Sagittal alignment of diverse mechanical complications following adult spinal deformity surgery.

PURPOSE: To compare the sagittal alignment of patients with diverse mechanical complications (MCs) following adult spinal deformity (ASD) surgery with that of patients without MCs. METHODS: A total of 371 patients who underwent ASD surgery were enrolled. The sagittal spinopelvic parameters were measured preoperatively and at the 6-month and last follow-up, and the global alignment and proportion (GAP) score was calculated. The subjects were divided into non-MC and MCs groups, and the MCs group was further divided into rod fracture (RF), screw breakage (SB), screw dislodgement (SD) and proximal junctional kyphosis (PJK) subgroups. RESULTS: Preoperatively, the RF group had greater thoracolumbar kyphosis (TLK) and relative upper lumbar lordosis (RULL); the SB group had the largest pelvic incidence (PI) and lumbar lordosis (LL); the SD group had the least global sagittal imbalance; and the PJK group had the highest thoracic kyphosis (TK), TLK and RULL. At the last follow-up, the RF and SB groups featured a large PI minus LL (PI-LL), while the PJK group featured a prominent TK; all the MCs subgroups had sagittal malalignment and a higher GAP score, and the SB group had the most severe cases. Logistic regressions showed that the relative spinopelvic alignment (RSA) score was correlated with RF, SB and SD, while the RSA and age scores were associated with PJK. CONCLUSION: Each patient with MCs had individual characteristics in the sagittal plane following ASD surgery, which may be helpful to understand the pathophysiology of poor sagittal alignment with its subsequent MCs and guide an eventual revision strategy.

Relationships between lumbar lordosis correction and the change in global tilt (GT) in adult spinal deformity.

PURPOSE: This study aimed to explore the relationships between lumbar lordosis (LL) correction and improvement of postoperative global sagittal alignment and to establish corresponding linear regressions to predict the change in global tilt (GT) based on the corrected LL following adult spinal deformity (ASD) surgery. METHODS: A total of 240 ASD patients who underwent lumbar correction were enrolled in this multicentre study. The following sagittal parameters were measured pre- and postoperatively: thoracic kyphosis (TK), LL, upper and lower LL (ULL and LLL), pelvic tilt (PT), sagittal vertical axis (SVA) and GT. The correlations among the changes in GT (△GT), SVA (△SVA), PT (△PT), TK (△TK), LL (△LL), ULL (△ULL) and LLL (△LLL) were assessed, and linear regressions were conducted to predict △GT, △SVA, △PT and △TK from △LL, △ULL and △LLL. RESULTS: △LL was statistically correlated with △GT (r = 0.798, P < 0.001), △SVA (r = 0.678, P < 0.001), △PT (r = 0.662, P < 0.001) and △TK (r = - 0.545, P < 0.001), and the outcomes of the linear regressions are: △GT = 3.18 + 0.69 × â–³LL (R2 = 0.636), △SVA = 4.78 + 2.57 × â–³LL (R2 = 0.459), △PT = 2.57 + 0.34 × â–³LL (R2 = 0.439), △TK = 7.06-0.43 × â–³LL (R2 = 0.297). In addition, △LLL had more correlations with △GT, △SVA and △PT, while △ULL had more correlations with △TK. CONCLUSION: Surgical correction of LL could contribute to the restoration of global sagittal morphology following ASD surgery. These models were established to predict the changes in sagittal parameters, in particular △GT, determined by △LL, which has not been previously done and may help to customize a more precise correction plan for ASD patients.

Risk factors of instrumentation failure after laminectomy and posterior cervical fusions (PCF).

