Low prevalence of vitamin D deficiency in adult residents in Hainan, the tropical island province of China.

BACKGROUND: Vitamin D deficiency is considered to be a global health problem. The purpose of this study was to evaluate the prevalence of vitamin D deficiency and analyze its related factors among adult residents in Hainan, a tropical island province of southern China. METHODS: A total of 1,700 healthy adults, aged 18-86 years (617 men and 1,073 women), were enrolled in our cross-sectional descriptive study. Binomial logistic regression analyses were performed to identify possible predictors of vitamin D status. RESULTS: The average serum 25-hydroxyvitamin D [25(OH)D] concentration was 37.66±10.77 ng/mL (males 43.60±11.8 ng/mL, females 34.20±8.40 ng/mL; I<0.001). The proportions of vitamin D sufficiency [25(OH)D ≥30 ng/mL], insufficiency [20 ng/mL ≤25(OH)D <30 ng/mL], and deficiency [25(OH)D <20 ng/mL] were 76.6%, 20.5%, and 2.9%, respectively. Vitamin D deficiency in the young, middle-aged, and elderly groups were 4.2%, 2.7%, and 1.7%, respectively. Vitamin D sufficiency was found to be positively associated with male sex (P<0.0001), age >40 years (P=0.014), habitation in a rural area (P<0.0001), summer/autumn seasons (P<0.0001), and having <13 years of formal education (P<0.0001). CONCLUSIONS: Our study was the first to assess the vitamin D status and analyze related factors among adult residents in Hainan Province, China. We found that vitamin D deficiency has low prevalence in this population, suggesting that before developing a strategy for the clinical use of vitamin D supplements in a region, the levels of vitamin D in generally healthy populations of that region should be assessed, to avoid unnecessary supplementation.

Henagliflozin as add-on therapy to metformin in patients with type 2 diabetes inadequately controlled with metformin: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of henagliflozin in patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. MATERIAL AND METHODS: This multicentre phase 3 trial included a 24-week randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients with a glycated haemoglobin (HbA1c) level of 7.0% (53 mmol/mol) to 10.5% (91 mmol/mol) were randomized and treated with once-daily placebo (n = 161), henagliflozin 5 mg (n = 162), or henagliflozin 10 mg (n = 160). After 24 weeks, patients on placebo were switched to 5 mg or 10 mg henagliflozin for the additional 28-week treatment, and patients on henagliflozin during 24-week treatment period maintained this initial therapy. The primary endpoint was change in HbA1c from baseline to Week 24. RESULTS: At Week 24, the least squares mean HbA1c changes versus placebo from baseline were - 0.76% (-8.3 mmol/mol) and - 0.80% (-8.7 mmol/mol) for henagliflozin 5 and 10 mg, respectively (all P < 0.0001). Compared with the placebo group, both doses of henagliflozin lowered fasting plasma glucose, 2-hour postprandial plasma glucose, body weight and blood pressure, and increased the proportions of patients achieving HbA1c <7.0% (53 mmol/mol) at Week 24. The trends in these improvements were sustained over an additional 28 weeks. Slightly higher proportions of ketosis and presence of urine ketone bodies were observed in patients treated with henagliflozin compared to placebo at Week 24. No diabetic ketoacidosis or episodes of severe hypoglycaemia were reported. CONCLUSIONS: Henagliflozin 5 mg or 10 mg as add-on therapy to metformin provided a new therapeutic option for the treatment of T2DM patients who have inadequate glycaemic control with metformin alone, and was generally well tolerated.

Henagliflozin monotherapy in patients with type 2 diabetes inadequately controlled on diet and exercise: A randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate henagliflozin, a novel sodium-glucose co-transporter-2 inhibitor, as monotherapy in patients with type 2 diabetes and inadequate glycaemic control with diet and exercise. MATERIALS AND METHODS: This multicentre trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Four hundred and sixty-eight patients with an HbA1c of 7.0%-10.5% were randomly assigned (1:1:1) to receive once-daily placebo, or 5 or 10 mg henagliflozin. After 24 weeks, patients on placebo were switched to 5 or 10 mg henagliflozin, and patients on henagliflozin maintained the initial therapy. The primary endpoint was the change in HbA1c from baseline after 24 weeks. RESULTS: At Week 24, the placebo-adjusted least squares (LS) mean changes from baseline in HbA1c were -0.91% (95% CI: -1.11% to -0.72%; P < .001) and -0.94% (-1.13% to -0.75%; P < .001) with henagliflozin 5 and 10 mg, respectively; the placebo-adjusted LS mean changes were -1.3 (-1.8 to -0.9) and -1.5 (-2.0 to -1.1) kg in body weight, and -5.1 (-7.2 to -3.0) and -4.4 (-6.5 to -2.3) mmHg in systolic blood pressure (all P < .05). The trends of these improvements were sustained for an additional 28 weeks. Adverse events occurred in 81.0%, 78.9% and 78.9% of patients in the placebo, henagliflozin 5 and 10 mg groups, respectively. No diabetic ketoacidosis or major episodes of hypoglycaemia occurred. CONCLUSIONS: Henagliflozin 5 mg and 10 mg as monotherapy provided effective glycaemic control, reduced body weight and blood pressure, and was generally well tolerated.

