Incident Impaired Fasting Glucose Research Articles

Acrolein Exposure Impaired Glucose Homeostasis and Increased Risk of Type 2 Diabetes: An Urban Adult Population-Based Cohort Study with Repeated Measures

Acrolein is an identified high-priority hazardous air pollutant ubiquitous in daily life and associated with cardiometabolic risk that attracts worldwide attention. However, the etiology role of acrolein exposure in glucose dyshomeostasis and type 2 diabetes (T2D) is unclear. This repeated-measurement prospective cohort study included 3522 urban adults. Urine/blood samples were repeatedly collected for determinations of acrolein metabolites (N-acetyl-S-(3-hydroxypropyl)-l-cysteine, N-acetyl-S-(2-carboxyethyl)-l-cysteine; acrolein exposure biomarkers), glucose homeostasis, and T2D at baseline and a three-year follow-up. We found that each 3-fold increment in acrolein metabolites was cross-sectionally associated with 5.91-6.52% decrement in homeostasis model assessment-insulin sensitivity (HOMA-IS) and 0.07-0.14 mmol/L, 4.02-4.57, 5.91-6.52, 19-20, 18-19, and 23-31% increments in fasting glucose (FPG), fasting insulin (FPI), HOMA-insulin resistance (HOMA-IR), risks of prevalent IR, impaired fasting glucose (IFG), and T2D, respectively; longitudinally, participants with sustained-high acrolein metabolite levels had increased risks of incident IR, IFG, and T2D by 63-80, 87-99, and 120-154%, respectively (P < 0.05). In addition, biomarkers of heme oxygenase-1 activity (exhaled carbon monoxide), lipid peroxidation (8-iso-prostaglandin-F2α), protein carbonylation (protein carbonyls), and oxidative DNA damage (8-hydroxy-deoxyguanosine) mediated 5.00-38.96% of these associations. Our study revealed that acrolein exposure may impair glucose homeostasis and increase T2D risk via mediating mechanisms of heme oxygenase-1 activation, lipid peroxidation, protein carbonylation, and oxidative DNA damage.

Intensive Blood Pressure Control and Diabetes Mellitus Incidence for Patients with Impaired Fasting Glucose: A Secondary Analysis of SPRINT.

Previous studies indicated that intensive blood pressure (BP) control (systolic BP < 120 mm·Hg) compared with standard BP control (<140 mm·Hg) was associated with an increased risk of type 2 diabetes (T2D) and impaired fasting glucose (IFG) among hypertensive patients with normoglycemia. However, the impact of intensive BP control on the incidence of T2D for those with IFG is still unknown. This was a secondary analysis of the SPRINT (Systolic Blood Pressure Intervention Trial) of the study. We included participants with IFG at randomization, which was defined as fasting blood glucose (FBG) between 100 and 125 mg/dL. The primary outcome was incident T2D, defined as events of reaching FBG ≥ 126 mg/dL, participant self-report T2D at annual examination, or a record of hypoglycemic medications at follow-up. The secondary outcome was incident IFG reversion (IFGR), defined as the time to first FBG back to normoglycemia (<100 mg/dl) among participants without incident T2D. Cox proportional hazards models were used to compare the cumulative incidence of outcomes between the two BP control groups. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. A total of 3310 participants were included in our primary outcome analysis (median age 67 years, 29% female). There were 293 participants who developed T2D among the intensive BP control group and 256 participants who developed T2D among the standard BP control group, resulting in 56.87 (50.36-63.39) versus 49.33 (43.29-55.37) events per 1000 person-years of treatment (HR 1.18 [95% CI, 1.00-1.40], P=0.052). After excluding 549 participants who developed T2D, 2761 participants were included in our secondary outcome analysis with 559 participants who developed IFGR among the intensive BP control group and 632 participants who developed IFGR among the standard BP control group, resulting in 141.20 (129.50-152.91) versus 158.20 (145.86,170.53) events per 1000 person-years of treatment (HR 0.9 [95% CI, 0.8-1.01], P=0.067). Our study found that in comparison to the standard BP control for hypertensive patients with IFG, intensive BP control was associated with a small increased risk of new-onset T2D, though it did not reach statistical significance. This kind of impact should be considered when implementing the strategy, especially for those with high risks of developing T2D. This trial is registered with NCT01206062.

Association of Non-Insulin-Based Insulin Resistance Indices with Risk of Incident Prediabetes and Diabetes in a Chinese Rural Population: A 12-Year Prospective Study.

