Clinical Study Of Fulminant Type 1 Diabetes

Background:Fulminant type 1 diabetes mellitus(fT1DM)is a distinct subtype of type 1 diabetes.The clinical features of the disease include rapid onset of hyperglycemia within one week,ketosis or ketoacidosis at onset,absolute deficiency in insulin secretion,and near-normal glycated hemoglobin(HbAic)level,elevated serum pancreatic enzyme levels,and islet-related autoantibodies undetectable.fT1DM can occurred during pregnancy or within 2 weeks after delivery,and was defined as pregnancy-associated fulminant type 1 diabetes(PF).In fT1DM and PF patients,plasma glucose(PG)levels have an abrupt rise while glycated hemoglobin(HbA1c)levels are not markedly elevated,resulting in a sharply-increased PG/HbA1c ratio.Methods:Part 1:We report 41 cases of fT1DM and study the PG/HbAic ratio as new clinical parameters in predicting fT1DM.The clinical and biochemical characteristics of 41 fT1DM and 51 diabetic ketoacidosis(DKA)patients in China were analyzed.Receiver-operating characteristic curves analysis was used to identify the cut-off points of PG/HbA1c ratio to detect fT1DM in DKA patients.Part 2:We studied 30 PF patients,21 non-pregnant fulminant type 1 diabetes(NPF)patients,and 26 female patients of child-bearing age(13-49 years)with diabetic ketoacidosis(DKA),all from China.We analyzed the PG/HbA1c ratio among these groups,with the goal of finding a method for predicting PF.The clinical and biochemical characteristics of the PF and NPF patients were analyzed and compared with the characteristics of the DKA patients.To detect PF in DKA patients,receiver-operating characteristic curves analysis was used to identify the cut-off points of the PG/HbA1c ratio.Part 3:Microarray analysis of circRNA expression profiles in healthy individuals and fT1DM were done.Results:PG/HbAic ratio was significantly higher in fT1DM patients(7.24± 2.49)than in DKA patients(2.60 ± 0.69;P<0.001).PG/HbAic ratio was>4.2 in 39 out of 41 fT1DM patients(95.1%),compared with only one of 51 DKA patients(1.9%).When we compared the clinical characteristics of these three groups,we found that the onset of hyperglycemic symptoms,arterial PH value,serum potassium,PG,HbAic,fasting and postprandial serum C-peptide concentration,glutamic acid decarboxylase(GAD)antibodies positivity were all significantly different(P<0.001).The PG/HbAic ratio was significantly higher in PF and NPF patients(5.29 ± 1.39 and 6.38± 2.62)than in DKA patients(1.93 ±0.55;P<0.001).Receiver operating characteristic(ROC)curves analyses showed that PG/HbAic ratio at a cut-off value of 3.3 resulted in the highest Youden index,with corresponding sensitivity of 93%and 100%specificity for identifying PF from DKA.Microarray analysis of circRNA expression profiles showed that 86 differential expressions were detected in fT1DM,of which 72 were up-regulated and 14 were down-regulated.Conclusions:PG/HbAic ratio is a simple tool that may be useful for DKA patients to identify high-risk patients,and the PG/HbAic ratio with a threshold of?4.2 can be adopted as a new clinical parameter in predicting fT1DM.PF patients showed a more severe acidosis,with maternal and fetal mortality rates being high.PG/HbAic ratio with a threshold of?3.3 can be used as a cut-off point in predicting PF from DKA in China.Elevated PG/HbAic ratio at the time of diagnosis is predictive for more severe insulin secretion dysfunction and poor prognosis.Microarray analysis of circRNA expression profiles suggest that circRNA may be involved in the pathogenesis of fT1DM.