Cardiometabolic correlates of low type 2 diabetes incidence in western Alaska Native people - The WATCH study.

AIMS: Previously rare among Alaska Native (AN) people, type 2 diabetes (DM2) prevalence as indicated by registry data has increased by as much as 300% in some western Alaska regions. We sought to determine prevalence and incidence of DM2 and analyze associated cardiometabolic risk factors in western AN people. METHODS: DM2 and prediabetes prevalence and incidence were determined by the Western Alaska Tribal Collaborative for Health using consolidated data from cohort studies conducted during 2000-2010. Crude and age-adjusted incidence for DM2 and prediabetes were calculated using 2010 American Diabetes Association criteria. Effects of covariates on DM2 and prediabetes were determined using univariate and multivariate Cox proportional hazards analyses, adjusted for age and sex. RESULTS: Excluding baseline diabetes (n=124, 4.5%), 53 cases of new DM2 were identified among 2630 participants. Age- and sex-adjusted DM2 incidence was 4.3/1000 (95% CI 2.9, 5.0) person-years over an average 5.9-year follow up. After excluding baseline prediabetes, 387 new cases of prediabetes were identified among 1841 participants; adjusted prediabetes incidence was 44.5/1000 (95% CI 39.5, 49.5) person years. Independent predictors for DM2 included age, impaired fasting glucose, and metabolic syndrome; family history of diabetes and obesity were additional independent predictors for prediabetes. CONCLUSIONS: DM2 incidence in western AN people is substantially lower than that for U.S. whites; however, incidence of prediabetes is more than 10-fold higher than western AN DM2 incidence and more closely aligned with U.S. rates. Interventions aimed at achieving healthy lifestyles are needed to minimize risk factors and maximize protective factors for DM2 in this population.

All-cause, cardiovascular, and cancer mortality in western Alaska Native people: western Alaska Tribal Collaborative for Health (WATCH).

OBJECTIVES: We determined all-cause, cardiovascular disease (CVD), and cancer mortality in western Alaska Native people and examined agreement between death certificate information and adjudicated cause of deaths. METHODS: Data from 4 cohort studies were consolidated. Death certificates and medical records were reviewed and adjudicated according to standard criteria. We compared adjudicated CVD and cancer deaths with death certificates by calculating sensitivity, specificity, predictive values, and κ statistics. RESULTS: Men (n = 2116) and women (n = 2453), aged 18 to 95 years, were followed an average of 6.7 years. The major cause of death in men was trauma (25%), followed by CVD (19%) and cancer (13%). The major cause of death in women was CVD (24%), followed by cancer (19%) and trauma (8%). Stroke rates in both genders were higher than those of US Whites. Only 56% of deaths classified as CVD by death certificate were classified as CVD by standard criteria; discordance was higher among men (55%) than women (32%; κs = 0.4 and 0.7). CONCLUSIONS: We found lower rates for coronary heart disease death but high rates of stroke mortality. Death certificates overestimated CVD mortality; concordance between the 2 methods is better for cancer mortality. The results point to the importance of cohort studies in this population in providing data to assist in health care planning.

Utilizing harmonization and common surveillance methods to consolidate 4 cohorts: the Western Alaska Tribal Collaborative for Health (WATCH) study.

BACKGROUND: According to health status reports, chronic disease prevalence appears to be rising in western Alaska Native (AN) people, and accurate population-based data are needed. Four cohort studies of western AN people were conducted in the Norton Sound and Yukon-Kuskokwim regions, but none have been large enough to allow reliable estimates of rates of chronic diseases and evaluate their risk factors. OBJECTIVE: In this article, the methods used to combine 4 major cohort studies of rural western AN people are described and the benefits and challenges encountered in combining data and standardizing surveillance methods for these studies are discussed. DESIGN: Tribal permission was obtained for each cohort study and the consolidated study. Data from baseline exams were directly combined or harmonized into new variables. Common surveillance methods were developed and implemented to identify incidence and risk factors for cardiovascular disease (CVD) events and type 2 diabetes. RESULTS: A cohort of 4,569 western AN participants (2,116 men and 2,453 women), aged 18-95 years, was established to study CVD and diabetes prevalence. Prospective surveillance data over an average 6.7-year follow-up can now be used to study CVD and diabetes incidence and associated risk factors in a subset of 2,754 western AN participants (1,218 men and 1,536 women) who consented to initial surveillance. CONCLUSIONS: The combined cohort provides statistical power to examine incidence rates and risk factors for CVD and diabetes and allows for analyses by geographic region. The data can be used to develop intervention programmes in these populations and others.

Lipid bodies are reservoirs of cyclooxygenase-2 and sites of prostaglandin-E2 synthesis in colon cancer cells.

Lipid bodies (lipid droplets) are emerging as dynamic organelles involved in lipid metabolism and inflammation. Increased lipid body numbers have been described in tumor cells; however, its functional significance in cancer has never been addressed. Here, we showed increased number of lipid bodies in tumor tissues from patients with adenocarcinoma of colon submitted to surgical resection when compared with an adjacent normal tissue. Accordingly, increased numbers of lipid bodies were observed in human colon adenocarcinoma cell lines and in a H-rasV12-transformed intestinal epithelial cell line (IEC-6 H-rasV12) compared with nontransformed IEC-6 cells. The functions of lipid bodies in eicosanoid synthesis in cancer cells were investigated. CACO-2 cells have increased expression of cyclooxygenase-2 (COX-2) when compared with IEC-6 cells. We showed by immunolocalization that, in addition to perinuclear stain, COX-2 and prostaglandin E (PGE) synthase present punctate cytoplasmic localizations that were concordant with adipose differentiation-related protein-labeled lipid bodies. The colocalization of COX-2 at lipid bodies was confirmed by immunoblot of subcellular fractionated cells. Direct localization of PGE(2) at its synthesis locale showed that lipid bodies are sources of eicosanoids in the transformed colon cancer cells. Treatment with either aspirin or the fatty acid synthase inhibitor C75 significantly reduced the number of lipid bodies and PGE(2) production in CACO-2 and in IEC-6 H-rasV12 cells with effects in cell proliferation. Together, our results showed that lipid bodies in colon cancer cells are dynamic and functional active organelles centrally involved in PGE(2) synthesis and may potentially have implications in the pathogenesis of adenocarcinoma of colon.