Blood coagulation in Prediabetes clusters-impact on all-cause mortality in individuals undergoing coronary angiography.

BACKGROUND: Metabolic clusters can stratify subgroups of individuals at risk for type 2 diabetes mellitus and related complications. Since obesity and insulin resistance are closely linked to alterations in hemostasis, we investigated the association between plasmatic coagulation and metabolic clusters including the impact on survival. METHODS: Utilizing data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study, we assigned 917 participants without diabetes to prediabetes clusters, using oGTT-derived glucose and insulin, high-density lipoprotein cholesterol, triglycerides, and anthropometric data. We performed a comprehensive analysis of plasmatic coagulation parameters and analyzed their associations with mortality using proportional hazards models. Mediation analysis was performed to assess the effect of coagulation factors on all-cause mortality in prediabetes clusters. RESULTS: Prediabetes clusters were assigned using published tools, and grouped into low-risk (clusters 1,2,4; n = 643) and high-risk (clusters 3,5,6; n = 274) clusters. Individuals in the high-risk clusters had a significantly increased risk of death (HR = 1.30; CI: 1.01 to 1.67) and showed significantly elevated levels of procoagulant factors (fibrinogen, FVII/VIII/IX), D-dimers, von-Willebrand factor, and PAI-1, compared to individuals in the low-risk clusters. In proportional hazards models adjusted for relevant confounders, elevated levels of fibrinogen, D-dimers, FVIII, and vWF were found to be associated with an increased risk of death. Multiple mediation analysis indicated that vWF significantly mediates the cluster-specific risk of death. CONCLUSIONS: High-risk prediabetes clusters are associated with prothrombotic changes in the coagulation system that likely contribute to the increased mortality in those individuals at cardiometabolic risk. The hypercoagulable state observed in the high-risk clusters indicates an increased risk for cardiovascular and thrombotic diseases that should be considered in future risk stratification and therapeutic strategies.

Association between glycemic status and all-cause mortality among individuals with dementia: a nationwide cohort study.

BACKGROUND: To examine the association between glycemic status and all-cause mortality risk among individuals with dementia. METHODS: We enrolled 146,832 individuals aged 40 and older with dementia as identified through the Korean National Health Insurance Service health screening test between 2008 and 2016. Mortality status was evaluated at the end of 2019. Participants were classified into normoglycemia, prediabetes, or diabetes mellitus (DM) categories. The duration of diabetes was noted in those with DM. This study focused on the association between glycemic status and all-cause mortality. RESULTS: The cohort, which was predominantly elderly (average age 75.1 years; 35.5% male), had a 35.2% mortality rate over an average 3.7-year follow-up. DM was linked with increased all-cause mortality risk (hazard ratio [HR] 1.34; 95% confidence interval [CI]: 1.32-1.37) compared to non-DM counterparts. The highest mortality risk was observed in long-term DM patients (≥ 5 years) (HR 1.43; 95% CI: 1.40-1.47), followed by newly diagnosed DM (HR 1.35; 95% CI: 1.30-1.40), shorter-term DM (< 5 years) (HR 1.17; 95% CI: 1.13-1.21), and prediabetes (HR 1.03; 95% CI: 1.01-1.05). These patterns persisted across Alzheimer's disease and vascular dementia, with more pronounced effects observed in younger patients. CONCLUSIONS: Glucose dysregulation in dementia significantly increased mortality risk, particularly in newly diagnosed or long-standing DM. These findings suggest the potential benefits of maintaining normal glycemic levels in improving the survival of patients with dementia.

The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) as a predictor of all-cause and cardiovascular mortality in US adults with diabetes or prediabetes: NHANES 1999-2018.

