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Zhi-guang Zhou

Publications and source records attributed to Zhi-guang Zhou.

At least 19 recordsLinked to original sources
PubMed2006

[Decrease of FOXP3 mRNA in CD4+ T cells in latent autoimmune diabetes in adult].

OBJECTIVE: To study the percentage of peripheral blood CD4(+)CD25(+) T cells and the expression of FOXP3 mRNA in the patients with latent autoimmune diabetes in adult (LADA). METHODS: Fresh peripheral blood samples were obtained from 60 patients with LADA, 30 patients with type 2 diabetes and 30 age- and sex-matched matched healthy nondiabetic control subjects without diabetic family history. Two-color staining (anti-CD4, anti-CD25, anti-CD3, and anti-CD8) flow cytometric analysis was employed to measure the CD4(+)CD25(+) T cells. The CD4 positive human cells were isolated with immunomagnetic beads, and then real time-PCR was used to test the expression of FOXP3 mRNA in the CD4(+) T cells. RESULTS: In the LADA group, the percentage of CD4(+)CD25(+) T cells was 4.1 +/- 1.9, significantly higher than that of the normal control group (2.8 +/- 1.5, P < 0.01), the ratio of CD4(+)CD25(+) to the CD4(+) T cells was 11.9 +/- 5.0, significantly higher than that of the normal control group (8.2 +/- 3.7, P < 0.01), the percentage CD8(+) T cells was 24.6 +/- 6.8, significantly higher than that of the normal control group (19.4 +/- 7.1, P < 0.01) and the CD4(+)/CD8(+) ratio was 1.5 +/- 0.5, significantly lower (1.9 +/- 0.6, P < 0.01). The expression of FOXP3 mRNA in CD4(+) T cells of the LADA group was 0.52 time that of the control group (P < 0.01). The CD4(+)/CD8(+) ratio of LADA group was significantly lower that of the type 2 diabetes group (1.8 +/- 0.8, P < 0.05), however, the other results were not significantly different between these 2 groups. The percentage of was positively correlated with the titer of glutamic acid decarboxylase antibody (GADA) (r = 0.292, P < 0.05). CONCLUSION: Though the percentage of CD4(+)CD25(+) T cells and the level of CD25 expression in CD4(+) T cells are elevated, the expression of FOXP3 mRNA in CD4(+) T cells is lower. in the patients with LADA. The regulatory T cells may have defective suppressor function in patients with LADA.

Adult↗
PubMed2006

[Characteristics of dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients].

OBJECTIVE: To investigate the characteristics of the dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients. METHODS: Intravenous glucose tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic patients and 48 subjects with normal glucose tolerance (NGT) and then blood samples were collected 1, 2, 4, 6, and 10 minutes later to measure the plasma glucose and insulin to calculate the acute insulin response (AIR) and the area under the curve of insulin (AUC of insulin), homeostasis model assessment beta-cell (Homabeta), and Homa IR (insulin resistance). RESULTS: The median AIR of the type 2 diabetic patients was -33.7 pmol/L, significantly lower than that of the NGT subjects (6962.0 pmol/L, P < 0.001). The median AUC of the type 2 diabetic patients was 834.2 pmol/L, significantly lower than that of the NGT subjects (7934.7 pmol/L, P < 0.001). When the fasting plasma glucose (FPG) of the type 2 diabetic patients was above 7.0 mmol/L, the AIR value was remarkably reduced with a median level of 317.3 pmol/L, and then subsequently disappeared when the FPG was above 9.0 mmol/L. After adjustment of the insulin resistance assessed by HOMA IR, the Homabeta of the type 2 diabetic patients was reduced to be 30% that of the NGT subjects (3.7 +/- 0.9 vs 5.9 +/- 0.9, P < 0.001). Both the fasting proinsulin concentration and the ratio of fasting proinsulin to fasting insulin of the type 2 diabetic patients were significantly higher those of the NGT subjects (22.6 pmol/L +/- 14.7 pmol/L vs 11.5 pmol/L +/- 7.1 pmol/L, P < 0.001; and 30.1% +/- 20.5% vs. 12.1% +/- 9.6%, P < 0.001). CONCLUSION: The dysfunction of islet beta-cell in newly diagnosed type 2 diabetic patients is mainly represented by the disappearance of AIR and the evident decline of AUC and HOMA B, and the decrease of quality of insulin secretion.

