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 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.

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.

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.

Differential risk factors and morbidity/mortality pattern in type 2 diabetes: A study among two Mendelian populations with different ancestry (India).

BACKGROUND AND AIMS: Association studies of type 2 diabetes mellitus (T2DM) with risk factors have shown variable results. Moreover, population-specific comparative investigations are negligible. Therefore, the present study aimed to evaluate the association of dyslipidemia and obesity with impaired fasting glucose (IFG) and T2DM among two ethnically, geographically and culturally different populations in India. METHODS: This was a cross-sectional study among Jats and Meiteis, each inhabiting a separate geographical region. A total of 2371 individuals, age ≥30 years were recruited through household survey. Obesity variables were captured using anthropometric measurements while fasting blood (2.5 mL) was drawn to measure lipid and glucose levels using enzymatic assay by spectrophotometer. Participants were categorized under normal, IFG and T2DM groups, indicative of diabetes progression stages. Statistical analysis was performed using SPSS 16.0 version. RESULTS: Significant differential distribution of lipid and obesity variables among IFG and T2DM in both populations were observed. Odds ratio revealed high TC and all obesity variables except BMI posed significant increased risk for T2DM among Jats. Abnormal TG, VLDL, WC, and WHtR posed significant increased risk for T2DM among Meiteis. Age-cohort wise prevalence of T2DM showed increasing trend at ≥60 years among Jats and decreasing trend at ≥60 years among Meiteis, suggesting a potential higher morbidity in the former and mortality in latter because of T2DM. CONCLUSIONS: The present study observed a differential association of risk factors for T2DM among Jats and Meiteis. This study emphasize the need to implement community-specific intervention programs for prevention, treatment and management of T2DM.

Preoperative disturbances of glucose metabolism and mortality after coronary artery bypass grafting.

BACKGROUND: Disturbances of glucose metabolism are important risk factors for coronary artery disease and are associated with an increased mortality risk. The aim was to investigate the association between preoperative disturbances of glucose metabolism and long-term all-cause mortality after coronary artery bypass grafting (CABG). METHODS: Patients undergoing a first isolated CABG in 2005-2013 were included. All patients without previously known diabetes underwent an oral glucose tolerance test (OGTT) before surgery. They were categorised as having normal glucose tolerance (NGT), pre-diabetes (impaired glucose tolerance and/or impaired fasting glucose) or newly discovered diabetes. Data were collected from nationwide healthcare registers. Cox regression was used to calculate adjusted HR with 95% CI for death in patients with pre-diabetes and diabetes, using NGT as reference. RESULTS: In total, 497 patients aged 40-86 years were included. According to OGTT, 170 (34%) patients had NGT, 219 (44%) patients with pre-diabetes and 108 (22%) patients had newly discovered diabetes. Baseline characteristics were similar between the groups except for slightly higher age among patients with newly discovered diabetes. There were 133 (27%) deaths during a mean follow-up time of 10 years. The cumulative 10-year survival was 77% (69%-83%), 83% (77%-87%) and 71% (61%-79%) in patients with NGT, pre-diabetes and newly discovered diabetes, respectively. There was no significant difference in all-cause mortality between the groups after multivariable adjustment. CONCLUSION: In this study, patients with pre-diabetes or newly discovered diabetes prior to CABG had similar long-term survival compared with patients with NGT.

Mortality risk in adults according to categories of impaired glucose metabolism after 18 years of follow-up in the North of Spain: The Asturias Study.

