Reproducibility of continuous glucose monitoring results under real-life conditions in an adult population: a functional data analysis.

Continuous glucose monitoring systems (CGM) are a very useful tool to understand the behaviour of glucose in different situations and populations. Despite the widespread use of CGM systems in both clinical practice and research, our understanding of the reproducibility of CGM data remains limited. The present work examines the reproducibility of the results provided by a CGM system in a random sample of a free-living adult population, from a functional data analysis approach. Functional intraclass correlation coefficients (ICCs) and their 95% confidence intervals (CI) were calculated to assess the reproducibility of CGM results in 581 individuals. 62% were females 581 participants (62% women) mean age 48 years (range 18-87) were included, 12% had previously been diagnosed with diabetes. The inter-day reproducibility of the CGM results was greater for subjects with diabetes (ICC 0.46 [CI 0.39-0.55]) than for normoglycaemic subjects (ICC 0.30 [CI 0.27-0.33]); the value for prediabetic subjects was intermediate (ICC 0.37 [CI 0.31-0.42]). For normoglycaemic subjects, inter-day reproducibility was poorer among the younger (ICC 0.26 [CI 0.21-0.30]) than the older subjects (ICC 0.39 [CI 0.32-0.45]). Inter-day reproducibility was poorest among normoglycaemic subjects, especially younger normoglycaemic subjects, suggesting the need to monitor some patient groups more often than others.

Age-Related Changes in Serum N-Glycome in Men and Women-Clusters Associated with Comorbidity.

(1) Aim: To describe, in a general adult population, the serum N-glycome in relation to age in men and women, and investigate the association of N-glycome patterns with age-related comorbidity; (2) Methods: The serum N-glycome was studied by hydrophilic interaction chromatography with ultra-performance liquid chromatography in 1516 randomly selected adults (55.3% women; age range 18-91 years). Covariates included lifestyle factors, metabolic disorders, inflammatory markers, and an index of comorbidity. Principal component analysis was used to define clusters of individuals based on the 46 glycan peaks obtained in chromatograms; (3) Results: The serum N-glycome changed with ageing, with significant differences between men and women, both in individual N-glycan peaks and in groups defined by common features (branching, galactosylation, sialylation, fucosylation, and oligomannose). Through K-means clustering algorithm, the individuals were grouped into a cluster characterized by abundance of simpler N-glycans and a cluster characterized by abundance of higher-order N-glycans. The individuals of the first cluster were older, showed higher concentrations of glucose and glycation markers, higher levels of some inflammatory markers, lower glomerular filtration rate, and greater comorbidity index; (4) Conclusions: The serum N-glycome changes with ageing with sex dimorphism. The N-glycome could be, in line with the inflammaging hypothesis, a marker of unhealthy aging.

Time above range for predicting the development of type 2 diabetes.

Aim: To investigate the prognostic value of time range metrics, as measured by continuous glucose monitoring, with respect to the development of type 2 diabetes (T2D). Research design and methods: A total of 499 persons without diabetes from the general population were followed-up for 5 years. Time range metrics were measured at the start and medical records were checked over the period study. Results: Twenty-two subjects (8.3 per 1,000 person-years) developed T2D. After adjusting for age, gender, family history of diabetes, body mass index and glycated hemoglobin concentration, multivariate analysis revealed 'time above range' (TAR, i.e., with a plasma glucose concentration of >140 mg/dL) to be significantly associated with a greater risk (OR = 1.06, CI 1.01-1.11) of developing diabetes (AUC = 0.94, Brier = 0.035). Conclusions: Time above range provides additional information to that offered by glycated hemoglobin to identify patients at a higher risk of developing type 2 diabetes in a population-based study.

Health self-perception is associated with life-styles and comorbidities and its effect on mortality is confounded by age. A population based study.

Background: Health self-perception (HSP) is the individual and subjective concept that a person has of their state of health. Despite its simplicity, HSP is considered a valid and relevant indicator employed in epidemiological research and in professional practice as an overall measure of health. Objectives: (1) To describe and analyze the associations between HSP and demographic variables, lifestyle and diseases prevalent in a population and (2) to investigate the relationship between HSP and mortality. Materials and methods: In a primary care setting, we conducted a longitudinal study of a random populational sample of a Galician municipality, stratified by decade of life. A total of 1,516 adults older than 18 years, recruited by the 2013-2015 AEGIS study, were followed-up for more than 5 years. During the clinical interview, data were collected on lifestyle and prevalent diseases. The HSP was grouped into 2 categories (good/poor). The statistical analysis consisted of a logistic regression, Kaplan-Meier curves and Cox regression. Results: A total of 540 (35.6%) participants reported poor HSP. At the end of the follow-up, 78 participants had died (5.1%). The participants with increased age and body mass index and chronic diseases (anxiety, depression, ischemic heart disease, diabetes, and cancer) presented a poorer subjective health. A high level of physical activity and moderate alcohol consumption were associated with better HSP. A poorer HSP was associated with increased mortality, an association that disappeared after adjusting for the rest of the covariates (HR, 0.82; 95% CI 0.50-1.33). Conclusion: (1) Health self-perception is associated with age, lifestyle, and certain prevalent diseases. (2) A poorer HSP is associated with increased mortality, but this predictive capacity disappeared after adjusting for potential confounders such as age, lifestyle, and prevalent diseases.