Adult↗
PubMed2006

[Inhibition of islet beta cell apoptosis and prevention diabetes by subcutaneous administration of insulin in NOD mice].

OBJECTIVE: To investigate the effects of subcutaneous administration of insulin on insulitis,beta cell apoptosis and diabetes in non-obese diabetic (NOD) mice, and to explore the mechanism of immune tolerance induced by insulin. METHODS: Sixty female NOD mice were randomly divided into insulin group (n=32) and phosphate buffered saline (PBS) group (PBS group, n=28). Insulin was subcutaneously injected with humulin N (60 microL, 6U)+IFA (60 microL) at 4, 12, 20, and 28 weeks respectively, while the PBS group received PBS (60 microL) + IFA (60 microL). Insulitis and beta cell apoptosis of islets were observed at 12 weeks. IL-4 and IFN-gamma in the sera were measured by enzyme linked immunosorbent assay (ELISA). The expression levels of I-Abeta(g7), IL-4, IFN-gamma, IL-1beta, and Fas mRNA of islets were measured by reverse transcription-polymerase chain reaction (RT-PCR) at 12 weeks. RESULTS: The incidences in the insulin group were significantly lower than those in the PBS group (21.4% vs 71.4% at 30 weeks, 28.6% vs 85.7% at 52 weeks, P<0.05). The insulitis scores in the insulin group were lower than those in the PBS group, but there was no statistical significance. Fas expression on islets and apoptotic beta cell rates in the insulin group were lower than those in the PBS group (P<0.05). In the insulin group, serum IL-4 levels were higher, but IFN-gamma levels were lower than those in the PBS group (P<0.05). The levels of I-Abeta g7, IFN-gamma, IL-1beta and Fas mRNA transcription in islets were lower in insulin group, but IL-4 mRNA levels were higher than those in the PBS group (P<0.05). CONCLUSION: The specific autoantigen insulin may induce immune tolerance and prevent diabetes in NOD mice, but it can't block the progression of insulitis. Subcutaneous administration of insulin can induce the regulatory T cells, and make Th1 to Th2 cytokine shifts in system and islets, thus preventing the Fas-mediated beta-cell apoptosis and diabetes.

Animals↗
PubMed2006

[Cross-sectional study of the relation between carboxypeptidase-H antibody and islet beta cell function in patients with latent autoimmune diabetes in adults].

OBJECTIVE: To explore the relation between carboxypeptidase-H antibody (CPH-Ab) and islet beta cell function in patients with latent autoimmune diabetes in adults (LADA) and to further confirm the diagnostic value of CPH-Ab for LADA. METHODS: Five hundred and forty-five patients who were initially diagnosed as Type 2 diabetes mellitus (T2DM) were tested with CPH-Ab and GAD-Ab by radioligand assay (RLA). T2DM patients, according to CPH-Ab and GAD-Ab status, were divided into CPH-Ab(+) group, GAD-Ab(+) group, and Ab(-) group to compare their islet beta cell function [represented by fasting C-peptide (FCP) and 2h postprandial C-peptide (2hCP)]. The relation between CPH-Ab and islet beta cell function in LADA was analyzed. RESULTS: The fasting C-peptide level in CPH-Ab(+) patients was between that of GAD-Ab(+) patients and that of Ab(-) patients (P<0.05), and the difference was still significant when the 3 groups were stratified with duration of disease (All P<0.05), but not with body mess index (all P>0.05). Corrected by concomitant variables including age, age at onset, duration of disease, and sex, the differences among the 3 groups were statistically significant (both P<0.001). Among the 3 groups FCP was lower than Ab(-) group in CPH-Ab(+) (P<0.05) and both FCP and PCP were lower than Ab(-) group in GAD-Ab(+) group (P<0.05 and P<0.01). The proportions of patients with insulin deficiency in CPH-Ab(+), GAD-Ab(+), and Ab(-) group were 27.6% (8/29), 48.1% (8/52) and 13.5% (54/400), respectively, which were significantly different among the 3 groups (P<0.001). GAD-Ab, BMI, and fasting blood glucose had effects on FCP and PCP in T2DM patients (All P<0.05), while CPH-Ab did not enter the equation in multivariable stepwise regressive analysis (P>0.05). CONCLUSION: The effect of CPH-Ab is less marked than that of GAD-Ab on islet beta-cell function in LADA patients. The value of CPH-Ab for the failure of islet beta-cell function in LADA should be determined prospectively.