People who develop type 2 diabetes (T2D) are known to have a higher mortality risk. We estimated all-cause, cardiovascular, and cancer mortality-risks in our patient cohort according to categories of impaired glucose metabolism. This 18-year retrospective analysis included a region-wide, representative sample of a population aged 30-75 years. Age- and sex-stratified hazard ratios (HRs) were calculated for 48 participants with diagnosed T2D, 83 with undiagnosed T2D (HbA1c ≥6.5%, fasting glycemia ≥126 mg/dL, or glycemia after 75 g glucose load ≥200 mg/dL); 296 with prediabetes (HbA1c 5.7%-6.4%, fasting glycemia 100-125 mg/dL, or glycemia after 75 g glucose load 140-199 mg/dL), and 607 with normoglycemia. Over 18,612 person-years, 32 individuals with undiagnosed T2D, 30 with diagnosed T2D, 62 with prediabetes, and 80 with normoglycemia died. Total sample crude mortality rate (MR) was 10.96 deaths per 1,000 person-years of follow-up. MR of the diagnosed T2D group was more than 3-times higher and that of newly diagnosed T2D was 2-times higher (34.72 and 21.42, respectively) than total sample MR. Adjusted HR for all-cause mortality was 2.02 (95% confidence interval 1.29-3.16) and 1.57 (95% CI 1.00-2.28) in the diagnosed T2D group and the newly diagnosed T2D group, respectively. Adjusted HR for cardiovascular mortality in the T2D group was 2.79 (95% CI 1.35-5.75); this risk was greatly increased in women with T2D: 6.72 (95% CI 2.50-18.07). In Asturias, age- and sex-standardized all-cause mortality is more than 2-times higher for adults with T2D than for adults without T2D. The HR for cardiovascular mortality is considerably higher in T2D women than in normoglycemic women.

Race-Ethnic Disparities in Cardiometabolic Risk Profiles among Stroke Survivors with Undiagnosed Diabetes and Prediabetes in the United States.

BACKGROUND AND PURPOSE: Up to 25% of the U.S. population has undiagnosed diabetes. Diabetes and stroke both disproportionately afflict race/ethnic minorities. We assessed race/ethnic differences in the prevalence of undiagnosed diabetes, prediabetes, and cardiometabolic risk profiles among stroke survivors in the United States. METHODS: The prevalence of diabetes and prediabetes among adults (≥20 years) with a self-reported history of stroke was assessed using the National Health and Nutrition Examination Surveys (NHANES) from 1999 to 2010. Cardiometabolic risk factors across race/ethnic groups were compared using linear and logistic regression before and after adjusting for covariates. RESULTS: From 1999 to 2010, 1070 individuals who participated in NHANES had a self-reported history of stroke. Among stroke survivors without a formal diagnosis of diabetes and prediabetes, 233 (32%) had undiagnosed prediabetes and 27 (3.7%) had undiagnosed diabetes. The prevalence of undiagnosed diabetes and prediabetes was the highest among non-Hispanic (NH) blacks (8% and 38%) compared with Mexican Americans (4% and 26%) and NH whites (3% and 32%). Compared with NH whites, NH blacks were significantly younger, more likely to take antihypertensive medications, more likely to smoke, and have poorly controlled diabetes. NH blacks were twice as likely as NH whites to have poorly controlled blood pressure, after adjustment for sociodemographic and vascular risk factors. CONCLUSION: In the United States, NH black stroke survivors have the highest rates of undiagnosed diabetes and prediabetes, and have poorer cardiometabolic risk factor control than their NH white counterparts.

Associations between prediagnostic blood glucose levels, diabetes, and glioma.

Previous literature indicates that pre-diagnostic diabetes and blood glucose levels are inversely related to glioma risk. To replicate these findings and determine whether they could be attributed to excess glucose consumption by the preclinical tumour, we used data from the Apolipoprotein MOrtality RISk (AMORIS) (n = 528,580) and the Metabolic syndrome and Cancer project (Me-Can) cohorts (n = 269,365). We identified individuals who were followed for a maximum of 15 years after their first blood glucose test until glioma diagnosis, death, emigration or the end of follow-up. Hazard ratios (HRs), 95% confidence intervals (CIs) and their interactions with time were estimated using Cox time-dependent regression. As expected, pre-diagnostic blood glucose levels were inversely related to glioma risk (AMORIS, P trend = 0.002; Me-Can, P trend = 0.04) and pre-diagnostic diabetes (AMORIS, HR = 0.30, 95% CI 0.17 to 0.53). During the year before diagnosis, blood glucose was inversely associated with glioma in the AMORIS (HR = 0.78, 95% CI 0.66 to 0.93) but not the Me-Can cohort (HR = 0.99, 95% CI 0.63 to 1.56). This AMORIS result is consistent with our hypothesis that excess glucose consumption by the preclinical tumour accounts for the inverse association between blood glucose and glioma. We discuss additional hypothetical mechanisms that may explain our paradoxical findings.

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.

Increased Vascular Disease Mortality Risk in Prediabetic Korean Adults Is Mainly Attributable to Ischemic Stroke.

