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.

Gender differences in screening for glucose perturbations, cardiovascular risk factor management and prognosis in patients with dysglycaemia and coronary artery disease: results from the ESC-EORP EUROASPIRE surveys.

BACKGROUND: Gender disparities in the management of dysglycaemia, defined as either impaired glucose tolerance (IGT) or type 2 diabetes (T2DM), in coronary artery disease (CAD) patients are a medical challenge. Recent data from two nationwide cohorts of patients suggested no gender difference as regards the risk for diabetes-related CV complications but indicated the presence of a gender disparity in risk factor management. The aim of this study was to investigate gender differences in screening for dysglycaemia, cardiovascular risk factor management and prognosis in dysglycemic CAD patients. METHODS: The study population (n = 16,259; 4077 women) included 7998 patients from the ESC-EORP EUROASPIRE IV (EAIV: 2012-2013, 79 centres in 24 countries) and 8261 patients from the ESC-EORP EUROASPIRE V (EAV: 2016-2017, 131 centres in 27 countries) cross-sectional surveys. In each centre, patients were investigated with standardised methods by centrally trained staff and those without known diabetes were offered an oral glucose tolerance test (OGTT). The first of CV death or hospitalisation for non-fatal myocardial infarction, stroke, heart failure or revascularization served as endpoint. Median follow-up time was 1.7 years. The association between gender and time to the occurrence of the endpoint was evaluated using Cox survival modelling, adjusting for age. RESULTS: Known diabetes was more common among women (32.9%) than men (28.4%, p < 0.0001). OGTT (n = 8655) disclosed IGT in 17.2% of women vs. 15.1% of men (p = 0.004) and diabetes in 13.4% of women vs. 14.6% of men (p = 0.078). In both known diabetes and newly detected dysglycaemia groups, women were older, with higher proportions of hypertension, dyslipidaemia and obesity. HbA1c was higher in women with known diabetes. Recommended targets of physical activity, blood pressure and cholesterol were achieved by significantly lower proportions of women than men. Women with known diabetes had higher risk for the endpoint than men (age-adjusted HR 1.22; 95% CI 1.04-1.43). CONCLUSIONS: Guideline-recommended risk factor control is poorer in dysglycemic women than men. This may contribute to the worse prognosis in CAD women with known diabetes.

Incidence and mortality of new-onset glucose disorders in peritoneal dialysis patients in China: a meta-analysis.

BACKGROUND: Dialysis patients are at high risk of developing glucose metabolism disturbances (GMDs), such as diabetes mellitus (DM), impaired fast glucose (IFG), and impaired glucose tolerance (IGT). However, it is unclear about the incidence of GMDs in Chinese patients with peritoneal dialysis (PD), as well as the influence of new-onset DM (NODM) on the prognosis of PD patients. Therefore, we conducted this meta-analysis to address these issues. METHODS: A comprehensive literature search was conducted using PubMed, Embase, Web of Science, SinoMed, and CNKI database for studies that evaluated the incidence of GMDs and mortality in patients with PD. Results were expressed as hazard ratio (HR), risk ratio (RR), or estimate (ES) with 95% confidence intervals (95%CIs).Meta-analysis was performed using a fixed-effects or random-effects model to pool the estimate. RESULTS: Fifteen studies met the inclusion criteria and were included in this meta-analysis. Pooled results showed that, the incidences of NODM, NOIGT, and NOIFG were 12% (95%CI: 9, 15%; P < 0.001), 17% (95%CI: 4, 10%; P < 0.001) and 32% (95%CI: 3, 30%, P < 0.001), respectively. Compared with patients without NODM, PD patients with NODM had an increased risk of mortality (HR = 1.59, 95%CI: 1.28, 1.98; P < 0.001). There was no significant difference in the incidence of NODM between PD and hemodialysis (HD) patients (RR = 1.23, 95%CI: 0.61, 2.51; P = 0.562). CONCLUSION: Dialysis patients in China had an increased risk of developing GMDs, however, the dialysis modality did not have any significant impact on the incidence of NODM. NODM increased the mortality risk in patients undergoing PD. Thus, physicians should pay attention to the plasma glucose level in patients undergoing dialysis.