Adult↗
PubMed2006

[Effect of complete Freund's adjuvant on islet beta cell apoptosis and its mechanism in non-obese diabetic mice].

OBJECTIVE: To investigate the effect of complete Freund's adjuvant (CFA) on islet beta cell apoptosis in preventing diabetes in non-obese diabetic (NOD) mice, and the influence on apoptotic related-gene expression. METHODS: Four-week-old female NOD mice were randomly divided into Group CFA (n=5) and Group saline (NS) control (n=5). Mice in Group CFA were injected in the hind footpad with 50 microL CFA and mice in Group NS with 50 microL NS. Blood sugar was monitored and diabetes was diagnosed if blood sugar was higher than 11.1 mmol/L for 2 continuous days in the NOD mice. The mice were sacrificed when diagnosed as diabetes or at 30 weeks of age. Pancreatic sections were made for: evaluation of insulitis severity with HE staining; counting of apoptotic beta cells with the terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate nick end labeling (TUNEL) method, and ABC immunohistochemical double labeling; counting of Fas, FasL and Bcl-x positive cells respectively with ABC immunohistochemical method. RESULTS: By 30 weeks of age, none of the 5 CFA-treated mice, compared with 3 of the 5 control mice, had developed diabetes. The insulitis score was lower (1.820+/-0.962 vs. 3.020+/-1.040, P<0.05), the rates of apoptotic beta cells, Fas positive cells and FasL positive cells were lower [(10.2+/-2.8)% vs. (15.9+/-6.5)%, (54.9+/-14.5)% vs. (75.7+/-12.9)%, (20.3+/-10.4)% vs. (27.9+/-12.0)%, P<0.05), and the Bcl-x positive cell rate was higher [(74.9+/-10.7)% vs. (66.0+/-18.3)%, P<0.05] in the CFA-treated group than those in the NS-treated group respectively. CONCLUSION: CFA may inhibit beta cell apoptosis in NOD mice by regulating Fas, FasL and Bcl-x expression on cells within islets.

Animals↗
PubMed2005

[Clinical and immunological characteristics in rapid-onset type 1 diabetes with hyperamylasemia].

OBJECTIVE: To investigate the clinical characteristics and different status of islet autoantibodies of rapid-onset type 1 diabetes in China with elevated serum pancreatic enzymes. METHODS: In accordance with the criteria Imagawa reported, 40 cases of acute-onset type 1 diabetics with ketosis or ketoacidosis were selected and 4 fell into the criteria of rapid-onset type 1 diabetes. Compared the clinical characteristics between fulminant (group F, n = 4) and nonfulminant (group NF, n = 36) type 1 diabetics. Same parameters were compared between the patients with diabetic symptoms within 1 week (group A, n = 11) and those beyond 1week (group B, n = 29). The percentage of elevated serum amylase were compared between patients with and without severe ketoacidosis. Islet autoantibodies, including glutamic acid decarboxylase antibody (GAD-Ab), protein tyrosine phosphatase antibody (IA-2Ab) and insulin autoantibody (IAA),, were detected by radioligand assays. RESULTS: We found 4 cases of rapid-onset type 1 diabetes in Chinese, accounted for 10% of acute-onset type 1 diabetes. Among 4 rapid-onset type 1 diabetics, 2 patients detected GAD-Ab positive. Patients with duration of diabetic symptoms within 1 week (group A) were found all with severe ketoacidosis and 10 of 11 patients were found serum amylase elevated and this group appeared higher blood glucose, lower PH and CO(2)CP, nearly normal HbA(1c) and more severe ketoacidosis, more patients with elevated amylase (P < 0.05) than those with duration of symptoms more than 1 week (group B). Patients with severe ketoacidosis (n = 20) owned higher percentage of elevated serum amylase than those with mild or moderate ketoacidosis (n = 20) (60% vs 20%, P < 0.05). CONCLUSION: (1) Rapid-onset type 1 diabetes cases are also observed in China. (2) Rapid-onset type 1 diabetes may be a group of syndromes with different etiology which immune and non-immune factors may both involved in. (3) Elevated pancreatic enzymes are not specific markers for rapid-onset type 1 diabetes, it may result from severe ketoacidosis and metabolic derangements.