BACKGROUND: For patients with multilevel degenerative cervical myelopathy, laminectomy and posterior cervical fusions (PCF) with instrumentation are widely accepted techniques for symptom relief. However, hardware failure is not rare and results in neck pain or even permanent neurological lesions. There are no in-depth studies of hardware-related complications following laminectomy and PCF with instrumentation. METHODS: The present study was a retrospective, single centre, observational study. Patients who underwent laminectomy and PCF with instrumentation in a single institution between January 2019 and January 2021 were included. Patients were divided into hardware failure and no hardware failure group according to whether there was a hardware failure. Data, including sex, age, screw density, end vertebra (C7 or T1), cervical sagittal alignment parameters (C2-C7 cervical lordosis, C2-C7 sagittal vertical axis, T1 slope, Cervical lordosis correction), regional Hounsfield units (HU) of the screw trajectory and osteoporosis status, were collected and compared between the two groups. RESULTS: We analysed the clinical data of 56 patients in total. The mean overall follow-up duration was 20.6 months (range, 12-30 months). Patients were divided into the hardware failure group (n = 14) and no hardware failure group (n = 42). There were no significant differences in the general information (age, sex, follow-up period) of patients between the two groups. The differences in fusion rate, fixation levels, and screw density between the two groups were not statistically significant (p > 0.05). The failure rate of fixation ending at T1 was lower than that at C7 (9% vs. 36.3%) (p = 0.019). The regional HU values of the pedicle screw (PS) and lateral mass screw (LMS) in the failure group were lower than those in the no failure group (PS: 267 ± 45 vs. 368 ± 43, p = 0.001; LMS: 308 ± 53 vs. 412 ± 41, p = 0.001). The sagittal alignment parameters did not show significant differences between the two groups before surgery or at the final follow-up (p > 0.05). The hardware failure rate in patients without osteoporosis was lower than that in patients with osteoporosis (14.3% vs. 57.1%) (p = 0.001). CONCLUSIONS: Osteoporosis, fixation ending at C7, and low regional HU value of the screw trajectory were the independent risk factors of hardware failure after laminectomy and PCF. Future studies should illuminate if preventive measures targeting these factors can help reduce hardware failure and identified more risk factors, and perform long-term follow-up.

Myth or fact: 3D-printed off-the-shelf prosthesis is superior to titanium mesh cage in anterior cervical corpectomy and fusion?

BACKGROUND: To find out if three-dimensional printing (3DP) off-the-shelf (OTS) prosthesis is superior to titanium mesh cages in anterior cervical corpectomy and fusion (ACCF) when treating single-segment degenerative cervical spondylotic myelopathy (DCSM). METHODS: DCSM patients underwent ACCF from January 2016 to January 2019 in a single center were included. Patients were divided into the 3DP group (28) and the TMC group (23). The hospital stays, operation time, intraoperative blood loss, and the cost of hospitalization were compared. The Japanese Orthopedic Association (JOA) scores and Neck Disability Index (NDI) were recorded pre-operatively, 1 day, 3, 6, 12, and 24 months post-operatively. Radiological data was measured to evaluate fusion, subsidence, and cervical lordosis. Patients were sent with SF-36 to assess their health-related quality of life (HRQoL). RESULTS: The differences in operative time, intraoperative blood loss, and hospital stay were not statistically significant between groups (p > 0.05). Postoperative dysphagia occurred in 2 cases in the 3DP group and 3 cases in the TMC group, which all relieved one week later. The difference in improvement of JOA and NDI between the two groups was not statistically significant (p > 0.05). No hardware failure was found and bony fusion was achieved in all cases except one in the 3DP group. The difference in cervical lordosis (CL), fused segmental angle (FSA), mean vertebral height (MVH), and subsidence rates between groups at each follow-up time point was not statistically significant and the results of the SF-36 were similar (p > 0.05). The total cost was higher in the 3DP group with its higher graft cost (p < 0.05). CONCLUSION: In treating single-segment DCSM with ACCF, both 3DP OTS prosthesis and TMC achieved satisfactory outcomes. However, the more costly 3DP OTS prosthesis was not able to reduce subsidence as it claimed.

Myoblast-derived exosomal Prrx2 attenuates osteoporosis via transcriptional regulation of lncRNA-MIR22HG to activate Hippo pathway.