Plasma BNP Levels and Diuretics Use as Predictors of Cardiovascular Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance.

PURPOSE: Although impaired glucose tolerance (IGT) promotes cardiovascular events, our Alpha-glucosidase-inhibitor Blocks Cardiac Events in Patients with Myocardial Infarction and Impaired Glucose Tolerance (ABC) study showed that alpha-glucosidase inhibitors do not prevent cardiovascular events in patients with myocardial infarction (MI) and IGT. The aim of the present study was to identify potential clinical factors for cardiovascular events in patients with MI and IGT. METHODS: Using the limitless-arity multiple testing procedure, an artificial intelligence (AI)-based data mining method, we analyzed 385,391 combinations of fewer than four clinical parameters. RESULTS: We identified 380 combinations predicting the occurrence of (1) all-cause hospitalization, (2) hospitalization due to worsening of heart failure (HF), (3) hospitalization due to non-fatal MI, and (4) hospitalization due to percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) for stable angina among 385,391 combinations in 853 patients. Among these, either plasma BNP levels ≥ 200 pg/dl or diuretic use exclusively predicted (1) all-cause hospitalization, (2) hospitalization due to worsening of HF, and (3) hospitalization due to a non-fatal MI, with plasma BNP levels ≥ 200 pg/dl being the sole predictor of hospitalization due to PCI and CABG. Importantly, each finding was verified by independently drawn Kaplan-Meier curves, revealing the unexpected role of plasma BNP levels in the progression of coronary stenosis determined as the necessity of PCI and CABG for stable angina. CONCLUSIONS: In patients with MI and IGT, high plasma BNP levels predicted the occurrence of coronary stenosis, recurrent MI, and worsening of HF, whereas diuretic use did not predict the progression of coronary stenosis but non-fatal MI and worsening of HF.

Newly diagnosed abnormal glucose tolerance determines post-MI prognosis in patients with hospital related hyperglycaemia but without known diabetes.

AIMS: Investigate if abnormal glucose tolerance (AGT) affects post-myocardial infarction (MI) prognosis in patients with hospital-related hyperglycaemia (HRH) but without known diabetes mellitus (KDM). METHODS: Post-MI survivors without KDM underwent pre-discharge oral glucose tolerance test. Cardiovascular death and non-fatal re-infarction (MACE) were recorded. We compare the ability of admission (APG), fasting (FPG) and 2 h post-load (2 h-PG) plasma glucose to predict MACE in patients with (HRH) and without HRH (NoHRH). RESULTS: 50.2% and 73% of NoHRH and HRH had AGT respectively. MACE occurred in 19.5% and 18.1% in HRH and NoHRH groups. MACE-free survival was lower in patient with AGT in both groups (NoHRH: HR 1.82, 95% CI 1.19-2.78, p = 0.005; HRH: HR 2.48, 95% CI 1.24-4.96, p = 0.010). AGT predicted MACE-free survival (NoHRH: HR 1.60, 95% CI 1.02-2.51, p = 0.042; HRH: HR 3.09, 95% CI 1.07-8.94, p = 0.037). 2 h-PG, but not FPG or APG, independently predicted MACE free survival (NoHRH: HR 1.17, 95% CI 1.07-1.27, p ≤0.001 and HRH: HR 1.18, 95% CI 1.03-1.37, p = 0.020). Addition of AGT and 2 h-PG, not FPG or APG, improved net reclassification of events in both groups. CONCLUSION: Post-MI prognosis is worse with AGT irrespective of presence of HRH. 2 h-PG, predicts prognosis in HRH and NoHRH groups.

Meta-analysis of the impact of alpha-glucosidase inhibitors on incident diabetes and cardiovascular outcomes.