Autoantibodies↗
PubMed2005

[Development and evaluation of quality of life scale for patients with type 2 diabetes mellitus].

OBJECTIVE: To develop a specific quality of life scale for Chinese Type 2 diabetes mellitus (DM) patients. METHODS: According to the quality of life definition of WHO, we used methods adhered to the rigorous guidelines of instrument development in item pool formation, item selection and scale validation with the data of 236 Type 2 diabetic patients recruited. RESULTS: An 87-item Quality of Life Scale for patients with Type 2 DM-prior test version ( DMQLS), including 5 domains ( disease, physical, social, psychological, and satisfaction ) was developed and showed good reliability and validity. The disease domain made up of Type 2 diabetes mellitus-specific sub-scale and the other 4 domains formed the generic sub-scale for adults. The test-retest correlation coefficient, Cronbach's Alpha coefficient and split-half reliability coefficient of DMQLS were 0.996, 0.969 and 0.879, respectively. Twenty-one common factors were extracted according to the conceptual model. The scale's correlations with SF-36 and Diabetes Quality of Life Measure ( DQOL ) were 0.763 and 0.658. DMQLS could discriminate among those with different quality of lives. CONCLUSION: DMQLS is reliable, valid and sensitive, and can be used to evaluate the curative effect of Type 2 diabetic patients.

Adult↗
PubMed2005

[Comparison of 3 working definitions of metabolic syndrome in male medical examinees].

OBJECTIVE: To compare the prevalence of the metabolic syndrome (MS) using 3 working definitions proposed respectively by the World Health Organization (WHO, 1999) , the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults ( ATP III, 2001 ), and the Chinese Diabetes Society ( CDS, 2003). METHODS: MS was diagnosed in 739 male medical examinees by the 3 working definitions respectively, then the prevalence and the concordance of 3 working definitions was compared. RESULTS: Among 739 participants the prevalence was 36.9% by the WHO definition, 11.8% by the ATP III definition and 21.0% by the CDS definition. Among all the testees 68.6% were classified as either having or not having the MS under the 3 definitions. The consistency in the diagnosis of MS was 72.5% by the WHO definition and the ATP III definition, 81.2% by the WHO definition and the CDS definition, and 83.5% by the ATP III definition and the CDS definition. The prevalence of insulin resistance was the highest among the components of the WHO definition. The prevalence of hypertension was the highest while the prevalence of obesity was the lowest by the ATP III definition. Among the components of the CDS definition, the prevalence of obesity was the highest. The fasting insulin and insulin resistant index (HOMA-IR) were both significantly higher in the MS subjects than that in the non-MS subjects. CONCLUSION: A universally accepted definition of the metabolic syndrome is needed.

Adult↗
PubMed2005

[Study on the postive frequency and distribution of glutamic acid decarboxylase antibody in phenotypic type 2 diabetec patients].

OBJECTIVE: To investigate the positive frequency and distribution of glutamic acid decarboxylase antibody(GAD-Ab) in phenotypic type 2 diabetic(T2DM) patients. METHODS: Sera 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↗
PubMed2004

[Mechanisms of human glutamic acid decarboxylase 65 DNA vaccine preventing diabetes in non-obese diabetic mice].

