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.

HbA1c variability as an independent predictor of diabetes retinopathy in patients with type 2 diabetes.

AIMS: To evaluate the association of both mean HbA1c and HbA1c variability with DR development in patients with type 2 diabetes. METHODS: Patients with type 2 diabetes who received dilated funduscopic examination annually and who underwent at least 2-year follow-up were included in this longitudinal study. Subjects were excluded if they took less than five HbA1c measurements during the follow-up period. HbA1C variability was expressed as A1c-SD, and the mean of HbA1c (A1c-Mean) was calculated. In addition, medical history and clinical data of all subjects were collected and analyzed. According to A1c-Mean above or below the value 7% and A1c-SD above or below the population mean value 0.76%, subjects were divided into four quartiles: Q1(A1c-Mean < 7%, A1c-SD < 0.76%); Q2(A1c-Mean < 7%, A1c-SD ≥ 0.76%); Q3(A1c-Mean ≥ 7%, A1c-SD < 0.76%); Q4(A1c-Mean ≥ 7%, A1c-SD ≥ 0.76%). RESULTS: 3152 participants were included in the study analysis with a median follow-up period of 3.95 years (2-5 years), 17.6% (n = 556) were found to have DR, and these patients also had higher HbA1c levels (P < 0.001). Linear mixed-effect models were performed after adjusting for the characteristics of participants and the results showed that HbA1c variability is an independent risk factor for DR. Cox regression revealed that patients in Q4 group had the highest DR prevalence (HR = 1.624, P < 0.001) while Q1 group had the lowest. In addition, patients in Q2 group (HR = 1.429, P = 0.006) had a higher risk of DR than those in Q3 group (HR = 1.334, P < 0.001). CONCLUSIONS: HbA1c variability is an independent predictor of DR in patients with type 2 diabetes in Asia. It may play a greater role in DR development than mean HbA1c does when the mean value of HbA1c variability index is above 0.75%, indicating that aggressive A1c lowering strategies may, in fact, contribute excessively to risk of DR in patients with type 2 diabetes; steady decline of A1c should be taken into consideration.

Gender-differential effects on blood glucose levels between acarbose and metformin in Chinese patients with newly diagnosed type 2 diabetes: a sub-analysis of the MARCH trial.

Using the data from the trial of Metformin and AcaRbose in Chinese as the initial Hypoglycemic treatment (MARCH), this study was performed to compare the differential effects of acarbose and metformin on glucose metabolism after stratification by gender. Six hundred and forty patients who had finished the whole 48-week follow-up were included. The reduction of haemoglobin A1c (HbA1c) was comparable between acarbose- and metformin-treated patients among either females or males, and it was also similar between males and females treated with either acarbose or metformin for 24 and 48 weeks. The dropping of fasting plasma glucose (FPG) in acarbose-treated females was significantly less than that in metformin-treated females at both 24 and 48 weeks. Furthermore, the decrease of 2-hour postprandial glucose (2hPPG) in acarbose-treated males was significantly greater than that in metformin-treated males at both 24 and 48 weeks. Multiple linear regression analysis showed that drug selection was an independent factor affecting the decrease of FPG in female patients while it independently influenced 2hPPG in males at week 24 and 48. The reductions of FPG and 2hPPG at week 24 and 48 were also significantly different between metformin-treated females and metformin-treated males although gender was not an independent regulating factor. Our study indicates that there might be gender-differential effects on FPG and 2hPPG reduction when the comparisons are made between acarbose and metformin treatments.

Standards of medical care for type 2 diabetes in China 2019.

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.

Comparison of Two Autoimmune Dysglycemia Syndromes: Insulin Autoimmune Syndrome (IAS) and Type B Insulin Resistance Syndrome (B-IRS).