BACKGROUND: The non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) serves as a novel composite lipid indicator for atherosclerosis. However, the association between NHHR and mortality in patients with diabetes or prediabetes remains unclear. Consequently, the objective of this study was to investigate the relationship between NHHR and both all-cause and cardiovascular mortality in US adults with diabetes or prediabetes. METHODS: This study included 12,578 adult participants with diabetes or prediabetes from the US National Health and Nutrition Examination Survey (1999-2018). Mortality outcomes were ascertained by linking to the National Death Index (NDI) record up to December 31, 2019. We employed a weighted multivariate Cox proportional hazards model and restricted cubic splines to assess the associations between NHHR and all-cause and cardiovascular mortality. A segmented Cox proportional hazards model was used for evaluating threshold effects. Furthermore, a competing risks analysis was performed to explore the relationship between NHHR and cardiovascular mortality. RESULTS: During a median follow-up period of 8.08 years, 2403 participants encountered all-cause mortality, with 662 of them specifically succumbing to cardiovascular mortality. The restricted cubic splines revealed a U-shaped association between NHHR and all-cause mortality, while an L-shaped association was observed for cardiovascular mortality. The analysis of threshold effects revealed that the inflection points for NHHR and all-cause and cardiovascular mortality were 2.72 and 2.83, respectively. Specifically, when the baseline NHHR was below the inflection points, a negative correlation was observed between NHHR and both all-cause mortality (HR: 0.76, 95% CI: 0.68-0.85) and cardiovascular mortality (HR: 0.70, 95% CI: 0.57-0.85). Conversely, when the baseline NHHR exceeded the inflection points, a positive correlation was observed between NHHR and both all-cause mortality (HR: 1.11, 95% CI: 1.06-1.16) and cardiovascular mortality (HR: 1.08, 95% CI: 1.00-1.16). CONCLUSIONS: Among US adults with diabetes or prediabetes, a U-shaped association was observed between NHHR and all-cause mortality, whereas an L-shaped association was identified with cardiovascular mortality. The inflection points for all-cause and cardiovascular mortality were 2.72 and 2.83, respectively.

Impaired glucose metabolism and the risk of vascular events and mortality after ischemic stroke: A systematic review and meta-analysis.

BACKGROUND: Diabetes mellitus (DM), prediabetes, and insulin resistance are highly prevalent in patients with ischemic stroke (IS). DM is associated with higher risk for poor outcomes after IS. OBJECTIVE: Investigate the risk of recurrent vascular events and mortality associated with impaired glucose metabolism compared to normoglycemia in patients with IS and transient ischemic attack (TIA). METHODS: Systematic literature search was performed in PubMed, Embase, Cochrane Library on 21st March 2024 and via citation searching. Studies that comprised IS or TIA patients and exposures of impaired glucose metabolism were eligible. Study Quality Assessment Tool was used for risk of bias assessment. Covariate adjusted outcomes were pooled using random-effects meta-analysis. MAIN OUTCOMES: Recurrent stroke, cardiac events, cardiovascular and all-cause mortality and composite of vascular outcomes. RESULTS: Of 10,974 identified studies 159 were eligible. 67% had low risk of bias. DM was associated with an increased risk for composite events (pooled HR (pHR) including 445,808 patients: 1.58, 95% CI 1.34-1.85, I2 = 88%), recurrent stroke (pHR including 1.161.527 patients: 1.42 (1.29-1.56, I2 = 92%), cardiac events (pHR including 443,863 patients: 1.55, 1.50-1.61, I2 = 0%), and all-cause mortality (pHR including 1.031.472 patients: 1.56, 1.34-1.82, I2 = 99%). Prediabetes was associated with an increased risk for composite events (pHR including 8,262 patients: 1.50, 1.15-1.96, I2 = 0%) and recurrent stroke (pHR including 10,429 patients: 1.50, 1.18-1.91, I2 = 0), however, not with mortality (pHR including 9,378 patients, 1.82, 0.73-4.57, I2 = 78%). Insulin resistance was associated with recurrent stroke (pHR including 21,363 patients: 1.56, 1.19-2.05, I2 = 55%), but not with mortality (pHR including 21,363 patients: 1.31, 0.66-2.59, I2 = 85%). DISCUSSION: DM is associated with a 56% increased relative risk of death after IS and TIA. Risk estimates regarding recurrent events are similarly high between prediabetes and DM, indicating high cardiovascular risk burden already in precursor stages of DM. There was a high heterogeneity across most outcomes.

Association of dietary antioxidant intake with depression risk and all-cause mortality in people with prediabetes.

People with diabetes has an elevated risk of depression, and depression contributes to a worse prognosis for people with diabetes. Dietary antioxidants have been shown to reduce the risk of depression in the general population. Therefore, we hypothesized that dietary antioxidants would also help to reduce the risk of depression and all-cause mortality in people with prediabetes. A total of 8789 participants aged 20 years and older from the 2005-2018 National Health and Nutrition Examination Surveys who met the diagnostic criteria for prediabetes were included in our study. The associations between six dietary antioxidant intakes and the composite dietary antioxidant index (CDAI) with depression risk and all-cause mortality were assessed using weighted logistic and Cox regression. Possible nonlinear associations were further explored using restricted cubic spline. To ensure the reliability of the findings, the multiple imputations by chained equation were applied to missing covariates to avoid potential bias. Our study found that moderate dietary antioxidant intake prevents depression and improves prognosis in people with prediabetes. Moreover, a CDAI score near three allows for maximum benefit. Our findings could provide clues for early intervention in people with diabetes.