OBJECTIVE: To investigate the mechanisms of human GAD65 DNA vaccine preventing insulitis and diabetes in NOD mice. METHODS: Female NOD mice at 4 weeks of age were randomly divided into PBS (n = 21), pcDNA (n = 20), and hGAD65 (n = 21) groups. Mice in each group received two intramuscular injections of 0.05 ml PBS alone, 50 microg pcDNA3.1 and 50 microg DNA vaccine emulsified in 0.05 ml PBS 7 days apart respectively. The accumulative diabetes incidence was followed-up to 30 weeks of age in each group of NOD mice. Pancreas was removed from NOD mice at 12 weeks of age in each group (n = 10) to score insulitis severity by routine H-E staining. The apoptotic beta cells in islets were observed with double-labeling technique of TUNEL in situ combined standard sensitive avdin-biotin complex (sABC) immunohistochemical method. Their spleens were for cell culture and total RNA extraction. Spleen IL-4, IFN-gamma, NF-ATc and NF-ATp mRNA levels were tested by RT-PCR. IL-4 and IFN-gamma levels in sera and supernatants of spleen cells were measured by ELISA. RESULTS: (1) At 30 weeks of age, the diabetes incidence was 95.2%, 80.0% and 61.9% in PBS, pcDNA and hGAD65 group respectively. The diabetes incidence in the PBS group was higher than that in hGAD65 group (P = 0.008). (2) At 12 weeks of age, the insulitis scores in hGAD65 group was lower than that in PBS group (P = 0.001) and pcDNA group (P = 0.027) respectively. (3) The apoptotic beta cell rates in hGAD65 group was lower than that in PBS group (P = 0.014) and pcDNA group (P = 0.023). (4) IL-4 levels in sera, spleen IL-4 and NF-ATc mRNA level in hGAD65 group were higher than those in PBS group (all P < 0.05) and pcDNA group (all P < 0.05) respectively, NF-ATp mRNA level in hGAD65 group was lower than that in PBS group (P < 0.05). CONCLUSION: Human GAD65 DNA vaccine via downregulating NF-ATp and upregulating NF-ATc and IL-4, makes Th cells deviate to Th2, and sequently prevents insulitis, beta-cell apoptosis and diabetes onset in NOD mice.

Animals↗
PubMed2004

[Etiological dissection in common anti-islet autoantibody-negative patients with type 1 diabetes].

OBJECTIVE: To explore the immunological and genetic factors of common anti-islet autoantibody-negative patients with type 1 diabetes. METHODS: Specimens of peripheral blood were collected from 33 common autoantibody (GAD-Ab, IA2-Ab, IAA, TGA and TPO-Ab) negative diabetic patients with new-onset of unprovoked ketosis (or ketoacidosis), and genome DNA was extracted. The antibodies to carboxypeptide-H (CPH) and SOX13 (ICA12) were detected by radioligand assay. The gene mutations of MODY3 (HNF-1alpha) and MODY6 (NeuroD1/Beta2) were detected by PCR-SSCP sequencing. Mitochondrial gene mutations were analyzed with PCR-RFLP. RESULTS: Two (6%) of the patients were SOX13-Ab positive, while none of them was positive for CPH-Ab. Gene mutation detection found one case of a new mutation, R321H (CGC-->CAC) in the exon 5 of HNF-1alpha gene and one case with ND1 mt3316 G-->A mutation in mitochondrial DNA. In addition to the diabetes-associated mutations described above, seven polymorphisms of HNF-1alpha gene, including L17L, I27L, L459L, S487N, IVS5 + 9 C > G, IVS6-42 G > T, and IVS7 + 7 G > A, and one NeuroD1/Beta2 gene polymorphic variant Ala45Thr, were found. CONCLUSION: Autoimmunity and gene mutations (such as MODY3 and mitochondrial genes mutations) may be etiological in a few cases initially diagnosed as autoantibody-negative type 1 diabetes. Autoimmunity and MODY and mitochondrial diabetes should be excluded if idiopathic type 1 (type 1B) diabetes is diagnosed.

