Long-term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered-matched landmark analysis over 25 years.

INTRODUCTION: We aimed to investigate the association between the onset of type 2 diabetes (T2D) and dementia incidence rates (IR) in the population with impaired glucose tolerance (IGT) identified in primary care in New Zealand (NZ) over 25 years. METHODS: Tapered matching and landmark analysis (accounting for immortal bias) were used to control for potential effects of known confounders. The association between T2D onset and 5- and 10-year IR of dementia was estimated by weighted Cox models. RESULTS: The onset of T2D was significantly associated with the 10-year IR of dementia, especially in the socioeconomically deprived, those of non-NZ European ethnicity, those currently smoking, and patients with higher metabolic measures. DISCUSSION: Our findings suggest that the onset of T2D is a significant risk factor for dementia in individuals with IGT. Dementia screening and structured diabetes prevention are vital in the population with IGT, particularly those from deprived or ethnic minority backgrounds. HIGHLIGHTS: Increased dementia incidence rate links with T2D onset in people with IGT. Significant incidence varied by ethnicity, socioeconomic status, and health factors. Results emphasize the diabetes manage and socioeconomic factors on dementia risk. Secondary analysis highlights the key role of vascular health in dementia prevention.

Effect of onset of type 2 diabetes on risks of cardiovascular disease and heart failure among new Zealanders with impaired glucose tolerance over 25 years: tapered-matched landmark analysis.

BACKGROUND: This study aimed to examine the association between the incident onset of T2DM and 5- and 10-year risks of CVD and HF in people with IGT identified in primary care in South and West Auckland, New Zealand (NZ) between 1994 and 2019. METHODS: We compared CVD and HF risks in patients with IGT and with/without T2D newly diagnosed within the exposure window (1-5 years). Tapered matching and landmark analysis (to account for immortal bias) were used to control for potential effects of known confounders. RESULTS: Among 26,794 patients enrolled with IGT, 845 had T2D newly diagnosed within 5 years from enrolment (landmark date) and 15,452 did not have T2D diagnosed. Patients progressing to T2D (vs. those not progressing) had a similar 5-year risk for CVD (hazard ratio 1.19; 95% CI 0.61-2.32) but significantly higher 10-year risk of CVD (2.45(1.40-4.29)), 5-year risk of HF (1.94(1.20-3.12)) and 10-year risk of HF (2.84(1.83-4.39). The association between the onset of T2D and risk of 10-year risk of CVD, 5-year and 10-year risk of HF was more likely among men, the socioeconomically deprived, those currently smoking, patients with higher metabolic measures and/or those with lower renal function. Patients of NZ European ethnicity had a lower 10-year risk of CVD. CONCLUSIONS: The study suggests that the diagnosis of T2D mediates the risk of CVD and HF in people with IGT. The development of risk scores to identify and better manage individuals with IGT at high risk of T2D is warranted.

Geographical pattern of minerals and its association with health disparities in the USA.

This study aimed to determine the common latent patterns of geographical distribution of health-related minerals across the USA and to evaluate the real-world cumulative effects of these patterns on overall population health. It was an ecological study using county-level data (3080 contiguous counties) on the concentrations of 14 minerals (i.e., aluminum, arsenic, calcium, copper, iron, lead, magnesium, manganese, mercury, phosphorus, selenium, sodium, titanium, zinc) in stream sediments (or surface soils), and the measurements of overall health including life expectancy at birth, age-specific mortality risks and cause-specific (summarized by 21 mutually exclusive groups) mortality rates. Latent class analysis (LCA) was employed to identify the common clusters of life expectancy-related minerals based on their concentration characteristics. Multivariate linear regression analyses were then conducted to examine the relationship between the LCA-derived clusters and the health measurements, with adjustment for potential confounding factors. Five minerals (i.e., arsenic, calcium, selenium, sodium and zinc) were associated with life expectancy and were analyzed in LCA. Three clusters were determined across the USA, the 'common' (n = 2056, 66.8%), 'infertile' (n = 739, 24.0%) and 'plentiful' (n = 285, 9.3%) clusters. Residents in counties with the 'infertile' profile were associated with the shortest life expectancy, highest mortality risks at all ages, and highest mortality rates for many reasons including the top five leading causes of death: cardiovascular diseases, neoplasms, neurological disorders, chronic respiratory conditions, and diabetes, urogenital, blood and endocrine diseases. Results remained statistically significant after confounding adjustment. Our study brings novel perspectives regarding environmental geochemistry to explain health disparities in the USA.

Geographical association of biodiversity with cancer and cardiovascular mortality rates: analysis of 39 distinct conditions.

