2-hour Postchallenge Glucose Research Articles

Assessing the causal association of pregnancy complications with diabetes and cardiovascular disease.

To the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases. A two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot. Genetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1-1.01, P<0.0001), yet correlated with lower 2-hour post-challenge glucose levels (OR=0.89, 95% CI=0.82-0.97, P=0.006). Genetic liability for pregnancy with abortive outcomes indicated decreased fasting insulin levels (OR=0.97, 95% CI=0.95-0.99, P=0.02), but potentially elevated glycated hemoglobin levels (OR=1.02, 95% CI=1.01-1.04, P=0.01). Additionally, hypertensive disorders in pregnancy was tentatively linked to increased risks of stroke (OR=1.11, 95% CI=1.04-1.18, P=0.002) and CHD (OR=1.3, 95% CI=1.2-1.4, P=3.11E-11). Gestational hypertension might have a potential causal association with CHD (OR=1.11, 95% CI=1.01-1.22, P=0.04). No causal associations were observed between preterm birth and diabetes, stroke, or CHD. The findings of this study provide genetic evidence that gestational diabetes, pregnancy with abortive outcomes, and hypertensive disorders in pregnancy may serve as early indicators for metabolic and cardiovascular risks. These insights are pivotal for the development of targeted screening and preventive strategies.

The difference between 2-hour post-challenge and fasting plasma glucose associates with the risk of cardiovascular disease in a normoglycemic population: the Tehran lipid and glucose study

BackgroundElevated fasting plasma glucose (FPG) and 2-hour post-challenge glucose (2hPG) levels are known to be independent risk factors for cardiovascular disease (CVD). However, there is limited data on the association of the difference between these measures and the risk of CVD. This study aims to investigate this association in normoglycemic Iranian adults, particularly in those with low-normal FPG levels.MethodsThis prospective cohort study included 4,594 30-65-year-old participants from the Tehran Lipid and Glucose Study. Using multivariable Cox proportional hazards regression models adjusting for age, sex, body mass index, hypertension, hypercholesterolemia, smoking, education level and FPG, hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated for the association between 2hPG-FPG, both as continuous and categorical variables, and the CVD risk. Analyses of receiver operating characteristic curves were undertaken to determine the optimal 2hPG-FPG cut-off value.ResultsDuring a median of 17.9 years of follow-up, 459 CVD events occurred. A one-unit increase in 2hPG-FPG was significantly associated with an elevated risk of cardiovascular disease in both normoglycemic (HR 1.10, 95% CI (1.01–1.19)) and low-normal FPG individuals (HR 1.16, 95% CI (1.04–1.30)); this association resisted adjustment for Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) among normoglycemic individuals. However, those with 2hPG levels greater than FPG levels had a non-significant increased risk of incident CVD compared to those with 2hPG levels of less than or equal to FPG, with corresponding HR values of 1.18 (95% CI: 0.95–1.46) in normoglycemic and 1.32 (95% CI: 0.98–1.79) in low-normal FPG, respectively. For incident CVD, the optimal cut-off value for the 2hPG-FPG was found to be 1.06 mmol/L, which was applicable for both normoglycemic and low FPG populations; using this criterion, the corresponding risks for incident CVD were 1.36 (95% CI: 1.12–1.64) and 1.57 (95% CI: 1.22–2.03), respectively.ConclusionsThe difference between 2hPG and FPG levels within the normoglycemic range is related to an increased risk of CVD, an issue that was independent of HOMA-IR. A cut-off point for 2hPG-FPG > 1.06 mmol/L may stratify persons at higher risk. These findings were particularly notable in those with low-normal FPG.

Can earlier biomarker measurements explain a treatment effect on diabetes incidence? A robust comparison of five surrogate markers

IntroductionWe measured and compared five individual surrogate markers—change from baseline to 1 year after randomization in hemoglobin A1c (HbA1c), fasting glucose, 2-hour postchallenge glucose, triglyceride–glucose index (TyG) index, and homeostatic...

Postprandial Dynamics of Proglucagon Cleavage Products and Their Relation to Metabolic Health.

