Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition).

With the deepening of aging in China, the prevalence of diabetes in older people has increased noticeably, and standardized diabetes management is critical for improving clinical outcomes of diabetes in older people. In 2021, the National Center of Gerontology, Chinese Society of Geriatrics, and Diabetes Professional Committee of Chinese Aging Well Association organized experts to write the first guideline for diabetes diagnosis and treatment in older people in China, the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2021 Edition). The guideline emphasizes that older patients with diabetes are a highly heterogeneous group requiring comprehensive assessment and stratified and individualized management strategies. The guideline proposes simple treatments and de-intensified treatment strategies for older patients with diabetes. This edition of the guideline provides clinicians with practical and operable clinical guidance, thus greatly contributing to the comprehensive and full-cycle standardized management of older patients with diabetes in China and promoting the extensive development of clinical and basic research on diabetes in older people and related fields. In the past 3 years, evidence-based medicine for older patients with diabetes and related fields has further advanced, and new treatment concepts, drugs, and technologies have been developed. The guideline editorial committee promptly updated the first edition of the guideline and compiled the Guideline for the Management of Diabetes Mellitus in the Elderly in China (2024 Edition). More precise management paths for older patients with diabetes are proposed, for achieving continued standardization of the management of older Chinese patients with diabetes and improving their clinical outcomes.

Retagliptin as add-on therapy to metformin in Chinese 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 retagliptin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin. MATERIALS AND METHODS: This multicentre, phase 3 trial consisted of a 16-week, randomized, double-blind, placebo-controlled period, where patients with HbA1c levels between 7.5% and 11.0% were randomized to receive either once-daily (QD) retagliptin 100 mg (n = 87) or placebo (n = 87), both as an add-on to metformin. The primary endpoint was the change in HbA1c from baseline to week 16. RESULTS: At week 16, the least squares mean change in HbA1c from baseline, compared with placebo, was -0.82% (95% CI, -1.05% to -0.58%) for the retagliptin 100 mg QD group (P < .0001) per treatment policy estimand. Significantly higher proportions of patients in the retagliptin 100 mg QD group achieved HbA1c levels of less than 6.5% (11.5%) and less than 7.0% (26.4%) compared with those receiving placebo (0% and 4.6%; P = .0016 and P < .0001, respectively) at week 16. Retagliptin 100 mg QD also lowered fasting plasma glucose and 2-hour postprandial plasma glucose levels. The incidence of adverse events (AEs) during the treatment period was similar between the two groups. However, slightly higher proportions of increased lipase and increased amylase in the retagliptin 100 mg QD group were observed. No patients discontinued treatment permanently because of AEs, and no episodes of severe hypoglycaemia were reported. CONCLUSIONS: Retagliptin 100 mg QD as an add-on therapy to metformin offers a new therapeutic option for treating Chinese patients with T2D inadequately controlled by metformin alone, and is generally well tolerated.

Barriers to the Use of Insulin Therapy and Potential Solutions: A Narrative Review of Perspectives from the Asia-Pacific Region.

The rising prevalence of type 2 diabetes (T2D) is posing major challenges for the healthcare systems of many countries, particularly in the Asia-Pacific Region, in which T2D can present at younger ages and lower body mass index when compared with Western nations. There is an important role for insulin therapy in the management of T2D in these nations, but available evidence suggests that insulin is under-utilized and often delayed, to the detriment of patient prognosis. The authors of this article gathered as an advisory panel (representative of some of the larger Asia-Pacific nations) to identify their local barriers to insulin use in T2D, and to discuss ways in which to address these barriers, with their outputs summarized herein. Many of the key barriers identified are well-documented issues of global significance, including a lack of healthcare resources or of an integrated structure, insufficient patient education, and patient misconceptions about insulin therapy. Barriers identified as more innate to Asian countries included local inabilities of patients to afford or gain access to insulin therapy, a tendency for some patients to be more influenced by social media and local traditions than by the medical profession, and a willingness to switch care providers and seek alternative therapies. Strategies to address some of these barriers are provided, with hypothetical illustrative case histories.