Aging of glucose profiles in an adult population without diabetes.

AIMS: This study aimed to determine the effect of aging on glucose profiles in a population without diabetes. METHODS: We investigated the evolution of glucose profiles in an adult population without diabetes using continuous glucose monitoring (CGM) in two periods separated by 5 years. Anthropometrics, laboratory tests (HbA1c, fasting blood glucose) and CGM data (mean glycemia level, coefficient of variation, time in range) were measured in both periods to study the change in values over time. RESULTS: 125 participants (68% women) mean age 43.1 ± 12.4 years and classified as normoglycemic at baseline were included. Of the total population 15.2% had worsened glycemic status after 5 years, age and baseline glucose values (HbA1c and percentage of values above 175 mg/dL) were the variables related with this change. Related to CGM, we found that after 5 years there was a decrease in the percentage of values between 70 and 99 mg/dl (45.0% to 38.7%, p = 0.002) and an increase in the 100-139 mg/dL range (52.9% to 57.5% p = 0.016). CONCLUSIONS: Our results indicate that in an adult population without diabetes there are changes in glucose profiles with aging highlighting the reduction of blood glucose values below 100 mg/dL.

Changes in Serum N-Glycome for Risk Drinkers: A Comparison with Standard Markers for Alcohol Abuse in Men and Women.

Background and aim: Glycomic alterations serve as biomarker tools for different diseases. The present study aims to evaluate the diagnostic capability of serum N-glycosylation to identify alcohol risk drinking in comparison with standard markers. Methods: We included 1516 adult individuals (age range 18-91 years; 55.3% women), randomly selected from a general population. A total of 143 (21.0%) men and 50 (5.9%) women were classified as risk drinkers after quantification of daily alcohol consumption and the Alcohol Use Disorders Identification Test (AUDIT). Hydrophilic interaction ultra-performance liquid chromatography (HILIC-UPLC) was used for the quantification of 46 serum N-glycan peaks. Serum gamma-glutamyltransferase (GGT), carbohydrate-deficient transferrin (CDT), and red blood cell mean corpuscular volume (MCV) were measured by standard clinical laboratory methods. Results: Variations in serum N-glycome associated risk drinking were more prominent in men compared to women. A unique combination of N-glycan peaks selected by the selbal algorithm shows good discrimination between risk-drinkers and non-risk drinkers for men and women. Receiver operating characteristics (ROC) curves show accuracy for the diagnosis of risk drinking, which is comparable to that of the golden standards, GGT, MCV and CDT markers for men and women. Additionally, the inclusion of N-glycan peaks improves the diagnostic accuracy of the standard markers, although it remains relatively low, due to low sensitivity. For men, the area under the ROC curve using N-glycome data is 0.75, 0.76, and 0.77 when combined with GGT, MCV, and CDT, respectively. In women, the areas were 0.76, 0.73, and 0.73, respectively. Conclusion: Risk drinking is associated with significant variations in the serum N-glycome, which highlights its potential diagnostic utility.

C-Reactive Protein versus Erythrocyte Sedimentation Rate: Implications Among Patients with No Known Inflammatory Conditions.

BACKGROUND: Measurements of C-reactive protein (CRP) concentration and erythrocyte sedimentation rate (ESR) are frequently ordered jointly in clinical practice. AIM: To investigate the factors associated with discordances between CRP concentration and ESR in adults. METHODS: We conducted a cross-sectional study of 1472 adults with no known inflammatory disorders (44.5% male; median age, 52 years; range, 18-91 years), randomly selected from a municipality in Spain. The participants underwent simultaneous measurements of ESR, serum CRP, and interleukin-6 concentrations. Alcohol consumption, smoking, and physical activity were evaluated by questionnaire. Body mass index (BMI) measurement and metabolic syndrome criteria were available for all participants. RESULTS: Most (n = 1123, 74.9%) of the participants showed normal CRP and ESR values. Sixty-nine (4.6%) participants showed high CRP and ESR values. Seventy-two (4.8%) participants showed a discordant pattern of high ESR and normal CRP values, which was associated with age after adjusting for sex, alcohol consumption, physical activity, BMI, and the presence of metabolic syndrome (odds ratio [OR], 1.052; 95% CI, 1.034-1.071; P < .001). A total of 208 (13.8%) participants showed a discordant pattern of high CRP and normal ESR values, which was associated with BMI after adjusting for covariates (OR, 1.099; 95% CI, 1.064-1.136; P < .001). BMI appeared to be the main determinant of serum CRP concentrations in this population. Serum interleukin-6 concentrations were positively associated with the discordant pattern of high CRP and normal ESR values. CONCLUSION: In this general adult population with no overt inflammatory disease, the discordant pattern of high ESR and normal CRP was associated with greater age, whereas the pattern of high CRP and normal ESR was associated with higher BMI.