IntroductionWhile oral glucose ingestion typically leads to a decrease in circulating glucagon levels, a substantial number of persons display stable or rising glucagon concentrations when assessed by radioimmunoassay (RIA). However, these assays show cross-reactivity to other proglucagon cleavage products. Recently, more specific assays became available, therefore we systematically assessed glucagon and other proglucagon cleavage products and their relation to metabolic health.Research Design and MethodsWe used samples from 52 oral glucose tolerance tests (OGTT) that were randomly selected from persons with different categories of glucose tolerance in an extensively phenotyped study cohort.ResultsGlucagon concentrations quantified with RIA were non-suppressed at 2 hours of the OGTT in 36% of the samples. Non-suppressors showed lower fasting glucagon levels compared to suppressors (p=0.011). Similar to RIA measurements, ELISA-derived fasting glucagon was lower in non-suppressors (p<0.001). Glucagon 1-61 as well as glicentin and GLP-1 kinetics were significantly different between suppressors and non-suppressors (p=0.004, p=0.002, p=0.008 respectively) with higher concentrations of all three hormones in non-suppressors. Levels of insulin, C-peptide, and free fatty acids were comparable between groups. Non-suppressors were leaner and had lower plasma glucose concentrations (p=0.03 and p=0.047, respectively). Despite comparable liver fat content and insulin sensitivity (p≥0.3), they had lower 2-hour post-challenge glucose (p=0.01).ConclusionsGlucagon 1-61, glicentin and GLP-1 partially account for RIA-derived glucagon measurements due to cross-reactivity of the assay. However, this contribution is small, since the investigated proglucagon cleavage products contribute less than 10% to the variation in RIA measured glucagon. Altered glucagon levels and higher post-challenge incretins are associated with a healthier metabolic phenotype.

Behavioural interventions to promote physical activity in a multiethnic population at high risk of diabetes: PROPELS three-arm RCT

Type 2 diabetes is a leading cause of mortality globally and accounts for significant health resource expenditure. Increased physical activity can reduce the risk of diabetes. However, the longer-term clinical effectiveness and cost-effectiveness of physical activity interventions in those at high risk of type 2 diabetes is unknown. To investigate whether or not Walking Away from Diabetes (Walking Away) - a low-resource, 3-hour group-based behavioural intervention designed to promote physical activity through pedometer use in those with prediabetes - leads to sustained increases in physical activity when delivered with and without an integrated mobile health intervention compared with control. Three-arm, parallel-group, pragmatic, superiority randomised controlled trial with follow-up conducted at 12 and 48 months. Primary care and the community. Adults whose primary care record included a prediabetic blood glucose measurement recorded within the past 5 years [HbA1c ≥ 42 mmol/mol (6.0%), < 48 mmol/mol (6.5%) mmol/mol; fasting glucose ≥ 5.5 mmol/l, < 7.0 mmol/l; or 2-hour post-challenge glucose ≥ 7.8 mmol/l, < 11.1 mmol/l] were recruited between December 2013 and February 2015. Data collection was completed in July 2019. Participants were randomised (1 : 1 : 1) using a web-based tool to (1) control (information leaflet), (2) Walking Away with annual group-based support or (3) Walking Away Plus (comprising Walking Away, annual group-based support and a mobile health intervention that provided automated, individually tailored text messages to prompt pedometer use and goal-setting and provide feedback, in addition to biannual telephone calls). Participants and data collectors were not blinded; however, the staff who processed the accelerometer data were blinded to allocation. The primary outcome was accelerometer-measured ambulatory activity (steps per day) at 48 months. Other objective and self-reported measures of physical activity were also assessed. A total of 1366 individuals were randomised (median age 61 years, median body mass index 28.4 kg/m2, median ambulatory activity 6638 steps per day, women 49%, black and minority ethnicity 28%). Accelerometer data were available for 1017 (74%) and 993 (73%) individuals at 12 and 48 months, respectively. The primary outcome assessment at 48 months found no differences in ambulatory activity compared with control in either group (Walking Away Plus: 121 steps per day, 97.5% confidence interval -290 to 532 steps per day; Walking Away: 91 steps per day, 97.5% confidence interval -282 to 463). This was consistent across ethnic groups. At the intermediate 12-month assessment, the Walking Away Plus group had increased their ambulatory activity by 547 (97.5% confidence interval 211 to 882) steps per day compared with control and were 1.61 (97.5% confidence interval 1.05 to 2.45) times more likely to achieve 150 minutes per week of objectively assessed unbouted moderate to vigorous physical activity. In the Walking Away group, there were no differences compared with control at 12 months. Secondary anthropometric, biomechanical and mental health outcomes were unaltered in either intervention study arm compared with control at 12 or 48 months, with the exception of small, but sustained, reductions in body weight in the Walking Away study arm (≈ 1 kg) at the 12- and 48-month follow-ups. Lifetime cost-effectiveness modelling suggested that usual care had the highest probability of being cost-effective at a threshold of £20,000 per quality-adjusted life-year. Of 50 serious adverse events, only one (myocardial infarction) was deemed possibly related to the intervention and led to the withdrawal of the participant from the study. Loss to follow-up, although the results were unaltered when missing data were replaced using multiple imputation. Combining a physical activity intervention with text messaging and telephone support resulted in modest, but clinically meaningful, changes in physical activity at 12 months, but the changes were not sustained at 48 months. Future research is needed to investigate which intervention types, components and features can help to maintain physical activity behaviour change over the longer term. Current Controlled Trials ISRCTN83465245. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 77. See the NIHR Journals Library website for further project information.