CircCDYL Contributes to Apoptosis, Ferroptosis, and Oxidative Stress of Ang II-Induced Vascular Smooth Muscle Cells in Thoracic Aortic Aneurysm.

Circular RNAs (circRNAs) have important regulation in thoracic aortic aneurysm (TAA). The function and mechanism of circCDYL (circ_0008285) was explored in TAA here. Angiotensin II (Ang II) was used to construct a TAA model. Real-time quantitative polymerase chain reaction (RT-qPCR) was performed for the detection of circCDYL, miR-1270, and a disintegrin and metalloproteinase 10 (ADAM10). Cell viability was examined via cell counting kit-8 (CCK-8) assay and proliferation was analyzed using Ethynyl-2'-deoxyuridine (EdU) assay. Apoptosis rate was assessed via flow cytometry. Western blot was used for protein detection. Oxidative stress was evaluated by commercial kits. CircCDYL was upregulated in TAA tissues and Ang II-induced circCDYL upregulation in vascular smooth muscle cells (VSMCs). Knockdown of circCDYL weakened Ang II-aroused inhibition of viability, proliferation, and promotion of apoptosis, ferroptosis, and oxidative stress in VSMCs. CircCDYL served as a miR-1270 sponge. The mitigated regulation of circCDYL knockdown for Ang II-induced injury was restored after miR-1270 downregulation. CircCDYL positively regulated ADAM10 through interacting with miR-1270. Overexpression of miR-1270 abated Ang II-induced injury by downregulating ADAM10. In conclusion, circCDYL was involved in the Ang II-induced VSMC injury in TAA via the miR-1270/ADAM10 axis.

A Biomechanical Comparison of 2 Different Topping-off Devices and Their Influence on the Sacroiliac Joint Following Lumbosacral Fusion Surgery.

OBJECTIVE: Interspinous spacer (ISS)-based and pedicle screw-rod dynamic fixator (PDF)-based topping-off devices have been applied in lumbar/lumbosacral fusion surgeries for preventing the development of proximal adjacent segment degeneration. However, little attention has been paid to sacroiliac joint (SIJ), which belongs to the adjacent joints. Accordingly, the objective of this study was to compare how these 2 topping-off devices affect the SIJ biomechanics. METHODS: A validated, normal finite-element lumbopelvic model (L3-pelvis) was initially adjusted to simulate interbody fusion with rigid fixation at the L5-S1 level, and then the DIAM or BioFlex system was instrumented at the L4-5 level to establish the ISS-based or PDF-based topping-off model, respectively. All the developed models were loaded with moments of 4 physiological motions using hybrid loading protocol. RESULTS: Compared with the rigid fusion model (without topping-off devices), range of motion and von-Mises stress at the SIJs were increased by 23.1%-64.1% and 23.6%-62.8%, respectively, for the ISS-based model and by 51.2%-126.7% and 50.4%-108.7%, respectively, for the PDF-based model. CONCLUSION: The obtained results suggest that the PDF-based topping-off device leads to higher increments in SIJ motion and stress than ISS-based topping-off device following lumbosacral fusion, implying topping-off technique could be linked to an increased risk of SIJ degeneration, especially when using PDF-based device.

Acetyllevocarnitine Hydrochloride for the Treatment of Diabetic Peripheral Neuropathy: A Phase 3 Randomized Clinical Trial in China.

