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.

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.

453-P: Metabolic Syndrome Severity Score, All-Cause Mortality, and Incident Vascular Events in Type 2 Diabetes: A 13-Year, Single-Centre, Follow-Up Study

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 453-P
Author(s):  
MONIA GAROFOLO ◽  
ELISA GUALDANI ◽  
DANIELA LUCCHESI ◽  
LAURA GIUSTI ◽  
VERONICA SANCHO-BORNEZ ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Severity Score ◽  
Single Centre ◽  
Vascular Events ◽  
Follow Up Study ◽  
All Cause Mortality

scholarly journals Associations of Diet Quality and All-Cause Mortality Across Levels of Cardiometabolic Health and Disease: A 7.6-Year Prospective Analysis From the Dutch Lifelines Cohort

2021 ◽  
Author(s):  
Petra C Vinke ◽  
Gerjan Navis ◽  
Daan Kromhout ◽  
Eva Corpeleijn
Keyword(s):  
Type 2 Diabetes ◽  
Diet Quality ◽  
Total Population ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Dietary Guidelines ◽  
Cardiometabolic Health ◽  
Ageing Population ◽  
All Cause Mortality

<b>Objective: </b>To simultaneously investigate the association of diet quality and all-cause mortality in groups with varying cardiometabolic diseases (CMDs) at baseline.<br><p> <b>Design:</b> From the population-based Lifelines cohort, 40,892 non-underweight participants aged ≥50 years with data on diet quality and confounding factors were included (enrollment 2006-2013). From food frequency questionnaire data, tertiles of the Lifelines diet score were calculated (T1 = poorest, T3 = best diet quality). Four CMD categories were defined: 1) CMD-free, 2) type 2 diabetes, 3) one cardiovascular disease (CVD), 4) two or more CMDs. Months when deaths occurred were obtained from municipal registries up until November 2019. Multivariable Cox proportional hazards models were applied for the total population and stratified by CMD categories.<br> <b>Results</b>: After a median follow-up of 7.6 years, 1,438 participants died. Diet quality and CMD categories were independently associated with all-cause mortality in crude and adjusted models (p < 0.001). A dose-response relationship of diet quality with all-cause mortality was observed in the total population (P for trend < 0.001, T2 vs. T3 = 1.22 (1.07-1.41), T1 vs. T3 = 1.57 (1.37-1.80)). In stratified analyses, the association was significant for CMD-free individuals (T1 vs. T3 = 1.63 (1.38-1.93)) and for type 2 diabetes patients (1.87 (1.17-3.00)), but not for patients with one CVD (1.39 (0.93-2.08)) or multiple CMDs (1.19 (0.80-1.76)).<br> <b>Conclusions</b>: A high-quality diet can potentially lower all-cause mortality risk in the majority of the ageing population. Its effect may be greatest for CMD-free individuals and patients with type 2 diabetes. Tailored dietary guidelines may be required for patients with extensive histories of CMDs. </p>

scholarly journals Testosterone deficiency is associated with increased risk of mortality and testosterone replacement improves survival in men with type 2 diabetes

2013 ◽  
Vol 169 (6) ◽  
pp. 725-733 ◽  
Author(s):  
Vakkat Muraleedharan ◽  
Hazel Marsh ◽  
Dheeraj Kapoor ◽  
Kevin S Channer ◽  
T Hugh Jones
Keyword(s):  
Type 2 Diabetes ◽  
Untreated Group ◽  
Testosterone Replacement ◽  
Testosterone Deficiency ◽  
Testosterone Levels ◽  
All Cause Mortality ◽  
Low Testosterone

ObjectiveMen with type 2 diabetes are known to have a high prevalence of testosterone deficiency. No long-term data are available regarding testosterone and mortality in men with type 2 diabetes or any effect of testosterone replacement therapy (TRT). We report a 6-year follow-up study to examine the effect of baseline testosterone and TRT on all-cause mortality in men with type 2 diabetes and low testosterone.Research design and methodsA total of 581 men with type 2 diabetes who had testosterone levels performed between 2002 and 2005 were followed up for a mean period of 5.8±1.3 s.d. years. Mortality rates were compared between total testosterone >10.4 nmol/l (300 ng/dl; n=343) and testosterone ≤10.4 nmol/l (n=238). The effect of TRT (as per normal clinical practise: 85.9% testosterone gel and 14.1% intramuscular testosterone undecanoate) was assessed retrospectively within the low testosterone group.ResultsMortality was increased in the low testosterone group (17.2%) compared with the normal testosterone group (9%; P=0.003) when controlled for covariates. In the Cox regression model, multivariate-adjusted hazard ratio (HR) for decreased survival was 2.02 (P=0.009, 95% CI 1.2–3.4). TRT (mean duration 41.6±20.7 months; n=64) was associated with a reduced mortality of 8.4% compared with 19.2% (P=0.002) in the untreated group (n=174). The multivariate-adjusted HR for decreased survival in the untreated group was 2.3 (95% CI 1.3–3.9, P=0.004).ConclusionsLow testosterone levels predict an increase in all-cause mortality during long-term follow-up. Testosterone replacement may improve survival in hypogonadal men with type 2 diabetes.