Three non-insulin-based insulin resistance (IR) indices, ie, triglyceride-glucose (TyG) index, triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and metabolic score for IR (METS-IR), were considered powerful and simplified alternatives for IR. However, evidence for the association between the three IR indices and incident type 2 diabetes mellitus (T2DM), especially impaired fasting glucose (IFG), remains limited. Therefore, this study aimed to explore the association among IR indices, incident IFG, and T2DM in a rural population cohort. We analyzed data from 2209 adults (aged 24-75 years) at baseline and from 1205 normoglycemic participants who were followed up. Cox proportional hazards models were used to evaluate the associations between the three indices and IFG or T2DM. Restricted cubic spline curves based on the Cox regression model were used to examine the association between baseline indices and incident T2DM. For the baseline data, logistic analyses demonstrated that the TyG index, TG/HDL-C ratio, and METS-IR had a significantly positive correlation with IFG or T2DM after multivariable adjustment. During a median follow-up of 12.17 years, 157 incident cases of IFG and 97 incident cases of T2DM were noted. The risk of T2DM, but not IFG, was strongly associated with the baseline TyG index in the adjusted model, and participants with the TyG index in the third tertile had a higher risk of developing T2DM (adjusted hazards ratio, 2.84; 95% confidence intervals, 1.26-6.37; p for trend <0.001) than those in the lowest tertile (reference). Moreover, a linear relationship was observed between the TyG index and T2DM incidence. The TG/HDL-C ratio and METS-IR had no significant relationship with the risk of IFG or T2DM. The TyG index is more useful than the TG/HDL-C ratio and METS-IR in predicting T2DM in the normoglycemic population.

The impact of long-term exposure to PM10, SO2, O3, NO2, and COon incident dysglycemia: a population-based cohort study.

To examine the associations between long-term exposure to five major air pollutants including SO2, PM10, O3, NO2, and CO, and incident dysglycemia, impaired fasting glucose (IFG), and diabetes, separately. A total of 4254 (1720 men) normoglycemic individuals aged 20-69years at baseline were followed from 2001 to 2018 every 3years. To measure the long-term hazards of air pollutants for incident dysglycemia, the Weibull proportional hazards models for every 10-unit increment adjusted for diabetes risk factors were fitted. The air pollutants were put in the models in the form of averages of 1-, 2-, and 3-year periods. During a median follow-up of 12.2years, we observed 1780 dysglycemia events. In contrast to NO2, the increase in SO2, O3, and PM10 levels were significantly associated with a higher risk of dysglycemia and IFG in all time spans excluding PM10 at 2years. The largest hazard ratios for incident dysglycemia and IFG were attributable to PM10 in 3years (2.20 (95% CI 1.67, 2.89) and 2.08 (1.55, 2.80), respectively). Moreover, exposure to all the pollutants except NO2 in 1year (0.89 (0.80, 0.98)) had no significant associations with incident diabetes. There was a signal that younger (< 45years) and never-smoker individuals were more predispose to dysglycemic effects of air pollution (all P for interactions > 0.03). Our findings suggested that long-term exposure to air pollution increased incident dysglycemia risk, the effect which was mainly attributable to IFG status.

Association of alcohol drinking with incident type 2 diabetes and pre-diabetes: The Guangzhou Biobank Cohort Study.

We examined associations of baseline alcohol drinking with incident type 2 diabetes (T2D) or impaired fasting glucose (IFG), and explore whether the associations were modified by genetic polymorphisms of aldehyde dehydrogenase-2 (ALDH2) and alcohol dehydrogenase-1B (ADH1B). All participants were aged 50+ (mean=60.45; standard deviation=6.88) years. Information of alcohol consumption was collected at baseline from 2003 to 2008. Incident T2D was defined as fasting glucose ≥7.0mmol/L or post-load glucose ≥11.1mmol/L at follow-up examination (2008-2012), self-reported T2D and/or initiation of hypoglycaemia medication or insulin during follow-up. Impaired fasting glucose was defined as fasting glucose ≥5.6mmol/L and <7mmol/L. Of 15,716 participants without diabetes and 11,232 participants without diabetes and IFG at baseline, 1624 (10.33%) developed incident T2D and 1004 (8.94%) developed incident IFG during an average 4years of follow-up. After multivariable adjustments, compared with never drinking, occasional or moderate alcohol drinking was not associated with risk of incident hyperglycaemia (T2D+IFG) (odds ratio (OR)=1.10, 95% confidence interval (CI) 0.95-1.27, and 0.90 (0.69-1.18), respectively), whereas heavy alcohol drinking was associated with a higher risk of incident hyperglycaemia (T2D+IFG) (OR=1.82, 95% CI 1.24-2.68). No interactions of sex, overweight/obesity and genetic polymorphisms of ADH1B/ALDH2 genes with alcohol drinking on incident T2D and/or IFG were found (P for interaction from 0.12 to 0.85). Our results support a detrimental effect of heavy alcohol use on IFG and T2D. No protective effect was found for those carrying lower risk alleles for ADH1B/ALDH2 genes.