Adolescent↗
PubMed2004

[Preventive effects of pioglitazone on diabetes and relevant mechanisms, experimental study on non-obese diabetic mice].

OBJECTIVE: To explore the effects of pioglitazone on insulitis and diabetes and relevant mechanism. METHODS: Seventy-three female non-obese diabetic (NOD)/Lt mice aged 4 weeks were randomly divided into 3 groups, control group (n = 25, fed with regular diet), low dosage pioglitazone group (n = 23, pioglitazone of the concentration of 0.01% was added into the feed) and high dosage pioglitazone group (n = 25, pioglitazone of the concentration of 0.04% was added into the feed). The mice were killed when diabetes developed or they reached the age of 30 weeks. The body weight and amount of food intake were measured every week and the amount of drug intake was calculated. Urine glucose was checked weekly from week 10 to week 30. When urine glucose was positive and relevant symptoms appeared, blood glucose was measured. The criterion of diagnosis of diabetes was the consecutive blood glucose level > or = 16.7 mmol/L for 2 times. At the 12th week 4-7 mice from the 3 groups respectively were killed and their pancreases were removed to be scored on insulitis by HE staining, the spleen cells were cultured. The IL-4 and IFN-r levels in serum and supernatants of spleen cell cultures were measured by ELISA. The pancreatic IFN-r mRNA level was tested using RT-PCR method. RESULTS: (1) At the age of 30 weeks, the diabetes incidence rates was 80% (20/25) in the control group, 60.9% (14/23) in the low dose group, and 60% (15/25) in the high dose group (P > 0.05). At the following time points the diabetes incidence rates of the 2 treated groups were lower than that of the control group (all P < 0.05): (1) 0% in the low dose group vs 16%: of the control group at the age of 100 days, and 39% vs 68% at the age of 185 days; and (2) 0% in the high dose group vs 16% in the control group at the age of 110 days, 4% vs 24% at the age of 120 days, and 12%vs 36% at the age of 135 days. (2) There was no difference in insulitis scores between the control group and low dose or high dose groups at the age of 12 weeks (1.99 +/- 0.75 vs 1.01 +/- 0.68 and 1.19 +/- 0.84, both P > 0.05), however, the score of the combined pioglitazone group (low dose group + high dos group) was significantly higher than that of the control group (1.12 +/- 0.75 vs 1.99 +/- 0.75, P < 0.05). (3) There was no differences in the IL-4/IFN-r ratios in serum and splenocyte culture supernatant and pancreatic IFN-r mRNA levels among the three groups (all P > 0.05). CONCLUSION: Pioglitazone, to some extent, lessens the insulitis severity and delays the diabetes onset. Its mechanism may be unrelated to immune deviation of Th1 to a Th2.

Animals↗
PubMed2004

[Subclassification of seronegative type 1 diabetic subjects with HLA-DQ genotypes].

