INTRODUCTIONInsulin resistance in latent autoimmune diabetes in adults (LADA) patients is controversial. The aim of this study was to evaluate insulin resistance and its related factors (metabolic syndrome parameters) among subjects with LADA and glutamic acid decarboxylase antibodies (GADA) negative diabetes, as well as the impact of these factors on insulin resistance.

MATERIALS AND METHODSGADA levels were investigated in 1140 diabetic patients aged between 30 and 70 years. Insulin resistance and metabolic syndrome parameters were assessed in LADA and GAD-negative diabetic patients by general linear model. In addition, the impact of metabolic syndrome factors on insulin resistance was assessed in LADA and glutamic acid decarboxylase (GAD)-negative diabetic patients.

RESULTSLADA was diagnosed in 33 subjects from 1140 Malaysian diabetic patients (prevalence = 2.9%). The results showed that LADA patients had higher insulin resistance and high density lipoprotein cholesterol (HDLc) (P = 0.003 and 0.00017 respectively) and lower body mass index (BMI) (P = 0.007) compared to GAD-negative diabetic patients. The HDLc was associated with decreased insulin resistance in LADA patients (P = 0.041), whereas HbA1c, triacylglycerides (TG) and waist were associated with increased insulin resistance in GAD-negative diabetic patients (P = 3.6×10⁻¹², 1.01×10⁻⁵ and 0.004 respectively). HbA1c was highly associated with decreasing β-cell function in both LADA (P = 0.009) and GAD-negative diabetic subjects (P = 2.2×10⁻²⁸).

CONCLUSIONInsulin resistance is significantly higher in LADA than GAD-negative diabetic Malaysian subjects.

Adult ; Antibodies ; blood ; Diabetes Mellitus, Type 1 ; blood ; metabolism ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Insulin Resistance ; Male ; Middle Aged

OBJECTIVETo investigate the relation between insulin resistance and glutamic acid decarboxylase antibody (GAD-Ab) titers in latent autoimmune diabetes in adults (LADA).

METHODSThe patients with phenotypic type 2 diabetes were screened for GAD-Ab positivity, and the 141 positive patients were divided into two subgroups according to the GAD-Ab titer, namely the high-titer group (LADA-1 subtype) and low-titer group (LADA-2 subgroup). The clinical features and insulin resistance were compared between the two groups. Insulin resistance was calculated by HOMA 2 software, and GAD-Ab and C peptide were determined with radioligand and radioimmune assay, respectively.

RESULTSCompared with low-titer LADA patients, the patients with high titers had younger age of onset, lower BMI, higher HbA1c level, and worse fasting and postprandial C peptide levels. The insulin resistance index by HOMA 2 was significantly lower in LADA-1 group than in LADA-2 group (1.6-/+1.1 vs 2.1-/+1.1, P=0.001). The HOMA2-IR index showed a negative correlation to GAD-Ab titer.

CONCLUSIONThe degree of insulin resistance is correlated to GAD-Ab titers in LADA, and low titer patients have higher insulin resistance level.

Adult ; Aged ; Autoantibodies ; blood ; Autoimmune Diseases ; diagnosis ; immunology ; Diabetes Mellitus, Type 2 ; diagnosis ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Insulin Resistance ; Islets of Langerhans ; immunology ; physiology ; Male ; Middle Aged

OBJECTIVETo investigate the prevalence of metabolic syndrome (MS) in latent autoimmune diabetes in adults (LADA) and to study the positivity of glutamic acid decarboxylase autoantibody (GADA) in diabetic patients with MS.

METHODSSera of 598 patients with an initial diagnosis of type 2 diabetes (T2DM) were screened for GADA with radioligand assay. These patients were divided into LADA and T2DM groups according to the titers of GADA to compare the prevalence of MS; the proportions of LADA in diabetic patients with and without MS were studied. We also compared the clinical characteristics of LADA patients with and without MS.

RESULTSAbout 23.7% of the LADA patients had MS. In patients with MS, the prevalence of LADA was 10.0%, of which approximately 95% had low GADA titers, that was, belonging to LADA-type 2. Compared with LADA patients with MS, LADA without MS were similar to classical type 1 diabetes and had features of low body weight, tendency to develop ketosis and impaired islet cell function.

CONCLUSIONAbout 23.7% patients with MS are found in LADA patients. The GADA levels in LADA patients with and without MS are significantly different, which may need different therapeutic strategies.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; immunology ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; immunology ; Diabetes Mellitus, Type 2 ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Male ; Metabolic Syndrome ; epidemiology ; immunology ; Middle Aged ; Prevalence

OBJECTIVETo compare the clinical characteristics between type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA) with different titers of glutamic acid decarboxylase autoantibody (GADA) and to define the two distinct subtypes of LADA.

METHODSSera of 750 patients with an initial diagnosis of T2DM from central south of China were screened for GADA using a radioligand assay. The distribution and frequency of GADA levels were described. Two hundred and ninety-five patients were divided into the T2DM group (n = 233) and the LADA group (n = 62) to compare the age of onset, body mass index, HbA(1c), C-peptide, hypertension, dyslipidemia and chronic diabetic complications. Furthermore, LADA patients with different GADA titers were subdivided to analyze the same indexes as the above.