A Higher Serum Anion Gap Is Associated with the Risk of Progressing to Impaired Fasting Glucose and Diabetes.

Impaired fasting glucose (IFG) is a reversible intermediate hyperglycemia stage with an increasing risk of diabetes and related complications. Our study was designed to identify the relationship between the serum anion gap and the risk of progressing to impaired fasting glucose and diabetes. Here, we performed a prospective, population-based study among 1191 Chinese individuals aged 22–87 years who took health examinations annually between 2006 and 2012 including clinical features and plasma metabolites. All of the participants had no history of diabetes or related chronic complications. Logistic regression analysis was designed to examine the associations between clinical and metabolomic factors and the risk of developing IFG or diabetes. Among them, 58 subjects whose fasting glucose were between 6.1 and 7 mmol/L were diagnosed as IFG or diabetes. After adjusting for age, sex, body mass index (BMI), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), systolic blood pressure (SBP), diastolic blood pressure (DBP), potassium, and albumin at baseline, the participants in the upper tertiles of serum anion gap (SAG) had higher odds of progressing to IFG or diabetes than those in the lower tertiles. A receiver operating characteristic (ROC) curve was analyzed, and the optimal cutoff level for the anion gap to predict incident IFG or diabetes was 13.76 mmol/L, and the area under the ROC curve (AUC) was 0.623. Our data demonstrate that a higher serum anion gap is associated with the risk of developing IFG or diabetes.

Change in Cardiovascular Health and Incident Type 2 Diabetes and Impaired Fasting Glucose: The Whitehall II Study.

Most previous studies on cardiovascular health (CVH) and incident type 2 diabetes (T2D) have used a single measure of CVH, and none have investigated the association with impaired fasting glucose (IFG). We examined the association between changes in CVH and incident T2D and IFG. Within the Whitehall II study, CVH was examined every 5 years from 1991/93 until 2015/16. Subjects with 0-2, 3-4, and 5-6 ideal metrics of CVH from the American Heart Association were categorized as having low, moderate, or high CVH, respectively. There were 6,234 participants (mean age 49.8 ± 6.0 years, 70% male) without prior cardiovascular disease and T2D, including 5,015 who were additionally free from IFG at baseline. Over a median follow-up of 24.8 (interquartile range 24.0-25.2) years, 895 and 1,703 incident cases of T2D and IFG occurred, respectively. Change in CVH between 1991/93 and 2002/04 was calculated among 4,464 participants free from CVD and T2D and among 2,795 participants additionally free from IFG. In multivariate analysis, compared with those with stable low CVH, risk of T2D was lower in those with initially high CVH (hazard ratio [HR] 0.21; 95% CI 0.09, 0.51), those who had persistently moderate CVH or changed from moderate to high CVH (moderate-moderate/high; HR 0.53; 95% CI 0.41, 0.69), low-moderate/high (HR 0.62; 95% CI 0.45, 0.86), and moderate-low (HR 0.74; 95% CI 0.56, 0.98). Results were similar for IFG, but the effect sizes were smaller. Compared with stable low CVH, other patterns of change in CVH were associated with lower risk of T2D and IFG.

