Efficacy of generic teriparatide and alendronate in Chinese postmenopausal women with osteoporosis: a prospective study.

The efficacy of generic teriparatide in improving BMD at lumbar spine in patients with osteoporosis was similar to that of alendronate. It provided a new choice for osteoporosis treatment in Chinese population. INTRODUCTION: To determine whether the efficacy of generic teriparatide is noninferior to alendronate for Chinese postmenopausal women with osteoporosis. METHODS: Eligible patients were randomly assigned (2:1) in a 48-week, open-label design to receive 20 µg sc daily teriparatide or 70 mg oral weekly alendronate. Primary outcome was percentage change in BMD at the lumbar spine from baseline to 48 weeks and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. RESULTS: Three hundred ninety-one and 196 participants were randomly assigned to the teriparatide or alendronate group, of whom 379 and 194 receiving at least one dose of teriparatide and alendronate treatment were eligible for the efficacy analysis. Teriparatide was non-inferior to alendronate for BMD change at lumbar spine (treatment difference: 0.7%, 95% CI: - 0.3 to 1.7%), which excluded the predefined non-inferiority margin of - 1.5%. However, teriparatide was not statistically superior to alendronate in improving BMD at lumbar spine (P = 0.169). At 48 weeks, changes in BMD at total hip were - 1.0% and 2.2% in teriparatide and alendronate group, respectively (P < 0.001). The incidence of new fracture showed no statistical difference between groups (P = 0.128). Serum P1NP and ß-CTX levels significantly increased in the teriparatide group and markedly decreased in alendronate group (all P < 0.001 vs baseline). The adverse events (AEs) and serious AEs were more common in the teriparatide group than in the alendronate group, which were mainly teriparatide-related hypercalcemia, elevated alkaline phosphatase or parathyroid hormone, dizziness, and arthralgia. CONCLUSIONS: Teriparatide was not inferior to alendronate in increasing BMD at lumbar spine in Chinese postmenopausal women, and they achieved these effects through different mechanisms.

A novel homozygous nonsense mutation in the CA2 gene (c.368G>A, p.W123X) linked to carbonic anhydrase II deficiency syndrome in a Chinese family.

BACKGROUND: Carbonic anhydrase II deficiency syndrome is an autosomal recessive osteopetrosis with renal tubular acidosis and cerebral calcifications. We tried to detect the causative mutation for carbonic anhydrase II deficiency syndrome in a five-generation Chinese family. MATERIALS AND METHODS: Genomic DNA was extracted from whole blood of the proband, his grandmother, parents, aunt, uncle and sister. The exomes were sequenced by whole exon sequencing followed by genetic analysis and Sanger sequencing validation. Then, physical and chemical properties studies and structure analysis were performed on mutated protein. Finally, Minigene model of vector plasmids for wild type and mutant type was constructed and transfected into human embryonic kidney 293T cells to further explore the expression change of CA2 transcript and protein after mutation. RESULTS: Sequencing and genetic analysis have revealed the homozygous nonsense mutation of CA2 gene (c.368G > A, p.W123X) in the exon 4 of chromosome 8 of the proband, while it was not found in his grandmother, parents, aunt, uncle and sister. Furthermore, Sanger sequencing in the proband and his parents validated the mutation. Properties and structure of mutated CA2 proteins changed after mutation, especially in change of protein modification and hindrance of zinc ions binding, which may lead to decreased protein expression level of CA2. CONCLUSIONS: We found a new homozygous nonsense mutation in CA2 gene (c.368G > A, p.W123X), which may be valuable in the early diagnosis and therapy of carbonic anhydrase II deficiency syndrome.

Effect of informatization-based blood glucose team management on the control of hyperglycaemia in noncritical care units.

