Publications by authors named "Zhiguang Zhou"

339 Publications

Residual β-cell function after 10 years of autoimmune type 1 diabetes: prevalence, possible determinants, and implications for metabolism.

Ann Transl Med 2021 Apr;9(8):650

National Clinical Research Center for Metabolic Disease, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Background: Type 1 diabetes (T1D) has long been considered a progressive autoimmune disease resulting in the failure of pancreatic β-cell function and absolute endogenous insulin deficiency. However, several studies have demonstrated patients with T1D have detectable C-peptide levels long after diagnosis, which has remarkable clinical significance. Since this issue has not been systematically explored in non-Caucasian populations, we aimed to identify the prevalence of residual β-cell function and its related clinical features in Chinese long-term T1D patients.

Methods: We enrolled 109 patients with T1D for ≥10 years and administered a mixed-meal tolerance test (MMTT). Fasting and postprandial C-peptide (FCP/PCP) levels were measured to evaluate the insulin secretion function of β-cells. Patients whose FCP and PCP levels were both below the lower detection limit (16.7 pmol/L) were grouped as 'β-cell function depleted', while others were thought to have 'residual β-cell function'. Demographic data, metabolic status, and diabetic complications were compared between patients with or without residual β-cell function.

Results: 38.5% of subjects retained residual β-cell function, and among those, 33.3% responded to MMTT by a two-fold or greater rise of their FCP levels. Clinical features associated with residual β-cell function were older age of diagnosis [27.5 (interquartile range:11.5-37.0) 17.0 (interquartile range: 8.0-30.0) years, P=0.037], lower HbA1c (64.6±20.3 72.4±18.5 mmol/mol, P=0.026), and reduced rate of hypoglycemia (23.8% 52.2%, P=0.003). Age of diagnosis was positively correlated with detectable FCP level (r=0.393, P=0.020). Individuals diagnosed after 30 years of age tended to retain residual β-cell function (OR =3.016, P=0.044). We found no association between residual β-cell function and chronic diabetic complications.

Conclusions: Residual β-cell function can be found in nearly 40% of long-term patients with T1D in China and is associated with older age at diagnosis and better glucose control. The relationship between residual β-cell function and chronic diabetic complications remains to be explored.
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http://dx.doi.org/10.21037/atm-20-7471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106063PMC
April 2021

Poor guideline adherence in type 1 diabetes education in real-world clinical practice: Evidence from a multicentre, national survey.

Patient Educ Couns 2021 Apr 17. Epub 2021 Apr 17.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China. Electronic address:

Objective: To examine how physicians implement guidelines to deliver insulin dosing education for type 1 diabetes patients in real-world settings.

Methods: A nationally representative sample of endocrinologists from top tertiary hospitals in China was obtained by a multistage random sampling method (n = 385). Knowledge, perceptions and practices of insulin dosing were assessed by validated questionnaires. Multivariable logistic regression was used to identify independent determinants of clinical practice and knowledge.

Results: Only 20.5% of endocrinologists correctly answered> 75% of the items regarding insulin dosing knowledge. Only 37.7% of endocrinologists reported often teaching insulin-to-carbohydrate ratio and insulin sensitivity factor. Practice behaviours were independently associated with guideline familiarity (OR: 5.92, 95% CI: 3.36-10.41), receiving standardized training (OR: 2.00, 95% CI:1.23-3.25), self-reported lack of time (OR: 0.58, 95% CI:0.34-0.99) and insufficient teaching approaches (OR: 0.57, 95% CI:0.33-0.97) CONCLUSIONS: There was a large gap between guidelines and clinical practice in insulin dosing education. Modifiable factors, including self-reported lack of time, unfamiliarity with guidelines, the shortage of medical training and educational tools hinder insulin dosing education.

Practice Implications: Sufficient medical training and educational tools are important to optimize insulin dosing education. The current care paradigm should also be modified to relieve the burden of physicians.
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http://dx.doi.org/10.1016/j.pec.2021.04.010DOI Listing
April 2021

Three-phasic pattern of C-peptide decline in type 1 diabetes patients with partial remission.

Diabetes Metab Res Rev 2021 Apr 29. Epub 2021 Apr 29.

Department of Metabolism and Endocrinology, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Aims: To explore the different patterns of C-peptide decline in patients with and without partial remission of newly diagnosed type 1 diabetes (T1D).

Materials And Methods: A total of 298 patients with new-onset T1D were followed up regularly at 3 months' interval to investigate the loss of C-peptide. Partial remission was determined by postprandial C-peptide ≥300 pmol/L or insulin dose-adjusted A1c ≤ 9 in the absence of C-peptide. Beta-cell function was defined as preserved, residual or failed by postprandial C-peptide of ≥200 pmol/L, 50-200 pmol/L or ≤50 pmol/L, respectively.

Results: Altogether, 199 out of 298 patients (125 adults) had partial remission. The pattern of C-peptide change in patients with partial remission was three-phasic, demonstrating an upward trend followed by a downward trend of fast first and then slow, while the pattern in patients without partial remission was biphasic, showing an initial fast fall and a subsequent slower decrease. The patterns remained consistent when patients were stratified by the age of onset. At 3 years, there were 71% of the patients with partial remission still had preserved or residual beta-cell function, while 89% of the patients who had no partial remission developed beta-cell function failure. In patients whose partial remission ended, the average C-peptide was still higher than duration-matched patients without partial remission.

Conclusions: Patients with partial remission of T1D have a distinct three-phasic pattern of C-peptide decline, other than the widely recognized biphasic pattern. The effect of partial remission still exist​s after remission ends.
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http://dx.doi.org/10.1002/dmrr.3461DOI Listing
April 2021

Anaemia and Related Nutritional Deficiencies in Chinese Patients with Obesity, 12 Months Following Laparoscopic Sleeve Gastrectomy.