Association between erectile dysfunction and the prevalence and prognosis of hyperglycemia in adults in the USA based on NHANES 2001-2004.

Prior research has demonstrated that erectile dysfunction (ED) is a significant risk factor for cardiovascular disease (CVD) and premature mortality. Few studies have examined the link between ED and hyperglycemia, and the predictive power of ED for mortality in individuals with hyperglycemia. A cohort of 1584 adults diagnosed with hyperglycemia, consisting of 583 individuals with diabetes and 1001 individuals with prediabetes, was selected from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. The study found a positive correlation between severe ED and hyperglycemia (OR, 2.03; 95% CI 1.53-2.68), while no significant relationship was observed between severe ED and CVD events (OR, 1.60; 95% CI 0.91-2.80). Additionally, no statistical association was found between diabetes or prediabetes status and ED. After multivariable adjustments, severe ED was found to be significantly associated with an increased risk of all-cause mortality (HR, 1.67; 95% CI 1.16-2.39), while no significant association was observed between severe ED and CVD mortality (HR, 1.92; 95% CI 0.92-3.98). Our study indicates a significant correlation between ED and hyperglycemia status. Hyperglycemia Individuals with ED generally exhibited an unfavorable prognosis for mortality due to all causes and CVD, particularly among those with low levels of physical activity.

Association of prediabetes with clinical outcomes in patients with chronic coronary syndrome: a post hoc analysis of the ISCHEMIA and ISCHEMIA-CKD trials.

BACKGROUND: There is conflicting evidence whether prediabetes is associated with adverse clinical outcomes in patients with chronic coronary syndrome. We aimed to assess the effect of prediabetes in patients with chronic coronary syndrome on clinical outcomes. METHODS: This is a secondary analysis of data from the ISCHEMIA and ISCHEMIA-CKD trials, including patients with chronic coronary syndrome determined by coronary computed tomography angiography or exercise-stress testing. Participants were assigned to the normoglycemia group (HbA1c < 5.7% [< 39 mmol/mol]), prediabetes group (HbA1c 5.7-6.4% [40-47 mmol/mol]), or diabetes group (HbA1c ≥ 6.5% [≥ 48 mmol/mol]). The primary end point of this study was all-cause mortality. Secondary endpoints included major adverse cardiovascular events and composites thereof. RESULTS: Overall, the primary endpoint all-cause mortality occurred in 330 (8.4%) of 3910 patients over a median follow-up time of 3.1 years (IQR 2.1-4.1). The primary endpoint all-cause mortality occurred in 37 (5.2%) of 716 patients in the normoglycemia group, in 63 (6.9%) of 911 in the prediabetes group, and in 230 (10.1%) of 2283 in the diabetes group. In the covariate-adjusted Cox model analysis, the estimated adjusted HR (aHR) in the prediabetes group as compared with the normoglycemia group was 1.45 (95%CI, 0.95-2.20). The aHR in the diabetes group as compared with the normoglycemia group was 1.84 (95%CI, 1.29-2.65). Prediabetes, compared with normoglycemia, was associated with an increased risk of stroke (aHR, 3.44, 95%CI, 1.15-10.25). Subgroup analyses suggested an increased risk of all-cause death associated with prediabetes in males and patients under 65 years. CONCLUSIONS: In patients with chronic coronary syndrome, diabetes but not prediabetes was associated with significantly increased risk of all-cause death within a median follow-up period of 3.1 years. Trial Registration NCT01471522, BioLINCC ID 13936.

Association of neutrophil-lymphocyte ratio with all-cause and cardiovascular mortality in US adults with diabetes and prediabetes: a prospective cohort study.

