Finite Schur filtration dimension for modules over an algebra with Schur filtration

Let G be GL_N or SL_N as reductive linear algebraic group over a field k of positive characteristic p. We prove several results that were previously established only when N 2^N. Let G act rationally on a finitely generated commutative k-algebra A. Assume that A as a G-module has a good filtration or a Schur filtration. Let M be a noetherian A-module with compatible G action. Then M has finite good/Schur filtration dimension, so that there are at most finitely many nonzero H^i(G,M). Moreover these H^i(G,M) are noetherian modules over the ring of invariants A^G. Our main tool is a resolution involving Schur functors of the ideal of the diagonal in a product of Grassmannians.Comment: 22 pages; final versio

Association Between Employment Status and Objectively Measured Physical Activity and Sedentary BehaviorThe Maastricht Study

Objective:To examine the association between employment status and physical activity and sedentary behavior.Methods:We included 2045 participants from The Maastricht Study, who used a thigh-worn accelerometer. We compared time spent sedentary, standing, stepping, and higher intensity physical activity between participants with different employment status (non-employed or low-, intermediate- or high-level occupation) with analysis of variance.Results:Participants in low-level occupations were less sedentary and standing and stepping more than those in other occupational categories and non-employed participants. Among the employed, the differences were mostly observed on weekdays, whereas the differences in sedentary time and standing between those in low-level occupations and non-employed participants were evident both on weekdays and weekend days.Conclusions:Those in low-level occupational category were less sedentary and more active than non-employed and those in other occupational categories, especially on weekdays

Glucose Variability Assessed with Continuous Glucose Monitoring:Reliability, Reference Values, and Correlations with Established Glycemic Indices-The Maastricht Study

Background: Glucose variability (GV) measured by continuous glucose monitoring (CGM) has become an accepted marker of glycemic control. Nevertheless, several methodological aspects of GV assessment require further study. We, therefore, investigated the minimum number of days needed to reliably measure GV, assessed GV reference values, and studied the correlation of GV with established glycemic indices (i.e., HbA(1c), seven-point oral glucose tolerance test [OGTT]-derived indices). Methods: We used cross-sectional data from The Maastricht Study, an observational population-based cohort enriched with type 2 diabetes. Participants with more than 48 h of CGM (iPro2; Medtronic) were included for analysis (n = 851; age: 60 +/- 9years; 49% women; 23% type 2 diabetes). We used mean sensor glucose (MSG), standard deviation (SD), and coefficient of variation (CV) as CGM-derived indices (the latter two for GV quantification). We calculated reliability using the Spearman-Brown prophecy formula, established reference values by calculating 2.5th-97.5th percentiles, and studied correlations using Spearman's rho. Results: Sufficient reliability (R > 0.80) was achieved with two (MSG and SD), or three monitoring days (CV). The reference ranges, assessed in individuals with normal glucose metabolism (n = 470), were 90.5-120.6 mg/dL (MSG), 7.9-24.8 mg/dL (SD), and 7.74%-22.45% (CV). For MSG, the strongest correlation was found with fasting plasma glucose (rho = 0.65 [0.61; 0.69]); for SD, with the 1-h OGTT value (rho = 0.61 [0.56; 0.65]); and for CV, with both the incremental glucose peak (IGP) during the OGTT (rho = 0.50 [0.45; 0.55]) and the 1-h OGTT value (rho = 0.50 [0.45; 0.55]). Conclusions: The reliability findings and reference values are relevant for studies that aim to investigate CGM-measured GV. One-hour OGTT and IGP values can be used as GV indices when CGM is unavailable

Estimated GFR, Albuminuria, and Cognitive Performance:The Maastricht Study

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. STUDY DESIGN: Cross-sectional analyses of a prospective population-based cohort study. SETTING & PARTICIPANTS: 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). PREDICTOR: eGFR and urinary albumin excretion (UAE). OUTCOMES: Memory function, information processing speed, and executive function. MEASUREMENTS: Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). RESULTS: UAE was <15mg/24 h in 2,439 (81.7%) participants, 15 to <30 mg/24 h in 309 (10.3%), and ≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (β [SD difference] = -0.148; 95% CI, -0.263 to -0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction < 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFRcr-cys), was 88.4±14.6 mL/min/1.73m(2). eGFRcr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFRcr-cys was associated with cognitive performance in older individuals. LIMITATIONS: Cross-sectional design, which limited causal inferences. CONCLUSIONS: In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFRcr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals

White Matter Connectivity Abnormalities in Prediabetes and Type 2 Diabetes:The Maastricht Study

OBJECTIVE: Prediabetes and type 2 diabetes are associated with structural brain abnormalities, often observed in cognitive disorders. Besides visible lesions, (pre)diabetes might also be associated with alterations of the intrinsic organization of the white matter. In this population-based cohort study, the association of prediabetes and type 2 diabetes with white matter network organization was assessed. RESEARCH DESIGN AND METHODS: In the Maastricht Study, a type 2 diabetes-enriched population-based cohort study (1,361 normal glucose metabolism, 348 prediabetes, and 510 type 2 diabetes assessed by oral glucose tolerance test; 52% men; aged 59 ± 8 years), 3 Tesla structural and diffusion MRI was performed. Whole-brain white matter tractography was used to assess the number of connections (node degree) between 94 brain regions and the topology (graph measures). Multivariable linear regression analyses were used to investigate the associations of glucose metabolism status with network measures. Associations were adjusted for age, sex, education, and cardiovascular risk factors. RESULTS: Prediabetes and type 2 diabetes were associated with lower node degree after full adjustment (standardized [st]βPrediabetes = -0.055 [95% CI -0.172, -0.062], stβType2diabetes = -0.256 [-0.379, -0.133], Ptrend < 0.001). Prediabetes was associated with lower local efficiency (stβ = -0.084 [95% CI -0.159, -0.008], P = 0.033) and lower clustering coefficient (stβ = -0.097 [95% CI -0.189, -0.005], P = 0.049), whereas type 2 diabetes was not. Type 2 diabetes was associated with higher communicability (stβ = 0.148 [95% CI 0.042, 0.253], P = 0.008). CONCLUSIONS: These findings indicate that prediabetes and type 2 diabetes are associated with fewer white matter connections and weaker organization of white matter networks. Type 2 diabetes was associated with higher communicability, which was not yet observed in prediabetes and may reflect the use of alternative white matter connections

Subcutaneous Adipose Tissue and Systemic Inflammation Are Associated With Peripheral but Not Hepatic Insulin Resistance in Humans

Obesity-related insulin resistance (IR) may develop in multiple organs, representing different etiologies towards cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in relation to liver or muscle IR by means of RNA sequencing in overweight/obese participants of the DiOGenes cohort (n=368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, whilst genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, CODAM (n=325) and the Maastricht Study (n=685), an increased systemic low-grade inflammation profile was specifically related to muscle IR, but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases. DiOGenes was registered at clinicaltrials.gov as NCT00390637

Prediabetes Is Associated With Structural Brain Abnormalities:The Maastricht Study

OBJECTIVE Structural brain abnormalities are key risk factors for brain diseases, such as dementia, stroke, and depression, in type 2 diabetes. It is unknown whether structural brain abnormalities already occur in prediabetes. Therefore, we investigated whether both prediabetes and type 2 diabetes are associated with lacunar infarcts (LIs), white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and brain atrophy. RESEARCH DESIGN and METHODS We used data from 2,228 participants (1,373 with normal glucose metabolism [NGM], 347 with prediabetes, and 508 with type 2 diabetes (oversampled); mean age 59.2 6 8.2 years; 48.3% women) of the Maastricht Study, a population-based cohort study. Diabetes status was determined with an oral glucose tolerance test. Brain imaging was performed with 3 Tesla MRI. Results were analyzed with multivariable logistic and linear regression analyses. RESULTS Prediabetes and type 2 diabetes were associated with the presence of LIs (odds ratio 1.61 [95% CI 0.98-2.63] and 1.67 [1.04-2.68], respectively; P trend = 0.027), larger WMH (b 0.07 log10-transformed mL [log-mL] [95% CI 0.00-0.15] and 0.21 log-mL [0.14-0.28], respectively; P trend <0.001), and smaller white matter volumes (b 24.0 mL [27.3 to 20.6] and 27.2 mL [210.4 to 24.0], respectively; P trend <0.001) compared with NGM. Prediabetes was not associated with gray matter volumes or the presence of CMBs. CONCLUSIONS Prediabetes is associated with structural brain abnormalities, with further deterioration in type 2 diabetes. These results indicate that, in middle-aged populations, structural brain abnormalities already occur in prediabetes, which may suggest that the treatment of early dysglycemia may contribute to the prevention of brain diseases