Diabetes Metab Syndr Obes 2021 12;14:1575-1587. Epub 2021 Apr 12.

National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, 410011, People's Republic of China.

Background: Laparoscopic sleeve gastrectomy (LSG) has become a predominant bariatric procedure at present. However, data are scarce regarding the nutritional impact of this procedure on Chinese patients. This study aimed to evaluate the prevalence of nutritional deficiency after LSG in Chinese patients.

Methods: Eighty-two patients with obesity were recruited from the Second Xiangya Hospital of Central South University, and all patients underwent LSG and completed the visit.

Results: Compared with the baseline, the serum albumin levels increased significantly at 1-12 months (<0.001) after surgery, and the hypoalbuminemia rate decreased from 8.5% to 0% throughout the study (=0.063). Anaemia was present in 7.3% of all patients before surgery, and its prevalence increased to 11.0% at 12 months post-operation (=0.109). The anaemia rate of fertile females was higher than that of males (21.4% vs 2.3%, =0.036). No significant changes were found in vitamin B12 deficiency throughout the study (0% vs 3.8%, =1.0). The increases in the folate deficiency were only discovered in the female group (3.7% vs 20%, =0.031) and the obese without type 2 diabetes (T2D) group after LSG (27.3% vs 47.1%, =0.031). A decrease in the ferritin levels and an increase in iron deficiency at 12 months post-surgery were found among all patients.

Conclusion: Based on 12 months of follow-up, LSG is effective in controlling metabolic syndrome and has a modest effect on nutritional deficiencies, which suggests that LSG is an effective and comparably safe procedure for Chinese patients considering nutritional deficiencies at 12 months post-surgery.
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http://dx.doi.org/10.2147/DMSO.S303320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8051959PMC
April 2021

A clinical diagnostic model based on an eXtreme Gradient Boosting algorithm to distinguish type 1 diabetes.

Ann Transl Med 2021 Mar;9(5):409

Department of Metabolism and Endocrinology, the Second Xiangya Hospital, Central South University, Changsha, China.

Background: Accurate classification of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in the early phase is crucial for individual precision treatment. This study aimed to develop a classification model having fewer and easier to access clinical variables to distinguish T1DM in newly diagnosed diabetes in adults.

Methods: Clinical and laboratory data were collected from 15,206 adults with newly diagnosed diabetes in this cross-sectional study. This cohort represented 20 provinces and 4 municipalities in China. Types of diabetes were determined based on postprandial C-peptide (PCP) level and glutamic acid decarboxylase autoantibody (GADA) titer. We developed multivariable clinical diagnostic models using the eXtreme Gradient Boosting (XGBoost) algorithm. Classification variables included in the final model were based on their scores of importance. Model performance was evaluated by area under the receiver operating characteristic curve (ROC AUC), sensitivity, and specificity. The performance of models with different variable combinations was compared. Calibration intercept and slope were evaluated for the final model.

Results: Among the newly diagnosed diabetes cohort, 1,465 (9.63%) persons had T1DM and 13,741 (90.37%) had T2DM. Body mass index (BMI) contributed the most to the model, followed by age of onset and hemoglobin A1c (HbA1c). Compared with models with other clinical variable combinations, a final model that integrated age of onset, BMI and HbA1c had relatively higher performance. The ROC AUC, sensitivity, and specificity for this model were 0.83 (95% CI, 0.80 to 0.85), 0.77, and 0.76, respectively. The calibration intercept and slope were 0.02 (95% CI, -0.03 to 0.06) and 0.90 (95% CI, 0.79 to 1.02), respectively, which suggested a good calibration performance.

Conclusions: Our classification model that integrated age of onset, BMI, and HbA1c could distinguish T1DM from T2DM, which provides a useful tool in assisting physicians in subtyping and precising treatment in diabetes.
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http://dx.doi.org/10.21037/atm-20-7115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033361PMC
March 2021

Decreased serum fibroblast growth factor 19 level is a risk factor for type 1 diabetes.

Ann Transl Med 2021 Mar;9(5):376

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Increasing evidence suggests that fibroblast growth factor 19 (FGF19) is a regulator of glucose metabolism and may provide a new therapeutic target for type 1 diabetes (T1D). However, the clinical relevance of FGF19 in T1D remains unclear. In this study, we examined the relationship between the serum FGF19 concentration and T1D.

Methods: This study included 81 newly diagnosed T1D patients and 80 sex- and age-matched healthy controls. The correlation between the FGF19 concentration and clinical characteristics of T1D patients and healthy controls was investigated. Logistic regression analysis was performed to determine whether levels of FGF19 were independently associated with T1D.

Results: The fasting serum FGF19 levels in the T1D group were significantly lower than those in the control group [159.9 (100.0-272.7) 205.0 (126.9-307.9) pg/mL, P=0.008]. In all subjects, serum FGF19 levels were negatively correlated with fasting blood glucose (FBG) (r=-0.192, P=0.015). In the control group, serum FGF19 levels were positively correlated with total cholesterol (TC) (r=0.338, P=0.002) and low-density lipoprotein cholesterol (LDL-c) (r=0.300, P=0.007). In addition to sex and body mass index (BMI), FGF19 was an independent impact factor for T1D [odds ratio (OR) =0.541, P=0.023; adjusted for sex, age, BMI, presence of hypertension, and presence of dyslipidemia].

Conclusions: Low serum FGF19 level is associated with T1D, which could serve as a risk factor for T1D.
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http://dx.doi.org/10.21037/atm-20-5203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8033349PMC
March 2021

Factors associated with diabetes distress among adolescents with type 1 diabetes.

J Clin Nurs 2021 Apr 7. Epub 2021 Apr 7.

