Investigating physiological glucose excursions before, during, and after Ramadan in adults without diabetes mellitus

© 2017 Elsevier Inc. Aim The study aimed to investigate physiological effects of Ramadan fasting on continuously monitored glucose levels in relation to Ramadan in young non-diabetic adults. Methods Continuous glucose monitoring was employed to measure interstitial glucose for several days 1–2 weeks before Ramadan, in the middle of Ramadan, and 4–6 weeks after Ramadan to assess glucose exposure and glucose variability. Results A total of 34,182 accurate glucose sensor readings and 438 capillary blood glucose values [mean absolute difference median (interquartile range) 8.5 (6.9–11.1)%] were obtained from 18 non-diabetic adults [13 females; aged 24 (21–27) years; baseline body mass index 23.9 (20.6–28.9) kg/m2]. The continuous glucose monitoring profiles showed an increase in the hyperglycemic (above 140 mg/dL) area under the curve after Ramadan compared to both before (P = 0.004) and during Ramadan (P = 0.003), along with an increased glucose variability after Ramadan (P = 0.014). Both the area under the interstitial glucose concentration curve for the entire day and the average glucose were positively associated with body mass index during (P = 0.004 and P = 0.005, respectively) and after Ramadan (P = 0.013 and P = 0.01, respectively). Atypical continuous glucose patterns were recognized in 11% of subjects, distinguished by a prolonged increased glucose exposure, particularly in response to a meal. Conclusion The time-point 4–6 weeks after Ramadan was distinguished by greater glucose exposure and wider glucose variability that may reflect ongoing changes in insulin sensitivity in response to altering lifestyle patterns in non-diabetic young adults across the spectrum of body weight

MHC II tetramers visualize human CD4+ T cell responses to Epstein-Barr virus infection and demonstrate atypical kinetics of the nuclear antigen EBNA1 response

Virus-specific CD4(+) T cells are key orchestrators of host responses to viral infection yet, compared with their CD8(+) T cell counterparts, remain poorly characterized at the single cell level. Here we use nine MHC II–epitope peptide tetramers to visualize human CD4(+) T cell responses to Epstein–Barr virus (EBV), the causative agent of infectious mononucleosis (IM), a disease associated with large virus-specific CD8(+) T cell responses. We find that, while not approaching virus-specific CD8(+) T cell expansions in magnitude, activated CD4(+) T cells specific for epitopes in the latent antigen EBNA2 and four lytic cycle antigens are detected at high frequencies in acute IM blood. They then fall rapidly to values typical of life-long virus carriage where most tetramer-positive cells display conventional memory markers but some, unexpectedly, revert to a naive-like phenotype. In contrast CD4(+) T cell responses to EBNA1 epitopes are greatly delayed in IM patients, in line with the well-known but hitherto unexplained delay in EBNA1 IgG antibody responses. We present evidence from an in vitro system that may explain these unusual kinetics. Unlike other EBNAs and lytic cycle proteins, EBNA1 is not naturally released from EBV-infected cells as a source of antigen for CD4(+) T cell priming

TRIALS STUDY PROTOCOL Open Access

to prevent cardiovascular events in early-stage chronic kidney disease (STOP-CKD): study protocol for a randomized controlled pilot tria