Insulin autoimmune syndrome (IAS) and type B insulin resistance syndrome (B-IRS) are rare autoimmune dysglycemia syndromes, but their treatment and prognosis are different. This study aimed to provide a basis for the clinical differential diagnosis of IAS and B-IRS. This was a retrospective study of the medical records of all patients diagnosed with IAS or B-IRS between January 2006 and March 2018 at the Chinese PLA General Hospital. Demographic, clinical, biochemistry, treatment, and follow-up data were examined. There were several different biochemical parameters between IAS (n=13) and B-IRS (n=6): white blood count (WBC, 7.05±3.06 vs. 2.70±0.73×109/l, p=0.004), platelet (249±56.6 vs. 111±68.0×109/l, p<0.001), serum creatine (59.0±17.8 vs. 43.1±7.05 µmol/l, p=0.013), serum albumin (42.3±5.17 vs. 33.6±3.40 g/l, p=0.002), triglyceride (median, 1.33 (1.01, 1.93) vs. 0.56 (0.50, 0.79) mmol/l, p=0.002), plasma IgG (1183±201 vs. 1832±469 mg/ml, p=0.018), IgA (328±140 vs. 469±150 mg/ml, p=0.018), and C3 (128±23.4 vs. 45.3±13.5 mg/l, p<0.001). Fasting insulin in the IAS and B-IRS patients was high (299-4708 vs. 118-851 mU/l, p=0.106), and there was a difference in 2 h oral glucose tolerance test insulin (4217-8343 mU/l vs. 274-1143 mU/l, p=0.012). Glycated hemoglobin (HbA1c) in the B-IRS patients was higher than in IAS patients (114±14.4. vs. 40.6±8.89 mmol/mol, p<0.001). Serum insulin-like growth factor-1 (IGF-1) was lower in all B-IRS patients (25±0.00 vs. 132±52.7 ng/ml, p<0.001). Although IAS and B-IRS are autoimmune hyperinsulinemic dysglycemic syndromes, several clinical parameters (body mass index, HbA1c, WBC, platelet, albumin, triglyceride, IgG, C3, and IGF-1) are different between these two syndromes.

Randomised study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Primary results of the BERSON clinical trial.

AIM: To evaluate the lipid-lowering efficacy and safety of evolocumab combined with background atorvastatin in patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. MATERIALS AND METHODS: BERSON was a double-blind, 12-week, phase 3 study (NCT02662569) conducted in 10 countries. Patients ≥18 to ≤80 years with type T2DM received atorvastatin 20 mg/d and were randomised 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or placebo Q2W or QM. Co-primary endpoints were the percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures, and adverse events (AEs). RESULTS: Overall, 981 patients were randomised and received ≥1 dose of study drug. Evolocumab significantly reduced LDL-C versus placebo at week 12 (Q2W, -71.8%; QM, -74.9%) and at the mean of weeks 10 and 12 (Q2W, -70.3%; QM, -70.0%; adjusted P < 0.0001 for all) when administered with atorvastatin. Non-high-density lipoprotein cholesterol, apolipoprotein B100, total cholesterol, lipoprotein (a), triglycerides, high-density lipoprotein cholesterol, and very low-density lipoprotein cholesterol improved significantly with evolocumab versus placebo. The overall incidence of AEs was similar between evolocumab and placebo-treated patients, and there were no clinically meaningful differences in changes over time in glycaemic variables (fasting serum glucose and HbA1c) between the two groups. CONCLUSIONS: In patients with T2DM and hyperlipidaemia or mixed dyslipidaemia on statin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Randomized study of evolocumab in patients with type 2 diabetes and dyslipidaemia on background statin: Pre-specified analysis of the Chinese population from the BERSON clinical trial.

AIM: The aim of this study was to evaluate the efficacy and safety of evolocumab with background atorvastatin in Chinese patients with type 2 diabetes mellitus (T2DM) and hyperlipidaemia or mixed dyslipidaemia. MATERIALS AND METHODS: This is a pre-specified analysis of patients in the BERSON study (ClinicalTrials.gov, NCT02662569) in China. Patients initiated background atorvastatin 20 mg/d, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Co-primary endpoints were percentage change in LDL cholesterol (LDL-C) from baseline to week 12 and from baseline to the mean of weeks 10 and 12. Additional endpoints included atherogenic lipids, glycaemic measures and adverse events (AEs). RESULTS: Among 453 patients randomized in China, 451 received at least one dose of study drug (evolocumab or placebo). Evolocumab significantly reduced LDL-C compared with placebo at week 12 (Q2W, -85.0%; QM, -74.8%) and at the mean of weeks 10 and 12 (Q2W, -80.4%; QM, -81.0%) (adjusted P < 0.0001 for all) when administered with background atorvastatin. Non-HDL-C, ApoB100, total cholesterol, Lp(a), triglycerides, HDL-C and VLDL-C significantly improved with evolocumab vs placebo. No new safety findings were observed with evolocumab. The incidence of diabetes AEs was higher with evolocumab compared with placebo. There were no differences over time between evolocumab and placebo in measures of glycaemic control. CONCLUSIONS: In patients in China with T2DM and hyperlipidaemia or mixed dyslipidaemia receiving background atorvastatin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycaemic measures.