Association of EDARV370A with breast density and metabolic syndrome in Latinos.

The ectodysplasin receptor (EDAR) is a tumor necrosis factor receptor (TNF) superfamily member. A substitution in an exon of EDAR at position 370 (EDARV370A) creates a gain of function mutant present at high frequencies in Asian and Indigenous American populations but absent in others. Its frequency is intermediate in populations of Mexican ancestry. EDAR regulates the development of ectodermal tissues, including mammary ducts. Obesity and type 2 diabetes mellitus are prevalent in people with Indigenous and Latino ancestry. Latino patients also have altered prevalence and presentation of breast cancer. It is unknown whether EDARV370A might connect these phenomena. The goals of this study were to determine 1) whether EDARV370A is associated with metabolic phenotypes and 2) if there is altered breast anatomy in women carrying EDARV370A. Participants were from two Latino cohorts, the Arizona Insulin Resistance (AIR) registry and Sangre por Salud (SPS) biobank. The frequency of EDARV370A was 47% in the Latino cohorts. In the AIR registry, carriers of EDARV370A (GG homozygous) had significantly (p < 0.05) higher plasma triglycerides, VLDL, ALT, 2-hour post-challenge glucose, and a higher prevalence of prediabetes/diabetes. In a subset of the AIR registry, serum levels of ectodysplasin A2 (EDA-A2) also were associated with HbA1c and prediabetes (p < 0.05). For the SPS biobank, participants that were carriers of EDARV370A had lower breast density and higher HbA1c (both p < 0.05). The significant associations with measures of glycemia remained when the cohorts were combined. We conclude that EDARV370A is associated with characteristics of the metabolic syndrome and breast density in Latinos.

ASSOCIATION OF SLEEP TIME WITH DIABETES MELLITUS AND IMPAIRED GLUCOSE TOLERANCE

Introduction: In the present study, we was examined the relation of self-reported usual sleep time to prevalence DM and IGT in a large hospital based sample of middle-aged and older adults.&#x0D; Methods: Cross-sectional study was conducted on 625 patients between age group 18-60 yrs and both sex. Usual sleep time was obtained by standardized questionnaire. Diabetes mellitus was defined as a serum glucose level of 126 mg/dL or more fasting or 200 mg/dL or more 2 hours following standard oral glucose challenge or medication use for DM. Impaired glucose tolerance was defined as a 2-hour post challenge glucose level of 140 mg/dL or more and less than 200 mg/dL. The relation of sleep time to DM and IGT was examined using categorical logistic regression.&#x0D; Results: 49.28% subjects sugar level was more than 200 mg/dl and 13.72% subjects sugar level less than 140 mg/dl. The association between sleeping time and blood sugar level was found statistically significant. The association between Sleeping time and blood sugar level was found statistically significant&#x0D; Conclusion: A sleep duration of 6 hours or less or 9 hours or more is associated with increased prevalence of DM and IGT. Because this effect was present in subjects without insomnia, voluntary sleep restriction may contribute to the large public health burden of DM.&#x0D; Keywords: DM, IGT, Hb1Ac