BACKGROUND: Sarcopenia and osteoporosis are common diseases that predominantly affect older individuals. The interaction between muscle and skeleton exerts pivotal roles in bone remodeling. This study aimed to explore the function of myoblast-derived exosomal Prrx2 in osteogenic differentiation and its potential mechanisms. METHODS: Exosomes were isolated from myogenic differentiated C2C12 cells. qRT-PCR and Western blotting were used to determine target molecule expression. Osteogenic differentiation of BMSCs was evaluated by Alizarin red staining, ALP activity and levels of OCN, OPN, RUNX2, and BMP2. Dual-luciferase reporter assay, RIP, and ChIP assays were performed to verify the interaction between molecules. The nuclear translocation of YAP1 was observed by immunofluorescence staining. In vivo osteoporotic model was established by ovariectomy in mice. Bone loss was examined using HE staining. RESULTS: Prrx2 expression was elevated in myogenic differentiated C2C12 cells and their exosomes. Myoblast-derived exosomal Prrx2 enhanced osteogenic differentiation of BMSCs. Delivering exosomal Prrx2 directly bond to MIR22HG promoter and promoted its transcription and expression. MIR22HG enhanced expression and nuclear translocation of YAP via sponging miR-128, thus facilitating BMSC osteogenic differentiation. Knockdown of exosomal Prrx2 suppressed osteogenic differentiation, which could be abolished by MIR22HG overexpression. Similarly, miR-128 inhibitor or YAP overexpression reversed the inhibitory effect of MIR22HG depletion or miR-128 mimics on osteogenic differentiation. Finally, myoblast-derived exosomal Prrx2 alleviated osteoporosis in mice via up-regulating MIR22HG and activating the Hippo pathway. CONCLUSION: Myoblast-derived exosomal Prrx2 contributes to transcriptional activation of MIR22HG to activate YAP pathway via sponging miR-128, thereby facilitating osteogenic differentiation of BMSCs.

Is 3D-printed prosthesis stable and economic enough for anterior spinal column reconstruction after spinal tumor resection? A retrospective comparative study between 3D-printed off-the-shelf prosthesis and titanium mesh cage.

OBJECT: To investigate the stability and cost-effectiveness of the three-dimensional-printed (3DP) off-the-shelf (OTS) prosthesis in the reconstruction of the anterior column of the thoracic/lumbar spine after tumor resection. METHODS: Thirty-five patients (26 with primary malignant tumors and nine with metastatic malignant tumors) who underwent tumor resection and anterior column reconstruction between January 2014 and January 2019 were included in a single institute. Patients were divided into the 3DP OTS prosthesis (3DP) group (n = 14) and the titanium mesh cage (TMC) group (n = 21) by the type of implant. The operation time, intraoperative blood loss, hospital stay, history of radiotherapy, surgical level and total cost were collected and compared between the two groups. Mechanical complications and radiological parameters including mean vertebral height, subsidence, fixation failure(nonunion, migration, screw loosening, rod breakage) rate were recorded at preoperation, 1 week, 3 months, 6 months, 12 months after surgery then at 1 year interval or stop until the end of survival. The follow-up patients were also sent with short form-36 to assess their health-related quality of life (HRQoL) and questions about the current condition of their disease. RESULTS: The mean overall follow-up was 24.6 months. Of the 35 patients involved, six patients died and six were lost to follow-up. The differences between the two groups in operative time, intraoperative blood loss, and hospital stay were not statistically significant (p > 0.05). The differences in fixation failure and the subsidence rate between the two groups were not statistical significant (p > 0.05). The difference of subsidence rate between the cases with and without osteoporosis, cases with and without radiotherapy was statistically significant within each group (p < 0.05). However, the difference of subsidence rate between the surgical level above or below T10 was not statistically significant (p > 0.05). The response rate of the questionnaire among the survived patients was 100% (23/23 patients). The results of the Short Form- (SF-)36 between the two groups were similar (p > 0.05). The total cost was higher in the 3DP group (p < 0.05) with its higher graft cost (p < 0.05), but the differences in internal fixation cost and other cost were not statistically significant between groups (p > 0.05). CONCLUSION: Compared to TMC, the 3DP OTS prosthesis achieved similar clinical and radiological results in spinal anterior spinal column reconstruction of thoracic/lumbar spinal tumor resection. However, the 3DP OTS prosthesis was more expansive than TMC.

Predicting thoracic kyphosis morphology and the thoracolumbar inflection point determined by individual lumbar lordosis in asymptomatic adults.