Identification of autoimmune type 1 diabetes and multiple organ-specific autoantibodies in adult-onset non-insulin-requiring diabetes in China: A population-based multicentre nationwide survey.

AIMS: To investigate the prevalence of adult-onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ-specific autoantibodies in people with phenotype of type 2 diabetes (T2D). MATERIALS AND METHODS: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform-8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21-hydroxylase (21-OH) autoantibodies in randomly selected participants with ADM and in age-matched, sex-matched and non-ADM controls with T2D plus controls with NGT. RESULTS: Post-normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3-6.8) in initially non-insulin-requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8-21.8), tTG autoantibodies 2.1% (95% CI 0.0-4.2), and 21-OH autoantibodies 1.8% (95% CI -0.2 to 3.8). Those participants with ADM who were GAD autoantibody-positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). CONCLUSIONS: A proportion of people with phenotype of T2D in China have ADM, with diabetes-associated autoantibodies, and may be at risk of developing other organ-specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations.

Low triglyceride as a marker for increased risk of cardiovascular diseases in patients with long-term type 2 diabetes: A cross-sectional survey in China.

BACKGROUND: There are inconsistent findings regarding associations between triglyceride levels and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). This study aimed to test whether the association between triglycerides and CVD depends upon duration of diabetes. METHODS: From April 1, 2012, to June 30, 2012, we conducted a cross-sectional survey of 223 612 patients with T2DM from 630 hospitals in China. Cardiovascular disease was defined as having either prior coronary heart disease or stroke, or diabetic foot. Binary logistic regression was used to estimate odds ratios of triglyceride for CVD. Relative excess risk due to interaction, attributable proportion due to interaction, and synergy index were used to estimate effect size of additive interaction between low triglyceride, ie, <1.7 mmol/L, and duration of diabetes, ie, ≥15 years. RESULTS: Among 223 612 T2DM patients, 31 898 (14.27%) suffered from CVD. A low level of triglyceride was associated with decreased risk of CVD (univariable OR, 0.91, 95% CI, 0.88-0.93; multivariable OR, 0.94, 95% CI, 0.92-0.97) among patients with <15 years of duration of diabetes but increased risk of CVD (univariable OR, 1.12, 95% CI, 1.04-1.21; multivariable OR, 1.18, 95% CI, 1.09-1.27) among those patients with 15 and more years of duration of diabetes with significant additive interactions (relative excess risk due to interaction, 0.39, 95% CI, 0.25-0.52; attributable proportion due to interaction, 0.20, 95% CI, 0.14-0.27; and synergy index, 1.80, 95% CI, 1.43-2.28). CONCLUSIONS: Whereas a high triglyceride level was associated with increased risk of CVD in short-term T2DM, low triglyceride was associated with increased CVD risk in long-term T2DM. Low triglyceride may be a marker of CVD risk in Chinese patients with long-term T2DM.

Clinical characteristics of type 2 diabetes patients with discordance between HbA1c and fasting plasma glucose in the real world: An analysis of the ORBIT study.

BACKGROUND: We aimed to determine the clinical characteristics of type 2 diabetes patients on basal insulin therapy with inadequate glucose control due to discordance between glycated haemoglobin (HbA1c ) and fasting plasma glucose (FPG) in the real world. METHODS: This was a retrospective analysis of data from the ORBIT study in China. Clinical characteristics of patients with discordance between HbA1c and FPG at baseline and at the end of 6 months of follow-up were analysed using multinomial logistic regression in 4 study groups divided by HbA1c and FPG. RESULTS: Overall, of 6721 patients initiated on basal insulin, 853 achieved HbA1c  < 7% but FPG ≥ 7 mmol/L (group 2), while 997 had FPG < 7 mmol/L but HbA1c  ≥ 7% (group 3) at the end of follow-up. Patients in group 3 had a longer duration of type 2 diabetes compared with those in group 2 (7.22 ± 5.30 vs 6.00 ± 4.80 y, P < .05). Patients on glargine (32.90%) or detemir (36.88%) treatment accounted for a higher proportion of patients with both HbA1c and FPG controlled than those on neutral protamine Hagedorn therapy (23.45%; P < .05). Per the multinomial logistic analysis, higher frequency of self-monitoring of blood glucose (SMBG) and use of glargine or detemir therapy were significantly inversely associated with risk of discordance between HbA1c and FPG, while dose of insulin was a risk factor for discordance at the end of follow-up (all P < .05). CONCLUSIONS: Patients treated with insulin analogues (glargine or detemir), instead of neutral protamine Hagedorn, and with more frequent SMBG are more likely to exhibit concordance between HbA1c and FPG.