Abstract P133: Added Sugar Intake Is Associated With Greater 2-hour Glucose And Lower Muscle Quality In Adults Free Of Diabetes: Coronary Artery Risk Development In Young Adults Study

Background: - Excess added sugar (AS) intake was shown to promote insulin resistance in skeletal muscle in animal studies, while sugar sweetened beverage (SSB) intake was associated with insulin resistance and lipids in skeletal muscle in humans. However, SSBs account for only 40% of AS intake. US adults consume excessive AS from foods and beverages relative to the 2015-2020 Dietary Guidelines recommendation which limit AS intake to &lt;10% of energy intake per day. We evaluated the hypothesis that AS intake is adversely associated with glucose metabolism, insulin, and lean muscle attenuation (MA) in Black and white men and women aged 18-30 years at baseline (Y0). Methods: - After exclusions for diabetes defined as MD diagnosis, insulin or oral agent use, fasting glucose ≥126 mg/dL, or HbA1c ≥6.5%, outlying energy intake, and missing 2-hour glucose, 2,016 adults were included in the analyses. Dietary intake was assessed by Diet History at Y0, Y7 and Y20. At Y25 follow-up, participants free of diabetes underwent a fasting blood draw for glucose, insulin, and triglycerides, an oral glucose tolerance test for 2-hour post-challenge glucose, and an abdominal CT scan for lean MA (an indicator of muscle quality). AS intake was averaged across Y0, Y7, and Y20 and divided into tertiles. General linear regression models estimated the associations across tertiles of AS intake with 2-hour glucose, fasting glucose, insulin, and triglycerides, and lean MA adjusted for potential confounders. Results: - AS intake (Table) was positively associated with 2-hour glucose and fasting insulin and triglycerides (p trend =0.004, 0.04, and 0.01, respectively) and inversely associated with lean MA (p trend =0.02). AS intake was not associated with fasting glucose (p trend =0.57). Conclusions: - Among adults free of diabetes, greater long-term AS intake was associated with higher 2-hour glucose and fasting insulin and triglycerides, and lower muscle quality. Our findings are consistent with the US Dietary Guidelines for Americans recommendation to limit AS intake.

Impaired fasting glucose levels in overweight or obese subjects for screening of type 2 diabetes in Korea.

Background/AimsWe examined the concordance rate among fasting plasma glucose (FPG), 2-hour post-challenge glucose (2hr PG), and hemoglobin A1c (HbA1c) in the diagnosis of diabetes in a population with a high-risk for type 2 diabetes mellitus (T2DM) in Korea.MethodsAmong the participants from the Korean Diabetes Prevention Study, individuals with FPG ≥ 100 mg/dL, body mass index (BMI) ≥ 23.0 kg/m2, and no previous history of T2DM were consecutively enrolled after a 75 g glucose tolerance test. We analyzed the differences in the clinical characteristics in subjects with stage 1 (FPG, 100 to 109 mg/dL) and stage 2 (FPG, 110 to 125 mg/dL) impaired fasting glucose (IFG).ResultsOf 1,637 participants, 27.2% had T2DM and 59.3% had IFG and/or impaired glucose tolerance (IGT). The mean age was 55.0 ± 8.1 years and the mean BMI was 26.3 ± 2.7 kg/m2. Based on FPG criteria, 515 (31.4%) and 352 (21.5%) subjects were classified as having stage 1 and stage 2 IFG, respectively. The 19.0% of stage 1 and 43.5% of stage 2 subjects showed 2hr PG levels in the diabetic range. Even for those in the normal FPG range, 63 (9.5%) participants showed a 2hr PG level of ≥ 200 mg/dL. Of 446 subjects with newly-diagnosed diabetes, 340 (76.2%) showed FPG levels < 126 mg/dL.ConclusionsThe oral glucose tolerance test should be actively considered for Korean adults who are overweight or obese with the IFG range (FPG, 100 to 125 mg/ dL) to allow for early detection of diabetes and prompt intervention.