Diabetic peripheral neuropathy (DPN) is a highly prevalent chronic complication in type 2 diabetes (T2D) for which no effective treatment is available. In this multicenter, randomized, double-blind, placebo-controlled phase 3 clinical trial in China, patients with T2D with DPN received acetyllevocarnitine hydrochloride (ALC; 1,500 mg/day; n = 231) or placebo (n = 227) for 24 weeks, during which antidiabetic therapy was maintained. A significantly greater reduction in modified Toronto clinical neuropathy score (mTCNS) as the primary end point occurred in the ALC group (-6.9 ± 5.3 points) compared with the placebo group (-4.7 ± 5.2 points; P < 0.001). Effect sizes (ALC 1.31 and placebo 0.85) represented a 0.65-fold improvement in ALC treatment efficacy. The mTCNS values for pain did not differ significantly between the two groups (P = 0.066), whereas the remaining 10 components of mTCNS showed significant improvement in the ALC group compared with the placebo group (P < 0.05 for all). Overall results of electrophysiological measurements were inconclusive, with significant improvement in individual measurements limited primarily to the ulnar and median nerves. Incidence of treatment-emergent adverse events was 51.2% in the ALC group, among which urinary tract infection (5.9%) and hyperlipidemia (7.9%) were most frequent.

Corrigendum: Screening and identification of hub genes in the development of early diabetic kidney disease based on weighted gene co-expression network analysis.

[This corrects the article DOI: 10.3389/fendo.2022.883658.].

Secondary analysis of newly diagnosed type 2 diabetes subgroups and treatment responses in the MARCH cohort.

OBJECTIVE: To incorporate new clusters in the MARCH (Metformin and AcaRbose in Chinese patients as the initial Hypoglycemic treatment) cohort of newly diagnosed type 2 diabetes (T2D) patients and compare the anti-glycemic effects of metformin and acarbose across different clusters. METHODS: K-means cluster analysis was performed based on six clinical indicators. The diabetic clusters in the MARCH cohort were retrospectively associated with the response to metformin and acarbose. RESULTS: A total of 590 newly diagnosed T2D patients were classified by data-driven clusters into the MARD (mild obesity-related diabetes) (34.1 %), MOD (mild obesity-related diabetes) (34.1 %), SIDD (severe insulin-deficient diabetes) (20.3 %) and SIRD (severe insulin-resistant diabetes) (11.5 %) subgroups at baseline. At 24 and 48 weeks, 346 participants had finished the follow-up. After the adjustment of age, gender, weight, baseline HbA1c, baseline fasting glucose and 2-h postprandial blood glucose (2hPG), metformin mainly decreased the fasting glucose (0.07 ± 0.89 vs -0.26 ± 0.83, P = 0.043) in the MARD subgroup presented with OGTT (oral glucose tolerance test) results compared with acarbose group at 24 weeks. Acarbose led to a greater decrease in 2hPG in the MOD subgroup compared with metformin group (0.08 ± 0.86 vs -0.24 ± 0.92, P = 0.037) at 24 weeks. There was a also significant interaction between cluster and treatment efficacy in HbA1c (glycated hemoglobin) reduction in metformin and acarbose groups at 24 and 48 weeks (pinteraction<0.001). CONCLUSIONS: Metformin and acarbose affected different metabolic variables depending on the diabetes subtype.

The Antidepressant Effects of GLP-1 Receptor Agonists: A Systematic Review and Meta-Analysis.

AIM/HYPOTHESIS: Emerging evidence suggests that glucagon-like peptide-1 receptor agonists (GLP-1RAs) may exert positive effects in patients with depression. Our aim was to conduct a systematic review and meta-analysis to examine the antidepressant effects of GLP-1RAs. METHODS: Randomized controlled trials and prospective cohort studies investigating the effects of GLP-1RAs versus placebo or other antidiabetic therapies on depressive symptoms were searched for using multiple electronic sources (CENTRAL, PubMed, EMBASE, PsycINFO, World Health Organization International Clinical Trials Registry Platform, ClinicalTrials.gov, China Network Knowledge Infrastructure, China Biomedical Database, Wan Fang data, and Chinese Scientific Journals Database) from inception to February 16, 2023. We utilized a random effects model to analyze standardized mean differences for the change in depression rating scales comparing GLP-1RA treated groups with control treated groups. RESULTS: The meta-analysis comprising 2,071 participants included 5 randomized controlled trials and 1 prospective cohort study. The meta-analysis indicated that the change from baseline in depression rating scale scores decreased significantly when patients received treatment with GLP-1RAs compared to control treatments (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 0%, pQ = 0.52). The subgroup analysis showed that the effects of GLP-1RAs on depressive symptoms were consistent in patients with Type 2 diabetes mellitus (SMD = -0.12, 95% CI [-0.21, -0.03], pSMD <0.01, I2 = 2%, pQ = 0.40). CONCLUSIONS: Adults treated with GLP-1RAs showed significant reductions in the depression rating scale scores compared to those treated with control substances. Our findings suggest that GLP-1RAs may be a potential treatment for alleviating depressive symptoms in humans.