Efficacy and safety of polyethylene glycol loxenatide monotherapy in type 2 diabetes patients: A multicentre, randomized, double-blind, placebo-controlled phase 3a clinical trial.

AIM: To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China. MATERIALS AND METHODS: In a multicentred, randomized, double-blinded, placebo-controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%-10.5%, fasting plasma glucose <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 µg or PEX168/200 µg. The 24-week treatment was followed by a 28-week extension, during which placebo-treated patients were randomly assigned to PEX168/100 µg or PEX168/200 µg. The primary efficacy endpoint was the HbA1c change from baseline to week 24. RESULTS: The three groups had similar demographics and baseline characteristics. The HbA1c least-square mean (95% CI) change from baseline to week 24 was greater for PEX168/100 µg (-1.02% [-1.21%, -0.83%]) and PEX168/200 µg (-1.34% [-1.54%, -1.15%]) than for placebo (-0.17% [-0.36%, 0.02%]); (superiority: P < .0001). The proportions of patients with less than 7% HbA1c in the placebo, PEX168/100 µg and PEX168/200 µg groups were 15.7%, 34.7% and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0% and 0% for PEX168/100 µg, PEX168/200 µg and placebo, respectively) and vomiting (2.4%, 8.3% and 0% for PEX168/100 µg, PEX168/200 µg and placebo, respectively). Six (1.6%) patients (PEX168/100 µg: N = 2 [1.6%], PEX168/200 µg: N = 3 [2.5%] and placebo: N = 1 [0.8%]) discontinued treatment because of AEs. Four (1.2%) patients (PEX168/100 µg: N = 3 [2.5%] and PEX168/200 µg: N = 1 [0.9%]) developed PEX168 antidrug antibodies. CONCLUSION: PEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon-like peptide-1 receptor agonists.

ABCC8-Related Maturity-Onset Diabetes of the Young (MODY12): A Report of a Chinese Family.

Maturity-onset diabetes mellitus of the young (MODY) is a monogenic diabetes characterized by autosomal dominant inheritance. Its atypical clinical features make diagnosis difficult and it can be misdiagnosed as type 1 or type 2 diabetes. Fourteen subtypes of MODY have been diagnosed so far, of which MODY12 is caused by mutation of the ABCC8 (ATP Binding Cassette Subfamily C Member 8) gene, which is rarely reported in China. This paper reports a Chinese family of MODY12 caused by a rare missense mutation on the ABCC8 gene, which has not been reported to be associated with MODY in China or in other countries, with the aim of increasing clinicians' awareness and attention to the disease.

Type A insulin resistance syndrome misdiagnosed as polycystic ovary syndrome: a case report.

BACKGROUND: Type A insulin resistance syndrome, one type of the hereditary insulin resistance syndromes, is a rare disorder. Patients with type A insulin resistance syndrome are nonobese and demonstrate severe hyperinsulinemia, hyperandrogenism, and acanthosis nigricans. The clinical features are more severe in affected females than in males, and they mostly become apparent at the age of puberty. In many cases, when severe insulin resistance is covered up by other signs or symptoms of type A insulin resistance syndrome, patients are often easily misdiagnosed with other diseases, such as polycystic ovary syndrome. CASE PRESENTATION: Our patient was a 27-year-old Han Chinese woman who sought treatment because of a menstrual disorder and hirsutism. Tests showed that her levels of insulin and testosterone were elevated, and gynecological color Doppler ultrasound suggested multiple cystic changes in the bilateral ovaries. After a diagnosis of polycystic ovary syndrome was made, pulsatile gonadotropin-releasing hormone therapy and metformin were administered, but the patient's symptoms did not improve in 1 year of follow-up. Considering that the previous diagnosis might have been incorrect, venous blood samples were collected from the patient and her relatives for genetic analysis. Subsequently, using Illumina sequencing, it was found that the proband, her father, and two brothers all had the c.3601C>T heterozygous missense mutation in exon 20 of the insulin receptor gene. The diagnosis was corrected to type A insulin resistance syndrome, and the patient's treatment was modified. CONCLUSION: We report a case of a young woman with type A insulin resistance syndrome that was misdiagnosed as polycystic ovary syndrome. We discuss the causes, clinical features, diagnosis, and treatment of type A insulin resistance syndrome to improve the recognition of the disease and reduce its misdiagnosis. Female patients with high androgen levels and severe hyperinsulinemia should be considered for the possibility of hereditary insulin resistance syndromes (such as type A insulin resistance syndrome). Gene sequencing helps in making an early diagnosis and developing a targeted treatment strategy.