Clinical Recognition and Management of Patients with Prediabetes

Objective: Early identification and management of prediabetes is critical to prevent progression to diabetes. We aimed to assess whether prediabetes is appropriately recognized and managed among patients with impaired fasting glucose (IFG). Methods: We carried out an observational study of Olmsted County residents evaluated at the Mayo Clinic between 1999-2017. We randomly selected 108 subjects with biochemical criteria of IFG and 105 normoglycemic subjects. We reviewed their health records at baseline (1999-2004) and during follow up (2005-2017) collecting demographic and clinical data including vitals, diagnoses, laboratory, and medications associated with cardiovascular comorbidities. The main outcome was documentation of any recognition of prediabetes and management recommendations (lifestyle changes and/or medications). Results: At baseline (1999-2004), 26.85% (29/108) of subjects with IFG were recognized as having prediabetes, and of these 75.86% (22/29) received management recommendations with 6.9% (2/29) getting metformin. During follow-up (2005-2017), 26.67% (28/105) of initial cohort of normoglycemic subjects developed incident IFG and of these, 85.71% (24/28) were recognized as having prediabetes, and 58.33% (14/24) received management recommendations. During the entire study period, 62.50% (85/136) were recognized as having prediabetes of which 75.29% (64/85) had documented management recommendations. High body mass index (BMI) (≥35) was associated with increased recognition (odds ratio [OR] 3.66; confidence interval [CI] 1.065, 12.500; P = .0395), and normal BMI (<25) was associated with a lack of recognition (OR 0.146; CI 0.189, 0.966; P = .0413). Conclusion: Despite evidence supporting the efficacy of lifestyle changes and medications in managing prediabetes, this condition is not fully recognized in routine clinical practice. Increased awareness of diagnostic criteria and appropriate management are essential to enhance diabetes prevention. Abbreviations: BMI = body mass index; CI = confidence interval; EHR = electronic health records; FBG = fasting blood glucose; IFG = impaired fasting glucose; IGT = impaired glucose tolerance; OR = odds ratio.

Circulating sphingolipids, fasting glucose, and impaired fasting glucose: The Strong Heart Family Study.

BackgroundAnimal studies suggest sphingolipids as an early marker of impaired glucose metabolism; however, research in humans is limited. We evaluated whether individual sphingolipid species were associated with fasting plasma glucose and incident impaired fasting glucose in a longitudinal cohort study.MethodsWe measured 15 sphingolipid species from blood samples collected in 2001–2003 from 2145 participants without prevalent diabetes in the Strong Heart Family Study. Fasting plasma glucose was measured in blood samples collected at baseline and follow-up (mean 5.5 years after baseline).FindingsThe average age of study participants was 38 years; 41% were men. Ceramide, sphingomyelin, and glucosylceramide species levels were higher in older participants; lactosyl-ceramide levels were higher in participants with lower BMIs. In adjusted analyses, greater concentrations of most ceramide species and lower lactosyl-ceramide with palmitic acid (LC-16) were associated with higher glucose levels at baseline. We did not observe associations of sphingomyelin species or glucosyl-ceramide species with glucose levels. Associations of sphingolipid levels with fasting glucose levels at follow-up were similar but had greater uncertainty than associations with baseline glucose. Although no statistically significant associations of sphingolipids with incident impaired fasting glucose were present, results were similar to glucose analyses.InterpretationWe identified several ceramide species associated with higher fasting glucose levels and one sphingolipid, LC-16, that was associated with lower fasting glucose levels. These findings compliment previous research, which linked these sphingolipids with fasting insulin levels, and suggest that higher levels of these ceramides and lower LC-16 may be an early marker of impaired glucose metabolism.FundUS National Institutes Health.

Both youth and long-term vitamin D status is associated with risk of type 2 diabetes mellitus in adulthood: a cohort study

Objectives: To determine whether vitamin D status in childhood and adolescence (herein collectively referred to as youth) and the long-term status from youth to adulthood is associated with risk of developing type 2 diabetes mellitus (T2DM) and impaired fasting glucose (IFG) in adulthood.Materials and methods: This was a 31-year follow-up study of 2300 participants aged 3–18 years. Multinomial logistic regression was used to assess the association of both (a) baseline 25-hydroxyvitamin D (25OHD) levels and (b) the mean of baseline and the latest follow-up 25OHD levels (continuous variable and quartiles) with incident T2DM and IFG (cut-off = 5.6 mmol/L) in adult life.Results: High serum 25OHD levels in youth and also mean values from youth to adulthood were associated with reduced risk of developing T2DM in adulthood (odds ratio, 95% confidence interval= 0.73, 0.57–0.95 and 0.65, 0.51–0.84, respectively, for each SD increment in 25OHD). Compared to Q1, a dose-dependent negative association was observed across other quartiles of youth 25OHD, while the strongest association was found in the Q3 for the mean 25OHD levels. Neither youth nor the mean 25OHD was associated with IFG.Conclusions: High serum 25OHD levels in youth, and from child to adult life, were associated with a reduced risk of developing T2DM in adulthood.Key MessagesHigh serum 25OHD levels in youth, and between youth and adulthood, were associated with a lower risk of T2DM in adulthood.Each SD (15.2 nmol/L) increment in youth serum 25OHD levels was associated with a 26% reduction in odds for T2DM, which was independent of a number of confounding variables and other risk factors for T2DM. A similar magnitude of association was observed for the long-term 25OHD levels between youth and adulthood.These findings suggest a potentially simple and cost-effective strategy for reducing adulthood risk of T2DM starting in an earlier stage of life – improving and maintaining vitamin D status throughout youth and early adulthood.