Whole-genome sequencing revealed armadillo repeat containing 5 (ARMC5) mutation in a Chinese family with ACTH-independent macronodular adrenal hyperplasia.

Primary macronodular adrenal hyperplasia (PMAH), also known in the past as bilateral macronodular adrenalhyperplasia or adrenocorticotropin (ACTH)-independent macronodular adrenal hyperplasia, is a rare type of Cushing's syndrome (CS) and is associated with bilateralenlargement of the adrenal glands. It accounts for <1% of all endogenous cases of CS. In order toidentify the pathogenic mutations in the causative gene of (AIMAH pedigrees, Whole-genome sequencing of three patients in family I was used to retrieve candidate causative genes. Meanwhile, the causative gene was identified by Sanger sequencing from the two pedigrees. Sequencing of ARMC5 exons of three patients was carried out to identify somatic mutations. Moreover, haploid clone of one tumor DNA sample was conducted. ARMC5 was the causative gene of two pedigrees confirmed by whole-genome sequencing (WGA) and Sanger sequencing. The variant sites of the two families were c.C943T (p.R315W) and c.C1960T (p.R654X), respectively. Autosomal dominant inheritance of AIMAH was confirmed by genotypes of one family member. Several somatic mutations were discovered in tumor DNA samples. In addition, haploid clone of tumor DNA was confirmed by germline mutation and somaticmutation, which suggested the pathogenic mechanism of "two-hit-model." ARMC5 was the causative gene of AIMAH pedigrees. This AIMAH in this study presented autosomal dominant inheritance, fitting to Mendelian inheritance law. However, the pathogenic mode of this disease showed as compound heterozygote.

Comparative effectiveness and safety of different basal insulins in a real-world setting.

AIMS: To compare glucose control and safety of different basal insulin therapies (BI, including Insulin NPH, glargine and detemir) in real-world clinical settings based on a large-scale registry study. METHODS: In this multi-center 6-month prospective observational study, patients with type 2 diabetes (HbA1c ≥ 7%) who were uncontrolled by oral anti-diabetic drugs (OADs) and were willing to initiate BI therapy were enrolled from 209 hospitals within 8 regions of China. Type and dose of BI were at the physician's discretion and the patients' willingness. Interviews were conducted at 0 months (visit 1), 3 months (visit 2) and 6 months (visit 3). Outcomes included change in HbA1c, hypoglycemia rate and body weight from baseline at 6 months. RESULTS: A total of 16 341 and 9002 subjects were involved in Intention-To-Treat (ITT) and per-protocol (PP) analysis, respectively. After PS regression adjustment, ITT analysis showed that reduction in HbA1c in glargine (2.2% ± 2.1%) and detemir groups (2.2% ± 2.1%) was higher than that in the NPH group (2.0% ± 2.2%) (P < .01). The detemir group had the lowest weight gain (-0.1 ± 2.9 kg) compared with the glargine (+0.1 ± 3.0 kg) and NPH (+0.3 ± 3.1 kg) groups (P < .05). The glargine group had the lowest rate of minor hypoglycaemia, while there was no difference in severe hypoglycaemia among the 3 groups. The results observed in PP analyses were consistent with those in ITT analysis. CONCLUSION: In a real-world clinical setting in China, treatment with long-acting insulin analogues was associated with better glycaemic control, as well as less hypoglycaemia and weight gain than treatment with NPH insulin in type 2 diabetes patients. However, the clinical relevance of these observations must be interpreted with caution.

Observational Registry of Basal Insulin Treatment (ORBIT) in patients with type 2 diabetes uncontrolled with oral antihyperglycaemic drugs: Real-life use of basal insulin in China.