BACKGROUND: The neutrophil-lymphocyte ratio (NLR) is a novel hematological parameter to assess systemic inflammation. Prior investigations have indicated that an increased NLR may serve as a potential marker for pathological states such as cancer and atherosclerosis. However, there exists a dearth of research investigating the correlation between NLR levels and mortality in individuals with diabetes and prediabetes. Consequently, this study aims to examine the connection between NLR and all-cause as well as cardiovascular mortality in the population of the United States (US) with hyperglycemia status. METHODS: Data were collected from a total of 20,270 eligible individuals enrolled for analysis, spanning ten cycles of the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018. The subjects were categorized into three groups based on tertiles of NLR levels. The association of NLR with both all-cause and cardiovascular mortality was evaluated using Kaplan-Meier curves and Cox proportional hazards regression models. Restricted cubic splines were used to visualize the nonlinear relationship between NLR levels and all-cause and cardiovascular mortality in subjects with diabetes after accounting for all relevant factors. RESULTS: Over a median follow-up period of 8.6 years, a total of 1909 subjects with diabetes died, with 671 deaths attributed to cardiovascular disease (CVD). And over a period of 8.46 years, 1974 subjects with prediabetes died, with 616 cases due to CVD. The multivariable-adjusted hazard ratios (HRs) comparing high to low tertile of NLR in diabetes subjects were found to be 1.37 (95% CI, 1.19-1.58) for all-cause mortality and 1.63 (95% CI, 1.29-2.05) for CVD mortality. And the correlation between high to low NLR tertile and heightened susceptibility to mortality from any cause (HR, 1.21; 95% CI, 1.03-1.43) and CVD mortality (HR, 1.49; 95% CI, 1.08-2.04) remained statistically significant (both p-values for trend < 0.05) in prediabetes subjects. The 10-year cumulative survival probability was determined to be 70.34%, 84.65% for all-cause events, and 86.21%, 94.54% for cardiovascular events in top NLR tertile of diabetes and prediabetes individuals, respectively. Furthermore, each incremental unit in the absolute value of NLR was associated with a 16%, 12% increase in all-cause mortality and a 25%, 24% increase in cardiovascular mortality among diabetes and prediabetes individuals, respectively. CONCLUSIONS: The findings of this prospective cohort study conducted in the US indicate a positive association of elevated NLR levels with heightened risks of overall and cardiovascular mortality among adults with diabetes and prediabetes. However, potential confounding factors for NLR and the challenge of monitoring NLR's fluctuations over time should be further focused.

Prediabetes, participation in the English National Health Service Diabetes Prevention Programme, and associations with COVID-19-related mortality: A whole population study.

AIMS: To assess the effects of non-diabetic hyperglycaemia (NDH, also known as pre-diabetes), including the impact of the NHS Diabetes Prevention Programme (NHS DPP), on COVID-19-related mortality during the pandemic. METHODS: This study included all 61,438,225 individuals registered with General Practices in England and alive on 1st March 2020. We assessed COVID-19-related mortality in the 2,290,280(3.7 %) individuals with diagnosed NDH between March 2020 and February 2022 compared to those without diagnosed NDH or diabetes using Cox regression to adjust for demographic factors and cardiovascular comorbidities. Individuals with diagnosed NDH were further sub-categorised based on their contact with the NHS DPP (N = 376,590). Analyses were stratified by age (years) (<50, 50-69 and ≥ 70). RESULTS: There were 158,070 COVID-19 deaths; 17,280(11 %) for people with diagnosed NDH. The adjusted hazard ratio (HR) was 0.95(0.93-0.96),p < 0.001 for those with diagnosed NDH compared to those without diagnosed diabetes or NDH. By age (years), HRs were, 2.53(2.23-2.88),p < 0.001 for < 50, 1.29(1.24-1.35),p < 0.001 for 50-69 and 0.87(0.85-0.89),p < 0.001 for ≥ 70. NHS DPP attendance was associated with lower COVID-19 mortality with a dose-response relationship with engagement. CONCLUSIONS: Younger people with diagnosed NDH were at higher relative risk of COVID-19 mortality. Attendance at the NHS DPP was associated with significantly lower COVID-19-related mortality.

Associations of diabesity with all-cause and cardiovascular disease mortality: Findings from the Mexico City Prospective Study.

AIM: To investigate the joint associations of diabetes and obesity with all-cause and cardiovascular disease (CVD) mortality in the Mexico City Prospective Study. MATERIALS AND METHODS: In total, 154 128 participants (67.2% women) were included in this prospective analysis. Diabetes was self-reported, while body mass index was used to calculate obesity. Using diabetes and obesity classifications, six groups were created: (a) normal (no diabetes and normal weight); (b) normal weight and diabetes; (c) overweight but not diabetes (overweight); (d) overweight and diabetes (prediabesity); (e) obesity but not diabetes (obesity); and (f) obesity and diabetes (diabesity). Associations between these categories and outcomes were investigated using Cox proportional hazard models adjusted for confounder factors. RESULTS: During 18.3 years of follow-up, 27 197 (17.6%) participants died (28.5% because of CV causes). In the maximally adjusted model, participants those with the highest risk {hazard ratio (HR): 2.37 [95% confidence interval (CI): 2.24-2.51]}, followed by those with diabesity [HR: 2.04 (95% CI: 1.94-2.15)]. Similar trends of associations were observed for CVD mortality. The highest CV mortality risk was observed in individuals with diabesity [HR: 1.80 (95% CI: 1.63-1.99)], followed by normal weight and diabetic individuals [HR: 1.78 (95% CI: 1.60-1.98)]. CONCLUSION: This large prospective study identified that diabetes was the main driver of all-cause and CVD mortality in all the categories studied, with diabesity being the riskiest. Given the high prevalence of both conditions in Mexico, our results reinforce the importance of initiating prevention strategies from an early age.