Background: Biodiversity has been recognized as a positive contributor to human health and wellbeing. Cardiovascular disease and cancer are the two most significant global health burdens, and understanding their relationship with biodiversity forms an essential step toward promoting biodiversity conservation and human health. Methods: The species richness of birds is a common indicator of biodiversity, given their vast numbers, distinctive distribution, and acute sensitivity to environmental disturbances. This ecological study utilized avian observation data derived from the eBird database, human health data from the International Health Metrics and Evaluation, and county-level statistics, including population characteristics, socio-economics, healthcare service, residential environment, and geographic and climatic characteristics in 2014. We aimed to extensively explore the individual associations between biodiversity (i.e., avian species richness) and age-standardized cause-specific mortalities for different types of cancers (29 conditions) and cardiovascular diseases (10 conditions) across the United States (US). Results: Our multiple regression analyses that adjusted for a variety of socio-demographic and geographical factors showed that increased rarefied species richness of birds was associated with reduced mortality rates for three of the five most common cancers, namely, tracheal, bronchus, and lung cancer, breast cancer (in women only), and colon and rectal cancer. For cardiovascular conditions, a similar relationship was observed for ischemic heart disease and cerebrovascular disease-the two most frequent causes of mortality. This study provided extended details regarding the beneficial effects of biodiversity on human health.

Relating biodiversity with health disparities of human population: An ecological study across the United States.

Understanding biodiversity's contributions to human health is the first step toward fostering synergies between biodiversity conservation and health promotion - two major targets of UN's Sustainable Development Goals. The One Health approach acknowledges the health of people and biodiversity are interconnected and facing common threats. In this study, we aimed to unveil the geographical association between avian biodiversity and population health across the US. In this ecological study, we combined citizen science bird data from eBird, population health data from the Institute for Health Metrics and Evaluation, and county-level statistics of population characteristics, including socio-economics, healthcare service etc. Multivariate linear regression analyses were performed between bird biodiversity (measured by rarefied species richness of birds), key indicators of general public health (e.g., cause-specific mortality rate), and socio-economic health determinants of 2751 US counties. We found that a higher number of bird species was significantly associated with longer life expectancy after confounding adjustment (regression coefficient (95% CIs), 0·005 (0·003, 0·008)). Bird species richness calculated using the rarefied method consistently accounted for variance in age-specific mortality risks in both very young and old age groups (R2 from 2% to 4%). Rarefied species richness of birds was negatively correlated with the majority of cause-specific deaths (12 out of 21 mutually exclusive causes of death), indicating a general synergy effect between biodiversity and human health. The associations with the top causes of deaths were regarded as highly significant, with considerable effect sizes, for example, for cardiovascular diseases (regression coefficient (95% CIs), -0·242 (-0·311, -0·174)). Our findings show human health is inseparable from the health of the shared environment and the well-being of all species. Bird species richness offers a valuable means to understand large-scale relationships between human health and the health of the environment. To enable equitable sharing of biodiversity's benefits to human health, more efforts should be made to understand two-way socio-ecological mechanism underlying human-biodiversity interactions.

Association Between Onset of Type 2 Diabetes and Risk of Atrial Fibrillation in New Zealanders With Impaired Glucose Tolerance Over 25 Years.

Background The association between the onset of type 2 diabetes (T2D) and atrial fibrillation (AF) risk in individuals with impaired glucose tolerance (IGT) remains unclear. This study aimed to investigate the relationship between the incident onset of T2D and 5- and 10-year (after the landmark period) risks of AF in people with IGT identified in South and West Auckland primary care settings between 1994 and 2019. Methods and Results We compared AF risk in patients with IGT with and without newly diagnosed T2D within a 1- to 5-year exposure window. Tapered matching and landmark analysis (to address immortal bias) were used to control for confounding variables. The cohorts incorporated 785 patients who had T2D newly diagnosed within 5 years from enrollment (landmark date) and 15 079 patients without a T2D diagnosis. Patients progressing to T2D exhibited significantly higher 5-year (after the landmark period) AF risk (hazard ratio [HR], 1.34 [95% CI, 1.10-1.63]) and 10-year (after the landmark period) AF risk (HR, 1.28 [95% CI, 1.02-1.62]) compared with those without incident T2D. The association was more pronounced among men, older patients, socioeconomically deprived individuals, current smokers, those with higher metabolic measures, and lower renal function. New Zealand European ethnicity was associated with a lower 5- and 10-year risk of AF. Conclusions This study found a mediating effect of T2D on the risk of AF in a population with IGT in New Zealand. The development of risk scores and future replication studies can help identify and guide management of individuals with IGT at the highest risk of AF following incident T2D.

[Expression of ubiquitin in the spleen and its influence on the dendritic cell immunomodulation function in multiple organ dysfunction syndrome in mice].