The Effect of OSA Therapy on Glucose Metabolism: It's All about CPAP Adherence!

The Effect of OSA Therapy on Glucose Metabolism: It's All about CPAP Adherence!

VAMONOS (Veterans Affairs' Metabolism, Obstructed and Non-Obstructed Sleep) Study: Effects of CPAP Therapy on Glucose Metabolism in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM) are prevalent disorders that pose increased risk of cardiovascular disease and death. The objective of this study was to clarify if continuous positive airway pressure (CPAP) therapy for OSA affects T2DM control and emergence. Point-of-care, comparative effectiveness study; cross-sectional and longitudinal analyses. Our cohort included 928 consecutive patients; 13% were women; 36% were Caucasians and 61% African-Americans. OSA was diagnosed in approximately 738 patients and CPAP was initiated in 718 patients; median duration of therapy was 5 mo (25% to 75% interquartile range [IQR] 3-14). Patients with OSA used CPAP therapy for a median duration of 4.8 h, 34.5% of the nights. Adherence to CPAP was prespecified as follows: good (≥ 70% nights and ≥ 4 h/night), excellent (≥ 80% nights and ≥ 6 h/night) or outstanding (≥ 90% of nights and 8 h/night). Based on objective data, good, excellent, and outstanding compliance were found in only 30%, 20%, and 6%, respectively. Three percent of subjects without CPAP follow-up and less than 4% of those nonadherent to CPAP therapy (based on the established criteria) developed incident T2DM. Incident T2DM developed in only 0.8% of those with good compliance and in none (0%) of those in the excellent and outstanding groups. During follow-up, median weight change was +0.3 kg (IQR -1.8 to 2.7). We found that an outstanding compliance to CPAP reduced fasting blood glucose in patients with OSA. Longitudinally, higher levels of therapeutic adherence may affect the rate of incident impaired fasting glucose, prediabetes, and T2DM, despite the observed weight gains. A commentary on this article appears in this issue on page 365.

Cognitive Performance at Late Adolescence and the Risk for Impaired Fasting Glucose Among Young Adults

Although dysglycemia is a risk factor for cognitive decline, it is unknown whether cognitive performance among young and apparently healthy adults affect the risk for impaired fasting glucose (IFG). This study aimed to characterize the relationship between cognitive function and the risk for IFG among young adults. This was a retrospective cohort study utilizing data collected at pre-military recruitment assessments with information collected at the screening center of Israeli Army Medical Corps. Normoglycemic adults (n = 17 348) (free of IFG and diabetes; mean age 31.0 ± 5.6 y; 87% men) of the Metabolic Lifestyle and Nutrition Assessment in Young Adults (MELANY) cohort with data regarding their General Intelligence Score (GIS), a comprehensive measure of cognitive function, at age 17 y. Fasting plasma glucose was assessed every 3-5 y at scheduled visits. Cox proportional hazards models were applied. The main outcome of the study was incident IFG (≥ 100 mg/dL and <126 mg/dL) at scheduled visits. During a median followup of 6.6 y, 1478 cases of IFG were recorded (1402 men). After adjustment for age and sex, participants in the lowest GIS category had a 1.9-fold greater risk for incident IFG compared with those in the highest GIS category. In multivariable analysis adjusted for age, sex, body mass index, fasting plasma glucose, family history of diabetes, country of origin, socioeconomic status, education, physical activity, smoking status, alcohol consumption, breakfast consumption, triglyceride level, white blood cell count, the risk for IFG was nearly doubled in the lowest GIS category compared with the highest GIS category (hazard ratio, 1.8; 95% confidence interval, 1.4-2.3; P < .001). These results persisted when GIS was treated as a continuous variable and when the model was adjusted also for body mass index at the end of followup. This study demonstrates that lower cognitive function at late adolescence is independently associated with an elevated risk IFG in both men and women.

Long-term weight change: association with impaired glucose metabolism in young Austrian adults.