BACKGROUND AND PURPOSE: Prediabetes is a known risk factor for vascular diseases; however, its differential contribution to mortality risk from various vascular disease subtypes is not known. METHODS: The subjects of the National Health Insurance Service in Korea (2002-2013) nationwide cohort were stratified into normal glucose tolerance (fasting glucose <100 mg/dL), impaired fasting glucose (IFG) stage 1 (100-109 mg/dL), IFG stage 2 (110-125 mg/dL), and diabetes mellitus groups based on the fasting glucose level. A Cox regression analysis with counting process formulation was used to assess the mortality risk for vascular disease and its subtypes-ischemic heart disease, ischemic stroke, and hemorrhagic stroke. RESULTS: When adjusted for age, sex, and body mass index, IFG stage 2, but not stage 1, was associated with significantly higher all-cause mortality (hazard ratio [HR], 1.26; 95% confidence interval [CI], 1.18-1.34) and vascular disease mortality (HR, 1.27; 95% CI, 1.08-1.49) compared with normal glucose tolerance. Among the vascular disease subtypes, mortality from ischemic stroke was significantly higher (HR, 1.60; 95% CI, 1.18-2.18) in subjects with IFG stage 2 but not from ischemic heart disease and hemorrhagic stroke. The ischemic stroke mortality associated with IFG stage 2 remained significantly high when adjusted other modifiable vascular disease risk factors (HR, 1.51; 95% CI: 1.10-2.09) and medical treatments (HR, 1.75; 95% CI, 1.19-2.57). CONCLUSIONS: Higher IFG degree (fasting glucose, 110-125 mg/dL) was associated with increased all-cause and vascular disease mortality. The increased vascular disease mortality in IFG stage 2 was attributable to ischemic stroke, but not ischemic heart disease or hemorrhagic stroke in Korean adults.

Association between diet-related inflammation, all-cause, all-cancer, and cardiovascular disease mortality, with special focus on prediabetics: findings from NHANES III.

INTRODUCTION: Chronic inflammation is associated with increased risk of cancer, cardiovascular disease (CVD), and diabetes. The role of pro-inflammatory diet in the risk of cancer mortality and CVD mortality in prediabetics is unclear. We examined the relationship between diet-associated inflammation, as measured by dietary inflammatory index (DII) score, and mortality, with special focus on prediabetics. METHODS: This prospective cohort study used data from the Third National Health and Nutrition Examination Survey (NHANES III). We categorized 13,280 eligible participants, ages 20-90 years, according to glycosylated hemoglobin (HgbA1c) level and identified 2681 with prediabetes, defined as a glycosylated hemoglobin percentage of 5.7-6.4. Computation of DII scores and all statistical analyses were conducted in 2015. The DII was computed based on baseline dietary intake assessed using 24-h dietary recalls (1988-1994). Mortality was determined from the National Death Index records through 2006. Over follow-up ranging between 135 and 168 person-months, a total of 3016 deaths were identified, including 676 cancer, 192 lung cancer, 176 digestive-tract cancer, and 1328 CVD deaths. Cox proportional hazard regression was used to estimate hazard ratios. RESULTS: The prevalence of prediabetes was 20.19 %. After controlling for age, sex, race, HgbA1c, current smoking, physical activity, BMI, and systolic blood pressure, DII scores in tertile III (vs tertile I) was significantly associated with mortality from all causes (HR 1.39, 95 % CI 1.13, 1.72), CVD (HR 1.44, 95 % CI 1.02, 2.04), all cancers (HR 2.02, 95 % CI 1.27, 3.21), and digestive-tract cancer (HR 2.89, 95 % CI 1.08, 7.71). Findings for lung cancer (HR 2.01, 95 % CI 0.93, 4.34) suggested a likely effect. These results were moderately enhanced after additional adjustment for serum low-density lipoprotein and triglyceride and following eliminating deaths during the first year. CONCLUSIONS: A pro-inflammatory diet, as indicated by higher DII scores, is associated with an increased risk of all-cause, CVD, all-cancer, and digestive-tract cancer mortality among prediabetic subjects.

HbA1c and Risks of All-Cause and Cause-Specific Death in Subjects without Known Diabetes: A Dose-Response Meta-Analysis of Prospective Cohort Studies.