Hyperhomocysteinemia as a Metabolic Risk Factor for Glucose Intolerance Among High-Risk Groups of Chinese Adults.

BackgroundImpaired glucose tolerance (IGT) is characterized by insulin resistance and causes atherosclerosis. Hyperhomocysteinemia is associated with insulin resistance and predicts cardiovascular diseases. In this study, we assessed the possible association between homocysteine and IGT.Material/MethodsThis was a cross-sectional study of 118 consecutive subjects with IGT (IGT group) and 128 consecutive subjects with normal glucose tolerance (NGT group). Homocysteine and clinical characteristics were measured.ResultsThe IGT group had higher homocysteine than the NGT group [18.00 (14.00, 22.25) vs. 12.50 (9.00, 15.00) μmol/L, p<0.001]. Homocysteine was positively associated with body mass index (BMI) (r=0.178, p=0.005), triglycerides (r=0.306, p<0.001), fasting blood glucose (FBG) (r=0.312, p<0.001), 2-hour postchallenge glucose (2hPG) (r=0.363, p<0.001), fasting insulin (FINS) (r=0.655, p<0.001), and homeostasis model assessment for insulin resistance (HOMA-IR) (r=0.643, p<0.001), and was negatively correlated with high-density lipoprotein cholesterol (HDL-C) (r=−0.250, p<0.001). After controlling for confounders, hyperinsulinemia (β=7.430, p<0.001) was independently related to hyperhomocysteinemia. In a logistic regression analysis, high triglycerides (OR=1.177, p<0.001) and homocysteine (OR=1.508, p=0.007), and low HDL-C (OR=0.315, p=0.026) were associated with IGT.ConclusionsPatients with IGT have higher homocysteine levels compared with subjects with normal glucose tolerance, and hyperhomocysteinemia might be correlated with IGT.

Associations of reallocating sitting time into standing or stepping with glucose, insulin and insulin sensitivity: a cross-sectional analysis of adults at risk of type 2 diabetes

ObjectiveTo quantify associations between sitting time and glucose, insulin and insulin sensitivity by considering reallocation of time into standing or stepping.DesignCross-sectional.SettingLeicestershire, UK, 2013.ParticipantsAdults aged 30–75 years at high risk of...

Insulin secretagogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus.

Insulin secretagogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus.

Do glycemic marker levels vary by race? Differing results from a cross-sectional analysis of individuals with and without diagnosed diabetes

ObjectiveIt is well known that A1c varies by race. However, racial differences in other biomarkers of hyperglycemia are less well characterized. The objective of this study was to determine whether...

Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep

Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state-dependent sympathetic activation and/or degree of hypoxemia. To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. A cross-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea-hypopnea index in REM (AHIREM) and non-REM sleep (AHINREM), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHIREM and AHINREM with fasting and post-prandial glucose levels and HOMA-IR. AHIREM and AHINREM were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHIREM was only associated with HOMA-IR (β = 0.04; 95% CI, 0.1-0.07; P = 0.01), whereas AHINREM was only associated with fasting (β = 0.93; 95% CI, 0.14-1.72; P = 0.02) and post-prandial glucose levels (β = 3.0; 95% CI, 0.5-5.5; P = 0.02). AHIREM is associated with insulin resistance but not with fasting glycemia or glucose intolerance.