AIMS: To examine treatment patterns following basal insulin (BI) introduction in type 2 diabetes mellitus (T2DM) patients under real-world conditions across China. MATERIALS AND METHODS: Overall, 18 995 patients inadequately controlled (HbA1c ≥ 53 mmol/mol [7%]) with oral antihyperglycaemic drugs (OADs) and willing to receive BI treatment were registered at 209 hospitals and followed at baseline (visit 1), 3 months (visit 2) and 6 months (visit 3). Type of BI was initiated at physicians' discretion. RESULTS: Retention with BI therapy at 6 months was 75.6%. Use of long-acting BI predominated, with insulin glargine accounting for 71%, detemir 13% and Neutral Protamine Hagedorn (NPH) insulin 16%. Over 70% of long-acting users maintained the same initial BI at visit 3, while 40% of NPH users switched treatment and 24.4% of participants initiated BI with prandial insulin. The initial mean (± SD) dose of BI and total insulin was 0.18 ± 0.07 and 0.25 ± 0.19 IU/kg, respectively, with a mean increase of daily dose by 0.03 and 0.02 IU/kg after 6 months, respectively. Only 56.6% of insulin users reported dose titration at visit 3. Mean HbA1c was 81 mmol/mol (9.6%) at baseline and 57 mmol/mol (7.4%) at 6 months. The frequency of hypoglycaemia was 1.61 and 2.07 episodes/patient-year at baseline and 6 months, respectively. CONCLUSIONS: In real-world clinical settings, add-on BI therapy in T2DM patients is associated with significant improvement in glycaemic control without overtly compromising safety related to hypoglycaemia and weight gain. Evolution of insulin treatment regimens varied among patients, but dose titration was suboptimal. More active BI dose titration might further improve glycaemic outcome in patients receiving BI therapy. VIDEO ABSTRACT: A free Video Abstract to accompany this article is available at https://vimeo.com/212655959.

Significant inverse association between serum osteocalcin and incident type 2 diabetes in a middle-aged cohort.

BACKGROUND: Accumulating evidence indicates that osteocalcin links bone formation to glucose homeostasis. However, the correlation between osteocalcin and incident type 2 diabetes has been controversial based on the limited results of cohort studies. We examined the link between serum osteocalcin and glucose homeostasis including incident type 2 diabetes in a 3-year follow-up study. METHODS: This retrospective study enrolled 1870 middle-aged subjects (1279 men, 591 women) at Chinese PLA General Hospital who were followed-up for 3 years. Cox proportional hazards regression was used to determine whether incident type 2 diabetes was influenced by the osteocalcin concentrations measured with an electrochemiluminescence immunoassay. RESULTS: At baseline, the blood glucose levels and prevalence of metabolic syndrome varied inversely with the osteocalcin quartiles. During follow-up, type 2 diabetes developed in 80 of the 1870 subjects. The prevalence decreased with osteocalcin quartiles (P = 0.016). In models adjusted for metabolism-related parameters, osteocalcin was inversely associated with fasting plasma glucose {ß = -0.017 [95% confidence interval (CI), -0.034-0.00], P = 0.040}. Osteocalcin was inversely related to the risk of incident type 2 diabetes assessed using a model adjusted for glucose metabolic parameters, 25-hydroxy vitamin D3 and parathyroid hormone (hazard ratio [HR] = 0.09 [95% CI, 0.01-0.96], P = 0.046). The onset risk of diabetes in the first osteocalcin quartile was higher than in the fourth quartile (HR = 1.67 [95% CI, 0.96-3.48], P = 0.035). The correlation was strongly significant after fully adjusting for glucose related parameters and bone turnover (HR = 3.02 [95% CI, 1.25-7.32], P = 0.014). CONCLUSIONS: Low serum osteocalcin concentrations at baseline were independently related to an increased risk of incident type 2 diabetes. Copyright © 2016 John Wiley & Sons, Ltd.

Type B insulin resistance syndrome with Scleroderma successfully treated with multiple immune suppressants after eradication of Helicobacter pylori infection: a case report.