BACKGROUND: Alpha-glucosidase inhibitors (AGIs) have been shown to reduce incident type 2 diabetes but their impact on cardiovascular (CV) disease remains controversial. We sought to identify the overall impact of AGIs with respect to incident type 2 diabetes in individuals with impaired glucose tolerance (IGT), and CV outcomes in those with IGT or type 2 diabetes. METHODS: We used PubMed and SCOPUS to identify randomized controlled trials reporting the incidence of type 2 diabetes and/or CV outcomes that had compared AGIs with placebo in populations with IGT or type 2 diabetes, with or without established CV disease. Eligible studies were required to have ≥ 500 participants and/or ≥ 100 endpoints of interest. Meta-analyses of available trial data were performed using random effects models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident type 2 diabetes and CV outcomes. RESULTS: Of ten trials identified, three met our inclusion criteria for incident type 2 diabetes and four were eligible for CV outcomes. The overall HR (95% CI) comparing AGI with placebo for incident type 2 diabetes was 0.77 (0.67-0.88), p < 0.0001, and for CV outcomes was 0.98 (0.89-1.10), p = 0.85. There was little to no heterogeneity between studies, with I2 values of 0.03% (p = 0.43) and 0% (p = 0.79) for the two outcomes respectively. CONCLUSIONS: Allocation of people with IGT to an AGI significantly reduced their risk of incident type 2 diabetes by 23%, whereas in those with IGT or type 2 diabetes the impact on CV outcomes was neutral.

Impaired glucose tolerance and albuminuria in patients with chronic heart failure: a subanalysis of the SUPPORT trial.

AIMS: The study aims to evaluate the prognostic significance of impaired glucose tolerance (IGT) with reference to albuminuria in patients with chronic heart failure (CHF). METHODS AND RESULTS: We examined 535 CHF patients (mean 66 years, women 25%) in the control arm of our SUPPORT trial, in which we examined additive impact of olmesartan in hypertensive patients with symptomatic CHF treated with ß-blockers and/or angiotensin-converting enzyme inhibitors. We examined the association between glycaemic abnormality (assessed by 75 g of oral glucose tolerance test) and albuminuria for a composite outcome of all-cause death, myocardial infarction, stroke, and HF hospitalization. IGT patients (N = 113, mean 67.2 years) were older and more frequently treated with ß-blockers compared with those with normal glucose regulation (N = 142, mean 64.0 years) and those with diabetes mellitus (N = 280, mean 65.7 years). Multivariable Cox proportional hazard models revealed that, as compared with normal glucose regulation (NGR), IGT was associated with increased risk of the outcome when complicated by albuminuria [hazard ratio (HR) 2.25; 95% confidence interval (CI) 1.14-4.42; P = 0.019] but not when uncomplicated by albuminuria (HR 0.76; 95% CI 0.35-1.60, P = 0.47) (P for interaction = 0.041). This was also the case for diabetes mellitus and albuminuria (HR 2.06; 95% CI 1.17-3.61; P = 0.012). Among IGT patients without albuminuria, 21 (29%) developed albuminuria at 1-year visit, which was again associated with poor prognosis (HR 7.36; 95% CI 1.39-38.98, P = 0.019). CONCLUSIONS: These results indicate that IGT is associated with poor prognosis when complicated by albuminuria in CHF patients, demonstrating the importance of combined early stages of glucose intolerance and renal dysfunction in the management of CHF.

Prediabetes and Risk for Cardiac Death Among Patients With Coronary Artery Disease: The ARTEMIS Study.

OBJECTIVE: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes. RESEARCH DESIGN AND METHODS: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes (n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status (n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points. RESULTS: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death (P = 0.069), 32% lower adjusted risk for all-cause mortality (P = 0.076), and 36% lower adjusted risk for MACE (P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality (P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status. CONCLUSIONS: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status.

HbA1c predicts long-term postoperative mortality in patients with unknown glycemic status at admission for vascular surgery: An exploratory study.