Sex-specific associations between haemoglobin glycation index and the risk of cardiovascular and all-cause mortality in individuals with pre-diabetes and diabetes: A large prospective cohort study.

AIM: The aim of this study was to investigate the relationship between the haemoglobin glycation index (HGI), and cardiovascular disease (CVD) and all-cause mortality in adults with pre-diabetes and diabetes. METHODS: This study included 10 267 adults with pre-diabetes and diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Sex-differentiated relationships between HGI and mortality were elucidated using multivariate Cox proportional hazards models, restricted cubic splines and a two-piecewise Cox proportional hazards model. RESULTS: During the median follow-up time of 103.5 months, a total of 535 CVD deaths and 1918 all-cause deaths were recorded. After multivariate adjustment, in males with pre-diabetes and diabetes, there was a U-shaped relationship between HGI and CVD mortality and all-cause mortality, with threshold points of -0.68 and -0.63, respectively. Before the threshold point, HGI was negatively associated with CVD mortality [hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.41, 0.89] and all-cause mortality (HR 0.56; 95% CI 0.43, 0.74), and after the threshold point, HGI was positively associated with CVD mortality (HR 1.46; 95% CI 1.23, 1.73) and all-cause mortality (HR 1.40; 95% CI 1.23, 1.59). In contrast, HGI had an L-shaped relationship with all-cause mortality and no significant association with CVD mortality in females. To the left of the threshold points, the risk of all-cause mortality decreased (HR 0.50; 95% CI 0.35, 0.71) progressively with increasing HGI. CONCLUSIONS: In the cohort study, HGI in pre-diabetic and diabetic populations was found to have a U-shaped association with CVD mortality and all-cause mortality in males and an L-shaped association with all-cause mortality only in females. Further prospective and mechanistic studies are warranted.

Plant-based diets, mediating biomarkers, and mortality risk among adults with diabetes or prediabetes.

Background: A healthy eating pattern characterized by a higher intake of healthy plant foods has been associated with a lower risk of premature mortality, but whether this applies to individuals with varying glycemic status remains unclear. Methods: This study included 4621 participants with diabetes and 8061 participants with prediabetes from the US National Health and Nutrition Examination Survey (2007-2016). Using the dietary data assessed by two 24 h dietary recalls, a healthful plant-based diet index (hPDI) and an unhealthful plant-based diet index (uPDI) were created based on 15 food groups and were assessed for their relationships with mortality risk. Results: Over a median follow-up of 7.2 years, there were 1021 deaths in diabetes and 896 deaths in prediabetes. A higher hPDI (highest vs. lowest quartile) was associated with a 41% (HR = 0.59, 95% CI: 0.49-0.72; P-trend < 0.001) lower risk of all-cause mortality in diabetes and a 31% (HR = 0.69, 95% CI: 0.55-0.85; P-trend < 0.001) lower risk in prediabetes. A higher uPDI was associated with an 88% (HR = 1.88, 95% CI: 1.55-2.28; P-trend < 0.001) higher risk of mortality in diabetes and a 63% (HR = 1.63, 95% CI: 1.33-1.99; P-trend < 0.001) higher risk in prediabetes. Mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.0% to 10.9% of the relationships between hPDI or uPDI and all-cause mortality among participants with diabetes. Conclusions: For adults with diabetes as well as those with prediabetes, adhering to a plant-based diet rich in healthier plant foods is associated with a lower mortality risk, whereas a diet that incorporates less healthy plant foods is associated with a higher mortality risk.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

AIM: Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. METHODS: Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. RESULTS: During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). CONCLUSION: Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.

Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies.

