Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis.

BACKGROUND: Few studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk. METHODS AND FINDINGS: We assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies. CONCLUSION: Our findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Bronze Age population dynamics and the rise of dairy pastoralism on the eastern Eurasian steppe.

Recent paleogenomic studies have shown that migrations of Western steppe herders (WSH) beginning in the Eneolithic (ca. 3300-2700 BCE) profoundly transformed the genes and cultures of Europe and central Asia. Compared with Europe, however, the eastern extent of this WSH expansion is not well defined. Here we present genomic and proteomic data from 22 directly dated Late Bronze Age burials putatively associated with early pastoralism in northern Mongolia (ca. 1380-975 BCE). Genome-wide analysis reveals that they are largely descended from a population represented by Early Bronze Age hunter-gatherers in the Baikal region, with only a limited contribution (∼7%) of WSH ancestry. At the same time, however, mass spectrometry analysis of dental calculus provides direct protein evidence of bovine, sheep, and goat milk consumption in seven of nine individuals. No individuals showed molecular evidence of lactase persistence, and only one individual exhibited evidence of >10% WSH ancestry, despite the presence of WSH populations in the nearby Altai-Sayan region for more than a millennium. Unlike the spread of Neolithic farming in Europe and the expansion of Bronze Age pastoralism on the Western steppe, our results indicate that ruminant dairy pastoralism was adopted on the Eastern steppe by local hunter-gatherers through a process of cultural transmission and minimal genetic exchange with outside groups.

Prevalence of pregnancy hypertensive disorders in Mongolia.

OBJECTIVE: To estimate the prevalence of preeclampsia in a contemporary population of Mongolian women living in urban and rural areas. We determined the sensitivity and specificity of diagnosis based on established diagnostic criteria and assessed whether local diagnostic criteria were similar to those used in the US. STUDY DESIGN: Cross-sectional study of urban and nomadic pregnant women recruited in Ulaanbaatar (n=136) and rural provinces (n=85). MAIN OUTCOME MEASURES: Preeclampsia defined as hypertension new to pregnancy after 20weeks and proteinuria (or protein creatinine ratio ⩾0.3 and dipstick reading>+1) or in the absence of proteinuria, hypertension and onset of: renal insufficiency, impaired liver function, thrombocytopenia, pulmonary edema, cerebral/visual symptoms. Prevalence of preeclampsia based on established criteria was compared with prevalence based on local physician's diagnosis. RESULTS: Prevalence of local physician diagnosed preeclampsia was 9.5% (13.2% urban, 3.5% rural). Prevalence based on established diagnostic criteria was 4.1% (4.4% urban, 3.5% rural). Sensitivity of physician's diagnosis was 23.8%, specificity was 98.0%, false negative rate was 2.0% and false positive rate was 76.2%. While prevalence based on local physician's diagnosis was over double that based on diagnostic criteria, overdiagnosis did not result in adverse effects. Women fulfilling diagnostic criteria for preeclampsia had babies with higher birth weights than women who did not (p-value=0.006). CONCLUSION: The 4.1% prevalence of preeclampsia in Mongolia was consistent with global estimates of 2-8%, suggesting the pathophysiology of preeclampsia here may be similar to that found globally. Sensitivity of physician's diagnosis was low, specificity was high.

Breast cancer incidence in Mongolia.

PURPOSE: Data on international variation in breast cancer incidence may help to identify additional risk factors. Substantially lower breast cancer rates in Asia than in North America and Western Europe are established, but differences within Asia have been largely ignored despite heterogeneity in lifestyles and environments. Mongolia's breast cancer experience is of interest because of its shared genetics but vastly different diet compared with other parts of Asia. METHODS: Age-standardized breast cancer incidence and mortality rates obtained from the International Association of Cancer Registries are presented for several Asian countries. Mongolian incidence rates obtained from its cancer registry describe incidence within the country. RESULTS: Breast cancer incidence in Mongolia (age standardized 8.0/100,000) is almost a third of rates in China (21.6/100,000), and over five times that of Japan (42.7/100,000) and Russia (43.2/100,000). Rates within Mongolia appear to have increased slightly over the last decade and are higher in urban than rural areas (annual percentage increase of age-standardized rates from 1998 to 2005 was 3.60 and 2.57 %, respectively). The increase in breast cancer incidence with age plateaus at menopause, as in other Asian populations. CONCLUSIONS: Mongolia's low breast cancer incidence is of particular interest because of their unusual diet (primarily red meat and dairy) compared with other Asian countries. More intensive study of potential dietary, reproductive and lifestyle factors in Mongolia with comparison to other Asian populations may provide more clarity in what drives the international breast cancer rate differences.

The development of diabetes mellitus in Wistar rats kept on a high-fat/low-carbohydrate diet for long periods.

The present study was performed to determine the effect of long-term feeding with a high-fat/low-carbohydrate (HF/LC) diet on the onset of type-2 diabetes mellitus in normal rats. Male Wistar Imamichi rats were kept on a Control (carbohydrate 60%, fat 15%) or HF/ LC (carbohydrate 10%, fat 65%) diet for 16 mo. An intraperitoneal glucose tolerance test was performed once every 2 mo. Glucose tolerance was impaired 2 mo after the start of HF/LC diet feeding, accompanied by a decrease in the insulinogenic index. Along with time of HF/LC diet feeding, the glucose tolerance was further deteriorated with more serious impairment of insulin secretion and sensitivity. At the end of the experiment, 15 of 18 rats in the HF/LC group were diabetic, whereas only 4 of 17 rats in the Control group were diabetic. The present results demonstrate that longterm feeding with a HF/LC diet decreases the secretion and sensitivity of insulin, and induces diabetes mellitus in rats. Furthermore, long-term feeding with such a diet may produce adverse effects on the blood plasma lipid profile, with elevated levels of triglycerides, nonesterified fatty acids, total cholesterol, and reduced levels of high density protein cholesterol in the plasma.