PURPOSE: The aims of this study were to explore the correlations between thoracic kyphosis (TK) and lumbar lordosis (LL) parameters and to build corresponding linear regressions to predict TK morphology and the thoracolumbar inflection point (IP) determined by individual LL parameters in asymptomatic adults. METHODS: A total of 280 adult healthy volunteers were recruited, and full-spine X-rays were performed for each subject in a standing posture. The following sagittal parameters were measured: cumulative TK, LL, proximal LL (PLL), the apices of TK (TKA) and LL (LLA), the IP and the distance from the plumb line of the thoracic apex (TAPL) and the lumbar apex (LAPL) to the gravity line. The correlations between TK and LL parameters were analyzed, and the corresponding linear regressions were conducted. RESULTS: Extensive variations existed in TK alignment, including angular and morphological parameters. In addition, there were statistical correlations of all cumulative TK angles with LL (r values from - 0.173 to - 0.708) and PLL (r values from - 0.206 to - 0.803), TKA and IP with LLA (rs = 0.359 and 0.582, respectively) and TAPL with LAPL (rs = 0.335). The common predictive formulas employed in ASD surgery could include T10-L1 = - 3.6-0.2*LL (R2 = 0.201), T4-L1 = 3.4-0.5*LL (R2 = 0.457), TKA = - 10.3 + 1.1*LLA (R2 = 0.180) and IP = - 12.7 + 1.6*LLA (R2 = 0.330). CONCLUSION: There were intimate associations between TK and LL parameters in asymptomatic adults. Moreover, predictive models for thoracic alignment, particularly cumulative TK, based on LL parameters were proposed, which could better delineate anatomical relationships, guide thoracic construction during adult spinal deformity surgery and may help preventing proximal junctional failure.

Predictive formulae of ideal lumbar lordosis determined by individual pelvic incidence and thoracic kyphosis in asymptomatic adults.

BACKGROUND: The precise prediction of ideal lumbar lordosis (LL) has become increasingly important in clinical practice. The aim of this study was to explore the regulatory mechanisms of sagittal spinopelvic alignment and to predict ideal LL based on individual pelvic incidence (PI) and thoracic kyphosis (TK) parameters in asymptomatic adults. METHODS: A total of 233 asymptomatic subjects older than 18 years were consecutively enrolled in our study between April 2017 and December 2019. A full-spine, standing X-ray was performed for each subject. The following parameters were measured in the sagittal plane: the apex of lumbar lordosis (LLA), the distance between the plumb line of the lumbar apex (LAPL) and the gravity plumb line, the inflection point (IP), LL, the upper arc and lower arc of lumbar lordosis (LLUA and LLLA, respectively), PI and TK. Stepwise multiple linear regressions were conducted, and the statistical significance level was P < 0.05. RESULTS: Both PI and TK were two important predictive variables for LLA, LAPL, IP and LL. In addition, the LLUA was mainly explained by TK, while the LLLA was explained by PI. The corresponding predictive models are listed as follows: LLA = 17.110 - 0.040∗PI + 0.023∗TK (R2 = 0.380), LAPL = 31.296 + 0.467∗PI - 0.126∗TK (R2 = 0.309), IP = 10.437 + 0.091∗TK - 0.029∗PI (R2 = 0.227), LL = 2.035 + 0.618∗PI + 0.430∗TK (R2 = 0.595), LLUA = 0.893 + 0.418∗TK (R2 = 0.598), LLLA = 3.543 + 0.576∗PI (R2 = 0.433). CONCLUSION: The specific sagittal lumbar profile should be regulated by both pelvic and thoracic morphology. Such predictive models for lumbar parameters determined by individual PI and TK parameters have been established, which are meaningful for surgeons to better understand the regulatory mechanisms of sagittal spinopelvic alignment and reconstruct a satisfactory lumbar alignment.

Predictive model of global tilt (GT) determined by individual thoracic kyphosis, lumbar lordosis and pelvic incidence in the human degenerative spine.