The impact of obstructive sleep apnea hypopnea syndrome on glucose metabolism

To study the influence of obstructive sleep apnea hypopnea syndrome (OSAHS) on glucose metabolism and comprehensively analyze its related factors. A total of 180 snoring patients were recruited in Sleep Disorder Center of Nanfang Hospital of Southern Medical University between January 2010 to June 2011. There were 140 patients with OSAHS and 40 subjects without OSAHS. All patients underwent both a full polysomnography (PSG) and plasma glucose measure, including fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT). The FPG, 1-hour post-challenge glucose (1 hPG) and 2-hour post-challenge glucose (2 hPG) were respectively compared in patients with different apnea hypopnea index (AHI), the lowest saturation of pulse oximetry (SpO₂) and sleep architecture. The incidence of glucose metabolism disorders was higher in patients with OSAHS than that of those without (diabetes: 21.4% vs 5.0%; prediabetes: 34.3% vs 25.0%). The FPG, 1 hPG and 2 hPG in patients with different AHI was significantly different respectively (all P < 0.01), so as in patients with different lowest oxygen saturation (all P < 0.01). Post-load glucose levels of patients with different AHI were still significantly different after adjustment for neck circumference (1 hPG: P = 0.004; 2 hPG: P = 0.048). FPG, 1 hPG and 2 hPG were associated with AHI (r = 0.167, 0.277, 0.196, all P < 0.05), mean SpO₂(r = -0.154, -0.214, -0.182, all P < 0.05) and the lowest SpO₂(r = -0.224, -0.231, -0.159, all P < 0.05); While FPG, 1 hPG and 2 hPG were not significantly associated with N1 + N2, N3 and rapid eye movement (REM) sleeps (all P > 0.05). The risk of glucose metabolism disorders increased with the severity of OSAHS. Compared with fasting glucose, post-load glucose was more affected by OSAHS independent of obesity. Compared with sleep architecture or sleep efficiency, glucose metabolism disorders seem to be associated with hypoxia caused by OSAHS.

Effect of the PPARG2 Pro12Ala Polymorphism on Associations of Physical Activity and Sedentary Time with Markers of Insulin Sensitivity in Those with an Elevated Risk of Type 2 Diabetes.

BackgroundPeroxisome proliferator-activated receptor gamma (PPARγ) is an important regulator of metabolic health and a common polymorphism in the PPAR-γ2 gene (PPARG2) may modify associations between lifestyle behaviour and health.ObjectiveTo investigate whether the PPARG2 Pro12Ala genotype modifies the associations of sedentary behaviour and moderate-to-vigorous intensity physical activity (MVPA) with common measures of insulin sensitivity.MethodsParticipants with a high risk of impaired glucose regulation were recruited, United Kingdom, 2010-2011. Sedentary and MVPA time were objectively measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated using Matsuda-ISI and HOMA-IS. DNA was extracted from whole blood. Linear regression examined associations of sedentary time and MVPA with insulin sensitivity and examined interactions by PPARG2 Pro12Ala genotype.Results541 subjects were included (average age = 65 years, female = 33%); 18% carried the Ala12 allele. Both sedentary time and MVPA were strongly associated with HOMA-IS and Matsuda-ISI after adjustment for age, sex, ethnicity, medication, smoking status and accelerometer wear time. After further adjustment for each other and BMI, only associations with Matsuda-ISI were maintained. Every 30 minute difference in sedentary time was inversely associated with a 4% (0, 8%; p = 0.043) difference in Matsuda-ISI, whereas every 30 minutes in MVPA was positively associated with a 13% (0, 26%; p = 0.048) difference. The association of MVPA with Matsuda-ISI was modified by genotype (p = 0.005) and only maintained in Ala12 allele carriers. Conversely, sedentary time was not modified by genotype and remained inversely associated with insulin sensitivity in Pro12 allele homozygotes.ConclusionThe association of MVPA with Matsuda-ISI was modified by PPARG2 Pro12Ala genotype with significant associations only observed in the 18% of the population who carried the Ala12 allele, whereas associations with sedentary time were unaffected.