PURPOSE: To provide a new system of in-hospital blood glucose team management combined with a network blood glucose monitoring system and analyse the effect on hyperglycaemic participants' blood glucose control in noncritical care units. METHODS: Hyperglycaemic participants in noncritical care units were divided into two groups. They underwent active intervention by the hospital's blood glucose management team or the routine consultation group. The better method, based on a shorter length of stay (LOS) and lower hospital cost, could be selected by comparing the two blood glucose management strategies. RESULTS: Compared with the routine consultation group, the team management group had a higher detection rate of hyperglycaemia (18.49% vs 16.17%, P<0.01) and glycosylated haemoglobin (51.53% vs 30.97%, P<0.01) and a lower incidence rate of hyperglycaemia (59.24% vs 61.59%, P<0.01), severe hyperglycaemia (3.56% vs 5.19%, P<0.01) and clinically significant hypoglycaemia (0.26% vs 0.35%, P<0.05). Simultaneously, blood glucose drift (mmol/L) (2.50 (1.83, 3.25) vs 2.76 (2.01, 3.57), P<0.01), blood glucose coefficient of variation (%) (28.86 (22.70, 34.83) vs 29.80 (23.47, 36.13), P<0.01), maximum blood glucose fluctuation (mmol/L) (9.30 (6.20, 13.10) vs 10.10 (7.00, 14.40), P<0.01) and nosocomial infection (5.42% vs 8.05%, P<0.05) were all lower among participants in the team management group. In addition, the LOS (P<0.001) and hospital costs (P<0.001) of participants were lower in the team management group. CONCLUSION: In-hospital blood glucose team management combined with a network blood glucose monitoring system effectively improved the blood glucose control and fluctuation levels of participants who were admitted to noncritical care units, thereby reducing LOS and hospital cost.

Effect of serum 25-hydroxyvitamin D3 on insulin resistance and ß-cell function in newly diagnosed type 2 diabetes patients.

AIMS/INTRODUCTION: To evaluate serum 25-hydroxyvitamin D3 (25(OH)D3) in newly diagnosed type 2 diabetes patients and to explore the associations of 25(OH)D3 with insulin resistance and ß-cell function. MATERIALS AND METHODS: A total of 97 newly diagnosed type 2 diabetes patients and 69 healthy controls were recruited. Serum 25(OH)D3 was determined using high-pressure liquid chromatography. Insulin resistance was measured using a homeostasis model assessment of insulin resistance (HOMA-IR). ß-Cell function was determined using the HOMA ß-cell function index (HOMA-ß), early-phase insulin secretion index (ΔI30/ΔG30) and area under the insulin curve (AUCins). Correlation analysis was carried out using Pearson's correlation and multiple stepwise regression analysis. RESULTS: Serum 25(OH)D3 was much lower in patients with newly diagnosed type 2 diabetes (t = -13.00, P < 0.01), and the prevalence of hypovitaminosis 25(OH)D3 was 62.9% (61/97) in diabetic patients. Among the diabetic patients, patients with hypovitaminosis 25(OH)D3 showed higher glycosylated hemoglobin and AUCglu (P < 0.01) as well as lower HOMA-ß, ΔI30/ΔG30 and AUCins. Serum 25(OH)D3 was independently positively correlated with ΔI30/ΔG30 and AUCins (P < 0.05), but was not significantly correlated with either HOMA-IR or HOMA-ß. Only triglycerides, glycosylated hemoglobin and ΔI30/ΔG30 emerged as independent factors associated with serum 25(OH)D3 in both diabetes patients and the health control group. CONCLUSIONS: The present results further showed a low serum 25(OH)D3 concentration in patients with newly diagnosed type 2 diabetes. 25(OH)D3 deficiency is associated with disturbances in glucose metabolism and lipid metabolism. Serum 25(OH)D3 is not correlated with basal insulin resistance or ß-cell function, but is significantly positively correlated with glucose-stimulated insulin secretion and ß-cell function.

Comparison between recombinant human parathyroid hormone (1-34) and elcatonin in treatment of primary osteoporosis.