PURPOSE: Previous studies only investigated the simple linear relationships of global tilt (GT) with thoracic kyphosis (TK), lumbar lordosis (LL) and pelvic incidence (PI). This study aimed to establish multiple linear regressions of GT based on individual TK, LL and PI in patients with degenerative spines. METHODS: Four hundred sixty-nine adult patients aged older than 35 years with various degenerative spinal diseases were enrolled in this two-centre study between January 2017 and December 2020. Full-spine X-rays were performed for all the subjects in a standing position. The following regional and global parameters were measured in the sagittal plane: TK, LL, PI, pelvic tilt (PT), sagittal vertical axis (SVA) and GT. The correlations of the GT, PT and SVA with the TK, LL and PI were analysed, and then multiple linear regressions were constructed. RESULTS: GT was statistically correlated with TK, LL and PI. Additionally, TK, LL and PI were significant predictors for the GT, PT and SVA models. The relevant predictive formulae were as follows: GT = -9.60 + 1.09*PI + 0.89*LL + 0.42*TK (R2 = 0.935), PT = -4.49 + 0.81*PI + 0.56*LL + 0.24*TK (R2 = 0.792) and SVA = -25.68 + 2.98*LL + 2.37*PI + 1.67*TK (R2 = 0.416). CONCLUSION: The specific sagittal spinopelvic morphology, evaluated by GT parameters, should be determined by individual TK, LL and PI values in the degenerative spine. Surgeons can utilize such predictive models to better understand the degenerative evolution of sagittal alignment and recognize the relationships between regional parameters and global sagittal alignment to customize a precise correction strategy.

Correlation between the apex of lumbar lordosis and pelvic incidence in asymptomatic adult.

PURPOSE: The objective of this study was to test the correlation between the apex of lumbar lordosis (LLA) and pelvic incidence (PI) in asymptomatic adults, and to establish predictive formulae based on the PI to obtain the reference values of lumbar sagittal parameters. METHODS: A cohort of 183 asymptomatic volunteers older than 18 years was enrolled in this study between April 2017 and May 2019. A full-spine, standing X-ray was taken for each subject. The following parameters in the sagittal plane were measured: the LLA, the distance between the plumb line of the lumbar apex (LAPL) and gravity plumb line, lumbar lordosis (LL), the upper arc of lumbar lordosis (LLUA), the lower arc of lumbar lordosis (LLLA) and the PI. The correlations between lumbar parameters and PI were analysed, and simple linear regressions were simultaneously constructed. The statistical significance level was P < 0.05. RESULTS: The PI was statistically correlated with the LLA (rs = - 0.595, P < 0.001), LAPL (rs = 0.503, P < 0.001), LL (rs = 0.605, P < 0.001), LLUA (r = 0.354, P < 0.001) and the LLLA (r = 0.658, P < 0.001). The corresponding regression formulae were as follows: LLA = - 0.042*PI + 6.134 (R2 = 0.306), LAPL = 0.448*PI + 26.570 (R2 = 0.279), LL = 0.888*PI - 2.667 (R2 = 0.370), LLUA = 0.272*PI - 2.297 (R2 = 0.126) and LLLA = 0.607*PI + 0.177 (R2 = 0.433). CONCLUSION: The PI has strong correlations with the LLA, LAPL, LL, LLUA and LLLA, which demonstrates that the specific lumbar shape can be affected by the pelvic morphology. Moreover, predictive models for ideal lumbar sagittal parameters based on the PI have been developed, contributing to the design of precise and individualized preoperative plans. These slides can be retrieved under Electronic Supplementary Material.

Correlations between the inflection point and spinal sagittal alignment in asymptomatic adults.

PURPOSE: The purposes of this study were to analyse the correlations between the inflection point (IP) and spinal sagittal parameters and to establish the corresponding linear regressions in asymptomatic adults. METHODS: A total of 205 asymptomatic subjects older than 18 years were recruited between April 2017 and September 2019. A full-spine, standing X-ray was collected for each subject. The following parameters were documented: the IP, the apices of thoracic kyphosis (TKA) and lumbar lordosis (LLA), the distance between the plumb line of the thoracic apex (TAPL) or lumbar apex (LAPL) and gravity plumb line, thoracic kyphosis (TK), lumbar lordosis (LL) and the upper arc and the lower arc of lumbar lordosis (LLUA and LLLA, respectively). The correlations between the IP and the above parameters and between the thoracic and lumbar parameters were analysed. The level of significance was P < 0.05. RESULTS: The IP was statistically correlated with age (rs = 0.327), the TKA (rs = 0.639), the TAPL (rs = 0.338), TK (rs = 0.391), the LLA (rs = 0.545), the LAPL (rs = - 0.383), the LLUA (rs = 0.371) and the LLLA (rs = - 0.145) but was not linked with LL (rs = 0.118). In addition, there were relationships between the TKA and LLA (rs = 0.397), the TAPL and LAPL (rs = - 0.357), TK and LL (rs = 0.529), TK and the LLUA (rs = 0.742) and TK and the LLLA (rs = 0.148). CONCLUSION: The IP was significantly related to spinal sagittal alignment in asymptomatic adults. Moreover, predictive formulae for sagittal parameters as a function of the IP were developed, which are helpful for surgeons in comprehending the regulatory mechanisms of spinal sagittal alignment and designing an ideal therapeutic plan. These slides can be retrieved under Electronic Supplementary Material.

