| Objective To analyze and compare clinical characteristics of patients younger than 40 years old with type 1 diabetes mellitus(T1DM),latent autoimmune diabetes in adults(LADA),or type 2 diabetes mellitus(T2DM),and explore the risk factors of chronic complications.Methods Diabetes patients with a diagnosis age of less than 40 years old who were hospitalized in our endocrinology department in the past 2 years were screened clinically.General conditions were recorded,including height,weight,waist circumference,hip circumference,family history,spontaneous ketosis.OGTT was performed in all patients,and FPG,120 min PG,FCP,120 min CP,FINS,120 min INS,blood lipids,and Hb A1 C were measured.Patients' metabolic syndrome and chronic complications were systematically examined.The clinical characteristics of the three groups were compared and the risk factors for chronic complications were analyzed.Results A total of 322 patients with early-onset diabetes were included.45 cases(14%)were diagnosed as classic T1 DM.49 cases(15%)were LADA patients,among which 44.9% were GADA positive,and 14.3% were IAA positive.213 cases(66%)were diagnosed as T2DM,and 15 cases(5%)were other types of diabetes,including 2 cases from 53 patients who clinically suspected MODY3.1.Clinical characteristics of classic T1 DM,LADA,and T2DM patients: Compared with T2DM patients,T1 DM and LADA patients had lower FCP,120 min CP,FINS,and 120 min INS(all P<0.001),with earlier age of onset,lower BMI,TG,non-HDL,LDL,waist circumference,hip circumference,waist-hip ratio(all P<0.05).Classic T1 DM and LADA patients had higher Hb A1 C and HDL levels than T2DM patients(all P<0.001).However,there was no significant difference in 120 min PG and TC levels.The typical symptoms of diabetes,the prevalence of spontaneous ketosis in classic T1 DM and LADA were significantly higher than those in T2DM(all P <0.001),but the family history of diabetes,the incidence of metabolic syndrome were lower than those in T2DM(all P <0.001).The prevalence of neuropathy was highest in classic T1 DM and lowest in LADA(P<0.001).The incidence of macrovascular disease was highest in T2DM,and lowest in LADA(P<0.001),and there was no statistical difference in the incidence of microvascular disease(P=0.08).Comparison of islet function in the three groups: compared with T2DM group,HOMA-IR and HOMA-? were lower(both P<0.05),and IAI was higher(P<0.05)in classic T1 DM group and LADA group.2.Analysis of risk factors for microangiopathy: Disease duration(corresponding OR values were 4.44 and 3.366,both P<0.05)and poor blood glucose control(Hb A1C?7%,the OR values were 4.14 and 2.01 respectively,both P<0.05)were common risk factors for microangiopathy in LADA and T2DM patients.Non-HDL levels(OR was 17.532,P=0.008)were the risk factors for microangiopathy in LADA patients;TC>4.5mmol/L(OR was 1.926,P=0.043)was a high risk factor of microangiopathy in patients with T2DM.3.Analysis of risk factors for macroangiopathy: The disease duration,combination with MS,overweight/obesity,low HDL and high non-HDL levels were risk factors for macrovascular disease in T2DM patients(OR values were 2.812,1.721,3.637,2.258 respectively,all P<0.05).The risk factor for macrovascular disease in classic T1 DM patients were prolonged disease duration(OR 1.18,P=0.043).4.Analysis of risk factors for neurological disease: The disease duration(corresponding OR values were 1.276,5.2 and 5.392 respectively,all P<0.05)was a common risk factor for neurological impairment in patients with classic T1 DM,LADA and T2DM.Poor blood glucose control(Hb A1C?7%,OR was 1.61)is a risk factor for neurological impairment in patients with T2DM.Conclusion 1.Compared with patients with T2DM,patients with LADA and classic T1 DM had poorer islet function,smaller BMI and waist-hip circumference,and a lower incidence of metabolic syndrome and family history,a higher incidence of the typical symptoms of diabetes and spontaneous ketones.2.Risk factors for microangiopathy: The common risk factors for microangiopathy in patients with LADA and T2DM were disease duration and poor blood glucose control,and dyslipidemia may also be a common risk factor for microangiopathy in both groups.3.Risk factors for macroangiopathy: Risk factors for macroangiopathy in patients with T2DM were prolonged disease duration,combination with MS,overweight/obesity,and dyslipidemia.Prolonged disease duration was also a risk factor for macroangiopathy in classic T1 DM patients.4.Risk factors for neurological disease: The common risk factor for neurological impairment in patients with classic T1 DM,LADA,and T2DM was prolonged disease duration.Poor blood glucose control was another risk factor that causes neurological impairment in patients with T2DM.Objective So far,there has been no report on maturity onset diabetes of the young type 3(MODY3)in Inner Mongolia region of China.MODY3 is a type of autosomal dominant inherited disease caused by the mutation in the gene of hepatocyte nuclear factor(HNF1?),and is the most common but special type of diabetes in young children with diabetes onset.In order to further study the molecular genetic characteristics of HNF1? gene,we conducted an in-depth research on 2 cases of MODY3 families who were successfully found.Methods 1.According to clinical data and family data of 2 cases of proband: First of all,the history of the immediate family members of the proband was collected.Through field surveys,they were collected with general information,including family members' gender,age,generation,height,weight,and the time of blood glucose abnormality.Then the information was uniformly archived.Blood samples were taken from the subjects who were completely voluntary in the blood collection and the family map was drawn.2.Detection of HNF1? gene: Peripheral blood DNA was extracted from two family members,all exons of MODY3 were amplified by PCR,and the PCR products were purified and sequenced in two directions.The DNASTAR software was used to contrastively analyze the sequencing results with the normal sequence on NCBI.3.Collect clinical manifestations and follow-up of treatment: collect of clinical manifestations of all patients in 2 MODY3 families and treated with sulphonylureas for follow-up of glycemic control and chronic complications.Results 1.Through the sequencing of the 10 exons of the HNF1? gene in the proband,two gene mutations in MODY3 family were found successfully.The 171 codon,CGG?CGA,in exon 2 of three diabetic patients in family 1,is a missense mutation(Arg171Gln)that mutated arginine to glutamine,and five genetic polymorphism sites(Leu17Leu,Ile27 Leu,Leu459Leu,Ser574 Gly,Ser487Asn)were screened.In family 2,the 131 codon,AGC?AGT,in exon 2 of five diabetic patients,were found to be a missense mutation(Arg131Trp)that mutated arginine to tryptophan,and four gene polymorphism sites(Leu17Leu,Leu459 Leu,Ser574Gly,Ser487Asn)were found.2.In both cases of the proband,the age of onset was less than 40 years old,who had a family history,with the obvious symptoms of diabetes,the decreased level of hypersensitive C reactive protein(hs-CRP),the decreased range of threshold of renal sugar and sensibility to sulfonylureas.Conclusion 1.Two mutation sites(c.512G>A,p.Arg171 Gln and c.391C>T,and p.Arg131Trp)and 5 gene polymorphisms in HNF1? gene that had never been reported in Inner Mongolia were found,which seemed to be the most important cause of diabetes in MODY3 patients.2.The two families were consistent with the clinical characteristics of MODY3 and an autosomal dominant inheritance pattern. |
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