HbA 1C variability and hypoglycemia hospitalization in adults with type 1 and type 2 diabetes: A nested case-control study

Aims To determine association between HbA1C variability and hypoglycemia requiring hospitalization (HH) in adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). Methods Using nested case-control design in electronic health record data in England, one case with first or recurrent HH was matched to one control who had not experienced HH in incident T1D and T2D adults. HbA1C variability was determined by standard deviation of ≥ 3 HbA1C results. Conditional logistic models were applied to determine association of HbA1C variability with first and recurrent HH. Results In T1D, every 1.0% increase in HbA1C variability was associated with 90% higher first HH risk (95% CI, 1.25–2.89) and 392% higher recurrent HH risk (95% CI, 1.17–20.61). In T2D, a 1.0% increase in HbA1C variability was associated with 556% higher first HH risk (95% CI, 3.88–11.08) and 573% higher recurrent HH risk (95% CI,1.59–28.51). In T2D for first HH, the association was the strongest in non-insulin non-sulfonylurea users (P < 0.0001); for recurrent HH, the association was stronger in insulin users than sulfonylurea users (P = 0.07). The HbA1C variability-HH association was stronger in more recent years in T2D (P ≤ 0.004). Conclusions HbA1C variability is a strong predictor for HH in T1D and T2D

Dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes

Aims To determine the association between dietary intake and risk of non-severe hypoglycemia in adolescents with type 1 diabetes. Methods Type 1 adolescents from a randomized trial wore a blinded continuous glucose monitoring (CGM) system at baseline for one week in free-living conditions. Dietary intake was calculated as the average from two 24-h dietary recalls. Non-severe hypoglycemia was defined as having blood glucose < 70 mg/dL for ≥ 10 min but not requiring external assistance, categorized as daytime and nocturnal (11 PM–7AM). Data were analyzed using logistic regression models. Results Among 98 participants with 14,277 h of CGM data, 70 had daytime hypoglycemia, 66 had nocturnal hypoglycemia, 55 had both, and 17 had neither. Soluble fiber and protein intake were positively associated with both daytime and nocturnal hypoglycemia. Glycemic index, monounsaturated fat, and polyunsaturated fat were negatively associated with daytime hypoglycemia only. Adjusting for total daily insulin dose per kilogram eliminated all associations. Conclusions Dietary intake was differentially associated with daytime and nocturnal hypoglycemia. Over 80% of type 1 adolescents had hypoglycemia in a week, which may be attributed to the mismatch between optimal insulin dose needed for each meal and actually delivered insulin dose without considering quality of carbohydrate and nutrients beyond carbohydrate

Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events42Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases

Understanding the role of bitter taste perception in coffee, tea and alcohol consumption through Mendelian randomization

Consumption of coffee, tea and alcohol might be shaped by individual differences in bitter taste perception but inconsistent observational findings provide little insight regarding causality. We conducted Mendelian randomization analyses using genetic variants associated with the perception of bitter substances (rs1726866 for propylthiouracil [PROP], rs10772420 for quinine and rs2597979 for caffeine) to evaluate the intake of coffee, tea and alcohol among up to 438,870 UK Biobank participants. A standard deviation (SD) higher in genetically predicted bitterness of caffeine was associated with increased coffee intake (0.146 [95%CI: 0.103, 0.189] cups/day), whereas a SD higher in those of PROP and quinine was associated with decreased coffee intake (-0.021 [-0.031, -0.011] and -0.081 [-0.108, -0.054] cups/day respectively). Higher caffeine perception was also associated with increased risk of being a heavy (>4 cups/day) coffee drinker (OR 1.207 [1.126, 1.294]). Opposite pattern of associations was observed for tea possibly due to the inverse relationship between both beverages. Alcohol intake was only negatively associated with PROP perception (-0.141 [-1.88, -0.94] times/month per SD increase in PROP bitterness). Our results reveal that bitter perception is causally associated with intake of coffee, tea and alcohol, suggesting a role of bitter taste in the development of bitter beverage consumption.Jue-Sheng Ong, Liang-Dar Hwang, Victor W. Zhong, Jiyuan An, Puya Gharahkhani ... Deborah A. Lawlor ... et al