Age- and sex-related changes in fasting plasma glucose and lipoprotein in cynomolgus monkeys

BACKGROUND: The age-related dysfunction of glucose and lipid metabolism has a long-standing relationship with cardiovascular and neurodegenerative disease. However, the effects of metabolic dysfunction on men and women are different. Reasons for these sex differences remains unclear. Cynomolgus monkeys have been used, in the past, for the study of human metabolic diseases due to their biologically proximity to humans. Nevertheless, few studies to date have focused on both age- and sex-related differences in glucose and lipid metabolism. The present study was designed to specifically address these questions by using a large cohort of cynomolgus monkeys (N = 1,399) including 433 males and 966 females with ages ranging 4 to 24 years old. METHODS: Fasting plasma glucose (FPG) and lipid parameters including total cholesterol (T-Cho), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured. All these parameters were compared between ages and sexes. RESULTS: Among the entire cohort, age was strongly correlated with levels of FPG, TG and HDL. Consequently, sex-related analysis revealed that females had significantly higher average levels of FPG, T-Cho, TG, HDL-C and LDL-C than their male counterparts. In addition, more female (28.5 %) than male (16 %) monkeys qualified for impaired fasting plasma glucose (IFPG). In those IFPG animals, sex-related differences were also detected i.e. females had significantly increased levels of T-Cho, TG and LDL-C. CONCLUSIONS: The result, for the first time, demonstrated the similarities and differences in detail between male and female cynomolgus monkeys in relationship to age-related glucose and lipoprotein metabolisms, and differences under various physiological conditions. The detailed glucose and lipoprotein profiling should provide additional and important insights for prediabetic conditions. Cynomolgus monkeys appear to be an excellent model for translational research of diabetes and for novel therapeutic strategies testing to overt diabetes

Global, regional, and national burden of migraine and tension-type headache, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016

Background Through the Global Burden of Diseases, Injuries, and Risk Factors (GBD) studies, headache has emerged as a major global public health concern. We aimed to use data from the GBD 2016 study to provide new estimates for prevalence and years of life lived with disability (YLDs) for migraine and tension-type headache and to present the methods and results in an accessible way for clinicians and researchers of headache disorders. Methods Data were derived from population-based cross-sectional surveys on migraine and tension-type headache. Prevalence for each sex and 5-year age group interval (ie, age 5 years to ≥95 years) at different time points from 1990 and 2016 in all countries and GBD regions were estimated using a Bayesian meta-regression model. Disease burden measured in YLDs was calculated from prevalence and average time spent with headache multiplied by disability weights (a measure of the relative severity of the disabling consequence of a disease). The burden stemming from medication overuse headache, which was included in earlier iterations of GBD as a separate cause, was subsumed as a sequela of either migraine or tension-type headache. Because no deaths were assigned to headaches as the underlying cause, YLDs equate to disability-adjusted life-years (DALYs). We also analysed results on the basis of the Socio-demographic Index (SDI), a compound measure of income per capita, education, and fertility. Findings Almost three billion individuals were estimated to have a migraine or tension-type headache in 2016: 1·89 billion (95% uncertainty interval [UI] 1·71–2·10) with tension-type headache and 1·04 billion (95% UI 1·00–1·09) with migraine. However, because migraine had a much higher disability weight than tension-type headache, migraine caused 45·1 million (95% UI 29·0–62·8) and tension-type headache only 7·2 million (95% UI 4·6–10·5) YLDs globally in 2016. The headaches were most burdensome in women between ages 15 and 49 years, with migraine causing 20·3 million (95% UI 12·9–28·5) and tension-type headache 2·9 million (95% UI 1·8–4·2) YLDs in 2016, which was 11·2% of all YLDs in this age group and sex. Age-standardised DALYs for each headache type showed a small increase as SDI increased. Interpretation Although current estimates are based on limited data, our study shows that headache disorders, and migraine in particular, are important causes of disability worldwide, and deserve greater attention in health policy debates and research resource allocation. Future iterations of this study, based on sources from additional countries and with less methodological heterogeneity, should help to provide stronger evidence of the need for action. Funding Bill & Melinda Gates Foundation