RESULTSThe prevalence of LADA (defined as GADA > or = 0.05, namely GADA positive) was 9.7% in the 750 initially diagnosed type 2 diabetic patients. Compared with T2DM, LADA patients were younger at their ages of onset, had lower C-peptide and body mass index, and also had less cases with hypertension and with dyslipidemia. However, only patients with high titer of GADA had poorer beta cell functions and less diabetic complications compared to T2DM and low GADA titer of LADA patients. Patients with low GADA titer were similar to T2DM patients, except that they were prone to develop ketosis more frequently.

CONCLUSIONSTwo clinically distinct subtypes of LADA can be identified by GADA levels in patients initially-diagnosed as type 2 diabetes. Patients with high titer of GADA (GADA > or = 0.5) subsequently develop more insulin dependency, which are classified as LADA-type 1; while those with lower GADA titer (0.05 < or = GADA < 0.5) and having clinical and metabolic phenotypes of type 2 diabetes are classified as LADA-type 2.

Adult ; Aged ; Aged, 80 and over ; Autoantibodies ; analysis ; Autoimmune Diseases ; classification ; immunology ; Diabetes Mellitus, Type 1 ; classification ; immunology ; Diabetes Mellitus, Type 2 ; classification ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Male ; Middle Aged

OBJECTIVETo investigate the diagnostic value of serum islet autoantibody-glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) in patients with hepatogenic diabetes.

METHODSSerum GADA and ICA were measured with enzyme-linked immunosorbent assay (ELISA) in 217 patients with chronic hepatitis B (CH) or liver cirrhosis (LC). The positivity rate of GADA and ICA in different phases of CH and LC and their relations with diabetes mellitus were analyzed.

RESULTSThe positivity rate of the islet autoantibody in the circulation was 72% in CH and LC patients with diabetes mellitus and 30% in patients with normal glucose level, showing significant difference between the two patient groups (Chi2=36.620, P=0.000). CH patients with diabetes had much higher positivity rate for the antibody [52% than type 2 diabetic patients with liver dysfunction [8%, P<0.05]. The positivity rate was also much higher in CH and LC patients with lowered C peptide level [70%] than in those with normal C peptide level [40%, P<0.005].

CONCLUSIONBoth GADA and ICA have important value in the diagnosis of hepatogenic diabetes and may serve as indexed in laboratory test for distinguishing hepatogenic diabetes from type 2 diabetes.

Adult ; Autoantibodies ; blood ; Diabetes Mellitus, Type 1 ; complications ; diagnosis ; immunology ; Diabetes Mellitus, Type 2 ; complications ; diagnosis ; immunology ; Diagnosis, Differential ; Female ; Glutamate Decarboxylase ; immunology ; Hepatitis B, Chronic ; complications ; Humans ; Islets of Langerhans ; immunology ; Liver Cirrhosis ; complications ; Male ; Middle Aged ; Predictive Value of Tests

BACKGROUNDGlutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features.

METHODSTwo hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well.

RESULTSDuring the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of β cell function.

CONCLUSIONOur data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the β cell function in Chinese patients.

Adolescent ; Adult ; Aged ; Antibodies ; therapeutic use ; Asian Continental Ancestry Group ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1 ; drug therapy ; immunology ; Female ; Glutamate Decarboxylase ; immunology ; Glycated Hemoglobin A ; metabolism ; Humans ; Infant ; Male ; Middle Aged ; Protein Tyrosine Phosphatases ; immunology ; Young Adult

OBJECTIVETo investigate the cross-reactivity between glutamic acid decarboxylase (GAD)-I-A(g7) and I-A(d) tetramer in diabetes-prone non-obese diabetic (NOD) mice (I-A(g7)) and diabetes-free Balb/c mice (I-A(d)).

METHODSTwo GAD peptide I-A(g7) and I-A(d) tetramers were generated and compared for phenotype and function of sorted GAD peptide I-A(g7) and I-A(d) tetramer-positive (tet+) T cells.

RESULTSThe cross-reactivity is shown in either tetramer positive percentage or tetramer staining intensity. The NOD and Balb/c derived-tet+ T cells were able to be cross-stained by GAD peptide I-A(g7) and I-A(d) tetramers, and responded to both irradiated NOD and Balb/c splenotyes under stimulation by synthetic and recombinant GAD peptides.

CONCLUSIONAlthough I-A(g7) and I-A(d) are closely related in biochemical and biological aspects, their most notable difference is the presence or absence of a negatively charged residue at position beta57 that links to insulin-dependent diabetes mellitus.

Amino Acid Sequence ; Animals ; Cross Reactions ; Female ; Glutamate Decarboxylase ; immunology ; Histocompatibility Antigens Class II ; immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Molecular Sequence Data ; T-Lymphocytes ; immunology

OBJECTIVETo investigate the positive frequency and distribution of glutamic acid decarboxylase antibody(GAD-Ab) in phenotypic type 2 diabetic(T2DM) patients.