Whether HbA1c levels are associated with mortality in subjects without known diabetes remains controversial. Moreover, the shape of the dose-response relationship on this topic is unclear. Therefore, a dose-response meta-analysis was conducted. PubMed and EMBASE were searched. Summary hazard ratios (HRs) were calculated using a random-effects model. Twelve studies were included. The summary HR per 1% increase in HbA1c level was 1.03 [95% confidence interval (CI) = 1.01-1.04] for all-cause mortality, 1.05 [95% CI = 1.02-1.07) for cardiovascular disease (CVD) mortality, and 1.02 (95% CI = 0.99-1.07) for cancer mortality. After excluding subjects with undiagnosed diabetes, the aforementioned associations remained significant for CVD mortality only. After further excluding subjects with prediabetes, all aforementioned associations presented non-significance. Evidence of a non-linear association between HbA1c and mortality from all causes, CVD and cancer was found (all Pnon-linearity < 0.05). The dose-response curves were relatively flat for HbA1c less than around 5.7%, and rose steeply thereafter. In conclusion, higher HbA1c level is associated with increased mortality from all causes and CVD among subjects without known diabetes. However, this association is driven by those with undiagnosed diabetes or prediabetes. The results regarding cancer mortality should be treated with caution due to limited studies.

Metabolic Burden and Disease and Mortality Risk Associated with Impaired Fasting Glucose in Elderly Adults.

OBJECTIVES: To examine whether impaired fasting glucose (IFG) represents an intermediary condition between normal fasting glucose and diabetes mellitus and, specifically, whether elderly adults with IFG have higher disease burden, cardiovascular risk, and systemic inflammation and higher 2-year mortality and incident disease. DESIGN: Prospective observational study. SETTING: Population-derived cohort. PARTICIPANTS: Individuals with a mean age of 78.6 ± 4.7 (N = 945). MEASUREMENTS: Disease was ascertained using a standardized questionnaire at baseline and 2 years. Fasting metabolic, inflammatory, and oxidative metabolism markers were measured. Disease prevalence, cardiovascular risk, and biochemical markers were compared to determine disease burden and metabolic disturbances in IFG. Adjusted odds ratios (ORs) for 2-year all-cause mortality and incident disease were determined. RESULTS: IFG prevalence was 41%. Individuals with IFG had higher baseline rates of heart disease than those with normal fasting glucose (NFG), similar to that in individuals with diabetes mellitus. IFG was characterized by higher inflammatory markers and oxidative metabolism end products and was an intermediary between NFG and diabetes mellitus for triglycerides and malondialdehyde. Discriminant analysis showed that IFG was independently associated with stroke and higher triglycerides and oxidative stress. Two-year all-cause mortality was 3.9%. The 2-year adjusted ORs for all-cause mortality, incident cardiac disease, stroke, and cancer were similar between IFG and NFG, using both American Diabetes Association and World Health Organization IFG criteria. IFG did not predict secondary cardiac events, stroke, or cancer. CONCLUSION: IFG was an intermediary condition for heart disease, inflammation, and oxidative stress in elderly adults but not for 2-year incident disease or all-cause mortality. Longer-term prospective studies are needed to clarify whether IFG in elderly adults portends greater morbidity and mortality.

Impaired glucose metabolism among those with and without diagnosed diabetes and mortality: a cohort study using Health Survey for England data.