Little is known about the associations between long-term weight change and the natural history of impaired fasting glucose (IFG) in young adults. We investigated the association between long-term body mass index (BMI) change and the risk of IFG using data of 24,930 20- to 40-year-old participants from the Vorarlberg Health Monitoring and Promotion Program (VHM&PP) cohort. Poisson models were applied to estimate the 10-year risk for new development of IFG (≥5.6 mmol/L), and persistence of IFG. Over 10 years, most men (68.2%) and women (70.0%) stayed within their initial BMI category. The risk for incident IFG was highest for men and women with persisting obesity (37.4% and 24.1%) and lowest with persisting normal weight (15.7% and 9.3%). Men transitioning from normal to overweight increased their risk of incident IFG by factor 1.45 (95%-CI: 1.31, 1.62), women by 1.70 (95%-CI: 1.50, 1.93), whereas transitioning from overweight to normal weight decreased the risk in men by 0.69 (95%-CI: 0.53, 0.90) and 0.94 (95%-CI: 0.66, 1.33) in women. Relative risks for men and women transitioning from obesity to overweight were 0.58 and 0.44, respectively. In conclusion, 10 year weight increase was associated with an increased IFG risk, weight decrease with a decreased risk of IFG in young adults.

Age at Menarche and Cardiometabolic Risk in Adulthood: The Coronary Artery Risk Development in Young Adults Study

To examine the association of menarche timing with cardiometabolic risk factors into early to mid-adulthood, comparing African American and White women. Analyses included 2583 women (African American = 1333; White = 1250) from the Coronary Artery Risk Development in Young Adults cohort study over 25 years of follow-up (1985-2011). Outcomes included type 2 diabetes, metabolic syndrome, adiposity, glucose, insulin, blood pressure, and blood lipids. Cox models or repeated measures linear regression models estimated the association between age at menarche and the outcomes. Each 1-year earlier age at menarche was associated with higher mean body mass index among African American (0.88 ± 0.12 kg/m(2), P < .0001) and White (0.89 ± 0.10 kg/m(2), P < .0001) women. After body mass index adjustment, each 1-year earlier age at menarche was associated with higher triglycerides (2.26 ± 0.68 mg/dL, P = .001) and glucose (0.34 ± 0.11 mg/dL, P = .002), and greater risk for incident impaired fasting glucose (hazard ratio = 1.13, 95% CI 1.04-1.20) and metabolic syndrome (hazard ratio 1.19, 95% CI 1.11-1.26) among White women only. Excess adiposity associated with earlier menarche is sustained through mid-adulthood, and primarily drives higher cardiometabolic risk factor levels. However, White women with earlier menarche had increased risk of a number of insulin-resistance related conditions independent of adiposity. The cardiometabolic impact of earlier menarche was weaker in African American women despite higher average adiposity. Weight maintenance would likely reduce but may not completely eliminate the elevated cardiometabolic risk of earlier menarche.

Cross-sectional And Longitudinal Associations Between Objectively-measured Sedentary Time And Metabolic Disease

Mounting evidence suggests that prolonged sedentary time (ST), at the expense of both light-intensity and moderate-to-vigorous-intensity physical activity (MVPA), might be contributing to the diabetes (DM) epidemic. However, most studies have been cross-sectional and few have objectively measured ST. PURPOSE: To evaluate cross-sectional and 5-year longitudinal relationships between ST and metabolic parameters (fasting glucose, insulin, HOMA-IR, and HbA1c) and outcomes (impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and DM). METHODS: This was an analysis of 2,027 CARDIA participants (aged 38-50 years, 57% female, mean BMI of 29.0 ± 7.0 kg/m2) with accelerometry data (≥4 days with ≥10 hr/day) at the year 20 exam (2005-2006). Metabolic variables were assessed concurrently and 5 years later. IFG, IGT, and DM were defined by established cut points. Linear regression evaluated cross-sectional (including DM at baseline) and longitudinal (excluding DM at baseline) associations between ST (hr/day) and continuous metabolic parameters. Logistic regression evaluated relationships between categories of ST and prevalent or incident IFG, IGT, and DM. Adjustment included accelerometer wear time, demographics, smoking, alcohol, and MVPA. Analyses were repeated using % of wear time that was sedentary (%ST) or the ratio of sedentary vs. light activity (S/L ratio). RESULTS: Average ST was 8.1 ± 1.7 hr/day which corresponded to 55 ± 10% of wear time. Cross-sectionally, each additional hr/day of ST was associated with a 3% higher fasting insulin and HOMA-IR (both p<0.01), but not fasting glucose or HbA1c (both p>0.2). ST was not related to 5-year changes in these parameters. Being in the highest (≥10 hr/day) vs. lowest (<6 hr/day) ST category was associated with an OR=3.80 (p<0.001) for DM and an OR=2.47 (p=0.04) for IGT at baseline. ST was not associated with prevalent IFG or 5-year IFG, IGT, or DM incidence (all p>0.1). Use of %ST or S/L ratio produced consistent relationships with metabolic parameters and outcomes. CONCLUSIONS: ST was independently related to fasting insulin, HOMA-IR, prevalent DM and IGT, but did not predict 5-year changes or 5-year incidence of metabolic outcomes. Longer follow-up and repeated measures of ST could further clarify the temporal relationship between ST and metabolic disease.