Xiangya School of Nursing, Central South University, Changsha, China.

Aims: To describe the specific domains of diabetes distress and factors associated with these domains.

Background: Diabetes distress is a common problem but not well recognised in adolescents by healthcare providers or adolescents themselves. There is insufficient evidence on how specific domains of diabetes distress exist in adolescents, making it challenging to select precise components to alleviate diabetes stress.

Design: A quantitative, descriptive and cross-sectional study.

Methods: Data were collected on socio-demographic and clinical characteristics, diabetes distress, perceived stress, self-efficacy and diabetes self-management using established questionnaires. Multivariate linear regression was conducted to examine the associations between specific factors and four domains in diabetes distress. STROBE checklist was used as the guideline for this study.

Results: A total of 100 adolescents with type 1 diabetes aged 12 to 18 years participated in this study. Adolescents experienced the highest levels of distress in the regimen-related distress [2.41 (SD =0.82)] and physician-related distress [2.40 (SD =0.80)] domains. Older age, female gender, more diabetes problem-solving and higher levels of perceived stress were associated with higher regimen-related distress (β = 0.21 ~ 0.45, p < 0.05). Older age, female gender, a lower degree of endorsement of relevant diabetes-related goals and higher levels of perceived stress were associated with higher physician-related distress (β = -0.29 ~ 0.34, p < 0.05).

Conclusions: Diabetes distress was reported more on regimen-related and physician-related domains among adolescents with type 1 diabetes in China, associating with older age, female, increased perceived stress and poor diabetes-related problem-solving.

Relevance To Clinical Practice: Nurses need to screen the specific domains of diabetes distress among adolescents with type 1 diabetes, especially for the older adolescents and girls. This study highlighted the importance of incorporating diabetes-related problem-solving support and stress management strategies into diabetes management for adolescents with type 1 diabetes, which could help relieve diabetes distress.
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http://dx.doi.org/10.1111/jocn.15742DOI Listing
April 2021

Axial localization and tracking of self-interference nanoparticles by lateral point spread functions.

Nat Commun 2021 04 1;12(1):2019. Epub 2021 Apr 1.

Institute for Biomedical Materials and Devices (IBMD), Faculty of Science, University of Technology Sydney, Sydney, NSW, 2007, Australia.

Sub-diffraction limited localization of fluorescent emitters is a key goal of microscopy imaging. Here, we report that single upconversion nanoparticles, containing multiple emission centres with random orientations, can generate a series of unique, bright and position-sensitive patterns in the spatial domain when placed on top of a mirror. Supported by our numerical simulation, we attribute this effect to the sum of each single emitter's interference with its own mirror image. As a result, this configuration generates a series of sophisticated far-field point spread functions (PSFs), e.g. in Gaussian, doughnut and archery target shapes, strongly dependent on the phase difference between the emitter and its image. In this way, the axial locations of nanoparticles are transferred into far-field patterns. We demonstrate a real-time distance sensing technology with a localization accuracy of 2.8 nm, according to the atomic force microscope (AFM) characterization values, smaller than 1/350 of the excitation wavelength.
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http://dx.doi.org/10.1038/s41467-021-22283-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8016974PMC
April 2021

Emerging roles of rare and low-frequency genetic variants in type 1 diabetes mellitus.

J Med Genet 2021 May 22;58(5):289-296. Epub 2021 Mar 22.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China

Type 1 diabetes mellitus (T1DM) is defined as an autoimmune disorder and has enormous complexity and heterogeneity. Although its precise pathogenic mechanisms are obscure, this disease is widely acknowledged to be precipitated by environmental factors in individuals with genetic susceptibility. To date, the known susceptibility loci, which have mostly been identified by genome-wide association studies, can explain 80%-85% of the heritability of T1DM. Researchers believe that at least a part of its missing genetic component is caused by undetected rare and low-frequency variants. Most common variants have only small to modest effect sizes, which increases the difficulty of dissecting their functions and restricts their potential clinical application. Intriguingly, many studies have indicated that rare and low-frequency variants have larger effect sizes and play more significant roles in susceptibility to common diseases, including T1DM, than common variants do. Therefore, better recognition of rare and low-frequency variants is beneficial for revealing the genetic architecture of T1DM and for providing new and potent therapeutic targets for this disease. Here, we will discuss existing challenges as well as the great significance of this field and review current knowledge of the contributions of rare and low-frequency variants to T1DM.
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http://dx.doi.org/10.1136/jmedgenet-2020-107350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086251PMC
May 2021

Fatty acid binding protein 4 promotes autoimmune diabetes by recruitment and activation of pancreatic islet macrophages.

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

State Key Laboratory of Pharmaceutical Biotechnology.

Both innate and adaptive immune cells are critical players in autoimmune destruction of insulin-producing β cells in type 1 diabetes. However, the early pathogenic events triggering the recruitment and activation of innate immune cells in islets remain obscure. Here we show that circulating fatty acid binding protein 4 (FABP4) level was significantly elevated in patients with type 1 diabetes and their first-degree relatives and positively correlated with the titers of several islet autoantibodies. In nonobese diabetic (NOD) mice, increased FABP4 expression in islet macrophages started from the neonatal period, well before the occurrence of overt diabetes. Furthermore, the spontaneous development of autoimmune diabetes in NOD mice was markedly reduced by pharmacological inhibition or genetic ablation of FABP4 or adoptive transfer of FABP4-deficient bone marrow cells. Mechanistically, FABP4 activated innate immune responses in islets by enhancing the infiltration and polarization of macrophages to proinflammatory M1 subtype, thus creating an inflammatory milieu required for activation of diabetogenic CD8+ T cells and shift of CD4+ helper T cells toward Th1 subtypes. These findings demonstrate FABP4 as a possible early mediator for β cell autoimmunity by facilitating crosstalk between innate and adaptive immune cells, suggesting that pharmacological inhibition of FABP4 may represent a promising therapeutic strategy for autoimmune diabetes.
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http://dx.doi.org/10.1172/jci.insight.141814DOI Listing
April 2021

Long-term exposure to low doses of bisphenol S has hypoglycaemic effect in adult male mice by promoting insulin sensitivity and repressing gluconeogenesis.