Factors associated with serum IgM concentrations: a general adult population study.

BACKGROUND AND AIM: To investigate the influence of common factors on serum immunoglobulin M (IgM) concentrations in adults, and clinical associations with high and low values. METHODS: We measured serum IgM levels using immunonephelometry in a random sample of 1510 individuals (aged 18-91 years, 44.7% male). We obtained data defining metabolic syndrome from all participants, defined atopy by skin prick tests to aeroallergens, and assessed lifestyle factors by questionnaire. RESULTS: Women showed higher IgM concentrations than men; 95 (6.3%, mostly male) individuals showed low (<0.40 g/L) IgM values, and 64 (4.2%, mostly female) showed high (>2.30 g/L) IgM values. Individuals with abnormal IgM concentrations had no history of opportunistic infections nor a different atopy prevalence. Serum IgM concentrations decreased with age, and obesity was negatively associated with IgM concentrations. Alcohol consumption, smoking, physical activity, and metabolic syndrome had no significant influence in the multivariate analyses. CONCLUSIONS: Many adults in the general population show abnormally high or low IgM concentrations with no evidence of immunodeficiency-associated diseases. Sex and age should be considered when defining reference IgM concentrations.

Development and validation of a prognostic model based on comorbidities to predict COVID-19 severity: a population-based study.

BACKGROUND: The prognosis of patients with COVID-19 infection is uncertain. We derived and validated a new risk model for predicting progression to disease severity, hospitalization, admission to intensive care unit (ICU) and mortality in patients with COVID-19 infection (Gal-COVID-19 scores). METHODS: This is a retrospective cohort study of patients with COVID-19 infection confirmed by reverse transcription polymerase chain reaction (RT-PCR) in Galicia, Spain. Data were extracted from electronic health records of patients, including age, sex and comorbidities according to International Classification of Primary Care codes (ICPC-2). Logistic regression models were used to estimate the probability of disease severity. Calibration and discrimination were evaluated to assess model performance. RESULTS: The incidence of infection was 0.39% (10 454 patients). A total of 2492 patients (23.8%) required hospitalization, 284 (2.7%) were admitted to the ICU and 544 (5.2%) died. The variables included in the models to predict severity included age, gender and chronic comorbidities such as cardiovascular disease, diabetes, obesity, hypertension, chronic obstructive pulmonary disease, asthma, liver disease, chronic kidney disease and haematological cancer. The models demonstrated a fair-good fit for predicting hospitalization {AUC [area under the receiver operating characteristics (ROC) curve] 0.77 [95% confidence interval (CI) 0.76, 0.78]}, admission to ICU [AUC 0.83 (95%CI 0.81, 0.85)] and death [AUC 0.89 (95%CI 0.88, 0.90)]. CONCLUSIONS: The Gal-COVID-19 scores provide risk estimates for predicting severity in COVID-19 patients. The ability to predict disease severity may help clinicians prioritize high-risk patients and facilitate the decision making of health authorities.

Glycemic Variability and Its Association With Demographics and Lifestyles in a General Adult Population.

OBJECTIVE: The objective was to investigate glycemic variability indices in relation to demographic factors and common environmental lifestyles in a general adult population. METHODS: The A Estrada Glycation and Inflammation Study is a cross-sectional study covering 1516 participants selected by sampling of the population aged 18 years and over. A subsample of 622 individuals participated in the Glycation project, which included continuous glucose monitoring procedures. Five glycemic variability indices were analyzed, that is, SD, MAGE, MAG, CONGA1, and MODD. RESULTS: Participants had a mean age of 48 years, 62% were females, and 12% had been previously diagnosed with diabetes. In the population without diabetes, index distributions were not normal but skewed to the right. Distributional regression models that adjusted for age, gender, BMI, alcohol intake, smoking status, and physical activity confirmed that all indices were positively and independently associated with fasting glucose levels and negatively with heavy drinking. SD, MAGE, and CONGA1 were positively associated with aging, and MAG was negatively associated with BMI. None of the GVI studied were influenced by physical activity. Age-group-specific reference values are given for the indices. CONCLUSIONS: This study yielded age-specific reference values for glucose variability indices in a general adult population. Significant increases were observed with aging. Heavy drinking of more than 140 g/week was associated with significant decreases in variability indices. No differences were found between males and females. These normative ranges provide a guide for clinical care, and may offer an alternative treatment target among persons with diabetes.