BACKGROUND: Peripheral arterial disease (PAD) and diabetes mellitus (DM) represent major public health challenges and are tightly associated. To facilitate early diagnosis, HbA1c has been implemented as the preferred diagnostic tool for the diagnosis of type 2 DM. In this study, we compared and evaluated HbA1c, fasting plasma glucose (FPG), and 2-hour post-load glucose values to determine which test best predicted mortality in patients with PAD. METHODS: In all, 273 PAD patients with unknown glycemic status admitted to Haukeland University Hospital for elective surgery between October 2006 and September 2007 were included in the study. All 273 patients underwent a standard oral glucose tolerance test (OGTT) in addition to determination of HbA1c; patients were then grouped into those with DM, intermediate hyperglycemia, and normoglycemia according to World Health Organization and International Expert Committee criteria. RESULTS: All-cause mortality was 40% over a 9-year follow-up period. After adjusting for age, sex, and relevant medication, HbA1c was a predictor for mortality (hazard ratio [HR] 1.54; 95% confidence interval [CI] 1.03-2.32]; P = 0.04). The association did not achieve statistical significance in a fully adjusted Cox regression model, although the effect estimation of HbA1c on all-cause mortality remained largely unchanged (HR 1.39; 95% CI 0.92-2.09; P = 0.13). The OGTT was not a predictor of long-term mortality. CONCLUSIONS: The results indicate that HbA1c is a useful marker in the preoperative screening of patients of unknown glycemic status at the time of admission for vascular surgery, and may identify people at high risk of long-term mortality following surgical treatment for PAD.

Incident Diabetes in Survivors of Critical Illness and Mechanisms Underlying Persistent Glucose Intolerance: A Prospective Cohort Study.

OBJECTIVES: Stress hyperglycemia occurs in critically ill patients and may be a risk factor for subsequent diabetes. The aims of this study were to determine incident diabetes and prevalent prediabetes in survivors of critical illness experiencing stress hyperglycemia and to explore underlying mechanisms. DESIGN: This was a prospective, single center, cohort study. At admission to ICU, hemoglobin A1c was measured in eligible patients. Participants returned at 3 and 12 months after ICU admission and underwent hemoglobin A1c testing and an oral glucose tolerance test. Blood was also collected for hormone concentrations, whereas gastric emptying was measured via an isotope breath test. ß-cell function was modeled using standard techniques. SETTING: Tertiary-referral, mixed medical-surgical ICU. PATIENTS: Consecutively admitted patients who developed stress hyperglycemia and survived to hospital discharge were eligible. MEASUREMENTS AND MAIN RESULTS: Consent was obtained from 40 patients (mean age, 58 yr [SD, 10], hemoglobin A1c 36.8 mmol/mol [4.9 mmol/mol]) with 35 attending the 3-month and 26 the 12-month visits. At 3 months, 13 (37%) had diabetes and 15 (43%) had prediabetes. At 12 months, seven (27%) participants had diabetes, whereas 11 (42%) had prediabetes. Mean hemoglobin A1c increased from baseline during the study: +0.7 mmol/mol (-1.2 to 2.5 mmol/mol) at 3 months and +3.3 mmol/mol (0.98-5.59 mmol/mol) at 12 months (p = 0.02). Gastric emptying was not significantly different across groups at either 3 or 12 months. CONCLUSIONS: Diabetes and prediabetes occur frequently in survivors of ICU experiencing stress hyperglycemia. Based on the occurrence rate observed in this cohort, structured screening and intervention programs appear warranted.

The effect of change in fasting glucose on the risk of myocardial infarction, stroke, and all-cause mortality: a nationwide cohort study.

BACKGROUND: The effect of change in blood glucose levels on the risk of cardiovascular disease among individuals without diabetes is currently unclear. We aimed to examine the association of change in fasting serum glucose with incident cardiovascular disease and all-cause mortality among representative large population. METHODS: We analyzed the data from retrospective cohort of Korean National Health Insurance Service. In total, 260,487 Korean adults aged over 40 years, without diabetes mellitus and cardiovascular disease at baseline measured change in fasting serum glucose according to the criteria of impaired and diabetic fasting glucose status: normal fasting glucose (NFG, fasting glucose: < 100 mg/dL), impaired fasting glucose (IFG, fasting glucose: 100.0-125.9 mg/dL), and diabetic fasting glucose (DFG, fasting glucose: ≥ 126.0 mg/dL). Compared to the persistently unchanged group (i.e. NFG to NFG or IFG to IFG), Cox proportional hazards regression analyses were performed in the changed group to obtain the hazards ratio (HR) with 95% confidence interval (CI) for the subsequent median 8-year myocardial infarction, stroke, and all-cause mortality. RESULTS: Compared to individuals with persistent NFG (i.e., NFG to NFG), individuals who shifted from NFG to DFG had an increased risk of stroke (HR [95% CI]: 1.19 [1.02-1.38]) and individuals who shifted from NFG to IFG or DFG had increased risks of all-cause mortality (HR [95% CI]: 1.08 [1.02-1.14] for NFG to IFG and 1.56 [1.39-1.75] for NFG to DFG). Compared to individuals with persistent IFG, individuals who shifted from IFG to DFG had an increased risk of MI and all-cause mortality (HR [95% CI]: 1.65 [1.20-2.27] and 1.16 [1.02-1.33], respectively). CONCLUSIONS: Increasing fasting glucose in non-diabetic population is associated with risks of the MI, stroke, and all-cause mortality, which is more rapid, more severe.