A crossover study of the combination therapy of metformin and exenatide or biphasic insulin aspart 30 in overweight or obese patients newly diagnosed with type 2 diabetes mellitus.

The aim of the present study was to explore the effects of various combinations of exenatide, metformin (MET) and biphasic insulin aspart 30 (BIA30) on type 2 diabetes mellitus (T2DM). Two hundred overweight or obese patients newly diagnosed with T2DM were evenly randomized into two groups: A (twice daily for all: Phase I, 5 µg exenatide + 0.5 g MET for 4 weeks, then 10 µg exenatide + 0.5 g MET for 8 weeks; Phase II, 0.5 g MET for 12 weeks; Phase III, 0.3-0.4 U/kg/day BIA30 + 0.5 g MET for 12 weeks) and B (Phases I, II, III matched the phases III, II and I in group A). In groups A and B a significant decrease and increase, respectively, in glycated hemoglobin (HbAlc) and body mass index (BMI) was noted during Phase I. A 3.2±0.4-kg decrease in body weight in group A and a 2.6±0.3-kg increase in group B was observed. In Phase II, HbAlc was significantly increased in both groups (P<0.05). In Phase III, the BMI was increased in group A and reduced in group B (P<0.05). There was a 3.8±0.4-kg weight decrease in group B and 4.2±0.5-kg increase in group A (P<0.05). The combination of exenatide and MET promoted weight loss, glycemic control, ß-cell function index, C peptide and adiponectin levels. These results suggested that the combination of exenatide and MET is better than the combination of BIA and MET for the therapy of overweight or obese patients newly diagnosed with T2DM.

[Effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats].

OBJECTIVE: To explore the effect of methylprednisolone on bone mass, microarchitecture and microdamage in cortical bone of ulna in rats. METHODS: Twenty female Sprague-Dawley rats (3.5 months old) were randomly assigned to two groups: a treatment group and a control group (n=10 per group). The treatment group was subcutaneously injected with methylprednisolone 3.5 mg/(kg.d) while the control group was subcutaneously injected with same volume of vehicle (saline). Rats were sacrificed at 9 weeks after the treatments. Before the sacrifice, the body weight and total bone mineral density (BMD) were measured. The right forelimb was separated through humeral shoulder and then single axial fatigue loading was performed on the right ulna. After fatigue load, the middle ulna section was bulkstained in basic fuchsin. Bone histomorphometry and microdamage analysis were performed on the middle ulna section. RESULTS: Compared with the control group, the body weight, total bone BMD and ulnas BMD in the treatment group were decreased by 15%, 6.4% and 4.3% respectively (all P<0.05); the ulna inner perimeter and marrow area in the treatment group were increased by 23.3% and 32%, respectively (both P<0.05), while the outer perimeter were decreased by 3.1% (P>0.05). There was no significant difference in the cortical and total area between the 2 groups (both P>0.05). The number of microcrack, microcrack density and microcrack surface density in the treatment group were increased by 43%, 48% and 50%, respectively, compared with those in the control group (all P<0.05), but there was no significant difference in the mean length of microcrack between the 2 groups (P>0.05). CONCLUSION: Methylprednisolone can significantly induce the bone loss and the deterioration of microarchitecture and microdamage in ulna of rats.

Exenatide enhances INS-1 rat pancreatic ß­cell mass by increasing the protein levels of adiponectin and reducing the levels of C-reactive protein.

Type 2 diabetes mellitus (T2DM) is a complex and heterogeneous disorder affecting >220 million individuals worldwide; this is projected to reach 366 million by 2030. Exenatide, a long­acting glucagon­like peptide 1 receptor agonist, exhibits potential in the treatment of T2MD due to its ability to increase ß­cell mass. However, the molecular mechanism by which exenatide increases ß­cell mass is yet to be elucidated. Exenatide function was explored in the INS­1 rat pancreatic ß­cell line. Exenatide was found to increase adiponectin protein levels by 20% (P<0.05 versus the control group) and reduce the level of C­reactive protein (CRP) by 50% (P<0.01 versus the control group) in INS­1 cells, resulting in an increase in the INS­1 rat pancreatic ß­cell mass by 20% (P<0.01 versus the control group). These findings suggest that exenatide may ameliorate T2DM by increasing adiponectin protein levels and reducing the level of CRP.