Unveiling detection probability for multi-Gaussian correlated anomalous vortex modes in maritime atmospheric turbulence.

In this study, we employ the Rytov approximation to investigate the detection probability of orbital angular momentum (OAM) in multi-Gaussian correlated anomalous vortex (MGCAV) beams under non-Kolmogorov maritime atmospheric turbulence. Our results demonstrate that the OAM detection probability of a MGCAV beam is influenced by various factors, including beam parameters and the characteristics of maritime atmospheric turbulence. Specifically, an increase in propagation distance, beam order, and beam index, or a decrease in inner scale, spatial coherence width, and non-Kolmogorov parameter, leads to a decrease in the OAM detection probability. The phase characteristics of partially coherent vortex modes are affected by both atmospheric turbulence phase and initial random phase, resulting in reduced robustness compared to fully coherent vortex modes. Furthermore, a comparative analysis between Gaussian-Schell correlated anomalous vortex (GSCAV) beams and MGCAV beams reveals the superior resilience of GSCAV beams in mitigating the impact of maritime atmospheric turbulence. Moreover, specific combinations of beam order, topological charge, and beam waist, or the optimal beam width, yield maximum OAM detection probability or minimum scintillation. These findings provide valuable insights applicable to optical communication, particularly in scenarios above sea and ocean levels.

Renal elasticity and perfusion changes on ultrasonography in an early-stage diabetic rat model.

Background: Renal hemodynamic changes in early diabetes occur before the onset of significant structural abnormalities or clinical manifestations, and timely detection of these changes has clinical significance. This study aimed to evaluate renal elasticity and perfusion changes in an early-stage diabetic rat model by shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS), and to explore the potential correlations between renal elasticity and perfusion parameters. Methods: A total of 18 male Sprague-Dawley rats were randomly divided into three groups: a control group (group 1, n=6), a diabetic group (group 2, n=6), and a diabetic group receiving drug therapy (group 3, n=6). An intraperitoneal injection of streptozotocin (STZ) for 2 days combined with a high-fat diet (HFD) was used as the early-stage diabetic rat model. The diabetic rats in group 3 were treated with canagliflozin and losartan for 6 weeks, whereas the rats in groups 1 and 2 were given equal amounts of purified water. Renal stiffness on SWE and perfusion parameters on CEUS were measured and compared among the three groups, then the rats were sacrificed, and serum, urine, and renal histopathology were evaluated to confirm the development of early diabetes. Results: The early-stage diabetic rats without significant pathological changes exhibited bigger kidneys and higher blood glucose (all P<0.05). Among the CEUS parameters, peak enhancement (PE), wash-in area under the curve (WiAUC), wash-in perfusion index (WiPI), wash-out AUC (WoAUC), wash-in and wash-out AUC (WiWoAUC), rise time (RT), and time to peak (TTP) of diabetic rats in group 2 were significantly increased (all P<0.05), and the hyperperfusion ameliorated significantly after drug treatment. The renal elasticity measured by SWE varied in accordance with certain perfusion parameters, and was strongly positively correlated with WiAUC (r=0.701, P<0.001), WoAUC (r=0.647, P<0.001), and WiWoAUC (r=0.655, P<0.001), and moderately positively correlated with PE (r=0.539, P=0.001), WiPI (r=0.555, P<0.001), RT (r=0.425, P=0.010), and TTP (r=0.439, P=0.007). Conclusions: Renal elasticity and perfusion changes in the early stage of diabetes, and renal elasticity was positively associated with delayed and increased perfusion.

