5 cases/1000 persons/year. Since at baseline, the median SF concentration was higher in subjects who developed type 2 diabetes (107.0 µg/L vs. 60.3 µg/L; p < 0.001), SF was considered an independent risk predictor for type 2 diabetes; the multivariable-adjusted HRs for incident type 2 diabetes across SF quartiles 1–4 were 1.00 (reference), 0.95 (95% CI = 0.85–1.06), 1.18 (95% CI = 1.65–1.31) and 1.51 (95% CI = 1.36–1.65), respectively. Our study suggested that higher baseline SF was significantly associated with an increased risk of new-onset type 2 diabetes in Catalan primary healthcare users, supporting the relevance of monitoring iron stores in order to improve the diagnosis and management of diabetes in clinical practice.


2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1452-1452
Author(s):  
Ze-Lei Miao ◽  
Ju-Sheng Zheng ◽  
Yu-Ming Chen

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.


Author(s):  
Avishai M Tsur ◽  
Shir Hershkovich ◽  
Inbar Zucker ◽  
Miri Lutski ◽  
Orit Pinhas-Hamiel ◽  
...  

Abstract Purpose To investigate the association between stuttering in adolescence and incident type 2 diabetes in young adulthood. Methods This nationwide population-based study included 2 193 855 adolescents of age 16 to 20 years who were assessed for military service between 1980 and 2013. Diagnoses of stuttering in adolescence were confirmed by a speech-language pathologist. Diabetes status for each individual as of December 31, 2016, was determined by linkage to the Israeli National Diabetes Registry. Relationships were analyzed using regression models adjusted for socioeconomic variables, cognitive performance, coexisting morbidities, and adolescent body mass index. Results Analysis was stratified by sex (Pinteraction = 0.035). Of the 4443 (0.4%) adolescent men with stuttering, 162 (3.7%) developed type 2 diabetes, compared with 25 678 (2.1%) men without stuttering (adjusted odds ratio [OR] 1.3; 95% CI, 1.1-1.6). This relationship persisted when unaffected brothers of men with stuttering were used as the reference group (adjusted OR = 1.5; 95% CI, 1.01-2.2), or when the analysis included only adolescents with unimpaired health at baseline (adjusted OR = 1.4; 95% CI, 1.1-1.7). The association was stronger in later birth cohorts, with an adjusted OR of 2.4 (1.4-4.1) for cases of type 2 diabetes before age 40. Of the 503 (0.1%) adolescent women with stuttering 7 (1.4%) developed type 2 diabetes, compared with 10 139 (1.1%) women without stuttering (OR = 2.03; 95% CI, 0.48-2.20). Conclusions Adolescent stuttering is associated with an increased risk for early-onset type 2 diabetes among men.


Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2460 ◽  
Author(s):  
Spiga ◽  
Mannino ◽  
Mancuso ◽  
Averta ◽  
Paone ◽  
...  

Magnesium (Mg2+) is an enzyme co-factor that plays a key role in many biochemical reactions, as well as in glucose metabolism. Clinical evidences have demonstrated that depletion of serum Mg2+ increases exponentially with the duration of type 2 diabetes mellitus (T2DM). Diabetes is associated with low Mg2+, and hypomagnesemia is associated with insulin resistance, inflammation, and increased risk for cardiovascular disease. In subjects at high risk of inflammation and insulin resistance, supplementation of Mg2+ alone ameliorates both phenotypes, slowing the development and progression of hepatic steatosis. We analyze the relationship between serum Mg2+ levels and the onset of T2DM in a large cohort of well-characterized adult white individuals participating in the CATAMERI study, who were reexamined after a mean follow-up of 5.6 ± 0.9 years. In our analysis we acquired a significant negative correlation between Mg2+ levels, fasting glucose, and 2h-post load glucose in subjects who underwent an OGTT. Moreover, Mg2+ levels correlated negatively with fasting insulin levels, and positively with the lipid profile. As for the detrimental effect of lower circulating Mg2+ levels, our data revealed a significant reduction of T2DM risk of about 20% for each 1 mg/dL increase of circulating Mg2+. The present results are consistent with the theory that Mg2+ supplementation could ameliorate insulin sensitivity reducing the risk to develop T2DM.


2021 ◽  
Author(s):  
Mei Jiao Li ◽  
Jing Ren ◽  
Wei Sen Zhang ◽  
Chao Qiang Jiang ◽  
Ya Li Jin ◽  
...  

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.


2021 ◽  
Author(s):  
Chaterina Sujana ◽  
Veikko Salomaa ◽  
Frank Kee ◽  
Simona Costanzo ◽  
Stefan Söderberg ◽  
...  

<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>


Circulation ◽  
2015 ◽  
Vol 131 (suppl_1) ◽  
Author(s):  
Duck-chul Lee ◽  
Carl J. Lavie ◽  
Timothy S. Church ◽  
Xuemei Sui ◽  
Steven N. Blair

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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