Impaired Fasting Glucose Is the Major Determinant of the 20-Year Mortality Risk Associated With Metabolic Syndrome in Nondiabetic Patients With Stable Coronary Artery Disease.

BACKGROUND: We wanted to explore the association of metabolic syndrome (MetS) versus its individual components with 20-year all-cause mortality among patients with stable coronary artery disease. METHODS AND RESULTS: The cohort comprised 12 403 nondiabetic patients with stable coronary artery disease who were enrolled in the Bezafibrate Infarction Prevention Registry between February 1990 and October 1992 and followed up through December 2014. The study cohort was divided into 4 groups: patients without MetS or impaired fasting glucose (IFG), patients with IFG but without MetS, patients with MetS but without IFG, and patients with both MetS and IFG. Kaplan-Meier survival analysis showed that at 20 years of follow-up, the rates of all-cause mortality were the highest among patients with both MetS and IFG (66%). Patients with IFG without MetS experienced a significantly higher mortality rate compared with those with MetS without IFG (61% versus 56%; log-rank P<0.001). Multivariable Cox proportional hazard analysis showed that the final Cox model demonstrated that the additive effect of MetS (hazard ratio, 1.13; 95% confidence interval, 1.1-1.16; P=0.02) and IFG (hazard ratio, 1.54; 95% confidence interval, 1.46-1.62; P<0.001) on 20 years mortality was nonsignificant (hazard ratio, 1.01; 95% confidence interval, 0.93-1.11; P=0.69). IFG was associated with the most pronounced increase in mortality risk among the individual components (hazard ratio, 1.22; 95% confidence interval, 1.14-1.3; P<0.001). CONCLUSIONS: Our findings suggest that IFG alone is a major independent predictor of long-term mortality among patients with stable coronary artery disease versus other components of the MetS.

All-Cause Mortality Risk in Australian Women with Impaired Fasting Glucose and Diabetes.

AIMS: Impaired fasting glucose (IFG) and diabetes are increasing in prevalence worldwide and lead to serious health problems. The aim of this longitudinal study was to investigate the association between impaired fasting glucose or diabetes and mortality over a 10-year period in Australian women. METHODS: This study included 1167 women (ages 20-94 yr) enrolled in the Geelong Osteoporosis Study. Hazard ratios for all-cause mortality in diabetes, IFG, and normoglycaemia were calculated using a Cox proportional hazards model. RESULTS: Women with diabetes were older and had higher measures of adiposity, LDL cholesterol, and triglycerides compared to the IFG and normoglycaemia groups (all p < 0.001). Mortality rate was greater in women with diabetes compared to both the IFG and normoglycaemia groups (HR 1.8; 95% CI 1.3-2.7). Mortality was not different in women with IFG compared to those with normoglycaemia (HR 1.0; 95% CI 0.7-1.4). CONCLUSIONS: This study reports an association between diabetes and all-cause mortality. However, no association was detected between IFG and all-cause mortality. We also showed that mortality in Australian women with diabetes continues to be elevated and women with IFG are a valuable target for prevention of premature mortality associated with diabetes.

BMI and All-Cause Mortality in Normoglycemia, Impaired Fasting Glucose, Newly Diagnosed Diabetes, and Prevalent Diabetes: A Cohort Study.

