Factors associated with nonattendance at annual diabetes check-up in Ningbo, China: a case-control study.

Background: Type 2 diabetes mellitus (T2DM) is a grave issue in China. The annual check-up is recommended in clinical guidelines on T2DM. It plays an important role in monitoring and managing the condition and detecting and managing any comorbidities and T2DM-related complications. However, people with T2DM may miss the annual check-up, and the benefits of this check-up are lost. Therefore, this study aimed to determine the factors associated with nonattendance at the annual T2DM check-up in Ningbo, China. Methods: A case-control study was conducted using the Ningbo National Metabolic Management Center dataset. Cases were people with T2DM who were alive but did not attend the first annual check-up, scheduled between 1 March 2019 and 28 February 2022 (n = 1,549). Controls were people with T2DM who were alive and attended the first annual check-up during the same period (n = 1,354). The characteristics of cases and controls were compared using logistic regressions. Results: The odds of being a female [odds ratio (OR) 1.26, 95% confidence interval (CI) 1.06-1.50], alcohol drinker (1.26, 1.06-1.49), and with glycated hemoglobin A1c (HbA1c) ≥7% (1.67, 1.42-1.97) were higher among case patients than controls. The odds of being a high school graduate (0.77, 0.66-0.89) and on standard treatments in addition to lifestyle modification (oral hypoglycemic drug 0.63, 0.42-0.96; oral hypoglycemic drug and injection therapy 0.48, 0.32-0.73) were lower among case patients than controls. Conclusion: The factors associated with nonattendance at the annual T2DM check-up in Ningbo, China were female sex, not a high school graduate, alcohol drinker, HbA1c ≥7%, and only on lifestyle modification. The study findings should be used for improving attendance at the annual check-up among people with T2DM in Ningbo.

Dissatisfaction of people with type 2 diabetes with the care received at a diabetes clinic in Ningbo, China: A cross-sectional study.

Aim: The study aimed to assess the dissatisfaction of people with type 2 diabetes mellitus (T2DM) with the care that they received at a diabetes outpatient clinic in Ningbo, China and to determine the associated factors. Methods: A cross-sectional study was conducted among 406 adults with T2DM in 2020-2021. Those who were treated at the diabetes outpatient clinic for at least six consecutive months before the survey date were eligible. The Short Assessment of Patient Satisfaction scale was used to assess participants' dissatisfaction with the care that they received. Results: Of the participants, 25.1% were not satisfied with the care that they received at the diabetes outpatient clinic in Ningbo. The odds of dissatisfaction were higher in physically active people compared to those who were not (odds ratio [OR]: 3.41; 95% confidence interval [CI]: 1.56-7.45) and those with >1-5 years of T2DM compared to ≤1 year (OR: 2.18; 95% CI: 1.05-4.53). Conclusion: A quarter of people with T2DM were dissatisfied with the care that they received at the diabetes outpatient clinic in Ningbo, China, and the factors associated with dissatisfaction were identified.

Diagnosis and treatment of MN1 C-terminal truncation syndrome.

BACKGROUND: MN1 C-terminal truncation (MCTT) is a rare syndrome; only 27 cases have been reported. We report the first case of an 8-year-old girl with MCTT syndrome complicated with moderate obstructive sleep apnea (OSA). METHODS: MCTT syndrome was diagnosed by whole-exome sequencing (WES) and validated by Sanger sequencing. The patient received 2 years of treatment with continuous positive airway pressure (CPAP) to relieve sleep apnea and hypoxia, and a reverse sector fan-shaped expander for maxillary expansion. RESULTS: WES revealed a de novo MN1 variant, c.3760C>T (p.[Q1254*]). An arachnoid cyst was found in the right occipital brain. The patient presented mild symptoms of classic MCTT syndrome. The patient did not experience hearing loss and only mild intellectual disability. Radiological examinations showed cleft secondary palate, narrow upper arch, narrow upper airway, and mandibular skeletal retrusion. Polysomnography indicated moderate OSA, with an apnea/hypopnea index of 6.8, which decreased to 1 after CPAP during the night. Two-year maxillary expansion widened the upper arch, and the cleft secondary palate became visible. The mandible moved forward spontaneously, resulting in the improvement of profile and upper airway widening. General physical conditions, such as motor delay, muscle weakness, and developmental delay, were significantly improved two years later. CONCLUSION: In conclusion, we discovered a MN1 variant [NM_002430.2: c.3760C>T, p.Q1254*] that causes mild MCTT symptoms compared to other MN1 variants. For patients with MCTT complicated with OSA, multidisciplinary combination therapy can improve maxillofacial development, widen the upper airway and relieve sleep apnea, improving the general physical condition.

Association Between Sleep Duration and Albuminuria in Patients with Type 2 Diabetes: A Cross-Sectional Study in Ningbo, China.