Environ Pollut 2021 May 23;277:116630. Epub 2021 Feb 23.

Shenzhen Center for Disease Control and Prevention, Shenzhen, 518055, China. Electronic address:

Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 μg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.
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http://dx.doi.org/10.1016/j.envpol.2021.116630DOI Listing
May 2021

Study of Thermal Expansion Coefficient of Graphene via Raman Micro-Spectroscopy: Revisited.

Small 2021 Mar 26;17(12):e2006146. Epub 2021 Feb 26.

State Key Laboratory of Surface Physics and Key Laboratory of Micro- and Nano-Photonic Structures (MOE), Department of Physics, Fudan University, Shanghai, 200433, China.

The thermal expansion coefficient (TEC) of a 2D material is a fundamental parameter for both material property and applications. A joint study is hereby reported, using Raman microspectroscopy and molecular dynamics (MD) simulations, of the substrate effects on thermal properties of graphene. It is found that besides the lateral strain induced by the substrate, out-of-plane coupling strongly affects the temperature-dependent vibrational modes and TEC of graphene. MD simulation shows significant reduction of the density of states for longer wavelength out-of-plane vibrations when the graphene is supported on an alkane substrate. The negative TEC of freestanding graphene becomes smaller when out-of-plane rippling is suppressed. In order to measure TEC of 2D materials with the out-of-plane coupling being taken into consideration, a Raman microspectroscopic scheme to separate the contributions of lateral strain and out-of-plane coupling to TEC is developed. The TEC of graphene on octadecyltrichlorosilane substrate is found to be (-0.6 ± 0.5) × 10 K at room temperature, which is fundamentally smaller than that of freestanding graphene. These results shed light on the fundamental understanding of the interaction between 2D material and substrate, and offer a general recipe for studying separately in-plane and out-of-plane couplings on supported materials.
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http://dx.doi.org/10.1002/smll.202006146DOI Listing
March 2021

Changes in fasting bile acid profiles after Roux-en-Y gastric bypass and sleeve gastrectomy.

Medicine (Baltimore) 2021 Jan;100(3):e23939

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Metabolic Syndrome Research Center, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Background: Bile acid is an essential factor that plays a role in metabolic regulation, but how bile acid is regulated after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) remains unclear. This meta-analysis aimed to investigate changes in the levels of fasting bile acids following RYGB and SG.

Methods: A systematic literature search of the PubMed, EMBASE, Cochrane Library and Web of Science databases through July 2020 was performed in accordance with the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The concentrations of bile acids were evaluated.

Results: Thirteen studies with 289 patients were included. Our results showed that patients who underwent RYGB had increased levels of fasting total bile acids, primary bile acids, secondary bile acids, conjugated bile acids, and unconjugated bile acids, but no significant differences in all these bile acid levels were observed in patients who underwent SG. Furthermore, 12a-hydroxylated bile acid levels and the 12a-hydroxylated/non-12a-hydroxylated bile acid ratio also increased following RYGB.

Conclusion: In this study, we found that fasting bile acid levels, especially 12a-hydroxylated bile acids levels, were increased after RYGB. However, no differences in fasting bile acid levels were observed following SG.
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http://dx.doi.org/10.1097/MD.0000000000023939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837931PMC
January 2021

Effectiveness of the Family Portal Function on the Lilly Connected Care Program (LCCP) for Patients With Type 2 Diabetes: Retrospective Cohort Study With Propensity Score Matching.

JMIR Mhealth Uhealth 2021 02 5;9(2):e25122. Epub 2021 Feb 5.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology of Ministry of Education, Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

Background: Diabetes is a major health concern worldwide. Family member engagement in diabetes self-management education programs can improve patients' diabetes management. However, there is limited evidence that the family portal on diabetes management apps is effective in the glycemic control of patients with diabetes.

Objective: We aimed to evaluate the effectiveness of family support through the family portal function on Lilly Connected Care Program (LCCP) platform.

Methods: This retrospective cohort study included patients with type 2 diabetes recruited to the LCCP platform from September 1, 2018, to August 31, 2019. Propensity score matching was used to match family (group A) and non-family (group B) portal use groups with similar baseline characteristics. The patients were followed up with for 12 weeks. The main objectives were differences in mean fasting blood glucose, proportion of patients achieving fasting blood glucose target <7mmol/L, mean postprandial blood glucose, proportion of patients achieving postprandial blood glucose target <10mmol/L, proportion of patients achieving both fasting blood glucose <7mmol/L and postprandial blood glucose <10mmol/L, self-monitoring of blood glucose frequency at week 12 and the number of diabetes education courses patients completed during the 12 weeks. Moreover, logistic regression analysis was used to explore the baseline factors which may be associated with the use of family portal, and odds ratios with 95% confidence intervals were calculated.