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.

scholarly journals Association between high-density lipoprotein cholesterol and type 2 diabetes mellitus among Chinese: the Beijing longitudinal study of aging

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xue Cao ◽  
Zhe Tang ◽  
Jie Zhang ◽  
Haibin Li ◽  
Manjot Singh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Density Lipoprotein ◽  
Hazards Model ◽  
New Onset

Abstract Background Some previous studies on different populations have yielded inconsistent findings with respect to the relationship between levels of high-density lipoprotein cholesterol (HDL-C) and future type 2 diabetes mellitus (T2DM) incidence. This study was designed to gain further insight into this relationship through a cohort study with a 25-year follow-up duration. Methods In total, 1462 individuals that were 55 years of age or older and were free of T2DM at baseline were enrolled in the present study. T2DM incidence among this study population was detected through self-reported diagnoses or the concentration of fasting plasma glucose. The data were derived from nine surveys conducted from 1992 to 2017. The correlation between HDL-C levels and the T2DM risk was assessed through Cox proportional-hazards model and proportional hazards model for the sub-distribution with time-dependent variables. Results Over the follow-up period, 120 participants were newly diagnosed with new-onset T2DM. When research participants were separated into four groups on the basis for quartiles of their levels of HDL-C measured at baseline, and incidence of diabetes declined with higher baseline HDL-C levels at 12.60, 9.70, 5.38, and 5.22 per 1000 person-years, respectively. Adjusted hazard ratios (HRs) were 0.98 (95% confidence interval [CI]: 0.62–1.55), 0.48 (95% CI: 0.27–0.85) and 0.44 (95% CI: 0.25–0.80) for individuals with HDL-C levels within the 1.15–1.39, 1.40–1.69, and ≥ 1.70 mmol/L ranges relative to participants with HDL-C levels < 1.15 mmol/L. Multiple sensitivity analyses similarly revealed reduced risk of diabetes incidence with increased HDL-C levels. Incorporating the levels of HDL-C into a multivariate model significantly enhanced the overall power of the predictive model (P values were 0.0296, 0.0011, respectively, for 5- and 10-year risk of diabetes). Conclusions Levels of HDL-C were independently and negatively associated with the risk of the new-onset T2DM among middle-aged and elderly Chinese.

scholarly journals Anxiety and Depressive Symptoms as Predictors of All-Cause Mortality among People with Insulin-Naïve Type 2 Diabetes: 17-Year Follow-Up of the Second Nord-Trøndelag Health Survey (HUNT2), Norway

PLoS ONE ◽  
2016 ◽  
Vol 11 (8) ◽  
pp. e0160861 ◽  
Author(s):  
Marjolein M. Iversen ◽  
Giesje Nefs ◽  
Grethe S. Tell ◽  
Birgitte Espehaug ◽  
Kristian Midthjell ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Depressive Symptoms ◽  
Health Survey ◽  
All Cause Mortality

scholarly journals C-peptide and the risk for incident complications and mortality in type 2 diabetic patients: a retrospective cohort study after a 14-year follow-up

2012 ◽  
Vol 167 (2) ◽  
pp. 173-180 ◽  
Author(s):  
S Bo ◽  
L Gentile ◽  
A Castiglione ◽  
V Prandi ◽  
S Canil ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Retrospective Cohort ◽  
Microvascular Complications ◽  
Chronic Complications ◽  
C Peptide ◽  
All Cause Mortality

ObjectiveC-peptide, a cleavage product of insulin, exerts biological effects in patients with type 1 diabetes mellitus, but its role in type 2 diabetes mellitus is controversial. Our aim was to examine the associations between fasting C-peptide levels and all-cause mortality, specific-cause mortality and the incidence of chronic complications in patients with type 2 diabetes.DesignRetrospective cohort study with a median follow-up of 14 years.MethodsA representative cohort of 2113 patients with type 2 diabetes mellitus and a subgroup of 931 individuals from this cohort without chronic complications at baseline from a diabetic clinic were studied.ResultsPatients with higher C-peptide levels had higher baseline BMI and triglyceride and lower HDL-cholesterol values. During the follow-up, 46.1% of the patients died. In a Cox proportional hazard model, after multiple adjustments, no significant association was found between the C-peptide tertiles and all-cause mortality or mortality due to cancer, diabetes or cardiovascular diseases. In the subgroup of 931 patients without chronic complications at baseline, the incidence of microvascular complications decreased from the first to the third C-peptide level tertile, while the incidence of cardiovascular disease did not differ. The risks for incident retinopathy (hazard ratio (HR)=0.33; 95% confidence interval (CI) 0.23–0.47), nephropathy (HR=0.27; 95% CI 0.18–0.38) and neuropathy (HR=0.39; 95% CI 0.25–0.61) were negatively associated with the highest C-peptide tertile, after adjusting for multiple confounders.ConclusionsHigher baseline C-peptide levels were associated with a reduced risk of incident microvascular complications but imparted no survival benefit to patients with type 2 diabetes mellitus.

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