Clocks in the clinic: circadian rhythms in health and disease.

Circadian rhythms are endogenously generated recurring patterns of around 24 hours with well-established roles in physiology and behaviour. These circadian clocks are important in both the aetiology and treatment of various psychiatric and metabolic diseases. To maintain physiological homeostasis and optimal functioning, living life synchronised to these clocks is desirable; modern society, however, promotes a '24/7' lifestyle where activity often occurs during the body's 'biological night', resulting in mistimed sleep and circadian misalignment. This circadian desynchrony can increase the risk of disease and can also influence treatment response. Clinicians should be aware of the influence that circadian desynchrony can have on health and disease, in order to potentially develop new therapeutic strategies and to incorporate chronotherapeutics into current treatment strategies to enhance their utility.

An exploratory study of associations between sleep timing variability and cardiometabolic health in middle-aged adults with type 2 diabetes mellitus.

Sleep is increasingly recognised as an important risk factor for metabolic disease, and as an important influence on severity in established metabolic disease. Recent evidence suggests that sleep timing variability (the day-to-day fluctuations of sleep timing) may be an important factor in metabolic diseases such as type 2 diabetes mellitus. In the current study, we explore the associations between measures of sleep timing variability and cardiometabolic measures in a group of healthy middle-aged adults with and without type 2 diabetes mellitus. Healthy controls (N = 27) and adults with well-controlled uncomplicated type 2 diabetes mellitus (N = 30) wore actiwatches for an average of 9 days for objective assessment of sleep timing parameters, and also underwent a detailed clinical assessment. We found greater self-reported social jetlag in the diabetes group, but no groupwise differences in measures of sleep timing variability. In the diabetes patients, HbA1c levels were inversely correlated with variability in the time of sleep onset and midsleep, and with sleep duration. HOMA-IR did not correlate with any sleep timing variability measure, nor were there associations between sleep timing variability and other metabolic biomarkers (cholesterol, LDL, HDL, triglycerides and uric acid). Systolic blood pressure was inversely correlated with actigraphically defined social jetlag in both the control and diabetes groups. The results of this study indicate associations between sleep timing variability and HbA1c, but the direction of these relationships is at variance with some other recent reports. Our results indicate a need for future hypothesis-testing studies to further explore the impact of sleep timing variance on metabolic health.

Multiple endocrine neoplasia type 1 in children and adolescents: Clinical features and treatment outcomes.

BACKGROUND: Clinical manifestations and treatment outcomes in children and adolescents with multiple endocrine neoplasia type 1 are not well characterized. METHODS: We conducted a retrospective cohort study of 80 patients with multiple endocrine neoplasia type 1 who commenced tumor surveillance at ≤18 years of age. RESULTS: Fifty-six patients (70%) developed an endocrine tumor by age ≤18 years (median age = 14 years, range = 6-18 years). Primary hyperparathyroidism occurred in >80% of patients, with >70% undergoing parathyroidectomy, in which less-than-subtotal (<3-gland) resection resulted in decreased disease-free outcomes versus subtotal (3-3.5-gland) or total (4-gland) parathyroidectomy (median 27 months versus not reached; P = .005). Pancreaticoduodenal neuroendocrine tumors developed in ∼35% of patients, of whom >70% had nonfunctioning tumors, >35% had insulinomas, and <5% had gastrinomas, with ∼15% having metastases and >55% undergoing surgery. Pituitary tumors developed in >30% of patients, and ∼35% were macroprolactinomas. Tumor occurrence in male patients and female patients was not significantly different. Genetic analyses revealed 38 germline MEN1 mutations, of which 3 were novel. CONCLUSION: Seventy percent of children aged ≤18 years with multiple endocrine neoplasia type 1 develop endocrine tumors, which include parathyroid tumors for which less-than-subtotal parathyroidectomy should be avoided; pancreaticoduodenal neuroendocrine tumors that may metastasize; and pituitary macroprolactinomas.

Greater social jetlag associates with higher HbA1c in adults with type 2 diabetes: a cross sectional study.

BACKGROUND/OBJECTIVES: Later chronotype has been associated with poorer glycemic control in type 2 diabetes. It is unclear whether this is a direct relationship, or if personality factors or social jetlag ([SJL], ie, chronic circadian misalignment reflecting the discrepancy between the entrained phase of the circadian clock and socially-determined behavioural cycles) play a role. This study aimed to determine the relationships among chronotype, SJL, personality factors and glycemic control in type 2 diabetes, independently of sleep disturbances and daily caloric distribution. METHODS: In sum, 252 type 2 diabetes patients attending an annual review outpatients' clinic completed questionnaires, including the Munich Chronotype Questionnaire to assess chronotype and SJL, the Pittsburgh Sleep Quality index (PSQI), the Big Five Personality Inventory and the Center for Epidemiologic Studies Depression Scale. Chart review provided information on diabetes duration, Hemoglobin A1c (HbA1c), body mass index (BMI) and other clinical variables. Caloric intake was assessed via 24-h dietary recall. RESULTS: Hierarchical linear regression revealed that SJL, but not chronotype or personality factors, was a significant predictor of HbA1c levels (ß = 0.16, p < 0.05). There was a significant relationship between later chronotype and HbA1c levels, but only in patients who had more than 90 min SJL (r = 0.51, p = 0.002). Younger age was associated with a higher HbA1c (r = -0.23, p < 0.001), and this effect was partially mediated through SJL (Pm = 0.22). CONCLUSIONS: We identify SJL as a novel factor that may impact on glycemic control in type 2 diabetes. Further study is needed to determine whether interventions aimed at reducing SJL may lead to improvements in glycemic control.