Results: A total of 6582 adult patients (aged ≥18 years) with type 2 diabetes who were receiving insulin therapy were enrolled in the study. Overall, 6.1% (402/6582) of the patients chose to engage their family members to use the family portal. Two groups of 394 patients were well-matched regarding baseline characteristics. After matching, mean fasting blood glucose and postprandial blood glucose at week 12 were significantly lower in group A than in group B (fasting blood glucose: 7.12 mmol/L, SD 1.70 vs 7.42 mmol/L, SD 1.88, respectively, P=.02; postprandial blood glucose: 8.56 mmol/L, SD 2.51 vs 9.10 mmol/L, SD 2.69, respectively, P=.002). When comparing group A to group B, the proportion of patients achieving both fasting blood glucose <7mmol and postprandial blood glucose <10mmol/L at week 12 (46.8% vs 39.4%, respectively, P=.04), self-monitoring of blood glucose frequency at week 12 (8.92 times per week, SD 6.77 vs 8.02 times per week, SD 5.97, respectively, P=.05) and number of diabetes education courses completed in 12 weeks (23.00, IQR9.00-38.00 vs 15.00, IQR 4.00-36.00, respectively, P<.001) was higher. Additionally, multivariate logistic regression analysis showed that higher age (OR=0.987, 95% CI 0.978-0.996, P=.006) and higher baseline fasting blood glucose (OR=0.914, 95% CI 0.859-0.972, P=.004) were correlated with less use of the family portal function, while increased baseline self-monitoring of blood glucose frequency (OR=1.022, 95% CI 1.012-1.032], P<.001) as well as increased education courses (OR=1.026, 95% CI 1.015-1.036, P<.001) were associated with more use of the family portal function.

Conclusions: Family support through the LCCP family portal is effective for glycemic control and self-management behavior improvement in type 2 diabetes patients.
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http://dx.doi.org/10.2196/25122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895638PMC
February 2021

Frequency, clinical features, inflammatory cytokines and genetic background of latent autoimmune diabetes in youth in youth-onset type 2 diabetes: Results from a nationwide, multicentre, clinic-based, cross-sectional study (LADA China).

Diabetes Obes Metab 2021 Jun 23;23(6):1282-1291. Epub 2021 Mar 23.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Aim: To investigate the frequency, clinical phenotype, inflammatory cytokine levels and genetics of glutamic acid decarboxylase autoantibody (GADA)-positive phenotypic youth-onset type 2 diabetes.

Materials And Methods: This nationwide, multicentre, cross-sectional study included 5324 newly diagnosed subjects with phenotypic type 2 diabetes aged 15 years or older enrolled in the LADA China study. GADA was screened in 248 subjects with youth-onset type 2 diabetes aged 15-29 years. Subjects who presented as GADA-positive were defined as having latent autoimmune diabetes in youth (LADY). We added subjects with LADY, type 1 diabetes, type 2 diabetes and controls from the Diabetes Center of Central South University, and measured serum concentrations of interleukin-6, lipocalin 2, high-sensitivity C-reactive protein, adiponectin and human leukocyte antigen (HLA) genotyping in subjects with LADY, age- and sex-matched GADA-negative type 2 diabetes, type 1 diabetes and controls.

Results: Twenty-nine of the 248 subjects (11.7%) were GADA positive. Compared with subjects with type 2 diabetes, subjects with LADY were less probable to have metabolic syndrome (27.6% vs. 59.4%; p = .001). The fasting C-peptide levels tended to be lower in subjects with LADY than in subjects with type 2 diabetes, but the difference was not statistically significant (LADY vs. type 2 diabetes: 0.21 [0.17-0.64] vs. 0.47 [0.29-0.77] nmol/L; p = .11). The cytokine levels of subjects with LADY were indistinguishable from subjects with type 1 diabetes, but subjects with LADY presented increased adiponectin levels compared with subjects with type 2 diabetes after adjusting for age, sex and body mass index (7.19 [4.05-11.66] vs. 3.42 [2.35-5.74] μg/mL; p < .05). The frequency of total susceptible HLA genotypes (DR3/3, -3/9 and -9/9) in subjects with LADY and type 1 diabetes were similarly higher than controls (LADY and type 1 diabetes vs. controls: 21.4% and 30.8% vs. 2.6%, respectively; p < .001).

Conclusions: A high GADA positivity was observed in youth-onset type 2 diabetes subjects in China. As subjects with LADY had an increased susceptible HLA genetic load and different cytokine levels compared with subjects with type 2 diabetes, differentiating LADY from phenotypic type 2 diabetes subjects is important.
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http://dx.doi.org/10.1111/dom.14336DOI Listing
June 2021

Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial.

J Clin Endocrinol Metab 2021 Mar;106(4):e1529-e1541

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, Hunan, China.

Context: The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear.

Objective: To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin.

Design And Setting: A randomized controlled trial at the Second Xiangya Hospital.

Methods: Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months.

Main Outcome Measures: Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals.

Results: During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P < .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P < .01 vs baseline), which were higher than in the CONT group.

Conclusion: Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.
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http://dx.doi.org/10.1210/clinem/dgab026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993585PMC
March 2021

Kdm2a deficiency in macrophages enhances thermogenesis to protect mice against HFD-induced obesity by enhancing H3K36me2 at the Pparg locus.

Cell Death Differ 2021 Jan 18. Epub 2021 Jan 18.

The Center for Biomedical Research, Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Respiratory Diseases, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Kdm2a catalyzes H3K36me2 demethylation to play an intriguing epigenetic regulatory role in cell proliferation, differentiation, and apoptosis. Herein we found that myeloid-specific knockout of Kdm2a (LysM-Cre-Kdm2a, Kdm2a) promoted macrophage M2 program by reprograming metabolic homeostasis through enhancing fatty acid uptake and lipolysis. Kdm2a increased H3K36me2 levels at the Pparg locus along with augmented chromatin accessibility and Stat6 recruitment, which rendered macrophages with preferential M2 polarization. Therefore, the Kdm2a mice were highly protected from high-fat diet (HFD)-induced obesity, insulin resistance, and hepatic steatosis, and featured by the reduced accumulation of adipose tissue macrophages and repressed chronic inflammation following HFD challenge. Particularly, Kdm2a macrophages provided a microenvironment in favor of thermogenesis. Upon HFD or cold challenge, the Kdm2a mice manifested higher capacity for inducing adipose browning and beiging to promote energy expenditure. Collectively, our findings demonstrate the importance of Kdm2a-mediated H3K36 demethylation in orchestrating macrophage polarization, providing novel insight that targeting Kdm2a in macrophages could be a viable therapeutic approach against obesity and insulin resistance.
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http://dx.doi.org/10.1038/s41418-020-00714-7DOI Listing
January 2021

DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production.

