scholarly journals Plasma Metabolites Associate with All-Cause Mortality in Individuals with Type 2 Diabetes

Metabolites ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 315
Author(s):  
Filip Ottosson ◽  
Einar Smith ◽  
Céline Fernandez ◽  
Olle Melander
Keyword(s):  
Type 2 Diabetes ◽  
Premature Mortality ◽  
Population Based ◽  
Plasma Metabolites ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Prospective Cohorts ◽  
Diet And Cancer

Alterations in the human metabolome occur years before clinical manifestation of type 2 diabetes (T2DM). By contrast, there is little knowledge of how metabolite alterations in individuals with diabetes relate to risk of diabetes complications and premature mortality. Metabolite profiling was performed using liquid chromatography-mass spectrometry in 743 participants with T2DM from the population-based prospective cohorts The Malmö Diet and Cancer-Cardiovascular Cohort (MDC-CC) and The Malmö Preventive Project (MPP). During follow-up, a total of 175 new-onset cases of cardiovascular disease (CVD) and 298 deaths occurred. Cox regressions were used to relate baseline levels of plasma metabolites to incident CVD and all-cause mortality. A total of 11 metabolites were significantly (false discovery rate (fdr) <0.05) associated with all-cause mortality. Acisoga, acylcarnitine C10:3, dimethylguanidino valerate, homocitrulline, N2,N2-dimethylguanosine, 1-methyladenosine and urobilin were associated with an increased risk, while hippurate, lysine, threonine and tryptophan were associated with a decreased risk. Ten out of 11 metabolites remained significantly associated after adjustments for cardiometabolic risk factors. The associations between metabolite levels and incident CVD were not as strong as for all-cause mortality, although 11 metabolites were nominally significant (p < 0.05). Further examination of the mortality-related metabolites may shed more light on the pathophysiology linking diabetes to premature mortality.

scholarly journals Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

2020 ◽  
Vol 9 (1) ◽  
pp. 246
Author(s):  
Emanuela Orsi ◽  
Enzo Bonora ◽  
Anna Solini ◽  
Cecilia Fondelli ◽  
Roberto Trevisan ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Haemoglobin A1c ◽  
Vital Status ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Severe Comorbidity ◽  
Potential Risks ◽  
Risk Of Treatment

The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A1c, anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA1c and then assigned to three target categories, based on whether HbA1c was ≤0.5% below or above (on-target), >0.5% below (below-target) or >0.5% above (above-target) their HbA1c goal, personalized according to the number of potential risks among age > 70 years, diabetes duration > 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA1c category (≥8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22–1.47), p < 0.001) and those above-target (1.42 (1.29–1.57), p < 0.001). Risk was increased among individuals in the lowest HbA1c category (<6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03–1.29), p = 0.01 and 1.10 (1.01–1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA1c goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia.

Abstract MP21: Circulating Biomarkers of Dairy Fat and Incident Type 2 Diabetes in Two US Prospective Cohorts

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
Mohammad Y Yakoob ◽  
Peilin Shi ◽  
Frank B Hu ◽  
Hannia Campos ◽  
Kathryn M Rexrode ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lower Incidence ◽  
Lower Risk ◽  
Circulating Biomarkers ◽  
Dairy Fat ◽  
Fat Consumption ◽  
Increased Risk ◽  
Prospective Cohorts

Background: Prior observational studies suggest that self-reported consumption of dairy foods is associated with lower risk of type 2 diabetes (DM). Few studies have used circulating biomarkers that provide objective measures of dairy fat consumption. Aim: To test the hypothesis that plasma fatty acid biomarkers of dairy fat, 15:0, 17:0, 16:1 n-7t and 14:0, are associated with lower incidence of DM. Methods: We used gas-liquid chromatography to measure plasma 15:0, 17:0, 16:1 n-7t and 14:0 biomarkers in 3,347 adults aged 30-75 years and free of prevalent DM at baseline in two separate U.S. prospective cohorts, Nurses’ Health Study (NHS) and Health Professionals’ Follow Up Study (HPFS). Incident DM was identified through 2008 and confirmed by validated supplementary questionnaire using symptoms, diagnostic tests, and medical therapy. Cox proportional hazards regression was used and cohort findings pooled by fixed-effects meta-analysis. Results: During mean ± SD follow-up of 14.0 ± 4.9 years, 254 new cases of DM were diagnosed. Correlations with self-reported dairy fat consumption were modest for 17:0 (r=0.19), 16:1 n-7t (r=0.21) and 15:0 (r=0.27), and weaker for 14:0 (r=0.12). In pooled multivariate analyses, comparing highest to lowest quartiles, lower risk of DM was seen for 17:0 [HR=0.57 (95% CI: 0.39 - 0.82), P-trend=0.001] and 16:1 n-7t [HR=0.60 (0.42 - 0.87), P-trend=0.007], while 14:0 was positively associated [HR=1.98 (1.35 - 2.91), P-trend <0.0001] and 15:0 was not associated [HR=1.11 (0.75 - 1.63), P-trend=0.80] ( Table ). Conclusion: In separate prospective cohorts, two biomarkers of dairy fat (17:0 and 16:1 n-7t) were associated with lower incidence of DM. 14:0, which is also obtained from beef, and is a marker of de novo lipogenesis, was associated with increased risk. Further research is needed on plausible biological and mechanistic pathways.