BACKGROUND: Type B insulin resistance is a rare autoimmune disease characterized by the presence of autoantibodies against the insulin receptor. Helicobacter pylori (H pylori) infection may play a causative role in the autoimmune diseases. CASE PRESENTATION: Here, we present a rare case of a 48-year old female patient, who had type B insulin resistance with systemic scleroderma and was successfully treated with multiple immune suppressants after eradication of Helicobacter pylori infection. CONCLUSION: The present case suggests H pylori infection-related pathological mechanism may contribute to type B insulin resistance syndrome and autoimmune disorders. Treatment toward H pylori may be helpful to relieve syndrome of type B insulin resistance for H pylori positive patients.

[Type B insulin resistance syndrome: 3 cases report and literature review].

OBJECTIVE: To understand type B insulin resistance syndrome (B-IRS) by reviewing 3 cases from our center and cases from literatures. METHODS: The clinical characteristics, diagnosis, treatment and follow-up data of the 3 patients with B-IRS were evaluated. RESULTS: All the 3 patients were middle-aged women with severe hyperglycemia or paradoxical hypoglycemia. The clinical findings were as follows. (1)B-IRS was associated with several autoimmune diseases such as systemic lupus erythematosus (SLE) and sclerosis. (2) The metabolic abnormalities of B-IRS include weight loss, severe hyperinsulinemia, high level of adiponectin, and low level of insulin-like growth factor type 1(IGF-1) and TG. (3)B-IRS was characterized with nonspecific serological disorders (such as leukopenia, thrombocytopenia and hypoalbuminemia) and changes (decreased complements and elevated IgG and/or IgA), and with specific immunological abnormalities[such as high titer of antinuclear antibody(ANA), positive in anti-SSA, anti-SSB and anti-dsDNA antibodies). Positive in anti-insulin receptor antibody was of diagnostic value but not necessary. (4) Treatments include insulin in combination with immunosuppressive therapy. Patients with H. pylori (Hp) infection may be benefit with eradication therapy. CONCLUSIONS: B-IRS is rare but not difficult to identify. Treatments include therapy of the underlying diseases and high dose of insulin.

Identification of a novel COL1A1 frameshift mutation, c.700delG, in a Chinese osteogenesis imperfecta family.

Osteogenesis imperfecta (OI) is a family of genetic disorders associated with bone loss and fragility. Mutations associated with OI have been found in genes encoding the type I collagen chains. People with OI type I often produce insufficient α1-chain type I collagen because of frameshift, nonsense, or splice site mutations in COL1A1 or COL1A2. This report is of a Chinese daughter and mother who had both experienced two bone fractures. Because skeletal fragility is predominantly inherited, we focused on identifying mutations in COL1A1 and COL1A2 genes. A novel mutation in COL1A1, c.700delG, was detected by genomic DNA sequencing in the mother and daughter, but not in their relatives. The identification of this mutation led to the conclusion that they were affected by mild OI type I. Open reading frame analysis indicated that this frameshift mutation would truncate α1-chain type I collagen at residue p263 (p.E234KfsX264), while the wild-type protein would contain 1,464 residues. The clinical data were consistent with the patients' diagnosis of mild OI type I caused by haploinsufficiency of α1-chain type I collagen. Combined with previous reports, identification of the novel mutation COL1A1-c.700delG in these patients suggests that additional genetic and environmental factors may influence the severity of OI.

[Effectiveness and safety of initiation of once-daily insulin detemir in Chinese patients with type 2 diabetes previously treated with different quantities of oral anti-diabetic drugs: subgroup analysis of the Chinese SOLVE™ Study].

OBJECTIVE: To evaluate the effectiveness and safety on once-daily (OD) insulin detemir (IDet) in Chinese patients with type 2 diabetes mellitus (T2DM) who were treated with different types or combinations of oral anti-diabetic drugs (OADs). METHODS: The SOLVE™ study was a 24-week observational study on the initiation of IDet OD in T2DM patients with uncontrolled hyperglycemia on diet, exercise, and one or more OADs. Subjects were grouped based on the numbers of OADs taken before (>2-OAD, 2-OAD, and 1-OAD groups). Efficacy and safety endpoints were evaluated and compared in different groups. RESULTS: This study includes 3 272 patients, among them 464 (14.2%) were treated with more than 2 OADs, 1511 (46.2%) with 2 OADs, and 1 218 (37.2%) with 1 OAD before the study. The mean glycosylated hemoglobin A1c (HbA1c) was 8.4%, 8.3%, 8.4% at baseline, and 7.3%, 7.2%, 7.1% at the end of 24-week in each 3 groups (all P<0.001 vs. baseline values). The HbA1c reductions were not statistically significant different among groups. Body weight tended to decrease in patients from all groups, however, only that in the 2-OAD group reached statistically significance. No major hypoglycaemia events were reported. However, the overall minor hypoglycaemia rate in the 2-OAD group was higher at the end of the study than that at baseline (P<0.05). No differences in the rate of nocturnal minor hypoglycaemia were observed in all groups after IDet treatment. CONCLUSION: Initiation of IDet OD was effective and well-tolerated in Chinese patients with T2DM whose glycemia was poorly controlled on OADs irrespective of the number of OADs taken before. (registration number NCT00825643).