Efficacy and safety of saxagliptin in combination with metformin as initial therapy in Chinese patients with type 2 diabetes: Results from the START study, a multicentre, randomized, double-blind, active-controlled, phase 3 trial.

AIM: To assess the efficacy and safety of saxagliptin plus metformin over 24 weeks in pharmacotherapy-naïve Chinese patients with type 2 diabetes mellitus and inadequate glycaemic control (HbA1c, 8.0%-12.0%). RESEARCH DESIGN AND METHODS: In this multicentre, double-blind, active-controlled study (The START study: NCT02273050, clinicaltrials.gov), patients were randomized (1:1:1) to saxagliptin 5 mg plus metformin, saxagliptin 5 mg plus placebo or metformin plus placebo. Saxagliptin was taken once daily; metformin was taken once/twice daily and was titrated from 500 mg to a maximum of 2000 mg/d over 8 weeks. The primary end point was change in HbA1c from baseline to Week 24. RESULTS: Data from 630 patients (66.5% men; mean age, 50.1 years; mean body mass index, 26.6 kg/m2 ; mean HbA1c, 9.4%; mean diabetes duration, 0.81 years) were analysed. Mean reduction in HbA1c was greater with saxagliptin plus metformin (-3.0%) than with saxagliptin plus placebo (-2.1%; P < .001) or metformin plus placebo (-2.8%; P = .034). Changes in mean fasting plasma glucose, 120-minute postprandial glucose, and 180-minute postprandial glucose area under the curve were greater, and more patients achieved a therapeutic glycaemic response, with saxagliptin plus metformin than with either monotherapy. Hypoglycaemic events were infrequent (<2%). Incidence of adverse events was similar among groups; upper respiratory tract infection and diarrhoea were most common. CONCLUSIONS: Saxagliptin 5 mg plus metformin significantly improved glycaemic control compared with either monotherapy in treatment-naïve Chinese patients with type 2 diabetes, and was well tolerated.

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.

Association between socioeconomic status and metabolic control and diabetes complications: a cross-sectional nationwide study in Chinese adults with type 2 diabetes mellitus.

BACKGROUND: Low socioeconomic status (SES) is associated with adverse cardiovascular risk factor patterns and poor outcomes in patients with diabetes. The aim of this study was to determine whether SES is associated with the control of blood glucose, blood pressure, blood cholesterol (3Bs), and diabetic complications in Chinese adults with type 2 diabetes. METHODS: Data regarding patients' demographics, social economics, diabetes complications, and cardiovascular risk profiles were analyzed for 25,454 patients. The outcomes of interest were the proportions of patients with HbA1c <7.0 %, blood pressure <140/80 mmHg, total serum cholesterol <4.5 mmol/L, and diabetes complications. Multivariable logistic regression was used for analysis. RESULTS: Of the 25,454 patients, the least educated patients (1695, 6.7 %) had the highest chances of developing cardiovascular diseases (p = 0.048), cerebrovascular diseases (p < 0.001), and retinopathy (p < 0.001). The patients with lowest household income (10,039, 40.8 %) had the highest prevalence of retinopathy (p < 0.001) and neuropathy (p < 0.001). The most educated patients were more likely than the least educated patients to achieve HbA1c <7.0 % [adjusted odds ratio (OR) 1.38; 95 % confidence interval (95 % CI) 1.22-1.56] and 3B goals (adjusted OR 1.30; 95 % CI 1.11-1.53). The patients with highest household income were more likely to achieve BP < 140/80 mmHg (adjusted OR 1.16; 95 % CI 1.07-1.27), but less likely to reach HbA1c < 7.0 % (adjusted OR 0.90; 95 % CI 0.83-0.98) than those lowest income patients. CONCLUSIONS: Low SES was associated with poor metabolic control and more diabetes complications in adult patients in China. Individual diabetes management based on the SES of patients is encouraged.