OBJECTIVE: To evaluate the efficacy and safety of rhPTH (1-34) vs. elcatonin. METHODS: Sixty patients with primary OP were randomly divided into two groups according to the ratio of 3:1. rhPTH (1-34) group (PTH group) was treated with subcutaneous injection of rhPTH (1-34) 20 µ g daily for 18 months, and the elcatonin group (CT group) was treated with intramuscular injection of elcatonin 20 U weekly for 12 months. Bone mineral density (BMD) of the lumbar spine 2-4 (L2-4) and femoral neck, serum calcium and phosphorus, urinary calcium, serum bone specific alkaline phosphatase (BSAP), and urinary c-terminal telopeptides of type I collagen/creatinine (uCTX-I/Cr) were tested at baseline, and 6, 12, and 18 months after treatment. RESULTS: In PTH group, BMD of L2-4 at 6, 12, and 18 months, BDM of femoral neck at 18 month, BSAP at 6 and 12 months and uCTX- I/Cr at 6, 12 and 18 months were all significantly raised. In CT group, BMD of L2-4 at 12 month and that of femoral neck at 12 and 18 months were significantly elevated, while BSAP was significantly decreased at 12 and 18 months, and no significant difference on CTX- I/Cr was observed. When BMD growth and growth rate between two groups were compared, PTH group had better improvement in L2-4 BMD and growth rate than CT group at 6, 12, and 18 months. BMD growth and growth rate of femoral neck at 12 month and its growth at 18 month in CT group were higher than in PTH group, but there was no significant difference between two groups regarding the growth rates at 18 month. Besides, there were no significant differences regarding the rates of adverse reactions between two groups. CONCLUSIONS: rhPTH (1-34), is safe and effective in the treatment of primary OP. It is superior to elcatonin in improving vertebral BMD at onset time, growth rate and growth range, but inferior to elcatonin at BMD of femoral neck.

Biphasic insulin aspart 30 improved glycemic control in Chinese patients with type 2 diabetes poorly controlled on oral glucose-lowering drugs: a subgroup analysis of the A1chieve study.

BACKGROUND: The effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials, while results from clinical practice remain limited. This subgroup analysis was to provide such findings from a large-scale non-interventional study. METHODS: A1chieve was a multinational, prospective, open-label, non-interventional, 24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia, Africa, Europe, and Latin America. After physician had taken the decision to use this insulin, any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible. Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control were collected at baseline, week 12 and 24. This is a report of a Chinese subgroup analysis from the A1chieve study. RESULTS: Totally, 4 100 patients constituted this subgroup. No serious adverse drug reactions were reported. Rates of total, major, nocturnal hypoglycemic events (events/patient per year) were 1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively. Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%, reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5 mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6 mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001). CONCLUSION: In this subgroup analysis of the A1chieve study, biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.

The diagnosis of diabetic acute complications using the glucose-ketone meter in outpatients at endocrinology department.

OBJECTIVE: To determine urine ketone and blood ß-hydroxybutyrate acid (ß-HBA) in outpatients of endocrinology department and to investigate the association between urine ketone or blood ß-HBA and diabetic ketosis (DK) or diabetic ketoacidosis (DKA). METHODS: Urine ketone, blood ß-HBA, body mass index (BMI) and glycosylated hemoglobin (HbA1c) were determined in 134 patients with blood glucose ≥ 13.9 mmol/L. RESULTS: In 134 patients with severe hyperglycemia, there were 30 patients (22.4%) with acute complications of diabetes, including 24 patients (17.9%) diagnosed with DK and 6 patients (4.5%) diagnosed with DKA. Among them, 6 patients (20%) were withdrawal, 2 (6.7%) were infected, and 19 (63.3%) were not treated. When there was a negative urine ketone, 10% patients would have had blood ß-HBA ≥ 0.3 mmol/L. When there was a positive urine ketone (+ to +++), 22.62% patients would have had blood ß-HBA < 0.3 mmol/L. CONCLUSIONS: Blood ß-HBA had a positive correlation with blood glucose (r = 0.34, P < 0.001). Complications of severe hyperglycemia could be diagnosed quickly and accurately by analyzing blood ß-HBA using the glucose-ketone meter.

Comparison of parathyroid hormone (1-34) and elcatonin in postmenopausal women with osteoporosis: an 18-month randomized, multicenter controlled trial in China.