OBJECTIVE: This study examined associations between BMI and mortality in individuals with normoglycemia, impaired fasting glucose (IFG), newly diagnosed diabetes, and prevalent diabetes and identified BMI ranges associated with the lowest mortality in each group. RESEARCH DESIGN AND METHODS: A total of 12,815,006 adults were prospectively monitored until 2013. Diabetes status was defined as follows: normoglycemia (fasting glucose <100 mg/dL), IFG (100-125 mg/dL), newly diagnosed diabetes (≥126 mg/dL), and prevalent diabetes (self-reported). BMI (kg/m2) was measured. Cox proportional hazards model hazard ratios were calculated after adjusting for confounders. RESULTS: During a mean follow-up period of 10.5 years, 454,546 men and 239,877 women died. U-shaped associations were observed regardless of diabetes status, sex, age, and smoking history. Optimal BMI (kg/m2) for the lowest mortality by group was 23.5-27.9 (normoglycemia), 25-27.9 (IFG), 25-29.4 (newly diagnosed diabetes), and 26.5-29.4 (prevalent diabetes). Higher optimal BMI by worsening diabetes status was more prominent in younger ages, especially in women. The relationship between worsening diabetes status and higher mortality was stronger with lower BMI, especially at younger ages. Given the same BMI, people with prevalent diabetes had higher mortality compared with those with newly diagnosed diabetes, and this was more striking in women than men. CONCLUSIONS: U-curve relationships existed regardless of diabetes status. Optimal BMI for lowest mortality became gradually higher with worsening diabetes for each sex and each age-group.

Elevated levels of adipokines predict outcome after acute myocardial infarction: A long-term follow-up of the Glucose Tolerance in Patients with Acute Myocardial Infarction cohort.

OBJECTIVE: Adiponectin and leptin are associated with insulin resistance and cardiovascular disease. Information on the prognostic value after an acute myocardial infarction is still conflicting. METHODS: Patients (n = 180) without known diabetes and with admission glucose of <11 mmol/L admitted for an acute myocardial infarction in 1998-2000 were followed for mortality and cardiovascular events (first of cardiovascular mortality/acute myocardial infarction/stroke/heart failure) until the end of 2011 (median: 11.6 years). Plasma adiponectin and leptin were related to outcome in Cox proportional-hazard regression analyses. RESULTS: Median age was 64 years and 69% were male. Total mortality was 34% (n = 61) and 44% (n = 80) experienced a cardiovascular event. Adiponectin at discharge predicted cardiovascular events (hazard ratio; 95% confidence interval; 1.45; 1.02-2.07, p = 0.038), total mortality (2.53; 1.64-3.91, p < 0.001) and cancer mortality (3.64; 1.51-8.74, p = 0.004). After adjustment for age, sex, body mass index, previous myocardial infarction and heart failure, adiponectin predicted total mortality (1.79; 1.07-3.00, p = 0.027) but not cardiovascular events. High levels of leptin were associated with cardiovascular events during the first 7 years, after which the association was attenuated. Leptin did not predict total mortality. CONCLUSION: In patients with acute myocardial infarction but without previously known diabetes, high levels of adiponectin at discharge predicted total mortality. The present results support the hypothesis that high rather than low levels of adiponectin predict mortality after acute myocardial infarction.

Copeptin in patients with acute myocardial infarction and newly detected glucose abnormalities - A marker of increased stress susceptibility? A report from the Glucose in Acute Myocardial Infarction cohort.

