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Branched-chain amino acid (BCAA) levels are increased in individuals with obesity and are associated with worse metabolic health and future insulin resistance. In this Review, Christopher Lynch and Sean Adams discuss whether and how impaired BCAA metabolism might occur in obesity and how perturbations in BCAA levels reflect the insulin resistant and type 2 diabetes mellitus pathophenotypes.
Stem cells have an important role in the embryogenesis and homeostasis of the adrenal gland. Walczak and Hammer discuss the molecular networks that regulate the establishment and maintenance of the stem cell population in the fetal and definitive adrenal glands and how genetic defects that perturb these pathways contribute to the development of adrenal disease.
Hypoglycaemia is a frequent adverse effect of some therapies for diabetes mellitus, and can have serious consequences. This Review describes the epidemiology of hypoglycaemia in adults with diabetes mellitus, principally in those treated with insulin. The consequences of hypoglycaemia are discussed, with particular focus on the cardiovascular and neurological morbidities that can occur.
A large-scale study with 5.24 million participants has found statistically significant associations between increased BMI and 17 of 22 frequent cancers. The strongest associations were observed for cancers of the endometrium, kidney, gallbladder and uterus. Questions remain as to whether several of the weaker associations reported in this study reflect genuinely causal relationships.
The prevalence of obesity has increased to epidemic proportions. In the past few years, whether patients with obesity can be metabolically healthy has been debated. This Review discusses the controversy regarding metabolically healthy obesity, as well as the debate regarding the relative importance of fatness versus fitness for overall, and particularly cardiovascular, health.
Determination, differentiation and development of the gonads are important processes in early mammalian development. This article is focused on the genetic networks underlying these processes, whose disruption in humans can lead to disorders of sex development. The authors discuss the pathways controlling sex-specific gonadal development, from the bipotential gonad to the fully differentiated ovary or testis.
The prevalence of type 2 diabetes mellitus (T2DM) is increasing in young Asian adults; however, little is known about the associated clinical characteristics and the prevalence of complications. A recent Asia-wide prospective cohort study has revealed poor metabolic control in patients with young-onset T2DM, indicating more efficient health-care strategies are warranted to manage this vulnerable population.
Mitochondria have a fundamental role in regulating metabolic pathways and in maintaining energy balance. In this Review, Carole Nasrallah and Tamas Horvath discuss the contribution of mitochondrial function, in particular mitochondrial dynamics, to central metabolism from the hypothalamic perspective and describe how mitochondrial dysfunction can lead to the development of metabolic diseases.
The recently published HPS2–THRIVE study has shown that the addition of extended release niacin to statin therapy in patients with well-controlled levels of LDL cholesterol does not reduce the risk of cardiovascular events and might even increase harm. Consequently, the use of niacin to increase levels of HDL cholesterol is not recommended.
Polycystic ovary syndrome (PCOS) is associated with anovulatory infertility. Many clinicians focus on the use of assisted reproductive technologies other than medical induction of ovulation. A new study demonstrating that the aromatase inhibitor letrozole is superior to clomiphene citrate (the current first-line therapy) for ovulation induction in women with PCOS returns attention to this area.
Although important risk factors for coronary heart disease (CHD) are well known, advances in research might facilitate improved risk stratification of patients. This Review discusses the latest developments in metabolic biomarkers of cardiovascular disease, including lipoproteins, homocysteine, calcium metabolism and glycaemic markers. It also discusses whether these biomarkers' associations with CHD are sufficient to improve current risk-stratification metrics.