AIMS/HYPOTHESIS: The term prediabetes is used for individuals who have impaired glucose metabolism whose glucose or HbA1c levels are not yet high enough to be diagnosed as diabetes. Prediabetes may already be associated with an increased risk of chronic 'diabetes-related' complications. This umbrella review aimed to provide a systematic overview of the available evidence from meta-analyses of prospective observational studies on the associations between prediabetes and incident diabetes-related complications in adults and to evaluate their strength and certainty. METHODS: For this umbrella review, systematic reviews with meta-analyses reporting summary risk estimates for the associations between prediabetes (based on fasting or 2 h postload glucose or on HbA1c) and incidence of diabetes-related complications, comorbidities and mortality risk were included. PubMed, Web of Science, the Cochrane Library and Epistemonikos were searched up to 17 June 2021. Summary risk estimates were recalculated using a random effects model. The certainty of evidence was evaluated by applying the GRADE tool. This study is registered with PROSPERO, CRD42020153227. RESULTS: Ninety-five meta-analyses from 16 publications were identified. In the general population, prediabetes was associated with a 6-101% increased risk for all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, heart failure, atrial fibrillation and chronic kidney disease, as well as total cancer, total liver cancer, hepatocellular carcinoma, breast cancer and all-cause dementia with moderate certainty of evidence. No associations between prediabetes and incident depressive symptoms and cognitive impairment were observed (with low or very low certainty of evidence). The association with all-cause mortality was stronger for prediabetes defined by impaired glucose tolerance than for prediabetes defined by HbA1c. CONCLUSIONS/INTERPRETATION: Prediabetes was positively associated with risk of all-cause mortality and the incidence of cardiovascular outcomes, CHD, stroke, chronic kidney disease, cancer and dementia. Further high-quality studies, particularly on HbA1c-defined prediabetes and other relevant health outcomes (e. g. neuropathy) are required to support the evidence.

Impact of prediabetes and diabetes on 3-year outcome of patients treated with new-generation drug-eluting stents in two large-scale randomized clinical trials.

BACKGROUND: Diabetes is associated with adverse outcomes after percutaneous coronary intervention with drug-eluting stents (DES), but for prediabetes this association has not been definitely established. Furthermore, in patients with prediabetes treated with contemporary stents, bleeding data are lacking. We assessed 3-year ischemic and bleeding outcomes following treatment with new-generation DES in patients with prediabetes and diabetes as compared to normoglycemia. METHODS: For this post-hoc analysis, we pooled patient-level data of the BIO-RESORT and BIONYX stent trials which both stratified for diabetes at randomization. Both trials were multicenter studies performed in tertiary cardiac centers. Study participants were patients of whom glycemic state was known based on hemoglobin A1c, fasting plasma glucose, or medically treated diabetes. Three-year follow-up was available in 4212/4330 (97.3 %) patients. The main endpoint was target vessel failure, a composite of cardiac death, target vessel myocardial infarction, or target vessel revascularization. RESULTS: Baseline cardiovascular risk profiles were progressively abnormal in patients with normoglycemia, prediabetes, and diabetes. The main endpoint occurred in 54/489 patients with prediabetes (11.2 %) and 197/1488 with diabetes (13.7 %), as compared to 142/2,353 with normoglycemia (6.1 %) (HR: 1.89, 95 %-CI 1.38-2.58, p < 0.001, and HR: 2.30, 95 %-CI 1.85-2.86, p < 0.001, respectively). In patients with prediabetes, cardiac death and target vessel revascularization rates were significantly higher (HR: 2.81, 95 %-CI 1.49-5.30, p = 0.001, and HR: 1.92, 95 %-CI 1.29-2.87, p = 0.001), and in patients with diabetes all individual components of the main endpoint were significantly higher than in patients with normoglycemia (all p ≤ 0.001). Results were consistent after adjustment for confounders. Major bleeding rates were significantly higher in patients with prediabetes and diabetes, as compared to normoglycemia (3.9 % and 4.1 % vs. 2.3 %; HR:1.73, 95 %-CI 1.03-2.92, p = 0.040, and HR:1.78, 95 %-CI 1.23-2.57, p = 0.002). However, after adjustment for confounders, differences were no longer significant. CONCLUSIONS: Not only patients with diabetes but also patients with prediabetes represent a high-risk population. After treatment with new-generation DES, both patient groups had higher risks of ischemic and bleeding events. Differences in major bleeding were mainly attributable to dissimilarities in baseline characteristics. Routine assessment of glycemic state may help to identify patients with prediabetes for intensified management of cardiovascular risk factors. TRIAL REGISTRATION: BIO-RESORT ClinicalTrials.gov: NCT01674803, registered 29-08-2012; BIONYX ClinicalTrials.gov: NCT02508714, registered 27-7-2015.