Nat Commun 2021 01 12;12(1):326. Epub 2021 Jan 12.

National Clinical Research Center for Metabolic Diseases, Metabolic Syndrome Research Center, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, 410011, Changsha, Hunan, China.

Adipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.
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http://dx.doi.org/10.1038/s41467-020-20665-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7804451PMC
January 2021

Toll-like receptor 7 deficiency suppresses type 1 diabetes development by modulating B-cell differentiation and function.

Cell Mol Immunol 2021 Feb 11;18(2):328-338. Epub 2021 Jan 11.

Section of Endocrinology, Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT, USA.

Innate immunity mediated by Toll-like receptors (TLRs), which can recognize pathogen molecular patterns, plays a critical role in type 1 diabetes development. TLR7 is a pattern recognition receptor that senses single-stranded RNAs from viruses and host tissue cells; however, its role in type 1 diabetes development remains unclear. In our study, we discovered that Tlr7-deficient (Tlr7) nonobese diabetic (NOD) mice, a model of human type 1 diabetes, exhibited a significantly delayed onset and reduced incidence of type 1 diabetes compared with Tlr7-sufficient (Tlr7) NOD mice. Mechanistic investigations showed that Tlr7 deficiency significantly altered B-cell differentiation and immunoglobulin production. Moreover, Tlr7 NOD B cells were found to suppress diabetogenic CD4 T-cell responses and protect immunodeficient NOD mice from developing diabetes induced by diabetogenic T cells. In addition, we found that Tlr7 deficiency suppressed the antigen-presenting functions of B cells and inhibited cytotoxic CD8 T-cell activation by downregulating the expression of both nonclassical and classical MHC class I (MHC-I) molecules on B cells. Our data suggest that TLR7 contributes to type 1 diabetes development by regulating B-cell functions and subsequent interactions with T cells. Therefore, therapeutically targeting TLR7 may prove beneficial for disease protection.
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http://dx.doi.org/10.1038/s41423-020-00590-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027372PMC
February 2021

Abnormal Neutrophil Transcriptional Signature May Predict Newly Diagnosed Latent Autoimmune Diabetes in Adults of South China.

Front Endocrinol (Lausanne) 2020 18;11:581902. Epub 2020 Dec 18.

National Clinical Research Center for Metabolic Diseases, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Objective: Latent autoimmune diabetes in adults (LADA) is an autoimmune diabetes characterized by slowly progressive of β-cell function deterioration. Our previous finding demonstrated that neutrophil numbers and migration abilities display distinct levels in different types of diabetes, including LADA, whereas its pathological alterations in the development of LADA remain unknown. We aimed to investigate the changes in transcriptional levels of peripheral neutrophils in newly diagnosed LADA.

Methods: Peripheral blood neutrophils were isolated from newly diagnosed LADA patients (n = 5) and age-and sex-matched healthy controls (n = 5). The Transcriptomic signature was determined by RNA sequencing (RNA-seq). Differentially expressed genes (DEG) were screened, followed by analyzing downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Real-time polymerase chain reaction (qPCR) was applied for validation in LADA patients (n = 9) and age-and sex-matched healthy controls (n = 18), including sequencing samples.

Results: Compared with controls, 4105 DEG were screened in LADA patients, including 2661 upregulated and 1444 downregulated DEG. In GO analysis, DEG are mainly involved in leukocyte degranulation, myeloid cell differentiation, and immune response-regulating signaling. The top enriched KEGG pathways included cytokine-cytokine receptor interaction, adhesion molecule signaling, nuclear factor-κB (NF-κB) signaling and Th17 cell differentiation. Consistent with RNA-seq results, , , , , , and are upregulated in neutrophils by qPCR.

Conclusion: The present study results provided a profile of DEG in the newly diagnosed LADA of south China. Our study reveals an abnormality in neutrophil disposition at the transcriptional level in LADA. Several essential genes may be involved in of LADA's pathological process, which may be useful to guide prediction for LADA and further investigation into the pathogenesis for this disease.
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http://dx.doi.org/10.3389/fendo.2020.581902DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775642PMC
December 2020

Emerging Roles of Exosomes in T1DM.

Front Immunol 2020 26;11:593348. Epub 2020 Nov 26.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha, China.

Type 1 diabetes mellitus (T1DM) is a complex autoimmune disorder that mainly affects children and adolescents. The elevated blood glucose level of patients with T1DM results from absolute insulin deficiency and leads to hyperglycemia and the development of life-threatening diabetic complications. Although great efforts have been made to elucidate the pathogenesis of this disease, the precise underlying mechanisms are still obscure. Emerging evidence indicates that small extracellular vesicles, namely, exosomes, take part in intercellular communication and regulate interorgan crosstalk. More importantly, many findings suggest that exosomes and their cargo are associated with the development of T1DM. Therefore, a deeper understanding of exosomes is beneficial for further elucidating the pathogenic process of T1DM. Exosomes are promising biomarkers for evaluating the risk of developingty T1DM, monitoring the disease state and predicting related complications because their number and composition can reflect the status of their parent cells. Additionally, since exosomes are natural carriers of functional proteins, RNA and DNA, they can be used as therapeutic tools to deliver these molecules and drugs. In this review, we briefly introduce the current understanding of exosomes. Next, we focus on the relationship between exosomes and T1DM from three perspectives, i.e., the pathogenic role of exosomes in T1DM, exosomes as novel biomarkers of T1DM and exosomes as therapeutic tools for T1DM.
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http://dx.doi.org/10.3389/fimmu.2020.593348DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725901PMC
November 2020

The association of HLA-DP loci with autoimmune diabetes in Chinese.