Resting heart rate and the risk of developing impaired fasting glucose and diabetes: the Kailuan prospective study.

To investigate the association between resting heart rate and the risk of developing impaired fasting glucose (IFG), diabetes and conversion from IFG to diabetes. The prospective analysis included 73,357 participants of the Kailuan cohort (57,719 men and 15,638 women). Resting heart rate was measured via electrocardiogram in 2006. Incident diabetes was defined as either the fasting blood glucose (FBG) ≥ 7.0 mmol/l or new active use of diabetes medications during the 4-year follow-up period. IFG was defined as a FBG between 5.6 and 6.9 mmol/l. A meta-analysis including seven published prospective studies focused on heart rate and diabetes risk, and our current study was then conducted using random-effects models. During 4 years of follow-up, 17,463 incident IFG cases and 4,649 incident diabetes cases were identified. The corresponding adjusted hazard ratios (HRs) for each 10 beats/min increase in heart rate were 1.23 [95% confidence interval (CI): 1.19, 1.27] for incident diabetes, 1.11 (95% CI: 1.09, 1.13) for incident IFG and 1.13 (95% CI: 1.08, 1.17) for IFG to diabetes conversion. The risks of incident IFG and diabetes were significantly higher among participants aged < 50 years than those aged ≥ 50 years (P-interaction < 0.02 for both). A meta-analysis confirmed the positive association between resting heart rate and diabetes risk (pooled HR for the highest vs lowest heart rate quintile = 1.59, 95% CI:1.27, 2.00; n = 8). Faster resting heart rate is associated with higher risk of developing IFG and diabetes, suggesting that heart rate could be used to identify individuals with a higher future risk of diabetes.

Smoking cessation and the risk of diabetes mellitus and impaired fasting glucose: three-year outcomes after a quit attempt.

Weight gain after smoking cessation may increase diabetes mellitus and impaired fasting glucose (IFG) risk. This study evaluated associations between smoking cessation and continued smoking with incident diabetes and IFG three years after a quit attempt. The 1504 smokers (58% female) were mean (standard deviation) 44.7 (11.1) years old and smoked 21.4 (8.9) cigarettes/day. Of 914 participants with year 3 data, the 238 abstainers had greater weight gain, increase in waist circumference, and increase in fasting glucose levels than the 676 continuing smokers (p≤0.008). In univariate analyses, Year 3 abstinence was associated with incident diabetes (OR = 2.60, 95% CI 1.44–4.67, p = .002; 4.3% absolute excess) and IFG (OR = 2.43, 95% CI 1.74–3.41, p<0.0001; 15.6% absolute excess). In multivariate analyses, incident diabetes was associated independently with older age (p = 0.0002), higher baseline body weight (p = 0.021), weight gain (p = 0.023), baseline smoking rate (p = 0.008), baseline IFG (p<0.0001), and baseline hemoglobin A1C (all p<0.0001). Smoking more at baseline predicted incident diabetes among eventual abstainers (p<0.0001); weighing more at baseline predicted incident diabetes among continuing smokers (p = 0.0004). Quitting smoking is associated with increased diabetes and IFG risk. Independent risk factors include older age, baseline body weight, baseline glycemic status, and heavier pre-quit smoking. These findings may help target smokers for interventions to prevent dysglycemia.Trial RegistrationClinicaltrials.gov NCT00332644

Abstract MP50: Metabolic Predictors of Type 2 Diabetes in American Indians: The Strong Heart Family Study