Two-dimensional ambipolar carriers of giant density at the diamond/cubic-BN(111) interfaces: toward complementary logic and quantum applications.

The extremely difficult ambipolar doping activation greatly hinders the outstanding performance of diamond for electronic devices. The main concern has been devoted to surface conduction by two-dimensional (2D) carriers. 2D hole gas (2DHG) in the diamond is induced by surface transfer doping dominated by the adsorbate's status and faces stability issues. Meanwhile, a feasible way to generate the other essential ambipolar carrier-2D electron gas (2DEG) is still lacking. We propose that the well-lattice-matched diamond/cBN(111) interfaces can spontaneously induce 2D ambipolar carriers with a giant density of 4.17 × 1014 cm-2, an order higher than other competitors. 2DEG and 2DHG can be separately achieved near the hetero-interfaces consisting of C-N and C-B bonds, respectively. Interestingly, the robust 2D charges are derived from a novel bulk-induced polarization-discontinuity at the interfaces, which can be attributed to an unexpected non-zero formal polarization of centrosymmetric cBN along the [111] direction. The existence of 2D ambipolar carriers at the diamond/cBN(111) interfaces has resolved the missing n-type conduction in diamond, thus opening up possibilities for complementary logic applications. Additionally, the high density of quantum-confined 2D ambipolar carriers provides an excellent platform for strongly correlated systems, which could lead to novel quantum information processing applications.

Medications and medical expenditures for diabetic patients with osteoporosis in Beijing, China: A retrospective study.

AIMS: This study aimed to clarify the changes in treatment regimens and medical expenditures in diabetic patients with osteoporosis. METHODS: We recruited 2,853,036 diabetic patients from the Beijing medical insurance database between 2016 and 2018. Among them, 406,221 patients also had osteoporosis. Clinical characteristics, treatment regimens, and medical costs were investigated in diabetic patients with and without osteoporosis. RESULTS: Diabetes and osteoporosis were most prevalent in participants aged 45---84 years. Compared with diabetic patients without osteoporosis, those with osteoporosis were prone to developing comorbidities and diabetic complications. They often required multiple glucose-lowering drugs and had a higher rate of insulin use. Similarly, osteoporosis leads to an increased number of medications for non-hypoglycemia as well as higher healthcare costs. These medications and costs increased with the number of complications and comorbidities. Interestingly, from 2016 to 2018, although diabetic patients with osteoporosis took more drugs, medical costs were lower year by year. CONCLUSIONS: Osteoporosis might contribute to a worse condition in diabetic patients, and this population often requires more medications with higher medical costs.

Data-driven subgroups of newly diagnosed type 2 diabetes and the relationship with cardiovascular diseases at genetic and clinical levels in Chinese adults.

BACKGROUND: To subgroup Chinese patients with newly diagnosed type 2 diabetes (T2D) by K-means cluster analysis on clinical indicators, and to explore whether these subgroups represent different genetic features and calculated cardiovascular risks. METHODS: The K-means clustering analysis was performed on two cohorts (n = 590 and 392), both consisting of Chinese participants with newly diagnosed T2D. To assess genetic risks, multiple polygenic risk scores (PRSs) and mitochondrial DNA copy numbers (mtDNA-CN) were calculated for all participants. Furthermore, Framingham risk scores (FRS) of cardiovascular diseases in two cohorts were also calculated to verify the genetic risks. RESULTS: Four clusters were identified including the mild age-related diabetes (MARD)(35.08%), mild obesity-related diabetes (MOD) (34.41%), severe autoimmune diabetes (SAID) 19.15%, and severe insulin-resistant diabetes (SIRD) 11.36% subgroups in the MARCH (metformin, and acarbose in Chinese patients as the initial hypoglycemic treatment) cohort. There was a significant difference in PRS for cardiovascular diseases (CVD) across four subgroups in the MARCH cohort (p < 0.05). Compared with the SIDD and SIRD subgroups, patients in the MOD subgroup had a relatively lower PRS for CVD (p < 0.05) in the MARCH cohort. Females had a higher PRS compared to males, with no significant difference in FRS across the four clusters. The MOD subgroup had a significantly lower FRS which was consistent with the results of PRS. Similar results of PRS and FRS were also replicated in the CONFIDENCE (comparison of glycemic control and b-cell function among newly diagnosed patients with type 2 diabetes treated with exenatide, insulin or pioglitazone) cohort. CONCLUSION: There are different CVD risks in diabetic subgroups based on clinical and genetic evidence which may promote precision medicine.