Diabetes Res Clin Pract 2021 Mar 8;173:108582. Epub 2020 Dec 8.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China. Electronic address:

Aims: To determine if HLA-DP loci independently contribute to classic type 1 diabetes (T1D) of all ages, childhood-onset T1D and latent autoimmune diabetes in adults (LADA) among Chinese Han population.

Methods: A total of 518 patients with classic T1D (Among them 180 participants manifested T1D between 1 and 14 years), 519 patients with LADA and 527 normal controls were genotyped for both HLA-DPA1 and -DPB1 loci. The frequencies of DP alleles and haplotypes in patients were directly compared to those in controls, followed by adjustment for linkage disequilibrium (LD) with DR-DQ haplotypes.

Results: In the direct comparison, DPA1*01:03, DPB1*04:01 and DPA1*01:03-DPB1*04:01 showed disease-predisposing effects in both the overall T1D group and the childhood-onset T1D group mainly due to their conjunction with the known susceptible DR3 haplotype. Conditioning on DR-DQ haplotypes, only DPA1*02:02-DPB1*02:02 significantly increased T1D risk among those diagnosed during childhood (OR = 2.02, 95% CI = 1.35-3.01). Whether or not adjusted for LD, no statistically significant HLA-DP association could be observed for LADA.

Conclusion: HLA-DP is implicated in the pathogenesis of childhood-onset T1D in Chinese, independent of the predominant DR-DQ loci and might serve as additional markers in genetic models for the recognition of those genetically at-risk individuals.
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http://dx.doi.org/10.1016/j.diabres.2020.108582DOI Listing
March 2021

Simple and rapid determination of dioxin in fish and sea food using a highly sensitive reporter cell line, CBG 2.8D.

J Environ Sci (China) 2021 Feb 18;100:353-359. Epub 2020 Aug 18.

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China; University of Chinese Academy of Sciences, Beijing 100085, China. Electronic address:

Food, especially animal origin food is the main source of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), and dioxin-like polychlorinated biphenyls (dl-PCBs) for human exposure. So, a simple, rapid and cheap bioassay method is needed for determination of dioxins in food samples. In this study, we used a new highly sensitive reporter cell line to determine the concentration of dioxins in 33 fish and seafood samples. The samples were extracted by shaking with water/isopropanol (1:1 v/v) and hexane and cleaned-up by a multi layered silica gel column and an alumina column, then analyzed using CBG 2.8D cell line. We compared the results obtained from the CBG 2.8D cell assay to those obtained from conventional High-Resolution Gas Chromatography-High Resolution Mass Spectrometry (HRGC-HRMS) analysis. Good correlations were observed between these two methods (r=0.93). While the slope of regression line was 1.76, the bioanalytical equivalent (BEQ) values were 1.76 folds higher than WHO-TEQ values and the conversion coefficient was 0.568 (the reciprocal of 1.76). In conclusion, CBG 2.8D cell assay was an applicable method to determine dioxins levels in fish and sea food samples.
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http://dx.doi.org/10.1016/j.jes.2020.07.006DOI Listing
February 2021

Cardiovascular disease in patients with type 1 diabetes: Early evaluation, risk factors and possible relation with cardiac autoimmunity.

Diabetes Metab Res Rev 2020 Nov 30. Epub 2020 Nov 30.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, Changsha, Hunan, China.

Cardiovascular disease now is the leading cause of mortality among patients with type 1 diabetes (T1D). The risk of death from cardiovascular events in subjects with T1D is 2-10 times higher than the general population, depending on blood glucose control. Although complications of cardiovascular disease occur in middle and old age, pathological processes begin in childhood. Some methods used to evaluate subclinical cardiovascular disease, such as carotid intima-media thickness and pulse wave velocity, can detect early cardiovascular abnormalities in adolescence. The effect of risk factors including hypertension, dyslipidemia and diabetic nephropathy on cardiovascular disease has been well studied. According to the current clinical practice recommendations from the American Diabetes Association, cardiovascular risk factors should be systematically assessed at least annually and treated as recommended. And yet, the effects of intensive insulin therapy on cardiovascular risk, as well as the mechanisms of cardiac autoimmunity require further studying. This review concentrates on the cardiovascular risk in type 1 diabetes in order to provide a comprehensive outlook of its epidemiology, early assessment, risk factors and possible relations with cardiac autoimmunity, aiming to propose promising therapeutic strategies.
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http://dx.doi.org/10.1002/dmrr.3423DOI Listing
November 2020

Reply to "Novaferon, treatment in COVID-19 patients".

Int J Infect Dis 2021 02 25;103:336-337. Epub 2020 Nov 25.

Department of Infectious Diseases, The Second Xiangya Hospital, Central South University, Changsha, China. Electronic address:

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http://dx.doi.org/10.1016/j.ijid.2020.11.179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7687364PMC
February 2021

Sodium-glucose cotransporter inhibitors as add-on therapy in addition to insulin for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials.

J Diabetes Investig 2021 Apr 19;12(4):546-556. Epub 2020 Sep 19.

Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

Aims/introduction: Several clinical trials reported the effects of sodium-glucose cotransporter (SGLT) inhibitors in type 1 diabetes patients. This meta-analysis aimed to assess the efficacy and safety of SGLT inhibitors in type 1 diabetes patients.