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
Keyword(s):  
Type 2 Diabetes ◽  
Beta Carotene ◽  
Population Based ◽  
Functional Connection ◽  
Incident Type ◽  
Increased Risk ◽  
Incident Type 2 Diabetes ◽  
Study Participants

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.

scholarly journals Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study

2016 ◽  
Vol 101 (5) ◽  
pp. 1963-1969 ◽  
Author(s):  
Sumit R. Majumdar ◽  
Robert G. Josse ◽  
Mu Lin ◽  
Dean T. Eurich
Keyword(s):  
Type 2 Diabetes ◽  
Cohort Study ◽  
Fracture Risk ◽  
Large Population ◽  
Osteoporotic Fractures ◽  
Population Based ◽  
Increased Risk ◽  
Multivariable Analyses

Abstract Context: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin). Objective: To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study. Design, Setting, and Subjects: A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores. Main Outcomes: We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up. Results: At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8–1.4; P = .7), although insulin (P &lt; .001), sulfonylureas (P &lt; .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk. Conclusions: Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures.

scholarly journals IGF-I gene promoter polymorphism is a predictor of survival after myocardial infarction in patients with type 2 diabetes

2006 ◽  
Vol 155 (5) ◽  
pp. 751-756 ◽  
Author(s):  
Mojgan Yazdanpanah ◽  
Fakhredin A Sayed-Tabatabaei ◽  
Joop A M J L Janssen ◽  
Ingrid Rietveld ◽  
Albert Hofman ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Gene Promoter ◽  
Population Based ◽  
Promoter Polymorphism ◽  
Increased Risk ◽  
Igf I ◽  
Genetically Determined

Objective: Previously we observed that non-carriers of the most common alleles of an IGF-I promoter polymorphism have low circulating IGF-I levels and an increased risk of developing myocardial infarction (MI), particularly in patients with type 2 diabetes. Design: We investigated whether this IGF-I promoter polymorphism is associated with survival of type 2 diabetes in a Caucasian population aged 55 years and older. Methods: The study was embedded in the Rotterdam Study, a prospective population-based cohort study. At baseline, 668 patients with type 2 diabetes were diagnosed, among which, 55 incident MI were ascertained during follow-up. For the present study, we used two genotype groups: non-variant carriers (homozygous for 192, 194, or 192/194 bp genotypes), and variant carriers. Results: During a median follow-up of 8.8 years, 396 out of the 668 patients with type 2 diabetes (59.3%) died of various causes. The frequency of type 2 diabetes variant carrier and non-variant carriers was 28.7 and 71.3% respectively. The survival in patients with type 2 diabetes without an MI did not differ between the IGF-I genotype groups (hazard ratio (HR) = 0.8, 95% confidence interval (CI): 0.7–1.1, P = 0.1). In contrast, in those who developed an MI, variant carriers had a 2.4 times higher risk of mortality than non-variant carriers (95% CI: 1.2–4.8, P = 0.01). Conclusion: Our study suggests that genetically determined low IGF-I activity is an important determinant of survival in patients with type 2 diabetes who developed an MI. The IGF-I promoter polymorphism, therefore, may help to predict the future mortality risk in this group of patients.

scholarly journals Free testosterone and cardiometabolic parameters in men: comparison of algorithms

2021 ◽  
Author(s):  
Stine A. Holmboe ◽  
Ravi Jasuja ◽  
Brian Lawney ◽  
Lærke Priskorn ◽  
Niels Joergensen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Free Testosterone ◽  
Population Based ◽  
Total Testosterone ◽  
Binding Model ◽  
Free Androgen Index ◽  
Increased Risk

Objective. Calculating the free testosterone level has gained increasing interest and different indirect algorithms have been suggested. The objective was to compare free androgen index (FAI), free testosterone estimated using the linear binding model (Vermeulen: cFTV) and the binding framework accounting for allosterically coupled SHBG monomers (Zakharov: cFTZ) in relation to cardiometabolic conditions. Design. A prospective cohort study including 5,350 men, aged 30-70 years, participating in population-based surveys (MONICA I–III and Inter99) from 1982-2001 and followed until December 2012 with baseline and follow-up information on cardiometabolic parameters and vital status. Results. Using age-standardized hormone levels, FAI was higher among men with baseline cardiometabolic conditions, whereas cFTV and cFTZ levels were lower compared to men without these conditions as also seen for total testosterone. Men in highest quartiles of cFTV or cFTZ had lower risk of developing type 2 diabetes (cFTV: HR=0.74 (0.49-1.10), cFTZ: HR=0.59 (0.39-0.91)) than men in lowest quartile. In contrast, men with highest levels of FAI had a 74% (1.17-2.59) increased risk of developing type 2 diabetes compared to men in lowest quartile. Conclusion. The association of estimated free testosterone and the studied outcomes differ depending on algorithm used. cFTV and cFTZ showed similar associations to baseline and long-term cardiometabolic parameters. In contrast, an empiric ratio, FAI, showed opposite associations to several of the examined parameters and may reflect limited clinical utility.

