Clinical And Genetic Features Of Fulminant Type 1 Diabetes Mellitus

Objective: To investigate the clinical and genetic features of fulminant type 1diabetes mellitusMethods: Analyzed 5493 cases of the admitted diabetic mellitus patients in the Second hospital of Dalian Medical University from 2011 to 2014. 132 cases were type1 diabetes mellitus, in which 13 cases were new and abrupt onset type 1 diabetes mellitus including 5 cases of fulminant type 1 diabetes mellitus and 8 cases of non-fulminant type 1 diabetes mellitus. The place of origin of 13 cases of new and abrupt onset type 1 diabetes mellitus are northern in China. Analyzed the clinical features of FT1 DM patients, and compared with the group of non-FT1 DM patients,moreover forecasting their genetic features. Selected two patients out of 5 cases of fulminant type 1 diabetes mellitus underwent gene polymorphism detection. The‘direct sequencingr’ method was used to locate and observe following polymorphism:rs1800610 in TNF gene; rs2071800 in HLA-DQA2 gene; rs3763364 in TAP2 gene;rs2294689 in TTRAP gene.Results:1. Out of 5 cases with fulminant type 1 diabetes mellitus, four were male patients and only one was female. The age ranged between 20~36 with their BMI being23.41±3.52kg/m2 and course of disease lasted 3~6 days. 4 patients had predisposing factors and one patient did not. All of them had symptoms in digestive system and did not have history of allergic reactions to foods and medications.2. The blood glucose level of Patients with fulminant type 1 diabetes mellitus ranged from 22.34~50.50mmol/L, with a mean 34.24±10.89mmol/L. Hb A1 c ranged from6.2~7.3%, with a mean of 6.80±0.43%. Fasting C-peptide level ranged between0.00~0.28ng/ml with a mean of 0.14±0.11ng/ml. After meal C-Peptide ranged from0.01~0.48ng/ml with a mean of 0.19±0.19ng/ml. p H ranged from 7.060~7.212, with a mean of 7.14±0.06. When they were admitted all 5 cases showed negative to insulin related antibody, however, two male patients showed positive to I-AA after 3month and 1 year respectively and 3 cases showed negative to EBV-Ab, 4 cases showed raised WBC count, normal blood fat, 1 cases light elevation in ALT and AST, no anomaly found in CT and ultrasound on their upper abdomen. 2 patients showed the problems with electrolytes. Two patients showed Elevated Serum creatinine and blood amylase level. Two cases showed reduced Serum albumin.3.There was no significant difference in gender, age, and family history between the fulminant group and the non fulminant group. the mean of blood sugar level of the fulminant group is higher than that of the non-fulminant group, however, the difference is not significant(34.24±10.89mmol/L vs 23.02±13.35mmol/L,P>0.05).Patients with fulminant diabetes mellitus type 1 showed lower Hb A1 c, PCP(P<0.05)and higher BMI, ALT, Cr, K+, WBC count than those of patietns with normal diabetes mellitus after onset. Both groups had showed no difference in FCP,AST, ALB, TC, TG, HDL-C, LDL-C, Na+, p H, Hs-CRP(P>0.05). The insulin dosage used in treatment for both groups had no significant difference as well.(0.68±0.17U/kg vs 0.77±0.15 U/kg,P>0.05).4. After intensive insulin treatment the group with fulminent diabetes mellitus did not show improved function of pancreas, nor did the FCP, PCP. after 1month, 3months,and 12 months follow up, FCP and PCP did not improve, however they also did not show the tendency of microvascular disease.5.The length of PCR product of rs1800610 on gene TNF was 370 bp, the SNP of locus in both patients were G/G genotype and a heterozygous mutation c.186+364A>G in its intron region was observed in both patients. The length PCR product of rs2071800 on gene was 300 bp, the SNP of locus in both patients were G/G genotype, Some missense mutation: p.L254P; p.Q241R; p.M230V; p.L219 V in gene coding region near the locus rs2071800 were observed at the patient FT1DM5. the length of PCR product from rs3763364 in TAP2 gene was 360 bp, the SNP of locus in patient FT1DM4 was T/T genotype, while patient FT1DM5 was A/T genotype and Some heterozygous mutation: c.-1027 T>C; c.-1073 T>A; c.-1074 C>T in gene intron region near the locus rs3763364 were observed at the patient FT1DM5. thelength of PCR product from rs2294689 was 340 bp, the SNP of locus in both patients were C/G genotype, a nonsense mutation was observed at the both patients.Conclusion:1. the ratio of patients with diabetes mellitus type 1 with acute onset to the fulminent diabetes mellitus is not low. compared to the non-fulminent patietns, the patients with fulminent diabetes mellitus type 1 had more clear signs of symptoms, moreover disturbances in electrolytes and liver functions.2. Fulminant type1 diabetes causes severe damage to pancreatic functions making its casualty irreversible; no honeymoon period after intensive insulin treatment; no tendency to develop microvascular lesions.3. The genotype G/G at locus rs1800610 may be a susceptibility genotype for FT1 DM,a heterozygous mutation c.186+364A>G in its intron region have a direct correlation with the pathogenesis of fulminant type 1 diabetes.4. The genotype G/G at locus rs2071800 may be a susceptibility genotype for FT1 DM.Some missense mutation: p.L254P; p.Q241R; p.M230V; p.L219 V in gene coding region near the locus rs2071800 may be associated with the pathogenesis of FT1 DM.5. The genotype A/T and T/T at locus rs3763364 may be a susceptibility genotype for FT1 DM. Some heterozygous mutation: c.-1027 T>C; c.-1073 T>A; c.-1074 C > T in gene intron region near the locus rs3763364 may be associated with the pathogenesis of FT1 DM.6.The genotype C/G at locus rs2294689 may be a susceptibility genotype for FT1 DM.