The Effect Of Continuous Glucose Monitoring On Pregnant Women With Type 1 Diabetes

Background:Women with type 1 diabetes mellitus(T1DM)are at increased risk of adverse pregnancy outcomes.Comprehensive maternal care,especially optimal glycemic control improves pregnancy outcomes in women with T1DM.Glycated hemoglobin(HbA1c)reflects average glycemia over approximately 3 months and is most widely accepted as a main metric for glycemic control during pregnancy with T1DM,but HbA1c cannot reflect the immediate glucose level and is affected by various common clinical conditions during pregnancy.Continuous glucose monitoring(CGM)is increasingly used as an auxiliary means to self-monitoring of blood glucose in pregnancy,generating metrics that depict a more comprehensive profile of glycemic control,including time in range(TIR),time blow range(TBR),time above range(TAR),mean amplitude of glycemic excursions(MAGE).To provide reference for clinical practice,the Advanced Technologies and Treatments for Diabetes(ATTD)guidelines and consensus have proposed pregnancy-specific standards for glycemic control targets based on CGM data:A woman with T1D during pregnancy should reach a target that the percentage of time maintaining glucose level within 3.5 to 7.8 mmol/L(TIR3.5-7.8)should be no less than 70%,time above 7.8mmol/L no more than 25%,and the time below 3.5 mmol/L no more than 4%,respectively.However,data were limited regarding the relationship between pregnancy outcomes and this recommended combination of TIR parameter cut-off values,and little is known about the relationship between CGMS indexes and laboratory HbA1c.Methods:An observational study enrolled pregnant women with T1DM who wore CGM devices during pregnancy and postpartum from 11 hospitals in China from January 2015 to June 2019(the CARNATION study).CGM data,clinical information and pregnancy outcomes were collected and analyzed.(1)Receiver operator characteristics(ROC)curve analysis was performed to assess the performance of various glycemic metrics in predicting a composite adverse pregnancy outcome(CAPO),including maternal death,neonatal death,stillbirth,congenital malformation(s),large-for-gestational age,macrosomia,pre-eclampsia,and neonatal admission to the intensive care unit.(2)Relationships between the CGM metrics and HbAlc were explored.Linear and curvilinear regressions were conducted to investigate the best-fitting model to clarify the influence of HbAlc on the TIR-HbAlc relationship during pregnancy.(3)Mix-effect regression analysis with polynomial terms and cross-validation method were conducted to investigate the best-fitting model to calculate GMI from MBG obtained by CGM.Results:A total of 272 CGM data and corresponding HbAlc from 98 pregnant women with type 1 diabetes and their clinical characteristics were analyzed in this study.The pregnant women had a mean age of 28.80±3.90 years,with a diabetes duration of 8.72±6.10 years and a mean BMI of 21.07±2.48 kg/m2.Mean HbA1c and TIR3.5-7.8mmol/L were 6.49±1.29%and 76.16±17.97%during pregnancy,respectively.(1)Forty-seven(49.48%)of the included women had CAPO.TIR3.5-7.8mmol/L(adjusted odds ratio[aOR]0.64 per standard deviation[SD],95%CI 0.41-1.00),TAR7.8mmol/L(aOR 1.14 per SD,95%CI 1.00-1.30),and HbAlc(aOR 1.81 per SD,95%CI 1.12-2.92)were associated with CAPO.ROC analysis revealed that the guideline-recommended TIR3.8-7.8mmol/L>70%,TAR7.8mmol/L<25%and TBR3.5mmol/L<4%had a moderate area under the curve(AUC)of 0.576,suboptimal compared with that of HbA1c(0.660).A tighter target of TIR3.5-7.8mmol/L>78%,TAR7.8mmol/L<18%and TBR3.5mmol/L<4%rendered a better predictive performance with an AUC of 0.633.(2)HbA1c was moderately correlated with TIR3.5-7.8mmol/L(R=-0.429,P=0.001),mean glucose(R=0.405,P=0.001)and TAR7.8mmol/L(R=0.435,P=0.001),but was weakly correlated with TBR3.5mmol/L(R=0.034,P=0.001)during pregnancy.Based on the relationship between HbAlc and TIR,a 1%(11 mmol/mol)decrease in HbA1c corresponded to an 8.5%increase in TIR3.5-7.8mmol/L.During pregnancy,HbA1c of 6.0%,6.5%and 7.0%were equivalent to a TIR3.5-7.8mmol/L of 78%,74%,and 69%,respectively.(3)The MBG levels were lower during pregnancy than those at postpartum(6.49±1.11 mmol/L vs 7.11±1.46mmol/L,P=0.013).After adjusting the confounders of hemoglobin(Hb),BMI,trimesters,disease duration,MAGE and CV%,we developed a pregnancy-specific GMI-MBG equation:GMI for pregnancy(%)=0.84-0.28*[Trimester]+0.08*[BMI in kg/m2]+0.01*[Hb in g/mL]+0.50*[MBG in mmol/L].Conclusion:With the first cohort of pregnant women with type 1 diabetes in China,we derive a pregnancy specific GMI,which is a new CGMS metric corresponding to HbA1c for pregnant women with T1DM.To achieve the HbA1c target<6.0%recommended by ADA guidance,pregnant women with T1DM should strive for TIR3.5-7.8mmol/L>78%(18h 43min)during pregnancy,but not 70%.A stricter combination of TIR3.5-7.8mmol/L>78%,TAR7.8mmoL/L<18%and TBR3.5mmol/L<4%would have a higher predictive performance of pregnancy outcomes than TIR3.5-7.8mmol/L>70%,TAR7.8mmol/L<25%and TBR3.5mmol/L<4%among T1DM.