OBJECTIVE: To characterize copeptin levels and to explore its prognostic importance in patients with acute myocardial infarction with newly detected glucose abnormalities. METHODS: Copeptin was measured in 166 patients with acute myocardial infarction without known diabetes and in 168 age- and gender-matched controls. Participants were classified as having normal glucose tolerance or abnormal glucose tolerance (impaired glucose tolerance + type 2 diabetes mellitus) by oral glucose tolerance test. Study participants were followed over a decade for major cardiovascular event (acute myocardial infarction/stroke/congestive heart failure/cardiovascular death), cardiovascular and total death. RESULTS: Median copeptin level was higher in patients (10.5 pmol/L) than controls (5.9 pmol/L; p < 0.01). Patients with abnormal glucose tolerance had higher copeptin (12.2 pmol/L) than those with normal glucose tolerance (7.9 pmol/L; p < 0.01) but levels of copeptin did not differ in controls with abnormal glucose tolerance or normal glucose tolerance. Copeptin predicted major cardiovascular events [ n = 64; hazard ratio = 1.15 (1.01-1.32; p = 0.04)], cardiovascular mortality [ n = 29; hazard ratio = 1.24 (1.06-1.46; p = 0.01)] and total death [ n = 51; hazard ratio = 1.21 (1.05-1.40; p = 0.01)] in unadjusted Cox regression analyses in the patient cohort. In controls, copeptin predicted major cardiovascular events [ n = 26; hazard ratio = 1.17 (1.01-1.36; p = 0.03)]. CONCLUSION: Copeptin levels are highest among acute myocardial infarction patients with glucose disturbances and predict an adverse prognosis in unadjusted analyses. These findings imply that raised copeptin reflects stress rather than acting as a pathogenic factor for glucose abnormalities.

Changes in Mortality in People With IGT Before and After the Onset of Diabetes During the 23-Year Follow-up of the Da Qing Diabetes Prevention Study.

OBJECTIVE: People with impaired glucose tolerance (IGT) have increased risk of mortality and a high risk of progression to diabetes, but the extent that the excess mortality is associated with IGT per se or is the result of subsequent diabetes is unclear. RESEARCH DESIGN AND METHODS: We compared mortality before and after the development of diabetes among 542 persons with IGT initially who participated in a 6-year lifestyle diabetes prevention trial and were followed-up from 1986 to 2009. RESULTS: During the 23-year follow-up, 174 (32.1%) died, with an overall death rate of 15.9/1,000 person-years. The majority of deaths (74.7%; 130 of 174) occurred after progression to type 2 diabetes, with age-adjusted death rates of 11.1/1,000 person-years (95% CI 8.2-12.0) before and 19.4/1,000 person-years (95% CI 11.9-23.3) after the development of type 2 diabetes. The cumulative mortality was 37.8% (95% CI 33.1-42.2%) in participants who developed type 2 diabetes during first 10 years of follow-up, 28.6% (95% CI 21.6-35.0%) in those who progressed to type 2 diabetes in 10-20 years, and 13.9% (95% CI 7.0-20.3%) in those who did not develop to type 2 diabetes within 20 years. Time-dependent multivariate Cox proportional hazards analyses, with adjustment for baseline age, sex, intervention, and other potential confounding risk factors, showed that the development of type 2 diabetes was associated with a 73% higher risk of death (hazard ratio 1.73 [95% CI 1.18-2.52]). CONCLUSIONS: As elsewhere, IGT is associated with increased risk of mortality in China, but much of this excess risk is attributable to the development of type 2 diabetes.

Diabetes, glucose tolerance, and the risk of sudden cardiac death.

BACKGROUND: Diabetes predisposes to sudden cardiac death (SCD). However, it is uncertain whether greater proportion of cardiac deaths are sudden among diabetes patients than other subjects. It is also unclear whether the risk of SCD is pronounced already early in the course of the disease. The relationship of impaired glucose tolerance (IGT) and SCD is scarcely documented. METHODS: A general population cohort of 10594 middle-aged subjects (mean age 44 years, 52.6 % male, follow-up duration 35-41 years) was divided into diabetes patients (n = 82), subjects with IGT (n = 3806, plasma glucose ≥9.58 mmol/l in one-hour glucose tolerance test), and controls (n = 6706). RESULTS: Diabetes patients had an increased risk of SCD after adjustment confounders (hazard ratio 2.62, 95 % confidence interval 1.46-4.70, p = 0.001) but risk for non-sudden cardiac death was similarly increased and the proportion of SCD of cardiac deaths was not increased. The SCD risk persisted after exclusion of subjects with baseline cardiac disease or non-fatal cardiac events during the follow-up. Subjects with IGT were at increased risk for SCD (univariate hazard ratio 1.51; 95 % confidence interval 1.31-1.74; p < 0.001) and also for non-sudden cardiac deaths and non-fatal cardiac events but adjustments for other risk factors attenuated these effects. CONCLUSIONS: Diabetes was associated with increased risk of SCD but also the risk of non-sudden cardiac death was similarly increased. The proportion of cardiac deaths being sudden in subjects with diabetes was not increased. The higher SCD risk in diabetes patients was independent of known cardiac disease at baseline or occurrence of non-fatal cardiac event during the follow-up.