BACKGROUND: The extent that controlled diabetes impacts upon mortality, compared with uncontrolled diabetes, and how pre-diabetes alters mortality risk remain issues requiring clarification. METHODS: We carried out a cohort study of 22,106 Health Survey for England participants with a HbA1C measurement linked with UK mortality records. We estimated hazard ratios (HRs) of all-cause, cancer and cardiovascular disease (CVD) mortality and 95% confidence intervals (CI) using Cox regression. RESULTS: Average follow-up time was seven years and there were 1,509 deaths within the sample. Compared with the non-diabetic and normoglycaemic group (HbA1C <5.7% [<39 mmol/mol] and did not indicate diabetes), undiagnosed diabetes (HbA1C ≥6.5% [≥48 mmol/mol] and did not indicate diabetes) inferred an increased risk of mortality for all-causes (HR 1.40, 1.09-1.80) and CVD (1.99, 1.35-2.94), as did uncontrolled diabetes (diagnosed diabetes and HbA1C ≥6.5% [≥48 mmol/mol]) and diabetes with moderately raised HbA1C (diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol]). Those with controlled diabetes (diagnosed diabetes and HbA<5.7% [<39 mmol/mol]) had an increased HR in relation to mortality from CVD only. Pre-diabetes (those who did not indicate diagnosed diabetes and HbA1C 5.7-<6.5% [39-<48 mmol/mol]) was not associated with increased mortality, and raised HbA1C did not appear to have a statistically significant impact upon cancer mortality. Adjustment for BMI and socioeconomic status had a limited impact upon our results. We also found women had a higher all-cause and CVD mortality risk compared with men. CONCLUSIONS: We found higher rates of all-cause and CVD mortality among those with raised HbA1C, but not for those with pre-diabetes, compared with those without diabetes. This excess differed by sex and diabetes status. The large number of deaths from cancer and CVD globally suggests that controlling blood glucose levels and policies to prevent hyperglycaemia should be considered public health priorities.

Prediabetes, elevated iron and all-cause mortality: a cohort study.

OBJECTIVES: Data have indicated low to non-existent increased mortality risk for individuals with prediabetes, but it is unclear if the risk is increased when the patient has elevated iron markers. Our purpose was to examine the mortality risk among adults with prediabetes in the context of coexisting elevated transferrin saturation (TS) or serum ferritin. SETTING: Data collected by the third National Health and Nutrition Examination Survey 1988-1994 (NHANES III) in the USA and by the National Center for Health Statistics for the National Death Index from 1988 to 2006. PARTICIPANTS: Individuals age 40 and older who participated in the NHANES and provided a blood sample. PRIMARY OUTCOME VARIABLE: Mortality was measured as all-cause mortality. RESULTS: Adjusted analyses show that prediabetes has a small increased mortality risk (HR=1.04; 95% CI 1.00 to 1.08). Persons who had prediabetes and elevated serum ferritin had an increased HR for death (HR=1.14; 95% CI 1.04 to 1.24) compared with those who had normal ferritin and normal glucose. Among persons with prediabetes who had elevated TS, they had an increased mortality risk (HR=1.88; 95% CI 1.06 to 3.30) compared with those with normal TS levels and normal glucose. CONCLUSIONS: The mortality risk of prediabetes is low. However, among individuals who have coexisting elevated iron markers, particularly TS, the risk rises substantially.

Diabetes, prediabetes and the survival of nasopharyngeal carcinoma: a study of 5,860 patients.

BACKGROUND: The incidence of diabetes is increasing. But the impact of diabetes and prediabetes on survival of patients with nasopharyngeal carcinoma (NPC) has received little evaluation. METHODS: In a cohort of 5,860 patients, we compared the disease specific survival (DSS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) of patients with diabetes, prediabetes and normoglycemia defined by pretreatment fasting plasma glucose (FPG) using Kaplan-Meier method, log-rank test and Cox proportional hazards model. RESULTS: Comparing to normoglycemic patients, the diabetic and the prediabetic were generally older, fatter, had hypertension, heart diseases and hyperlipaemia and usually received radiotherapy alone. But both the diabetic and the prediabetic had similar DSS, LRFS and DMFS to normoglycemic patients, even adjusting for such important factors as age, gender, smoking, drinking, hypertension, heart diseases, body mass index, hyperlipaemia, titer of VCA-IgA and EA-IgA, pathology, T-stage, N-stage, chemotherapy and radiotherapy (P>0.05 for all). Additionally, the findings remained unchanged in sensitivity analysis by excluding patients with known diabetes history and in subgroups of the various factors. CONCLUSIONS: The diabetic and prediabetic NPC patients had similar survival to normoglycemic NPC patients. These data, in the largest reported cohort, are the first to evaluate the association between diabetes, prediabetes and the survival in NPC. The findings are relevant to patient management and provided evidence of the effect on this disease exerted by comorbidities.

Fitness, fatness, and survival in adults with prediabetes.