Purpose: Type 2 diabetes mellitus (T2DM) can lead to microvascular complications including diabetic kidney disease. Albuminuria is an important marker to diagnose kidney injury in T2DM patients and healthy sleep duration is important for maintaining good health in patients with T2DM. However, the association between sleep duration and albuminuria in T2DM patients is unclear. Thus, this study aimed to investigate the association between sleep duration and albuminuria in patients with T2DM in Ningbo, China. Methods: A cross-sectional study was conducted at National Metabolic Management Centre (MMC) - Ningbo First Hospital from March 2018 to February 2021. Adult patients with T2DM were included in the study. The sleep duration (daytime and nocturnal) was self-reported. Albuminuria was defined as the presence of urinary albumin-creatinine ratio ≥30 mg/g. Logistic regression analyses were performed to identify the association. Results: There were 2688 T2DM patients in the study. In the unadjusted model (1), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: OR 1.36, 95% CI 1.09-1.71; ≥61 minutes: 1.73, 1.33-2.24). Similarly, after adjusting for age and sex (model 2), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: 1.34, 1.07-1.68; ≥61 minutes: 1.69, 1.30-2.20). After adjusting for age, sex, physical activity, smoking, alcohol drinking, overweight/obesity, hypertension, hyperuricaemia, duration of T2DM, glycated haemoglobin, angiotensin-converting enzyme inhibitors/angiotensin receptor blocker usage and nocturnal sleep duration (model 3), the odds of albuminuria increased with the daytime sleep duration (31-60 minutes: 1.33, 1.04-1.71; ≥61 minutes: 1.71, 1.29-2.26). However, no relationship was found between nocturnal sleep duration and albuminuria. Conclusion: Longer daytime sleep is found to be associated with albuminuria in patients with T2DM in Ningbo, China but no association is found between nocturnal sleep duration and albuminuria. The findings are exploratory, and there is a need for longitudinal studies on this topic.

Achieving physical examination competence through optimizing hands-on practice cycles: a prospective cohort comparative study of medical students.

BACKGROUND: Deliberate practice (DP) was proposed for effective clinical skill training, which highlights focused, repetitive practice and feedback as the key points for practice. Although previous studies have investigated the effect of feedback in DP, little is known about the proper repetitive cycles of clinical skills training especially in physical examination (PE) training. METHODS: We drew learning curves and designed a comparative study to find out the optimal number of hands-on practice cycles, an important aspect of DP, in abdominal PE training for medical students. A comparative study was conducted to validate the optimal number of hands-on practice by dividing students into two cohorts including Cohort A (high-frequency hand-on training) and B (low-frequency hand-on training). RESULTS: The learning curve study of 16 students exhibited a threshold of four repetitive practices when 81.25% students reached the competence score. A total of 74 students' final exam scores were collected for analysis. Students in Cohort A (4-5 PEs) scored significantly higher than those in Cohort B (≤3 PEs) (84.41 ± 11.78 vs 76.83 ± 17.51] in the final exam (P = 0.030)). CONCLUSION: High-frequency practice can improve students' competence of abdominal PE skill. We recommend four cycles of hands-on practice for each student in a training course like PE training.

Identification of Hypoxia-Related Molecular Classification and Associated Gene Signature in Oral Squamous Cell Carcinoma.

The high heterogeneity of oral squamous cell carcinoma (OSCC) is the main obstacle for individualized treatment. Recognizing the characteristics of different subtypes and investigating the promising strategies for each subclass are of great significance in precise treatment. In this study, we systematically evaluated hypoxia-mediated patterns together with immune characteristics of 309 OSCC patients in the TCGA training set and 97 patients in the GSE41613 testing set. We further identified two different hypoxia subtypes with distinct immune microenvironment traits and provided treatment programs for the two subclasses. In order to assess hypoxia level individually, we finally constructed a hypoxia-related risk score, which could predict the clinical outcome and immunotherapy response of OSCC patients. In summary, the recognition of different hypoxia patterns and the establishment of hypoxia-related risk score might enhance our understanding of the tumor microenvironment of OSCC and provide more personalized treatment strategies in the future.