Association between plasma triglycerides and high-density lipoprotein cholesterol and microvascular kidney disease and retinopathy in type 2 diabetes mellitus: a global case-control study in 13 countries.

BACKGROUND: Microvascular renal and retinal diseases are common major complications of type 2 diabetes mellitus. The relation between plasma lipids and microvascular disease is not well established. METHODS AND RESULTS: The case subjects were 2535 patients with type 2 diabetes mellitus with an average duration of 14 years, 1891 of whom had kidney disease and 1218 with retinopathy. The case subjects were matched for diabetes mellitus duration, age, sex, and low-density lipoprotein cholesterol to 3683 control subjects with type 2 diabetes mellitus who did not have kidney disease or retinopathy. The study was conducted in 24 sites in 13 countries. The primary analysis included kidney disease and retinopathy cases. Matched analysis was performed by use of site-specific conditional logistic regression in multivariable models that adjusted for hemoglobin A1c, hypertension, and statin treatment. Mean low-density lipoprotein cholesterol concentration was 2.3 mmol/L. The microvascular disease odds ratio increased by a factor of 1.16 (95% confidence interval, 1.11-1.22) for every 0.5 mmol/L (≈1 quintile) increase in triglycerides or decreased by a factor of 0.92 (0.88-0.96) for every 0.2 mmol/L (≈1 quintile) increase in high-density lipoprotein cholesterol. For kidney disease, the odds ratio increased by 1.23 (1.16-1.31) with triglycerides and decreased by 0.86 (0.82-0.91) with high-density lipoprotein cholesterol. Retinopathy was associated with triglycerides and high-density lipoprotein cholesterol in matched analysis but not significantly after additional adjustment. CONCLUSIONS: Diabetic kidney disease is associated worldwide with higher levels of plasma triglycerides and lower levels of high-density lipoprotein cholesterol among patients with good control of low-density lipoprotein cholesterol. Retinopathy was less robustly associated with these lipids. These results strengthen the rationale for studying dyslipidemia treatment to prevent diabetic microvascular disease.

Patient-led versus physician-led titration of insulin glargine in patients with uncontrolled type 2 diabetes: a randomized multinational ATLAS study.

OBJECTIVE: Self-adjustment of insulin dose is commonly practiced in Western patients with type 2 diabetes but is usually not performed in Asian patients. This multinational, 24-week, randomized study compared patient-led with physician-led titration of once-daily insulin glargine in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering agents. METHODS: Patient-led (n = 275) or physician-led (n = 277) subjects followed the same dose-titration algorithm guided by self-monitored fasting blood glucose (FBG; target, 110 mg/dL [6.1 mmol/L]). The primary endpoint was change in mean glycated hemoglobin (HbA1c) at week 24 in the patient-led versus physician-led titration groups. RESULTS: Patient-led titration resulted in a significantly higher drop in HbA1c value at 24 weeks when compared with physician-led titration (-1.40% vs. -1.25%; mean difference, -0.15; 95% confidence interval, -0.29 to 0.00; P = .043). Mean decrease in FBG was greatest in the patient-led group (-2.85 mmol/L vs. -2.48 mmol/L; P = .001). The improvements in HbA1c and FBG were consistent across countries, with similar improvements in treatment satisfaction in both groups. Mean daily insulin dose was higher in the patient-led group (28.9 units vs. 22.2 units; P<.001). Target HbA1c of <7.0% without severe hypoglycemia was achieved in 40.0% and 32.9% in the patient-led and physician-led groups, respectively (P = .086). Severe hypoglycemia was not different in the 2 groups (0.7%), with an increase in nocturnal and symptomatic hypoglycemia in the patient-led arm. CONCLUSION: Patient-led insulin glargine titration achieved near-target blood glucose levels in Asian patients with uncontrolled type 2 diabetes who were on 2 oral glucose-lowering drugs, demonstrating that Asian patients can self-uptitrate insulin dose effectively when guided.

[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).