OBJECTIVE: To reveal the relationship between disease phenotype and HLA-DQ genotype in autoantibody-negative type 1 diabetics and to explore whether HLA-DQ genotypes can reclassify seronegative type 1 diabetic patients. METHODS: Sixty-one diabetics with unprovoked ketosis or ketoacidosis at presentation were tested for glutamic acid decarboxylase antibody (GAD-Ab), tyrosine phosphatase antibody (IA2-Ab), thyroglobulin antibody (TGA), thyroid peroxidase antibody (TPO-Ab) and HLA-DQ genotype. GAD-Ab and IA2-Ab were measured with radioligand assay. TGA and TPO-Ab were evaluated using RIA. Sequence-based genotyping (SBT) was used to determine the alleles of HLA-DQA1 and DQB1. Autoantibody negative patients were subdivided into group A (with type 1 diabetes susceptible alleles) and group B (without type 1 diabetes susceptible alleles). Clinical characteristics, including age, sex, mode of presentation, body mass index (BMI), islet beta-cell function and current treatment were compared between the autoantibody-positive and autoantibody-negative patients and between group A and B. RESULTS: Among the 61 patients, 29 (47.5%) were negative for all the antibodies tested, while 31 (50.8%) were positive for one or more antibodies tested. 5 (8.2%) were positive for all those 4 antibodies. As for genetic analysis, 18 of the 29 seronegative patients carried 1-4 HLA-DQ risk alleles, while the other 11 did not carry any type 1 diabetes susceptible alleles tested. As compared with the autoantibody-negative patients, younger age at onset, less obesity, severer degree of diabetic ketoacidosis (DKA) and lower C peptide were found in the autoantibody-positive ones. As compared with group B, less obesity [BMI: (22.4 +/- 4.4) kg/m(2) vs (25.8 +/- 3.7) kg/m(2), P = 0.03], severer degree of DKA [CO(2)CP: (16.3 +/- 7.1) mmol/L vs (19.2 +/- 2.0) mmol/L, P = 0.01; pH: 7.26 +/- 0.20 vs 7.34 +/- 0.06, P = 0.03], and lower C peptide [fasting C peptide: (254.6 +/- 189.4) pmol/L vs (458.7 +/- 274.1) pmol/L, P = 0.06] were observed in group A. During follow-up, 73% (8/11) patients in group B discontinued insulin therapy and maintained acceptable glycemic control by either diet or oral hypoglycemic agents (OHA), while only 28% (5/18) of the patients in group A discontinued and maintained control with OHA (28% vs 73%, P < 0.01). Among those who kept on using insulin, group A patients required higher insulin dosage than those of group B [(0.43 +/- 0.16) U x kg(-1) x d(-1) vs (0.24 +/- 0.18) U x kg(-1) x d(-1), P = 0.07]. CONCLUSIONS: Autoantibody-negative diabetics, if with susceptible HLA-DQ genotypes, presented more type 1A-like features, implying possible existence of as yet unidentified immunologic abnormalities in these patients. HLA-DQ risk genotypes may reclassify seronegative type 1 diabetics. Those who are autoantibody negative but carry susceptible HLA-DQ genotypes, should not be diagnosed as type 1B diabetes.

Adolescent↗
PubMed2004

[Adult-onset latent autoimmune diabetes and autoimmune thyroid disease].

OBJECTIVE: To investigate the relationship between latent autoimmune diabetes in adults (LADA) and thyroid autoimmunity. METHODS: The frequency of thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (TG-Ab) was determined with radioimmunoassay in 394 subjects, including 90 LADA, 104 classic type 1 diabetics (T1DM), 100 type 2 diabetics (T2DM) and 100 controls. Glutamic acid decarboxylase antibody (GAD-Ab) was measured with radioligand immunoassay. RESULTS: (1) TPO-Ab existed more frequently in LADA (16.7%, 15/90) than in T2DM patients (7.0%, 7/100; P < 0.05). The frequency of thyroid antibody (TPO-Ab or TG-Ab positivity) in LADA and T1DM was 18.9% (17/90) and 25.0% (26/104) respectively, being higher than that in the control group (8/100, 8.0%; P < 0.05). (2) Thyroid antibodies occurred more frequently in LADA patients with higher titer of GAD-Ab (GAD-Ab > or = 0.5) than those with lower ones (50.0% vs 12.5%, P < 0.05). (3) 47.1% (8/17) of LADA patients with thyroid autoimmunity had thyroid dysfunction as compared with 17.6% (6/34) in the group without thyroid antibodies (P < 0.05). CONCLUSIONS: (1) LADA patients, especially those with high titer of GAD-Ab, have high risk for thyroid autoimmunity. (2) The presence of thyroid antibody may predict high risk for thyroid dysfunction in LADA patients. (3) LADA may be one of the components in autoimmune polyendocrine syndrome.

Adolescent↗
PubMed2004

[Effects of glimepiride and metformin on free fatty acid in patients with Type 2 diabetes mellitus].