[The impact of glycosylated hemoglobin target value in treatment guidelines on glycemic control of type 2 diabetic in Chinese cities].

OBJECTIVE: To investigate the influence of glycosylated hemoglobin Al c (HbA1c) standard value (2007 and 2010 Chinese Diabetes Prevention Guide) on glycemic control and treatment of type 2 diabetic patients in Chinese cities. METHODS: A cross-sectional study was carried out in type 2 diabetes mellitus from outpatients in selected hospitals all over China in 2009 and 2012. Patients treated with oral antidiabetic drugs (OADs), insulin or OAD combined with insulin were enrolled. A questionnaire including general characters, therapy, complications and blood glucose was completed by trained surveyors. RESULTS: A total of 30 853 patients were enrolled in 2009, and 48 232 patients in 2012. The distribution of HbAlc < 6.5%, 6.5% - <7.0%, 7.0% - <8.0%, 8.0% - <9.0%, 9.0% - <10.0% and > or = 10.0% was 20.35%, 12.59%, 35.50%, 18.94%, 6.46% and 6.16% in 2012; 14. 81%, 27.72%,14.55%, 6.55% and 8.36% in 2009, respectively. The top three OAD were biguanides, sulfonylureas and thiazolidine. The most common treatment options for combined therapy are metformin combined with sulfonylurea in both 2009 and 2012. CONCLUSIONS: There is an increase in the proportion of patients with good and general blood glucose control in 2012. With the generalization of Chinese Diabetes Prevention Guide, a steady tendency is presented in blood gluense control.

[The changes in renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome].

OBJECTIVE: Cushing's syndrome is a clinical condition resulting from chronic exposure to excess glucocorticoid. As a consequence, long-term hypercortisolism contributes significantly to the development of systemic disorders by direct and/or indirect effects. The present study was to analyze the changes of renin-angiotensin-aldosterone-system in different subtypes of Cushing's syndrome on the standard posture test. METHODS: We retrospectively reviewed 150 patients with histologically confirmed Cushing's syndrome treated at the PLA General Hospital between 2002 and 2014. Among them, 128 patients were diagnosed as adreno-cortico-tropic-hormone (ACTH)-independent Cushing's syndrome, and 22 were ACTH-dependent Cushing's syndrome. All patients were undertaken the posture test. Plasma renin activity (PRA), angiotensin II, plasma aldosterone concertration (PAC) levels were measured before and after the test. RESULTS: Basal plasma PRA [0.5 (0.2,1.3)µg·L(-1)·h(-1), angiotensin II [(48.9±20.1) ng/L] and PAC [(285.0±128.1) pmol/L] levels were within the normal range in supine position. Compared with the subjects with ACTH-independent Cushing's syndrome, the basal PAC levels were higher in subjects with ACTH-dependent Cushing's syndrome [(348.0±130.4) pmol/L vs (274.2±125.0) pmol/L, P<0.05]. However, the PAC response in subjects with ACTH-dependent Cushing's syndrome [(49.7±26.4)%] was significantly lower than that in those with ACTH-independent Cushing's syndrome [(81.2±69.3)%] upon upright posture stimulation (P<0.05). There were no statistical significances in PRA and angiotensin II levels between the two groups. The basal PAC and PRA levels were positively correlated with ACTH, whereas PAC response was negatively correlated with ACTH. CONCLUSIONS: The renin-angiotensin-aldosterone-system activity in subjects with Cushing's syndrome was similar to that in normal control. The basal PAC level and its response to upright posture are differently associated with ACTH level in Cushing's syndrome.