Screening for Prediabetes and Type 2 Diabetes: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Type 2 diabetes is common and is a leading cause of morbidity and disability. Objective: To review the evidence on screening for prediabetes and diabetes to inform the US Preventive Services Task Force (USPSTF). Data Sources: PubMed/MEDLINE, Cochrane Library, and trial registries through September 2019; references; and experts; literature surveillance through May 21, 2021. Study Selection: English-language controlled studies evaluating screening or interventions for prediabetes or diabetes that was screen detected or recently diagnosed. Data Extraction and Synthesis: Dual review of abstracts, full-text articles, and study quality; qualitative synthesis of findings; meta-analyses conducted when at least 3 similar studies were available. Main Outcomes and Measures: Mortality, cardiovascular morbidity, diabetes-related morbidity, development of diabetes, quality of life, and harms. Results: The review included 89 publications (N = 68 882). Two randomized clinical trials (RCTs) (25 120 participants) found no significant difference between screening and control groups for all-cause or cause-specific mortality at 10 years. For harms (eg, anxiety or worry), the trials reported no significant differences between screening and control groups. For recently diagnosed (not screen-detected) diabetes, 5 RCTs (5138 participants) were included. In the UK Prospective Diabetes Study, health outcomes were improved with intensive glucose control with sulfonylureas or insulin. For example, for all-cause mortality the relative risk (RR) was 0.87 (95% CI, 0.79 to 0.96) over 20 years (10-year posttrial assessment). For overweight persons, intensive glucose control with metformin improved health outcomes at the 10-year follow-up (eg, all-cause mortality: RR, 0.64 [95% CI, 0.45 to 0.91]), and benefits were maintained longer term. Lifestyle interventions (most involving >360 minutes) for obese or overweight persons with prediabetes were associated with reductions in the incidence of diabetes (23 RCTs; pooled RR, 0.78 [95% CI, 0.69 to 0.88]). Lifestyle interventions were also associated with improved intermediate outcomes, such as reduced weight, body mass index, systolic blood pressure, and diastolic blood pressure (pooled weighted mean difference, -1.7 mm Hg [95% CI, -2.6 to -0.8] and -1.2 mm Hg [95% CI, -2.0 to -0.4], respectively). Metformin was associated with a significant reduction in diabetes incidence (pooled RR, 0.73 [95% CI, 0.64 to 0.83]) and reduction in weight and body mass index. Conclusions and Relevance: Trials of screening for diabetes found no significant mortality benefit but had insufficient data to assess other health outcomes; evidence on harms of screening was limited. For persons with recently diagnosed (not screen-detected) diabetes, interventions improved health outcomes; for obese or overweight persons with prediabetes, interventions were associated with reduced incidence of diabetes and improvement in other intermediate outcomes.

Prognostic value of subclinical myocardial necrosis using high-sensitivity cardiac troponin T in patients with prediabetes.

BACKGROUND: Risk stratification of patients with prediabetes is an unmet clinical need. Here, we examine the utility of subclinical myocardial necrosis assessed by high-sensitivity cardiac troponin T (hs-cTnT) in predicting health outcomes in stable subjects with prediabetes. METHODS: hs-cTnT was analyzed by a high-sensitivity assay (Roche 5th generation) in 2631 stable subjects with prediabetes (HbA1c 5.7-6.4% or fasting glucose 100-125 mg/dL without previous diagnosis of diabetes or glucose-lowering therapy) who underwent elective coronary angiography for cardiac evaluation, and followed for major adverse cardiac events (MACE; death, myocardial infarction, stroke) over 3 years and all-cause mortality over 5 years. RESULTS: In our study cohort, hs-cTnT was highly prevalent with a median level of 13 ng/L (interquartile range 8.2-21.6 ng/L). Hs-cTnT was independently associated with incident MACE at 3 years (Q4 vs. Q1 adjusted hazard ratio (HR) 2.42 [95% CI 1.69-3.46], P < 0.001) and 5-year mortality (adjusted HR 3.8 [95% CI 2.55-5.67], P < 0.001). This association remained significant in all subsets after adjustment for traditional risk factors and multiple factors known to increase hs-cTnT levels. Moreover, hs-cTnT independently predicted event risk in primary prevention subjects (n = 557, HR 5.46 [95% CI 1.50-19.89), p < 0.01) for MACE; HR 9.53 [95% CI 2.08-43.73] for all-cause mortality) and secondary prevention subjects (n = 2074, HR 1.86 [95% CI 1.31-2.66], P < 0.001 for MACE; and 2.7 [95% CI 1.79-4.08), P < 0.001 for all-cause mortality). CONCLUSIONS: In stable prediabetic subjects, the presence of subclinical myocardial necrosis as detected by hs-cTnT portends heightened long-term adverse cardiovascular event risk. Hs-cTnT levels may help to stratify risk and improve clinical decision making in patients with prediabetes. Trial registration ClinicalTrials.gov Identifier: NCT00590200.