Follicle-stimulating hormone and estradiol are associated with bone mineral density and risk of fractures in men with type 2 diabetes mellitus.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a higher fracture risk. Sex hormones are important for maintaining skeletal health. It is not clear which sex hormone(s) contribute(s) to bone mineral density (BMD) and fracture risk in males with T2DM. This study investigated the relationships of these parameters in males with T2DM. METHODS: This study involved 482 men with T2DM. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was assessed using the modified Fracture Risk Algorithm (FRAX) tool. Serum levels of sex hormones were measured. RESULTS: Follicle-stimulating hormone (FSH) and estradiol (E2) were associated with BMDs at L2-4 (FSH, ß = -.162, P < .05; E2, ß = .176, P < .001), and E2 was associated with BMD at FN (ß = .137, P < .05) and TH (ß = .140, P < .05). FSH was associated with major osteoporotic fractures (ß = .288, P < .001) and hip fractures (ß = .235, P < .001). Higher FSH was a risk factor for osteoporosis/osteopenia (odds ratios [OR] = 2.92, 95% CI = 1.66-5.14, P < .001), whereas higher E2 was a protective factor (OR = 0.37, 95% CI = 0.22-0.60, P < .001). Patients in the higher tertile of FSH and lower tertile of E2 had an increased risk of osteoporosis/osteopenia (OR = 5.05, 95% CI = 1.37-18.65, P < .05). CONCLUSIONS: For males with T2DM, FSH and E2 are significantly associated with BMD, osteoporosis/osteopenia, and fracture risk.

Associations of serum sex hormone binding globulin with bone mineral densities and higher 10-year probability of fractures in postmenopausal women with type 2 diabetes mellitus.

BACKGROUND: Postmenopause and type 2 diabetes mellitus (T2DM) are associated with higher fracture risk. Sex hormones are important in maintaining woman skeleton health. The relationships of sex hormone(s) with bone mineral density (BMD) and fracture risk are still unclear in diabetic-postmenopausal women. This study aimed to investigate the relationships of sex hormones with BMDs and fracture risk in postmenopausal women with T2DM. METHODS: Two hundred and fourteen postmenopausal women with T2DM were included. BMDs at lumbar spine (L2-4), femoral neck (FN) and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). The 10-year probability of fractures was accessed by modified fracture risk algorithm (FRAX) tool. Serum concentrations of sex hormones were measured. RESULTS: Sex hormone binding globulin (SHBG) was a determinant of BMDs at L2-4 (ß=-0.199, P<0.05), TH (ß=-0.233, P<0.05), major osteoporotic fracture (MOF) (ß=0.253, P<0.001) and hip fracture (HF) (ß=0.262, P<0.001). Per SD increase in SHBG caused a 2% increase in the risk of osteoporosis/osteopenia. SHBG in quartile-4 was associated with 4.21 higher risk of osteoporosis/osteopenia compared with SHBG in quartile-1. CONCLUSIONS: In postmenopausal women with T2DM, higher serum SHBG tended to be associated with lower BMDs, and increased the risk of osteoporosis/osteopenia and the fracture risk.

THE ASSOCIATIONS BETWEEN HYPOVITAMINOSIS D, HIGHER PTH LEVELS WITH BONE MINERAL DENSITIES, AND RISK OF THE 10-YEAR PROBABILITY OF MAJOR OSTEOPOROTIC FRACTURES IN CHINESE PATIENTS WITH T2DM.

OBJECTIVE: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture [MOF] and hip fracture [HF]) was assessed using the fracture risk assessment tool (FRAX). RESULTS: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH ( r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard ß = 0.073, P = .010) and HF (standard ß = 0.094, P = .004). CONCLUSION: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels. ABBREVIATIONS: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid.

Higher Serum Uric Acid Is Associated with Higher Bone Mineral Density in Chinese Men with Type 2 Diabetes Mellitus.

Accumulating evidence suggests that oxidative stress is associated with osteoporosis. Serum uric acid (UA) is a strong endogenous antioxidant. Therefore, we investigated the relationship between the serum UA and BMD in Chinese men with T2DM. In this cross-sectional study of 621 men with T2DM, BMDs at lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of UA, calcium (Ca), 25-OH vitamin D3 (vitD3), parathyroid hormone (PTH), and creatinine (Cr) were also tested. Data analyses revealed that serum UA levels were positively associated with BMD at all sites (p < 0.05) in men with T2DM after adjusting for multiple confounders. The serum UA levels were positively correlated with body weight (r = 0.322), body mass index (BMI) (r = 0.331), Ca (r = 0.179), and Cr (r = 0.239) (p < 0.001) and were also positively associated with the concentrations of PTH (r = 0.10, p < 0.05). When compared with those in the lowest tertile of UA levels, men with T2DM in the highest tertile had a lower prevalence of osteoporosis or osteopenia (adjusted odds ratio 0.54, 95% confidence interval [CI] 0.31-0.95). These data suggest that higher serum levels of UA are associated with higher BMDs and lower risks of osteoporosis in Chinese men with T2DM.

Glucagon-like peptide-1 receptor agonist Liraglutide has anabolic bone effects in ovariectomized rats without diabetes.

