Lipid Levels Related to Osteoporosis in Patients with Type 2 Diabetes.

OBJECTIVE: Osteoporosis is a systemic skeletal disorder characterizedby reduced bone mass, deteriorated bone structure. Various studies have tried to evaluate the association between lipid level and osteoporosis, but the results were proved to be controversial. The objectives of this study are to assess the correlation between BMD and serum lipid levels, to determine independent variables associated with osteoporosis and osteopenia in men and postmenopausal women with type 2 diabetes (T2D). MATERIALS AND METHODS: All participants of the study were carried out biochemical analysis of blood and the analysis of the lipid profile that included total cholesterol (TC) and triglyceride (TG). Physical examination and dual-energy X-ray absorptiometry examination were performed. Multiple linear regression and multivariate logistic regression were used to evaluate associations between serum TC and TG levels and the osteoporosis or osteopenia. RESULTS: The level of serum TG was directly correlated with BMD at the lumbar spine in all patients in multiple linear regression models. After adjusting for potential confounding factors, decreased level of serum TG was independent risk factor for osteoporosis(p=0.022) in T2D patients. It also showed that a greater BMI was protective factor for osteoporosis (p=0.019) and lower level of ß-CTX was an independent risk factor for osteopenia (p=0.008) and osteoporosis (p=0.001) in T2D patients. CONCLUSION: Among Chinese patients with type 2 diabetes, the decreased level of serum TG might indicate a risk of osteoporosis. Further research is needed to confirm the finding and to clarify the contradictions identified.

Sex-Specific Association of Serum 25-Hydroxyvitamin D3 with Insulin Resistance in Chinese Han Patients with Newly Diagnosed Type 2 Diabetes Mellitus.

This study aimed to explore the association between serum 25-hydroxyvitamin D (25(OH)D) and insulin resistance as well as ß-cell function in Chinese Han patients with newly diagnosed type 2 diabetes mellitus (T2DM). A total of 264 patients was included in this study. Serum 25(OH)D, plasma glucose, serum insulin and other biochemical parameters were assayed. Postprandial venous blood was collected after a mixed-nutrient load. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda insulin sensitivity index (Matsuda ISI). The ß-cell function was assessed by the homeostasis model assessment for insulin secretion (HOMA-ß) and the change in insulin divided by change in glucose from 0 to 30 min (ΔI0-30/ΔG0-30). Patients were divided into three groups according to tertiles of serum 25(OH)D levels. There were significant differences in HOMA-IR and Matsuda ISI among the three groups (HOMA-IR, p=0.005; Matsuda ISI, p=0.009). Pearson correlation analyses showed that serum 25(OH)D was negatively correlated with fasting serum insulin (FIns) (r=-0.209, p=0.012) and HOMA-IR (r=-0.273, p=0.001), and positively correlated with Matsuda ISI (r=0.219, p=0.009) only in the male population. Multiple stepwise regression analyses showed that in the male population, serum 25(OH)D was an independent predictor for both HOMA-IR and Matsuda ISI before and after adjustment for confounding factors, respectively (p<0.05 for both). This study indicates the association of vitamin D with insulin resistance in male patients with newly diagnosed T2DM, which may contribute to the understanding of the mechanism underlying the onset of T2DM in the Chinese Han population.

Abnormal Methylation Status of the GNAS Exon 1A Region in Pseudohypohyperparathyroidism Combined With Turner Syndrome.

Pseudohypohyperparathyroidism (PHHP) is a rare type of pseudohypoparathyroidism (PHP), which seems to have a normal skeletal response to parathyroid hormone but shows renal resistance. Almost all patients with PHHP have PHP Ib, a subtype of PHP that is usually caused by GNAS methylation defects, often in exon 1A. Some features of Albright hereditary osteodystrophy can occasionally be found in patients with PHHP, but these features are also common in Turner syndrome. The authors report on an extremely rare case of a patient with PHHP and Turner syndrome, a 47-year-old woman who sought medical attention for hypocalcemia and elevated parathyroid hormone. She had no family history of hypocalcemia and no STX16 gene deletions. She had a mosaic karyotype of 46, X, del(X)(p11.4)/45, XO. Pyrosequencing was performed to determine the GNAS exon 1A methylation. The degree of methylation found in exon 1A of the patient was lower than her unaffected relatives.

A novel type heterozygous mutation in the glucose-6-phosphatase gene in a Chinese patient with glycogen storage disease Ia.

Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen storage disease type Ia (GSD Ia). By genotype analysis of the affected pedigree, we identified a novel type mutation in a Chinese patient with GSD Ia. Mutation analysis was performed for the coding region of G6Pase gene using DNA sequencing and TaqMan gene expression assay was used to further confirm the novel mutation. The proband was compound heterozygous for c.311A>T/c.648G>T. Our report expands the spectrum of G6Pase gene mutation in China.

Mucolipidosis in a Chinese family with compound heterozygous mutations at the GNPTAB gene.

BACKGROUND: Mucopolysaccharidoses (MPS) are caused by the deficiency in the metabolism of one or more types of mucopolysaccharides or glycosaminoglycans (GAGs). Mucolipidoses (ML) are a group of genetic disorders in which both glycosaminoglycans (GAGs) and sphingolipids build up in the body. Both of MPS and ML belong to lysosomal storage diseases and show similar clinical manifestations. Distinction of these two types of diseases has not been always possible using conventional clinical diagnoses. Genetic test provides a definitive diagnosis for ML and MPS diseases. METHODS: The initial clinical diagnosis had suspected the proband as either MPS or ML. To verify the clinical diagnosis, linkage analysis was performed with a panel of microsatellite markers flanking 10 candidate genetic loci for mucopolysaccharidosis and 2 loci for mucolipidosis. Two-point logarithm of odds (lod) scores was calculated using Linkage Package 5.2 program. Direct DNA sequence analyses of GNPTAB in the family members were performed. RESULTS: By using linkage and mutational analyses, we have identified that the family members contain compound heterozygous mutations of p.R364X and c.2715+1G>A in the GNPTAB gene. We determine the family as MLIII based on the DNA-test and clinical diagnoses. CONCLUSION: Our study confirms the pathological relationship between the patients' genotype and phenotype in the clinical ML manifestation, and suggests that DNA-based diagnosis serves as a better way to define ML and MPS.

[A novel mutation of 428delG in DAX-1 gene causing X-linked adrenal congenital hypoplasia].

OBJECTIVE: To investigate the clinical features and to identify the DAX-1 gene mutation in a Chinese kindred with X-linked adrenal hypoplasia congenital(AHC). METHODS: Clinical data and peripheral blood samples were obtained from the affected individuals and their relatives. The genomic DNA was isolated from whole blood. Four pairs of primers were used to amplify the two exons of the DAX-1 gene, and PCR products were purified and sequenced directly. Sequencing results were compared to the human DAX-1 sequence in the public database. RESULTS: A novel hemizygous frameshift mutation (428delG) in exon 1 of the DAX-1 gene was found in both patients (the index case and his cousin). Some clinical features such as the age of onset were different although these 2 patients carried the same mutation. Three females in the family, including the mothers of the 2 patients and their grandmother were carriers of this mutation. No such mutation was detected in other healthy persons in the family. CONCLUSION: The result suggested that X-linked AHC in the kindred was caused by a novel mutation of 428delG in the DAX-1 gene, and the same mutation can give rise to variable phenotypes.