Clinical characteristics and outcomes of COVID-19 patients with prediabetes.

BACKGROUND AND AIMS: We aimed to examine the clinical characteristics and outcomes of coronavirus disease 2019 (COVID-19) patients with prediabetes. METHODS: This was a retrospective cohort study of 102 COVID-19 patients admitted to a tertiary care hospital in India between May and October 2020. RESULTS: Most patients had a poor clinical profile on admission. They had high rates of invasive mechanical ventilation (48%), intensive care unit admission (48%), complications (72.6%), and mortality (32.4%). CONCLUSION: People with prediabetes are at high risk for poor outcomes from COVID-19.

Prognostic value of fibrinogen in patients with coronary artery disease and prediabetes or diabetes following percutaneous coronary intervention: 5-year findings from a large cohort study.

BACKGROUND: Fibrinogen (FIB) is an independent risk factor for mortality and cardiovascular events in the general population. However, the relationship between FIB and long-term mortality among CAD patients undergoing PCI remains unclear, especially in individuals complicated with diabetes mellitus (DM) or prediabetes (Pre-DM). METHODS: 6,140 patients with CAD undergoing PCI were included in the study and subsequently divided into three groups according to FIB levels (FIB-L, FIB-M, FIB-H). These patients were further grouped by glycemic status [normoglycemia (NG), Pre-DM, DM]. The primary endpoint was all-cause mortality. The secondary endpoint was cardiac mortality. RESULTS: FIB was positively associated with hemoglobin A1c (HbA1c) and fasting blood glucose (FBG) in CAD patients with and without DM (P < 0.001). During a median follow-up of 5.1 years (interquartile range 5.0-5.2 years), elevated FIB was significantly associated with long-term all-cause mortality (adjusted HR: 1.86; 95% CI 1.28-2.69; P = 0.001) and cardiac mortality (adjusted HR: 1.82; 95% CI 1.15-2.89; P = 0.011). Similarly, patients with DM, but not Pre-DM, had increased risk of all-cause and cardiac mortality compared with NG group (all P < 0.05). When grouped by both FIB levels and glycemic status, diabetic patients with medium and high FIB levels had higher risk of mortality [(adjusted HR: 2.57; 95% CI 1.12-5.89), (adjusted HR: 3.04; 95% CI 1.35-6.82), all P < 0.05]. Notably, prediabetic patients with high FIB also had higher mortality risk (adjusted HR: 2.27; 95% CI 1.01-5.12). CONCLUSIONS: FIB was independently associated with long-term all-cause and cardiac mortality among CAD patients undergoing PCI, especially in those with DM and Pre-DM. FIB test may help to identify high-risk individuals in this specific population.

Association Between Serum 25-hydroxyvitamin D Concentrations and Mortality Among Adults With Prediabetes.

OBJECTIVES: To investigate the association of circulating 25-hydroxyvitamin D [25(OH)D] levels with mortality among adults with prediabetes. METHODS: This retrospective cohort study included 15,195 adults with prediabetes (aged ≥20 years) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 2001-2014. Mortality from all causes, cardiovascular disease (CVD), and cancer was linked to National Death Index mortality data. RESULTS: The median (interquartile range) concentration of serum 25(OH)D was 60.5 (45.3, 77.4) nmol/L, and only 23.1% had sufficient vitamin D (≥75 nmol/L). Elevated serum 25(OH)D concentrations were significantly associated with lower levels of insulin, homeostasis model assessment of insulin resistance, triglyceride, and C-reactive protein, and higher levels of high-density lipoprotein at baseline (all Ptrend < 0.05). During a median follow up of 10.7 years, 3765 deaths (including 1080 CVD deaths and 863 cancer deaths) were identified. Compared with participants with 25(OH)D <30 nmol/L, the multivariate-adjusted hazard ratios and 95% confidence intervals for participants with 25(OH)D ≥ 75 nmol/L were 0.66 (0.53, 0.82) for all-cause mortality (Ptrend < 0.001), 0.66 (0.48, 0.89) for CVD mortality (Ptrend = 0.001), and 0.82 (0.49, 1.35) for cancer mortality (Ptrend = 0.32). For per-unit increment in ln-transformed 25(OH)D, there was a 27% lower risk of all-cause mortality and a 34% lower risk of CVD mortality (both P < 0.01). CONCLUSIONS: These findings suggested that higher serum 25(OH)D concentrations were associated with lower all-cause and CVD mortality among individuals with prediabetes.