A Nationwide Cross-sectional Survey of Knowledge and Practices of Diabetes Drug Injection Techniques of Patients, Nurses, and Physicians: The China IT Improve Study.

OBJECTIVE: To investigate the knowledge and practices of diabetes drug injection techniques of diabetes patients, nurses, and physicians to support formulating national guidelines for standardized diabetes drug injection techniques. PATIENTS AND METHODS: In this nationwide multicenter cross-sectional survey conducted between November and December 2020, patients, nurses, and physicians were randomly chosen from 250 primary, 150 secondary, and 100 tertiary care hospitals using the stratified cluster sampling method. Their knowledge and/or practices of diabetes drug injection techniques were surveyed using the Diabetes Drug Injection Knowledge and Practice Questionnaire for Physicians, Nurses, and Patients. RESULTS: In total, 10,694, 2643, and 2816 eligible questionnaires were collected from patients, physicians, and nurses, respectively. Overall, 78.2% (7588/9709) type 2 diabetes patients failed to attain the target hemoglobin A1c. Hypoglycemic episodes and lipohypertrophy occurred in 19.8% and 34.7% of the patients, respectively. Needle reuse (odds ratio, 1.19; 95% CI, 1.07 to 1.33) and incorrect injection site rotation (odds ratio, 1.32; 95% CI, 1.16 to 1.51) were associated with failure to attain the target hemoglobin A1c. Overall, 48.9% physicians and 20.4% nurses had a poor knowledge domain score. Care setting and training, diabetes care experience, and regions were significant determinants of diabetes drug injection knowledge domain scores in both physicians and nurses. CONCLUSION: Poor glycemic control, occurrences of injection-associated complications in diabetes patients, and poor knowledge domain scores of a subset of physicians and nurses highlight the importance of regular assessment and education regarding diabetes drug injection techniques for physicians and nurses and development of national guidelines for diabetes drug injection. TRIAL REGISTRATION: Chictr.org.cn (ChiCTR2100045302).

Pharmacokinetics, pharmacodynamics, and safety of prandial oral insulin (N11005) in healthy subjects.

Aims: To verify whether the oral insulin N11005 is administered as a prandial insulin by assessing the pharmacokinetics (PK), pharmacodynamics (PD), and safety profiles of N11005 with a short-acting biosynthetic human insulin (Novolin R) as reference. Methods: This was a randomized, open-label, single-dose, crossover hyperinsulinemic-euglycemic clamp study in healthy Chinese male subjects. A total of 12 subjects were enrolled in the test (T) group (N11005, 300 IU, p.o.) and the reference (R) group (Novolin R, 0.1 IU/Kg, i.h.) with a washout period of 14 days. All subjects were administered on the same day of the clamp study. Glucose Infusion Rates (GIR), serum insulin, and C-peptide concentration were determined during every 8-hour clamp cycle. Trial registration: Clinicaltrials.gov identifier NCT04975022. Results: After administration, the ratios of mean serum C-peptide concentration to baseline concentration in both T and R groups were lower than 50%, which confirmed the stability of the clamp platform. T group (N11005) showed a more rapid onset of action (tGIR10%max≈11 min) and a comparable duration of action to the R group, which was basically in line with the characteristics of prandial insulins. No adverse events (AEs) occurred throughout the study, which demonstrated that N11005 and Novolin R are safe and well-tolerated. Conclusions: The PD profiles of the single-dose N11005 in the human body are similar to those of prandial insulins, with an excellent safety profile. Clinical trial registration: Clinicaltrials.gov, identifier NCT04975022.