BACKGROUND: Recombinant human parathyroid hormone (1-34) (rhPTH (1-34)) is the first agent in a unique class of anabolic therapies acting on the skeleton. The efficacy and safety of long-term administration of rhPTH (1-34) in Chinese postmenopausal women had not been evaluated. This study compared the clinical efficacy and safety of rhPTH (1-34) with elcatonin for treating postmenopausal women with osteoporosis in 11 urban areas of China. METHODS: A total of 453 postmenopausal women with osteoporosis were enrolled in an 18-month, multi-center, randomized, controlled study. They were randomized to receive either rhPTH (1-34) 20 µg (200 U) daily for 18 months, or elcatonin 20 U weekly for 12 months. Lumbar spine (L1-4) and femoral neck bone mineral density (BMD), fracture rate, back pain as well as biochemical markers of bone turnover were measured. Adverse events were recorded. RESULTS: rhPTH (1-34) increased lumbar BMD significantly more than did elcatonin after 6, 12, and 18 months of treatment (4.3% vs. 1.9%, 6.8% vs. 2.7%, 9.5% vs. 2.9%, P < 0.01). There was only a small but significant increase of femoral neck BMD after 18 months (2.6%, P < 0.01) in rhPTH groups. There were larger increases in bone turnover markers in the rhPTH (1-34) group than those in the elcatonin group after 6, 12, and 18 months (serum bone-specific alkaline phosphatase (BSAP) 93.7% vs. -3.6%; 117.8% vs. -4.1%; 49.2% vs. -5.8%, P < 0.01; urinary C-telopeptide/creatinine (CTX/Cr) 250.0% vs. -29.5%; 330.0% vs. -41.4%, 273.0% vs. -10.6%, P < 0.01). rhPTH (1-34) showed similar effect of pain relief as elcatonin. The incidence of clinical fractures was 5.36% (6/112) in elcatonin group and 3.2% (11/341) in rhPTH (1-34) group (P = 0.303). Both treatments were well tolerated. Hypercaluria (9.4%) and hypercalcemia (7.0%) in rhPTH (1-34) group were transient and caused no clinical symptoms. Pruritus (8.2% vs. 2.7%, P = 0.044) and redness of injection site (4.4% vs. 0, P = 0.024) were more frequent in rhPTH (1-34). Nausea/vomiting (16.1% vs. 6.2%, P = 0.001) and hot flushes (7.1% vs. 0.6%, P < 0.001) were more common in elcatonin group. CONCLUSIONS: rhPTH (1-34) was associated with greater increases in lumbar spine BMD and bone formation markers. It could increase femoral BMD after 18 months of treatment. rhPTH could improve back pain effectively. The results of the present study indicate that rhPTH (1-34) is an effective, safe agent in treating Chinese postmenopausal women with osteoporosis.

Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population.

BACKGROUND: At least twenty genes/loci were shown to be associated with type 2diabetes in European original populations. Five of these genes were shown to be associated with type 2 diabetes (T2D) in Chinese populations. The purpose of this study was to replicate the association of genetic vairants in the eight diabetes-related genes/loci with type 2 diabetes in a Han Chinese cohort from western part of China. Nineteen single nucleotide polymorphisms (SNPs) from the eight genes/loci including TCF7L2, HHEX, CDKAL1, SLC30A8, PPARG, IGF2BP2, KCNJ11, and CDKN2A/CDKN2B were genotyped in 1,529 cases and 1,439 controls in a Han Chinese population using the ABI SNaPshot method. The meta-analysis of the association between rs7903146 in TCF7L2 gene and T2D in the Han Chinese was performed. RESULTS: Among the eight genes/loci examined, we found that four were significantly associated with T2D. Although previous studies showed that the association between the SNP rs7903146 in the TCF7L2 gene and T2D was controversial within the Han Chinese population, we have confirmed the significant association between the SNP rs7903146 in the TCF7L2 gene and T2D in both this study and the meta-analysis in the population. In addition, we also confirmed that three SNPs (rs1111875, rs7923837 and rs5015480) in HHEX , one SNP (rs10946398) in CDKAL1, and three SNPs (rs13266634, rs3802177 and rs11558471) in SLC30A8 were significantly associated with T2D in the population being studied. CONCLUSIONS: We demonstrated that the variants in TCF7L2, CDKAL1, HHEX, and SLC30A8 genes are associated with T2D in a Han Chinese population.