Synergistic effect of alcohol consumption and body mass on serum concentrations of cytokeratin-18.

BACKGROUND: Cytokeratin-18 is an essential component of the cytoskeleton of epithelial cells (including hepatocytes). Serum concentrations of cytokeratin-18 (tissue polypeptide-specific antigen [TPS]) are used as a marker of epithelial neoplasms. Here, we investigated the potential interaction between alcohol and obesity in relation to serum TPS concentrations. METHODS: Alcohol consumption, body mass index, and components of metabolic syndrome were measured in a random sample (n = 420) of the adult population (aged 18 to 92 years, 45% men) from a single municipality. Regular alcohol intake of >20 g/d (women) or >30 g/d (men) was considered risky drinking. Serum TPS was measured with a commercial immunoassay. RESULTS: Risky drinking was associated with increased serum concentrations of TPS, which was particularly evident among obese individuals. Among individuals without risky drinking, TPS concentrations were similar for all levels of body mass. Conversely, among risky drinkers, serum TPS concentrations increased in parallel with body mass (p = 0.002). The odds ratio of a high (>100 U/l) TPS concentration for the combination of risky drinking and obesity was greater than the additive effect of the 2 separate factors, after adjusting for age and sex. A similar interaction was observed between risky drinking and abdominal adiposity, a major component of the metabolic syndrome. Serum TPS concentrations were correlated with markers of liver damage. Serum TPS was not superior to standard markers (gamma-glutamyl transferase and red blood cell mean volume) for the detection of risky drinking. CONCLUSIONS: There is a synergism between risky alcohol consumption and common metabolic disorders (particularly obesity) in relation to serum concentrations of cytokeratin-18 (TPS), which probably reflect liver disease.

Factors influencing serum total tryptase concentrations in a general adult population.

BACKGROUND: Serum tryptase measurements are increasingly being used in clinical practice. However, there is a paucity of studies focused on factors that influence tryptase concentrations. We investigated the relationships between total tryptase concentrations and age, gender, atopy, alcohol consumption, smoking, and common metabolic abnormalities in adults. METHODS: This was a cross-sectional study of a random sample from an adult population (n=420, age 18-92 years, 45% males) from a single municipality. Serum total tryptase was measured using a fluoro-enzyme immunoassay. RESULTS: The median tryptase concentration was 5.1 microg/L (range, <1-30.7 microg/L). There was a significant (p<0.0001) continual increase in tryptase with age; the median concentrations were 4.0 microg/L in 18-30 years old and 6.6 microg/L in those >80 years. Female gender and heavy ethanol use were negatively and independently associated with tryptase concentrations. Tryptase was higher in individuals that were non-atopic, overweight, or had metabolic syndrome compared to individuals that were atopic, normal weight, or did not have the metabolic syndrome. However, these associations were attenuated after adjusting for age. CONCLUSIONS: Serum total tryptase concentrations in adults are not significantly modified by atopy status, but may be modified by lifestyle factors, such as alcohol consumption and gender. Serum total tryptase concentrations are particularly dependent on age.

Serum levels of gamma-glutamyl transferase are associated with markers of nocturnal hypoxemia in a general adult population.

BACKGROUND: Serum gamma-glutamyl transferase (GGT) is a well-known marker of alcohol consumption and liver dysfunction. GGT is also associated with components of metabolic syndrome, cardiovascular risk factors and obstructive sleep apnea. In a population-based study, we investigated serum GGT levels in relation to markers of nocturnal hypoxemia, adjusting for potential confounders. In addition, we investigated the possible relationship between GGT concentrations and serum levels of tumour necrosis factor-alpha and interleukin-6. METHODS: Demographic data, alcohol consumption, components of metabolic syndrome, serum liver enzymes, pro-inflammatory cytokines and nocturnal pulse oximetry were available for 220 individuals, randomly selected from a general adult population. Of these, overnight polysomnography was available for 70. RESULTS: A smoothing regression model confirmed that serum GGT levels were associated positively and independently with male sex (P<0.001), ageing (P=0.001), heavy smoking (P=0.039), alcohol drinking (P<0.001), and body mass index (P=0.019). Serum GGT levels were associated negatively and independently with average arterial oxygen saturation during sleep (P=0.001). CONCLUSIONS: Serum concentrations of GGT are associated with nocturnal arterial oxygen desaturations.