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A gap currently exists between our expectations of tight blood glucose control and the reality of safely achieving it before and during pregnancy. Technological and pharmaceutical advances will not in isolation prevent poor pregnancy outcomes without recognising the social, cultural and behavioural context of the women living with diabetes. Neither will behavioural and/or educational programmes completely overcome the fundamentally disordered metabolic pathways and physiological challenges of pregnancy. Improved integration of the technological, behavioural and educational aspects of diabetes care will pave the way for truly personalized, interdisciplinary diabetes management and ultimately improved pregnancy outcomes for women with diabetes and their infants.

Objective: To evaluate the effectiveness of continuous glucose monitoring during pregnancy on maternal glycaemic control, infant birth weight, and risk of macrosomia in women with type 1 and type 2 diabetes., Design: Prospective, open label randomised controlled trial., Setting: Two secondary care multidisciplinary obstetric clinics for diabetes in the United Kingdom., Participants: 71 women with type 1 diabetes (n=46) or type 2 diabetes (n=25) allocated to antenatal care plus continuous glucose monitoring (n=38) or to standard antenatal care (n=33)., Intervention: Continuous glucose monitoring was used as an educational tool to inform shared decision making and future therapeutic changes at intervals of 4-6 weeks during pregnancy. All other aspects of antenatal care were equal between the groups., Main Outcome Measures: The primary outcome was maternal glycaemic control during the second and third trimesters from measurements of HbA(1c) levels every four weeks. Secondary outcomes were birth weight and risk of macrosomia using birthweight standard deviation scores and customised birthweight centiles. Statistical analyses were done on an intention to treat basis., Results: Women randomised to continuous glucose monitoring had lower mean HbA(1c) levels from 32 to 36 weeks' gestation compared with women randomised to standard antenatal care: 5.8% (SD 0.6) v 6.4% (SD 0.7). Compared with infants of mothers in the control arm those of mothers in the intervention arm had decreased mean birthweight standard deviation scores (0.9 v 1.6; effect size 0.7 SD, 95% confidence interval 0.0 to 1.3), decreased median customised birthweight centiles (69% v 93%), and a reduced risk of macrosomia (odds ratio 0.36, 95% confidence interval 0.13 to 0.98)., Conclusion: Continuous glucose monitoring during pregnancy is associated with improved glycaemic control in the third trimester, lower birth weight, and reduced risk of macrosomia., Trial Registration: Current Controlled Trials ISRCTN84461581.

Naegeli-Franceschetti-Jadassohn syndrome (NFJS) is a rare autosomal dominant disorder characterized by loss of dermatoglyphics, reticulate hyperpigmentation of the skin, palmoplantar keratoderma, abnormal sweating, and other developmental anomalies of the teeth, hair, and skin. We recently demonstrated that NFJS is caused by heterozygous nonsense or frameshift mutations in the E1/V1-encoding region of KRT14, but the mechanisms for their deleterious effects in NFJS remain elusive. In this study, we further expand the spectrum of NFJS-causing mutations and demonstrate that these mutations result in haploinsufficiency for keratin 14 (K14). As increased apoptotic activity was observed in the epidermal basal cell layer in NFJS patients and as previous data suggested that type I keratins may confer resistance to tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in epithelial tissues, we assessed the effect of down-regulation of KRT14 expression on apoptotic activity in keratinocytes. Using a HaCaT cell-based assay, we found that decreased KRT14 expression is associated with increased susceptibility to TNF-alpha-induced apoptosis. This phenomenon was not observed when cells were cultured in the presence of doxycycline, a known negative regulator of TNF-alpha-dependant pro-apoptotic signaling. Collectively, our results indicate that NFJS results from haploinsufficiency for K14 and suggest that increased susceptibility of keratinocytes to pro-apoptotic signals may be involved in the pathogenesis of this ectodermal dysplasia syndrome.

Objective: To examine the changes in glycemic excursions that occur during pregnancy using continuous glucose monitoring and to compare patterns of glycemia in pregnant women with type 1 and type 2 diabetes., Research Design and Methods: An observational data analysis was performed from a prospective randomized study of continuous glucose monitoring in 57 women with pregestational type 1 (n = 40) or type 2 (n = 17) diabetes with 7-day continuous glucose monitoring system profiles during each trimester. Serial glucose measurements were divided into periods of euglycemia (70-140 mg/dl), hyperglycemia (>140 mg/dl), and hypoglycemia (<70 mg/dl). Generalized linear mixed effects models were fitted to the repeated measures data to determine how these glycemic characteristics varied during gestation and by diabetes type., Results: A total of 180 continuous glucose profiles were examined (140 type 1 diabetes, 40 type 2 diabetes), providing 20,433 h of data for analysis (16,117 h type 1 diabetes, 4,316 type 2 diabetes). Women with type 2 diabetes spend approximately 33% less time hyperglycemic throughout pregnancy than women with type 1 diabetes (P = 0.005), with a significantly more rapid reduction in time spent hyperglycemic in early pregnancy (P = 0.02). Although women with type 2 diabetes spend less overall time hypoglycemic (P = 0.04), their risk of nocturnal hypoglycemia is equivalent to that of women with type 1 diabetes (blood glucose level <70 mg/dl, P = 0.9; blood glucose level <50 mg/dl, P = 0.2)., Conclusions: Continuous glucose monitoring reveals clear differences in the level of glycemic control that exist in women with type 1 and type 2 diabetes. These data will guide therapeutic interventions aimed at optimizing glycemic control and improving the pregnancy outcomes of both type 1 and type 2 diabetes.

Objective: The objective of this study was to examine the relationship between prepregnancy care, glycemic control, maternal hypoglycemia, and pregnancy outcomes in women with type 1 diabetes., Research Design and Methods: This was a prospective observational cohort study of women with type 1 diabetes who delivered from 1991 to 2002. Outcome measures were attendance at a clinic for prepregnancy care, maternal HbA(1c) (A1C) throughout pregnancy, maternal severe hypoglycemic episodes, macrosomia, preeclampsia, premature delivery (delivery before 37 weeks), very premature delivery (delivery before 34 weeks), spontaneous abortion, and adverse pregnancy outcome (defined as major malformation, stillbirth, and neonatal death)., Results: There were 290 pregnancies, in which 110 (38%) women had prepregnancy care. The prepregnancy care group contained more primiparous women (54.7 vs. 40.6%; P = 0.021) and fewer smokers (9.4 vs. 28.7%; P < 0.0001). They registered earlier (6.6 vs. 8.3 weeks, P < 0.0001) and had a lower A1C at the initial visit (6.5% vs. 7.6%; P < 0.0001). Adverse pregnancy outcomes and very premature deliveries were significantly lower in women who received prepregnancy care (2.9 vs. 10.2%; P = 0.03 and 5.0 vs. 14.2%; P = 0.02, respectively). In contrast, between groups, there was no difference in A1C after 24 weeks or in the rates of macrosomia, preeclampsia, or maternal severe hypoglycemic episodes., Conclusions: Prepregnancy care was associated with improved glycemic control in early pregnancy and significant reductions in adverse pregnancy outcome (malformation, stillbirth, and neonatal death) and very premature delivery. However, prepregnancy care failed to have an impact on glycemic control in later pregnancy or to reduce the risk of macrosomia and preeclampsia.