METHODSSera of 2035 phenotypic T2DM patients were screened for GAD-Ab with radioligand assay. The positive frequency of GAD-Ab and its relation with clinical features were analyzed.

RESULTS(1) The positivity of GAD-Ab in clinic-based, phenotypic T2DM patients was 7.1% (145/2035), comparable to that of data from Caucasians as shown by UKPDS(8.7% vs. 9.8%, P = 0.391) and ADOPT (8.0% vs. 4.2%, P = 0.000) but higher than that of Japanese in Ehime study(7.1% vs. 3.8%, P = 0.000). (2) The positive frequency and distribution of GAD-Ab titer were related to clinical features, including age at onset, body mass index (BMI) and fasting C peptide levels. Patients with younger age at onset (0.33 vs. 0.11, P < 0.05), less BMI (0.34 vs. 0.10, P < 0.05) and lower C peptide levels (0.38 vs. 0.11, P < 0.05) would have higher GAD-Ab titers.

CONCLUSION(1)The positivity of GAD-Ab in adult-onset phenotypic T2DM in Chinese was similar to that of Caucasians but higher than that of the Japanese. (2) The distribution of GAD-Ab titers was associated with clinical features, with high GAD-Ab titers for those having younger age at onset, less BMI and lower C peptide levels.

Adolescent ; Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Antibodies ; immunology ; metabolism ; Body Mass Index ; Case-Control Studies ; Child ; Child, Preschool ; Diabetes Mellitus, Type 2 ; diagnosis ; metabolism ; pathology ; physiopathology ; Female ; Glutamate Decarboxylase ; immunology ; Humans ; Infant ; Male ; Middle Aged ; Phenotype ; Young Adult

BACKGROUND: Type 1 diabetes mellitus is frequently associated with other autoimmune diseases. The occurrence of common features of autoimmune diseases and the coassociation of multiple autoimmune diseases in the same individual or family supports the notion that there may be common genetic factors. METHODS: To investigate potential clustering of autoimmune thyroid disease (ATD) among type 1 diabetes patients and the contribution of common susceptibility genes to this, HLA DR/DQ alleles as well as antithyroid autoantibodies were measured in 115 Korean patients with type 1 diabetes and their 96 first-degree family members. RESULTS: Twenty-five percent of the patients had ATD, whereas 3 of 36 (8%) age-matched normal controls had ATD (RR = 3.7, p < 0.05). Twenty-six of ninty-six (27%) type 1 diabetes family members had ATD. No differences in the distribution of HLA alleles/haplotypes and genotypes between the patients with and without ATD were found. CONCLUSION: From this finding, we could assess that individuals with type 1 diabetes and their relatives frequently develop ATD, perhaps due to common susceptibility genes that are shared among first degree relatives.
Adult ; Alleles ; Autoantibodies/blood ; Autoimmune Diseases/epidemiology* ; Child ; Child, Preschool ; Diabetes Mellitus, Insulin-Dependent/genetics ; Diabetes Mellitus, Insulin-Dependent/complications* ; Female ; Glutamate Decarboxylase/immunology ; HLA-DQ Antigens/genetics ; HLA-DR Antigens/genetics ; Human ; Male ; Prevalence ; Thyroid Diseases/epidemiology*

OBJECTIVETo evaluate the associations of human leukocyte antigen (HLA) DQB1 gene with onset age and autoantibodies in type 1 diabetes mellitus(T1DM) in Chinese Han population in Sichuan area.

METHODSForty-six type 1 diabetic patients and 52 healthy control subjects were involved in this study. HLA-DQB1 typing was performed by polymerase chain reaction-sequence specific primer(PCR-SSP). Glutamic acid decarboxylase antibody (GADA) and islet cell antibody (ICA) were qualitatively analyzed by enzyme linked immunosorbent assay (ELISA).

RESULTSThe positive rate of DQB1*0201 was higher in T1DM than in controls (OR=18, P<0.005), but those of DQB1*0601, *0602 were higher in controls than in T1DM(OR=0.07, 0.31 respectively, both P<0.05).The positive rate of DQB1*0602 in type 1 diabetic patients with onset age>or=20 years was higher than that in the patients with onset age <20 years (P<0.05). GADA was more frequent in DQB1*0201(+) patients than in DQB1*0201 (-) patients (P<0.025).

CONCLUSIONThe findings show that DQB1*0201 is susceptible to T1DM, whereas DQB1*0601, *0602 are protective in Chinese Han population in Sichuan area. DQB1*0602 may delay the onset of T1DM. The positive rate of DQB1*0201 correlates positively with that of GADA.

Adolescent ; Adult ; Age of Onset ; Autoantibodies ; immunology ; Child ; Child, Preschool ; China ; epidemiology ; Diabetes Mellitus, Type 1 ; epidemiology ; genetics ; immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Genetic Predisposition to Disease ; genetics ; Glutamate Decarboxylase ; immunology ; HLA-DQ Antigens ; genetics ; HLA-DQ beta-Chains ; Humans ; Male ; Membrane Glycoproteins ; genetics ; Middle Aged ; Polymerase Chain Reaction ; Young Adult