OBJECTIVE: The purpose of this study was to examine independent and joint associations of cardiorespiratory fitness (CRF) and different adiposity measures with mortality risk in individuals with prediabetes (or impaired fasting glucose). RESEARCH DESIGN AND METHODS: We examined associations of CRF and fatness with cardiovascular disease (CVD) and all-cause mortality in a cohort of 17,044 participants (89% men) with prediabetes (defined as 100 mg/dL ≤ fasting plasma glucose < 126 mg/dL), who did not have a history of diabetes, CVD, or cancer. RESULTS: We identified 832 deaths (246 from CVD) during 13.9 ± 7.0 years (mean ± SD) follow-up. Normal-weight individuals who were unfit (lowest one-third) had a higher risk of all-cause (hazard ratio 1.70 [95% CI 1.32-2.18]) and CVD (1.88 [1.13-3.10]) mortality compared with the normal-weight and fit (upper two-thirds) reference group in a model adjusted for age, sex, examination year, and multiple risk factors. The mortality risk for fit individuals who were overweight or obese did not differ significantly from the reference group. Similar patterns were observed for sex-specific thirds of waist circumference and % body fat. CONCLUSIONS: CRF markedly modifies the relationship between adiposity and mortality in persons with prediabetes. Unfit individuals have a higher and fit individuals have a lower mortality risk irrespective of adiposity level in this high-risk group.

Prevalence and severity of abnormal glucose regulation and its relation to long-term prognosis after coronary artery bypass grafting.

BACKGROUND: Diabetes is a strong predictor of a poor outcome after coronary artery bypass grafting (CABG). The prevalence of prediabetes and its impact on the prognosis after CABG is not well described. In this study, we evaluated the prevalence and prognostic impact of the different states of abnormal glucose regulation (AGR) after CABG. PATIENTS AND METHODS: In this prospective study, we included 244 patients undergoing CABG. An oral glucose tolerance test was used to stratify patients into three groups: normoglycaemia, prediabetes and diabetes. The primary outcome was a composite of all-cause mortality and hospitalization for a nonfatal cardiovascular event. RESULTS: Among the patients, 86 (35%) were normoglycaemic and 58 (24%) had prediabetes; 100 (41%) patients had diabetes, of whom 28 (28%) had newly diagnosed diabetes on the basis of oral glucose tolerance test. During a mean follow-up period of 5.3 years, 25% of the study population suffered the primary outcome. There was a successive increase in the primary outcome rate from normoglycaemia through prediabetes to diabetes (adjusted hazard ratio 1.40; 95% confidence interval 1.01-1.96; P=0.045). CONCLUSION: With increasing severity of AGR, there is an increasing risk of new cardiovascular events after CABG. AGR is prevalent and predicts a poor outcome after CABG. Systematic screening for AGR seems reasonable to identify these high-risk patients.

Association of serum C-peptide concentrations with cancer mortality risk in pre-diabetes or undiagnosed diabetes.

BACKGROUND: Known associations between diabetes and cancer could logically be attributed to hyperglycemia, hypersecretion of insulin, and/or insulin resistance. This study examined the relationship between initial glycemic biomarkers among men and women with impaired fasting glucose or undiagnosed diabetes and cancer mortality during follow up. METHODS: The cohort included subjects aged 40 years and above from the Third National Health and Nutrition Examination Survey (NHANES III) with fasted serum glucose >100 mg/dl without the aid of pharmaceutical intervention (insulin or oral hypoglycemics). Cancer mortality was obtained from the NHANES III-linked follow-up database (up to December 31, 2006). A Cox regression model was applied to test for the associations between cancer mortality and fasting serum glucose, insulin, glycosylated hemoglobin (HbA1c), C-peptide, insulin like growth factor (IGF-1), IGF binding protein 3 (IGFBP3) and estimated insulin resistance. RESULTS: A total of 158 and 100 cancer deaths were recorded respectively from 1,348 men and 1,161 women during the mean 134-month follow-up. After adjusting for the effect of age and smoking in women, all-cause cancer deaths (HR: 1.96 per pmol/ml, 95% CI: 1.02-3.77) and lung cancer deaths (HR: 2.65 per pmol/ml, 95% CI: 1.31-5.36) were specifically associated with serum C-peptide concentrations. Similar associations in men were not statistically significant. Serum glucose, HbA1c, IGF-1, IGFBP3 and HOMA were not independently related to long-term cancer mortality. CONCLUSION: C-peptide analyses suggest a modest association with both all-cause and lung cancer mortality in women but not in men. Further studies will be required to explore the mechanisms.