OBJECTIVE: To explore the expression change in ubiquitin (Ub) in the spleen and its significance in multiple organ dysfunction syndrome (MODS) in mice, and to study the effects of ubiquitination of major histocompatibility complex II (MHCII) on the activity and immunomodulation function of splenic dendritic cell (DC). METHODS: Two hundred and ten mice were divided into the normal control group (n = 30) and MODS group (n = 180) according to the method of random digital table, and MODS model was replicated by intraperitoneal injection of zymosan. The MODS group mice were further divided evenly into 6, 12, 24, 48-hour and 5-7-day and 10-12-day groups. Ub protein and expression of CD11c⁺DC and MHCII molecule I-A(b) were examined using immunohistochemistry and immunofluorescence methods. Ub mRNA expression in the spleen was measured by real-time quantitative reverse transcription--polymerase chain reaction (RT-PCR). RESULTS: (1)Immunohistochemistry results showed: the number of Ub positive cells in the spleen increased significantly at 6 hours in MODS group compared with that of the normal control group, and it reached the peak at 24 hours [(16.83 ± 0.38)% vs. (8.60 ± 0.86)%, P < 0.05] and then decreased gradually. At 10-12 days, the number of Ub positive cells decreased significantly compared with that of the normal control group [(4.66 ± 0.34)% vs. (8.60 ± 0.86)%, P < 0.05]. (2)RT-PCR results displayed: compared with normal control group, Ub mRNA expression in spleen increased at 6 hours in MODS group, and it reached the peak at 24 hours (2.17 ± 0.20 vs. 1.00 ± 0.00, P < 0.01). Then, it decreased gradually. At 10-12 days, Ub mRNA decreased significantly as compared with that of normal control group (0.72 ± 0.08 vs. 1.00 ± 0.00, P < 0.05). (3)Immunofluorescence results displayed: compared with normal control group, CD11c⁺DC increased significantly at 6 hours in MODS group and reached the peak at 24 hours [(7.55 ± 0.04)% vs. (2.08 ± 0.13)%, P < 0.05], and then it decreased gradually. At 10-12 days, it was close to that of the normal control group [(2.28 ± 0.06)% vs. (2.08 ± 0.13)%, P>0.05]. Compared with the normal control group, I-A(b) positive cells in the spleen was significantly increased at 6 hours in MODS group [(10.90 ± 1.40)% vs. (5.78 ± 0.47)%, P < 0.01], but it decreased at 24 hours [(3.32 ± 0.91)% vs. (5.78 ± 0.47)%, P < 0.05]. I-A(b) positive cells were restored to the normal level at 48 hours and 5--7 days, and decreased significantly again at 10-12 days [(2.20 ± 0.97)% vs. (5.78 ± 0.47)%, P < 0.05]. The number of Ub positive cells correlated positively to the expression of I-A(b) and the CD11c [r1 = 0.899, r2=0.987, both P < 0.05]. CONCLUSIONS: Ub might influence the maturation and activation of DC via ubiquitination of the MHCII molecule on DC, thereby influencing the immune response at different stages of MODS. The result might provide a new way to recognize immune response and also a new monitoring index for immune response regulation.

Remnant Cholesterol and Cardiovascular Mortality in Patients With Type 2 Diabetes and Incident Diabetic Nephropathy.

CONTEXT: The association between remnant cholesterol (remnant-C) and cardiovascular mortality in patients with type 2 diabetes (T2D) and incident diabetic nephropathy remains unclear. OBJECTIVE: To examinie the association between remnant-C and cardiovascular mortality in patients with T2D, chronic kidney disease (CKD) stages 3 to 5, and newly diagnosed DN. METHODS: This study determined the baseline lipid profile and searched for deaths with cardiovascular disease (CVD) within 2 years of baseline among 2282 adults enrolled between January 1, 2015 and December 31, 2016, who had T2D, CKD stages 3 to 5, and newly diagnosed DN. Adjusted logistic regression models were used to assess the associations between lipid, especially remnant-C concentration (either as continuous or categorical variables), and risk of cardiovascular mortality. RESULTS: In multivariable-adjusted analyses, low-density lipoprotein cholesterol (LDL-C) (odds ratio [OR], 1.022; 95% CI, 1.017-1.026, per 10 mg/dL), high-density lipoprotein cholesterol (HDL-C) (OR, 0.929; 95% CI, 0.922-0.936, per 5 mg/dL), non-HDL-C (OR, 1.024; 95% CI, 1.021-1.028, per 10 mg/dL), and remnant-C (OR, 1.115; 95% CI, 1.103-1.127, per 10 mg/dL), but not triglycerides were associated with cardiovascular mortality. Atherogenic dyslipidemia (triglycerides > 150 mg/dL [1.69 mmol/L] and HDL-C < 40 mg/dL in men or < 50 mg/dL in women) was also associated with cardiovascular mortality (OR, 1.073; 95% CI, 1.031-1.116). Remnant-C greater than or equal to 30 mg/dL differentiated patients at a higher risk of cardiovascular mortality from those with lower concentrations, especially with interaction with LDL-C level greater than 100 mg/dL: The highest risk was found in patients with higher levels both of remnant-C and LDL-C (OR, 1.696; 95% CI, 1.613-1.783). CONCLUSION: In patients with T2D, CKD stages 3 to 5, and incident DN, remnant-C was associated with a higher risk of death with CVD. Different from the general population, the interaction of remnant-C and LDL-C was associated with the highest risk of cardiovascular mortality.