Recently, a number of studies have demonstrated the potential beneficial role for novel anti-diabetic GLP-1 receptor agonists (GLP-1RAs) in the skeleton metabolism in diabetic rodents and patients. In this study, we evaluated the impacts of the synthetic GLP-1RA Liraglutide on bone mass and quality in osteoporotic rats induced by ovariectomy (OVX) but without diabetes, as well as its effect on the adipogenic and osteoblastogenic differentiation of bone marrow stromal cells (BMSCs). Three months after sham surgery or bilateral OVX, eighteen 5-month old female Wistar rats were randomly divided into three groups to receive the following treatments for 2 months: (1) Sham + normal saline; (2) OVX + normal saline; and (3) OVX + Liraglutide (0.6 mg/day). As revealed by micro-CT analysis, Liraglutide improved trabecular volume, thickness and number, increased BMD, and reduced trabecular spacing in the femurs in OVX rats; similar results were observed in the lumbar vertebrae of OVX rats treated with Liraglutide. Following in vitro treatment of rat and human BMSCs with 10 nM Liraglutide, there was a significant increase in the mRNA expression of osteoblast-specific transcriptional factor Runx2 and the osteoblast markers alkaline phosphatase (ALP) and collagen α1 (Col-1), but a significant decrease in peroxisome proliferator-activated receptor γ (PPARγ). In conclusion, our results indicate that the anti-diabetic drug Liraglutide can exert a bone protective effect even in non-diabetic osteoporotic OVX rats. This protective effect is likely attributable to the impact of Liraglutide on the lineage fate determination of BMSCs.

Ceramide is upregulated and associated with mortality in patients with chronic heart failure.

BACKGROUND: Ceramide is involved in apoptosis, inflammation, and stress responses, which are among the pathogenic components of chronic heart failure (CHF). However, no one has documented the levels of ceramide itself in CHF or determined its potential prognostic value. METHODS: In this study we recruited patients with heart failure consecutively from the hospital, of whom 423 stable patients were eventually selected to participate in this study after an observation period of at least 3 months after hospital discharge. All patents were followed up for all-cause death to December 31, 2013. RESULTS: Plasma ceramide levels were increased stepwise with New York Heart Association functional class (I, 5.32 ± 1.98; II, 5.81 ± 1.63; III, 6.14 ± 2.14; IV, 6.66 ± 2.61 ng/mL). During a mean follow-up of 4.4 years (interquartile range: 3.5-5.3 years), a total of 200 CHF patients died. The optimal threshold value of ceramide was 6.05 ng/mL. Ceramide levels as continuous and as dichotomous variables are risk factors for mortality in CHF (adjusted hazard ratio, 1.31; 95% confidence interval, 1.16-1.47; P < 0.001 and adjusted hazard ratio, 2.07, 95% confidence interval, 1.53-2.81; P < 0.001, respectively). When ceramide levels were combined with conventional CHF risk factors, the area under the curve increased from 0.68 (0.63-0.72) to 0.72 (0.68-0.76); P = 0.047. The continuous net reclassification index and integrated discrimination improvement index were 17.2% (5.0-29.9%; P = 0.027) and 0.04 (0.01-0.08; P = 0.020), respectively. CONCLUSIONS: Plasma ceramide levels were increased and correlated with the severity of CHF, and were an independent risk factor of mortality in patients with CHF and reduced left ventricular systolic function. Ceramide levels might provide additional predictive value after conventional risk assessment.

Elevation of ceramide and activation of secretory acid sphingomyelinase in patients with acute coronary syndromes.

BACKGROUND: Although there are several reported evidences for a pathogenic role of sphingolipid signaling in atherosclerosis, peripheral blood levels of ceramide and secretory acid sphingomyelinase (S-SMase) activity in patients with acute coronary syndromes (ACS) have not been evaluated. METHODS AND RESULTS: A total of 304 CAD patients and 52 healthy individuals were divided into four groups: control group (n=52), stable angina pectoris (SAP) group (n=98), unstable angina pectoris (UAP) group (n=92), and acute myocardial infarction (AMI) group (n=114). Plasma levels of sphingomyelin (SPM) were elevated in patients with UAP and AMI compared with those in the control and SAP participants. Plasma ceramide levels and S-SMase activity in patients with ACS (including UAP and AMI) on day 0 were significantly higher than those in the control and SAP participants. Elevation in plasma ceramide levels in patients with UAP and AMI was sustained until a day after percutaneous coronary intervention or day 7, respectively. Moreover, in patients with UAP, S-SMase activity elevation on day 0 was followed by a gradual decrease toward the SAP range up to a day after percutaneous coronary intervention. In patients with AMI, elevation in S-SMase activity showed a peak on day 3. CONCLUSION: Serial changes in plasma ceramide and S-SMase activity were documented in patients with ACS. These findings provide an insight into the molecular mechanism of plaque destabilization.