Abstract 06: Body Mass Index And The Risk Of All-cause Mortality Among Patients With Type 2 Diabetes

Circulation ◽  
2014 ◽  
Vol 129 (suppl_1) ◽  
Author(s):  
wenhui zhao ◽  
Peter Katzmarzyk ◽  
Ronald Horswell ◽  
Yujie Wang ◽  
Jolene Johnson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Mass Index ◽  
African Americans ◽  
Body Mass ◽  
Mortality Risk ◽  
Diabetic Patients ◽  
Increased Risk ◽  
All Cause Mortality

Background: Several prospective studies have evaluated the association between body mass index (BMI) and the risk of all-cause mortality among diabetic patients; however, the results are controversial. Aim: To investigate the association of BMI levels with all-cause mortality among patients with type 2 diabetes in the Louisiana State University Hospital-based Longitudinal study (LSUHLS). Methods: We performed a prospective cohort study (2000-2009) of diabetic patients including 19,785 African Americans and 15,534 whites. Cox proportional hazards regression models were used to estimate the association of BMI levels at baseline, during follow-up and at last visit with the risk of all-cause mortality. Results: During a mean follow up of 8.7 years, 4,206 deaths were identified. The multivariable-adjusted (age, sex, smoking, income and type of insurance) hazard ratios (HRs) of all-cause mortality associated with BMI levels (<23, 23-24.9, 25-29.9, 30-34.9 [reference group], 35-39.9, and ≥40 kg/m 2 ) at baseline were 2.53 (95% confidence interval [CI] 2.18-2.93), 1.76 (1.48-2.09), 1.23 (1.08-1.40), 1.00, 1.19 (1.02-1.38), and 1.22 (1.05-1.41) for African Americans, and 1.92 (1.63-2.27), 1.53 (1.28-1.82), 1.07 (0.95-1.21), 1.00, 1.07 (0.93-1.23), and 1.21 (1.06-1.39) for whites, respectively. When stratified by age, gender, smoking status or use of anti-diabetic drugs, a U-shaped association was still present. When we used an updated mean or last visit value of BMI, the U-shaped association of BMI with all-cause mortality risk did not change. Conclusions: The current study indicated a U-shaped association of BMI with all-cause mortality risk among African American and white patients with type 2 diabetes. A significantly increased risk of all-cause mortality was observed among African Americans with BMI<30 kg/m 2 and BMI ≥35 kg/m 2 , and among whites with BMI<25 kg/m 2 and BMI ≥40 kg/m 2 compared with patients with BMI 30-34.9 kg/m 2 .

scholarly journals Plasma trimethylamine N-oxide and its metabolic precursors and risk of mortality, cardiovascular and renal disease in individuals with type 2-diabetes and albuminuria

PLoS ONE ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. e0244402
Author(s):  
Signe Abitz Winther ◽  
Jens Christian Øllgaard ◽  
Tine Willum Hansen ◽  
Bernt Johan von Scholten ◽  
Henrik Reinhard ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Function ◽  
Proportional Hazards ◽  
Plasma Concentrations ◽  
Plasma Metabolites ◽  
Weighted Sum ◽  
Sum Score ◽  
All Cause Mortality

Aims The trimethylamine N-oxide (TMAO) pathway is related to intestinal microbiota and has been associated to risk of cardiovascular disease (CVD). We investigated associations between four plasma metabolites in the TMAO pathway and risk of all-cause mortality, CVD and deterioration in renal function in individuals with type 2-diabetes (T2D) and albuminuria. Materials and methods Plasma concentrations of TMAO, choline, carnitine, and betaine were measured by liquid chromatography-tandem mass spectrometry at baseline in 311 individuals with T2D and albuminuria. Information on all-cause mortality and fatal/non-fatal CVD during follow-up was obtained from registries. The association of each metabolite, and a weighted sum score of all four metabolites, with the endpoints were examined. Serum creatinine was measured at follow-up visits and the renal endpoint was defined as eGFR-decline of ≥30%. Associations were analysed using proportional hazards models adjusted for traditional risk factors. Results Baseline mean(SD) age was 57.2(8.2) years and 75% were males. Follow-up was up to 21.9 years (median (IQR) follow-up 6.8 (6.1–15.5) years for mortality and 6.5 (5.5–8.1) years for CVD events). The individual metabolites and the weighted sum score were not associated with all-cause mortality (n = 106) or CVD (n = 116) (adjusted p≥0.09). Higher choline, carnitine and the weighted sum score of the four metabolites were associated with higher risk of decline in eGFR (n = 106) (adjusted p = 0.001, p = 0.03 and p<0.001, respectively). Conclusions In individuals with T2D and albuminuria, higher choline, carnitine and a weighted sum of four metabolites from the TMAO pathway were risk markers for deterioration in renal function during long-term follow-up. Metabolites from the TMAO pathway were not independently related to risk of all-cause mortality or CVD.

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