Background: Type 2 diabetes (T2D) is characterized by profound metabolic abnormalities. Current glycemic indicators have limitations in identifying early metabolic alterations. Objective: To identify novel metabolic predictors of T2D in American Indians participating in the Strong Heart Family Study. Methods: Among 2,129 participants who had normal fasting glucose (NFG) at baseline (2001-2003) and also attended clinical examination after 5-year follow-up (2006-2009), 142 developed incident T2D, 514 developed incident impaired fasting glucose (IFG), and 1,473 remained to be NFG. The current analysis included all incident cases of T2D (n=142), 146 incident IFG (randomly selected from 514 participants with incident IFG) and 144 NFG (randomly selected from 1,473 participants with NFG at both visits). Baseline plasma metabolites were detected by high-resolution LC/MS. The prospective association of each metabolite with risk for T2D or IFG was investigated using weighted Cox’s hazard regression with frailty model, adjusting for sex, study center, age, BMI, renal function, fasting glucose and fasting insulin at baseline. Multiple testing was corrected by Bonferroni correction (significance level 2.8х10-6). Results: Thirty-nine metabolites from several major fuel sources, including sugar amino acids, amino acids, lipids, alkaloids, alkylamines, carboxylic acids, steroids, and aromatic homomonocylic/heteropolycyclic compounds, significantly predicted future risk of T2D (10 metabolites), or IFG (27 metabolites), or both (2 metabolites). Of these, N1,N12-diacetylspermine and betanidin, respectively, were the strongest predictors for increased (HR=4.59, 95% CI, 2.55-8.24, P=3.49х10-7) and decreased risk of T2D (HR=0.38, 95% CI, 0.28-0.52, P=4.64х10-10). The corresponding strongest predictors for IFG were hexanoic acid (HR=2.34, 95% CI, 1.84-2.98, P=3.15х10-12) and l-palmitoylcarnitine (HR=0.26, 95% CI, 0.18-0.37, P=1.14х10-13), respectively. Two metabolites, betanidin and dopamine, significantly predicted future onset of both T2D (HR=0.38, 95% CI, 0.28,0.52, P=4.64х10-10 for betanidin; HR=2.48, 95% CI, 1.71-3.58, P=1.42х10-6 for dopamine) and IFG (HR=0.52, 95% CI, 0.43,0.62, P=1.35х10-12 for betanidin; HR=2.24, 95% CI, 1.73,2.89, P=5.79х10-10 for dopamine). Multiple unknown compounds were also independently associated with risk of T2D, IFG or both. Conclusions: This study identifies both novel and known metabolic alterations associated with risk of diabetes in American Indians, an ethnic group suffering from disproportionately high rates of T2D. The incomplete overlapping of metabolic profiles between T2D and IFG highlights differential metabolic states of diabetes development. Our results not only provide novel insights in disease pathogenesis but also valuable data on potential new targets for risk prediction and treatment.

The impact of glucose disorders on cognition and brain volumes in the elderly: the Sydney Memory and Ageing Study

Type 2 diabetes predicts accelerated cognitive decline and brain atrophy. We hypothesized that impaired fasting glucose (IFG) and incident glucose disorders have detrimental effects on global cognition and brain volume. We further hypothesized that metabolic and inflammatory derangements accompanying hyperglycaemia contribute to change in brain structure and function. This was a longitudinal study of a community-dwelling elderly cohort with neuropsychological testing (n = 880) and brain volumes by magnetic resonance imaging (n = 312) measured at baseline and 2 years. Primary outcomes were global cognition and total brain volume. Secondary outcomes were cognitive domains (processing speed, memory, language, visuospatial and executive function) and brain volumes (hippocampal, parahippocampal, precuneus and frontal lobe). Participants were categorised as normal, impaired fasting glucose at both assessments (stable IFG), baseline diabetes or incident glucose disorders (incident diabetes or IFG at 2 years). Measures included inflammatory cytokines and oxidative metabolites. Covariates were age, sex, education, non-English speaking background, smoking, blood pressure, lipid-lowering or antihypertensive medications, mood score, apolipoprotein E genotype and baseline cognition or brain volume. Participants with incident glucose disorders had greater decline in global cognition and visuospatial function compared to normal, similar to that observed in baseline diabetes. Homocysteine was independently associated with the observed effect of diabetes on executive function. Apolipoprotein E genotype did not influence the observed effects of diabetes on cognition. Incident glucose disorders and diabetes were also associated with greater 2-year decline in total brain volume, compared to normal (40.0 ± 4.2 vs. 46.7 ± 5.7mm(3) vs. 18.1 ± 6.2, respectively, p < 0.005). Stable IFG did not show greater decline in global cognition or brain volumes compared to normal. Incident glucose disorders, like diabetes, are associated with accelerated decline in global cognition and brain volumes in non-demented elderly, whereas stable IFG is not. Preventing deterioration in glucose metabolism in the elderly may help preserve brain structure and function.