Cardiovascular and All-Cause Mortality Over a 23-Year Period Among Chinese With Newly Diagnosed Diabetes in the Da Qing IGT and Diabetes Study.

OBJECTIVE: Despite its growing prevalence in China, the extent to which diabetes leads to excess cardiovascular disease (CVD) mortality and all-cause mortality is unclear. RESEARCH DESIGN AND METHODS: We compared death rates and causes of death among 630 people with newly diagnosed diabetes (NDD) and 519 with normal glucose tolerance (NGT) who, in 1986, were identified as a result of screening 110,660 adults aged 25-74 years for diabetes in Da Qing, China. RESULTS: During 23 years of follow-up, 338 (56.5%) participants with NDD and 100 (20.3%) with NGT died. CVD was the predominant cause of death in those with diabetes (47.5% in men and 49.7% in women), almost half of which was due to stroke (52.3% in men and 42.3% in women). The age-standardized incidence of all-cause death was three times as high in those with NDD as in those with NGT with incidences (per 1,000 person-years) of 36.9 (95% CI 31.5-42.3) vs. 13.3 (10.2-16.5) in men (P < 0.0001) and 27.1 (22.9-31.4) vs. 9.2 (7.8-10.6) in women (P < 0.0001). The incidence of CVD deaths in men and women with NDD (17.5 [13.8-21.2] vs. 13.5 [10.5-16.5]) did not differ significantly. Significantly higher death rates attributable to renal disease and infection were also found in the NDD group. CONCLUSIONS: Diabetes is associated with a substantially increased risk of death in Chinese adults, especially from CVD, almost half of which is due to stroke.

Dysglycemia and long-term mortality: observations from the Israel study of glucose intolerance, obesity and hypertension.

BACKGROUND: We describe the relationship between dysglycemia and long-term mortality and elucidate the relationship between blood glucose levels during an oral glucose tolerance test (OGTT) and haemoglobin A1 (HbA1) and mortality. METHODS: A cohort of 1410 individuals was followed for 33 years since 1980. Fasting and post-OGTT glucose parameters were used to categorize the cohort according to baseline glycemic status. RESULTS: The mortality rate increased from 43% in normoglycemic individuals to 53.3, 61.7, 72.9 and 88.0% in those with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG/IGT and diabetes, respectively. The highest mortality rate, compared with the normoglycemic category, was observed in individuals with IFG/IGT and diabetes according to a Cox proportional hazard model (HR = 1.38, 95%CI 1.10-1.74 and HR = 2.14, 95%CI 1.70-2.70, respectively), followed by individuals with IGT and IFG, but this did not reach statistical significance. We speculate that the IFG group may represent a mixture of individuals en route from normal to the next two categories as well as another cohort whose glucose levels are stably set at the upper reaches of the normal distribution. Significant differences were found between 1 and 2 h glucose values (p < 0.001). Fasting, 60 and 120 min glucose values were positively associated with increasing HbA1 quintiles (p < 0.05). The mean HbA1 was significantly higher in those who died (p = 0.01). The highest mortality (58.8%) was observed in the upper HbA1 quintile that was also associated with the highest prevalence of the metabolic syndrome (17.2%). CONCLUSIONS: This study shows a continuous relationship between the severity of dysglycemia and long-term mortality and should promote the early recognition of prediabetes. The 1 h post-load glucose level was continuously associated with increasing HbA1 concentrations and may therefore serve as an early marker for abnormalities in glucose tolerance. An elevated 1 h post-load glucose level may potentially identify at-risk individuals well before the traditional 2 h glucose value.