| Objective:To investigate the clinical features of pregnancy-associated fulminant type 1diabetes mellitus（PF）,and to discuss the strategies for early detection,early diagnosis,and standardized management,thereby improving pregnancy outcomes and providing valuable insights for clinical practices.Methods:Clinical data of 91 cases related to PF in Chinese and English database from January2000 to January 2022 were collected,and other 6 patients from the Third Affiliated Hospital of Guangzhou Medical University（our hospital）from August 31,2017 to September 1,2020 were included in the present study.General data,laboratory indexes,and pregnancy outcomes of the patients were collected for analysis.The study consists of three parts:（1）A systematic clinical analysis of 97 PF patients was performed.（2）According to fetal prognosis,patients were divided to fetal live birth group and fetal loss group;also according to the regions of onset,patients were divided to domestic and foreign groups,then comparative study was peformed between two groups.（3）6 cases of PF in our hospital were analyzed separately.Result:（1）The mean age of the patients was 29.49±5.33 years old.51 cases described the parity,41.2%（21/51）were primipara,58.8%（30/51）were multipara.4.1%（4/97）occured in the first trimester,83.5%（81/97）in the second and third trimesters and 12.3%（12/97）within 2 weeks of Postpartum.There were 49 cases described the onset time（both reported in China）,22.4%（11/49）in spring,18.4%（9/49）in summer,20.4%（10/49）in autumn and 38.8%（19/49）in winter.There were 65 cases reported OGTT results during pregnancy,87.7%（57/65）were normal and 12.3%（8/65）were diagnosed with GDM.Number of cases rank the top four were Guangdong,Beijing,Guangxi and Shanghai.Number one in Southeast Asia was Japan.（2）The mean blood glucose at onset was 33.4±8.91 mmol/L;The mean value of Hb A1c was 6.07±0.65%;The mean value of PG/Hb A1c was 5.56±1.63;C-peptide was detected in 90 cases,the fasting serum C-peptide values<0.3 ng/m L and post-glucagon load C-peptide values<0.5 ng/m L.Test positive for islet autoantibodies occurred in 11of 80 patients（13.7%）.47.4%（46/97）had influenza-like symptoms,71.1%（69/97）had gastrointestinal symptoms,62.8%（59/97）had obstetric symptoms such as vaginal bleeding,uterine contraction pain and fetal movement reduction and so on prodromal symptoms.61.9%（60/97）had diabetes symptoms such as thirsty,polydipsia and polyuria.The incidence of Rhabdomyolysis（RM）was 2.1%（2/97）,acute renal failure（ARF）was 2.1%（2/97）;hyperkalemia was 45.4%（44/97）and metabolic acidosis was 98.9%（96/97）.The specific p H value was recorded in 89 cases,15.7%（14/89）were mild acidosis,21.3%（19/89）were moderate acidosis and 62.9%（56/89）were severe acidosis.The shortest time from admission to DKA been corrected last 7 hours and the longest last 3 days.No maternal deaths occurred.83 patients had fetal outcomes reported,with fetal loss rate 73.5%（61/83）,and live birth rate 26.5%（22/83）.（3）Grouping-based comparative study:Fetal live birth group and fetal loss group were 22 and 61cases.The comparison of the two groups suggested that the proportion of the first trimester,and blood glucose value in fetal loss group were higher than that in fetal live birth group,and Hb A1c in the fetal live birth group was higher than that in the fetal loss group,but it was not statistically significant.The between-group differences in islet autoantibodies,virus detection,premonitory symptoms,complications,and acidosis severity were not statistically significant.The domestic group and the foreign group were76 and 21 cases.The mean age of PF in the domestic group was lower than that of the foreign group（28.88±4.95 years vs31.71±6.15 years,P=0.03）,and the mean value of PG/Hb A1c was lower than that of the foreign group（5.37±1.29 vs 6.2±2.42,P=0.037）,and the incidence of consciousness disorder is lower than that of foreign PF（10.5%vs 42.9%,P=0.002）.But no evidence suggested more severeβcell destruction and metabolic disorder in domestic group.（4）The incidence of PF in our hospital was 0.026%（6/22693）.The mean age of 6patients was 31.50±5.35 years old;Its onset gestational week was during 21+2～34+4weeks,6 cases had flu-like or digestive tract or fetal movement abnormalities and other prodromal symptoms.The time from onset to development of DKA was 1.75±1.25 d.The mean initial blood glucose level upon admission was 26.91±4.01 mmol/L.The fasting serum and 2 h postprandial C-peptide values were extremely low（<0.01-0.13mmol/L）,and the mean Hb A1c was 6.25±0.69%.All the patients suffered moderate to severe acidosis.The duration from admission to correction of DKA ranged from 9 hours to 3 days.Regarding maternal and fetal outcomes,the mean gestational week of delivery was31.02±5.55 weeks.2 stillbirths and 4 live births were reported.2 cases of stillbirth were induced by Rivanol.As to the 4 live births,2 cases were terminated by cesarean section nearly 34 weeks upon onset,and the other 2 cases had gestation time prolonged for respectively 40 days and 109 days before cesarean section.Postpartum follow-up showed that all the 6 patients required insulin replacement therapy after delivery.2 of them had scheduled conception again,and achieved good maternal and infant outcomes with well-controlled blood glucose levels during pregnancy.Conclusions:1.PF is a rare.The incidence rate of PF in our hospital is 0.026%,with the highest incidence in the second and third trimester,followed by puerperium,then in the first trimester.Number of cases rank the top four in China were Guangdong,Beijing,Guangxi and Shanghai,totally accounting for more than 10%.There was a high incidence rate of PF in Southeast Asia,especially in Japan.It should be alerted that GDM pregnant women can also develop PF due to insulin allergy and other reasons.2.PF is a diabetes emergency and severe disease that can lead to high fetal loss and is often misdiagnosed.It characterized by acute onset and rapid progression from non-specific premonitory symptoms to DKA.and non-specific premonitory symptoms just like flu-like and gastrointestinal symptoms.The shortest time from admission to DKA been corrected last 7 hours and the longest last 3 days.PF patients maybe occur Serious complications such as disturbance of consciousness or coma,acute pancreatitis,rhabdomyolysis and acute renal failure and so on.3.Mostly PF patients require lifelong insulin replacement therapy.PF patients have more severeβcell destruction than NPF patients.The condition of PF in domestic group was no worse than that in foreign group.The factors affecting fetal survival in PF pregnant remain unclear,which may be related to the insufficient total number of cases.Hence,further research is demanded.4.It is key point that early detection and diagnosis of PF by timely monitoring of blood glucose and ketone body in pregnant women with non-specific premonitory symptoms.and the crucial management of PF is correcting DKA on time.Multi-Disciplinary Treatment（MDT）is required to improve the pregnancy outcomes.Abnormal fetal heart rate monitoring is not necessarily an indication for immediate delivery of PF pregnant.Comprehensive treatment can be performed to control and stabilize DKA conditions and prolong gestational weeks,and then individualized treatment can be implemented. |
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