OBJECTIVE: To investigate the effect of glimepiride and metformin on free fatty acid (FFA) in patients with Type 2 diabetes mellitus and to further study the relationship between free fatty acid and insulin resistance in patients with Type 2 diabetes mellitus. METHODS: A prospective and case-control study was conducted. Ninty-four patients with Type 2 diabetes mellitus (35-70 year-old) were divided into 3 groups: glimepiride treated group (n=33), metformin treated group (n=29) and glimepiride plus metformin treated group (n=32). These patients were followed up for 6 months. Free fatty acids were measured by using an enzymatic colorimetry. RESULTS: The concentration of FFA didn't significantly change in the glimepiride treated group at the end of treatment, but it obviously decreased in the metformin treated group and in the glimepiride plus metformin treated group (P < 0.05 and P < 0.001, respectively). The decrease of FFA in the glimepiride plus metformin treated group was more obvious than that in the glimepiride treated group (P < 0.05). The fasting serum FFA concentration is positively related to HOMA-IR( homeostasis model assessment-insulin resistance) and the choice of drugs by stepwise regression analysis. CONCLUSION: Metformin alone or metformin plus glimepiride can decrease FFA levels, body weight index, blood glucose and insulin resistance. FFA level can reflect the index of insulin resistance to some degree.

Adult↗
PubMed2003

[Identification of the two subtypes of latent autoimmune diabetes in adults by glutamic acid decarboxylase 65 antibody titers].

OBJECTIVE: To compare the clinical characteristics between type 2 diabetes and latent autoimmune diabetes in adults (LADA) and to define the two distinct types of LADA with different glutamic acid decarboxylase antibody (GADA) titers. METHODS: Sera of 750 patients with an initial diagnosis of type 2 diabetes mellitus (T2DM) were screened for GADA with radioimmunoprecipitation assay. The distribution and frequency of different GADA indices were described. Two hundred and ninety five patients were further studied and divided into four groups (T2DM; GADA index < 0.05; index > or = 0.5 and index > or = 0.05 but < 0.5) to compare the age of onset, body mass index, level of major component of adult hemoglobin (HbA1c) and C peptide as well as the rates of hypertension, hyperlipidemia and chronic complications. RESULTS: A total of 64 antibody-positive patients were identified. Compared with T2DM, these patients had younger age of onset, lower C peptide level (fasting C peptide 500 pmol/L vs 414 pmol/L, P < 0.01), lower body mass index (23.2 kg/m(2) vs 21.2 kg/m(2), P < 0.01) and also lower rates of hypertension (48.7% vs 31.7%, P < 0.05) and hyperlipidemia (60.2% vs 38.5%, P < 0.01). However, only the patients with high GADA titer had reduced beta cell function as compared with T2DM and low titer patients. Their diabetic complications were less than those of T2DM. Low GADA titer (index 0.05 - < 0.5) patients were similar to T2DM patients, except that they were prone to ketoacidemia. CONCLUSION: Two clinically distinct types of LADA can be identified by GADA titers. High titer GADA (GADA > or = 0.5) patients have more resemblance to insulin dependent diabetes and can be regarded as LADA-type 1 diabetes, while low titer GADA patients (0.05 - < 0.5) have clinical and metabolic phenotype of type 2 diabetes and can be regarded as LADA-type 2 diabetes.

Adult↗
PubMed2003

[Latent autoimmune diabetes in adults: an update].

Latent autoimmune diabetes in adults (LADA), presenting with a similar phenotype of type 2 diabetes at early stage, belongs to the slowly progressive subtype of autoimmune type 1 diabetes. LADA differs from classic juvenile-onset type 1 diabetes in which its autoimmune destructive process of islet beta-cells is much slower, so LADA may serve as a human model of autoimmune type 1 diabetes. Although no international standardized criteria for the diagnosis of LADA has been established, it should be noted that LADA has some specific features in clinical characteristics, susceptible genotypes, cellular and humoral immune markers, as well as islet pathology. Presence of islet autoantibodies is necessary for the diagnosis of LADA. Early insulin intervention may preserve residual islet beta-cell function in LADA. The different pathological manifestations of LADA with different autoantibody titers can help throw light on the autoimmune process, laying foundation of prevention or even cure of type 1 diabetes.

Adult↗