Objectively measured sedentary time and associations with insulin sensitivity: Importance of reallocating sedentary time to physical activity

ObjectiveThe aim of this study is to quantify associations between objectively measured sedentary time and markers of insulin sensitivity by considering allocation into light-intensity physical activity or moderate- to vigorous-intensity physical activity (MVPA). MethodsParticipants with an increased risk of impaired glucose regulation (IGR) were recruited (Leicestershire, United Kingdom, 2010–2011). Sedentary, light-intensity physical activity and MVPA time were measured using accelerometers. Fasting and 2-hour post-challenge insulin and glucose were assessed; insulin sensitivity was calculated by HOMA-IS and Matsuda-ISI. Isotemporal substitution regression models were used. Data were analysed in 2014. Results508 participants were included (average age=65years, female=34%). Reallocating 30min of sedentary time into light-intensity physical activity was associated a 5% (95% CI 1, 9%; p=0.024) difference in Matsuda-ISI after adjustment for measured confounding variables. Reallocation into MVPA was associated with a 15% (7, 25%; p<0.001) difference in HOMA-IS and 18% (8, 28%; p<0.001) difference in Matsuda-ISI. Results for light-intensity physical activity were modified by IGR status with stronger associations seen in those with IGR. ConclusionsReallocating sedentary time into light-intensity physical activity or MVPA was associated with differences in insulin sensitivity, with stronger and more consistent associations seen for MVPA.

Abstract P171: Hemoglobin A1c and Incident Albuminuria Among Individuals Without Diabetes: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

Background: Higher hemoglobin A1c (HbA1c) has been associated with an increased risk of reduced estimated glomerular filtration rate &lt;60 mls/min/1.73m2 among individuals without diabetes. However, it is unclear whether higher HbA1c in the non-diabetic glycemic range also is associated with an increased risk of albuminuria. This study investigated the association of HbA1c with incident albuminuria in a biracial cohort of middle-aged men and women without a history of diabetes in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Methods: The CARDIA Study is a prospective cohort study of 5,115 African-American and white adults, age 18-30 years at baseline (1985-86), from four field centers in the United States: Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. Participants with prevalent diabetes (defined as fasting glucose ≥126 mg/dL, 2-hour post-challenge glucose ≥ 200 mg/dL, HbA1c ≥ 6.5%, or used diabetes medications) or albuminuria (defined as a race- and sex-adjusted urine albumin-to-creatinine ratio ≥ 25 mg/g) at the year 20 examination (2005-06; baseline for this analysis) were excluded. This study included 2174 participants who had HbA1c measured at the year 20 examination and had urine albumin and creatinine measured at the year 25 examination (2010-11). Poisson regression with robust error variances was used to obtain risk ratios (RR) and 95% confidence intervals (CI) for the association of HbA1c, both as a continuous variable and dichotomous variable using its prediabetes cut-point, with albuminuria in unadjusted models and models adjusted for socio-demographics and cardiovascular risk factors. Results: During the follow-up period, 103 (4.7%) participants developed incident albuminuria. In unadjusted analyses, each 1% increase in HbA1c was associated with incident albuminuria (RR=2.55, 95% CI=1.48, 4.39). This association was attenuated and not statistically significant after adjustment for age, race, sex, and education (RR=1.68, 95% CI=0.98, 2.88) and further adjustment for cardiovascular risk factors (RR=1.42, 95% CI=0.81, 2.50). Additionally, individuals with HbA1c in the prediabetes range (5.7%-6.4%) had an increased risk of albuminuria (RR=1.59, 95% CI=1.04, 2.43) compared with those with HbA1c in the normal glycemic range (&lt;5.7%) in the unadjusted model. However, this association was attenuated after adjustment for socio-demographics (RR=1.11, 95% CI=0.71, 1.72) and cardiovascular risk factors (RR=0.98, 95% CI=0.61, 1.55). Conclusions: After taking into account socio-demographics and traditional cardiovascular risk factors, HbA1c was not associated with incident albuminuria among individuals without diabetes.

