[Effect of potassium iodide on prevention of experimental lead nephropathy and expression of nuclear factor-kappaB and fibronectin].

OBJECTIVE: To investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin. METHODS: The experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR. RESULTS: Electron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F. CONCLUSION: The potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

[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.

[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.