Correlates of prediabetes and type II diabetes in US South Asians: findings from the Mediators of Atherosclerosis in South Asians Living in America (MASALA) study

PurposeIn this study, we aim to elucidate the role of sociodemographic, lifestyle, and cultural factors in prediabetes and diabetes in South Asian immigrants to the United States, a population at high risk of type II diabetes. MethodsWe performed a cross-sectional analysis of a community-based cohort of 899 South Asians without known cardiovascular disease from the Mediators of Atherosclerosis in South Asians Living in America study. Glycemic status was determined by fasting glucose, 2-hour postchallenge glucose, and use of diabetes medication. We used multinomial logistic regression models to estimate the independent associations of sociodemographic, lifestyle, and cultural factors with prediabetes and diabetes, adjusting for confounders identified using directed acyclic graphs. ResultsApproximately 33% of participants had prediabetes and 25% had diabetes. In multivariate analyses, an independent correlate of prediabetes was low exercise. Additional covariates associated with diabetes included lower family income, less education, high chronic psychological burden score, and greater time spent watching television; and fasting monthly or annually was inversely associated with diabetes prevalence. ConclusionsWe found several modifiable risk factors associated with prediabetes and diabetes that may help guide diabetes prevention interventions for South Asian immigrants to the United States.

Abstract P145: Circulating and Dietary Trans-Fatty Acids and Incident Type-2 Diabetes Mellitus in Older Adults: The Cardiovascular Health Study

Background: While trans-fatty acids (TFA) influence CHD, their effects on type 2 diabetes mellitus (DM) are not established, with mixed findings of experimental, short-term intervention, and observational studies. Effects may vary depending on specific TFA subtype or method of assessment (circulating biomarkers vs. diet). Objectives: To examine prospective associations of circulating and estimated dietary TFA with risk of incident DM in older adults. Methods: Plasma phospholipid trans-(t-)16:1n9, total t-18:1, and cis/trans-(c/t-), t/c- and t/t-18:2(n6,9) were measured in blood stored among 3,076 adults in the Cardiovascular Health Study (CHS), aged 74±5y and free of prevalent DM in 1992. Dietary TFA was estimated among 4,246 adults free of prevalent DM when dietary questionnaires were initially administered in 1989 (n=3,917) or in 1996 (n=329). Incident DM up to 2009 was defined as new use of insulin or hypoglycemic drugs, fasting glucose≥126 mg/dL, nonfasting glucose≥200 mg/dL, or 2-hour post-challenge glucose≥200 mg/dL. The relative risk of incident DM associated with each TFA subtype was assessed using multivariate Cox proportional hazards regression. Results: Levels of each circulating TFA subtype varied from 2.00±0.73 (% of fatty acids) for t-18:1 to 0.05±0.02 for t/t-18:2. TFA subtypes were moderately to highly intercorrelated (r=0.4 to 0.8), except for t/t-18:2 which weakly correlated with all other TFAs (r&lt;0.1). During 30,927 person-years, 364 DM cases occurred among participants with plasma phospholipid TFA measures. Adjusting for demographics, lifestyle factors, and medical history, lower DM risk was associated with higher levels of t-16:1n9 (Quartile 4 vs. Quartile 1 HR=0.76, p trend=0.03), total t-18:1 (HR=0.71, p trend=0.02) and t/t-18:2 (HR=0.73, p trend=0.04). However, further mutual adjustment for the different TFA subtypes attenuated these inverse associations, and none of the 5 circulating TFA biomarkers were independently related to incident DM (p trend≥0.14 for all). During 50,508 person-years in the dietary analyses, 453 DM cases occurred. Adjusting for demographics, lifestyle, medical history, and other dietary habits, increased DM risk was observed among participants with higher consumption of total TFA (Quartile 4 vs. Quartile 1 HR=1.40, p trend=0.04) and t-18:2 (HR=1.49, p trend=0.006), and t-18:1 consumption (HR=1.32, p trend=0.08), although the latter was not statistically significant. Conclusions: Plasma phospholipid TFA subtypes were not associated, whereas dietary total TFA and t-18:2 were positively associated, with incident DM among older adults. These findings highlight the need to understand how dietary TFA may influence DM and why associations may differ for circulating versus dietary TFAs.