Materials And Methods: Relevant studies were identified in the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases through 1 April 2020. Differences were expressed as the 95% confidence interval (CI) or weighted mean difference (WMD) for continuous outcomes, and risk ratio (RR) for discontinuous outcomes.

Results: A total of 13 RCTs with 7,962 cases were included. SGLT inhibitors reduced the fasting plasma glucose level (WMD -1.320 mmol/L, 95% CI -1.609 to -1.031, P < 0.001), glycated hemoglobin level (WMD -0.386%, 95% CI -0.431 to -0.342, P < 0.001) and daily total insulin dose (WMD -5.403, 95% CI -7.218 to -3.859, P < 0.001). However, higher risks of diabetic ketoacidosis (RR 5.042, 95% CI 3.160-8.046, P < 0.001), urinary tract infections (RR 1.259, 95% CI 1.034-1.533,P = 0.022) and genital infections (RR 2.995, 95% CI 1.953-4.594, P < 0.001) were associated with SGLT inhibitors, but SGLT inhibitors did not increase the hypoglycemia risk (RR 0.980, 95% CI 0.840-1.144,P = 0.799). In subgroup analysis, with a significant reduction of fasting plasma glucose, glycated hemoglobin and daily insulin doses, SGLT1/2 inhibitor did not increase genitourinary tract infections compared with a placebo.

Conclusions: SGLT2 and SGLT1/2 inhibitors can improve glycemic control in patients with type 1 diabetes.
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http://dx.doi.org/10.1111/jdi.13387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8015835PMC
April 2021

An automated structured education intervention based on a smartphone app in Chinese patients with type 1 diabetes: a protocol for a single-blinded randomized controlled trial.

Trials 2020 Nov 23;21(1):944. Epub 2020 Nov 23.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology, Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.

Background: Although evidence had demonstrated the effectiveness of smartphone apps in diabetes care, the majority of apps had been developed for type 2 diabetes mellitus (T2DM) patients and targeted at populations outside of China. The effects of applying a smartphone app with structured education on glycemic control in type 1 diabetes mellitus (T1DM) are unclear. A digital, culturally tailored structured education program was developed in a smartphone app (Yi tang yun qiao) to provide an automated, individualized education program aimed at improving self-management skills in patients with T1DM in China. This trial aims to investigate the effectiveness of this smartphone app among Chinese T1DM patients.

Methods And Analysis: This single-blinded, 24-week, parallel-group randomized controlled trial of a smartphone app versus routine care will be conducted in Changsha, China. We plan to recruit 138 patients with T1DM who will be randomly allocated into the intervention group (automated, individualized education through an app) or routine care group. The intervention will last for 24 weeks. The primary outcome will be the change in glycated hemoglobin (HbA1c) from baseline to week 24. The secondary outcomes will include time in range, fasting blood glucose, levels of serum triglycerides and cholesterol, blood pressure, body mass index, quality of life, diabetes self-care activities, diabetes self-efficacy, depression, anxiety, and patient satisfaction. Adverse events will be formally documented. Data analysis will be conducted using the intention-to-treat principle with appropriate univariate and multivariate methods. Missing data will be imputed with a multiple imputation method under the "missing at random" assumption.

Discussion: This trial will investigate the effectiveness of an app-based automated structured education intervention for Chinese patients with T1DM. If the intervention is effective, this study will provide a strategy that satisfies the need for effective lifelong diabetes care to reduce the disease burden and related complications resulting from T1DM.

Trial Registration: ClinicalTrials.gov NCT04016987 . Registered on 29 October 2019.
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http://dx.doi.org/10.1186/s13063-020-04835-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681998PMC
November 2020

Utilizing Technology-Enabled Intervention to Improve Blood Glucose Self-Management Outcome in Type 2 Diabetic Patients Initiated on Insulin Therapy: A Retrospective Real-World Study.

Int J Endocrinol 2020 10;2020:7249782. Epub 2020 Nov 10.

National Clinical Research Center for Metabolic Diseases, Key Laboratory of Diabetes Immunology (Central South University), Ministry of Education, and Department of Metabolism and Endocrinology, The Second Xiangya Hospital of Central South University, Changsha 410011, Hunan, China.

Background: The aim of this study was to assess the benefits of a mobile-enabled app through Lilly Connected Care Program (LCCP) in achieving blood glucose control and adhering to self-monitoring of blood glucose in patients with type 2 diabetes mellitus (T2DM).

Methods: This retrospective study included T2DM patients who were initiated on insulin therapy (mostly premixed insulin) after failure to respond to oral antidiabetic drugs. Patients were provided with glucometers enabled with synchronous data transmission to healthcare providers and family members. The primary objective was to assess the benefits of LCCP based on changes in fasting blood glucose (FBG) and postprandial glucose (PPG) levels from baseline to 12 weeks. Paired -test was used to assess the change in blood glucose (BG) from baseline to week 12.

Results: In total, 14,085 T2DM patients were recruited. Compared with baseline, significant reductions in FBG and PPG were evident at week 12 (FBG: -0.39 mmol/L; PPG: -0.79 mmol/L; both < 0.001). Furthermore, at week 12, the proportion of patients attaining a target glucose level of FBG <7.0 mmol/L and PPG <10.0 mmol/L was 25.37% and 59.68%, respectively, with a statistically significant increase compared with that at baseline (6.74% and 45.59%, respectively, both < 0.001). The frequent monitoring of patients could gain a higher target achievement of FBG (28.1% vs 24.2%) and PPG (64.4% vs 55.1%) than the occasional monitoring patients. Additionally, the incidence of hypoglycemia gradually decreased and was significantly lower than the baseline level.

Conclusions: In T2DM patients with poor glycemic control, the application of mobile enabled intervention (LCCP) along with insulin significantly reduced the hypoglycemia while improving glycemic control during period of naïve initiating insulin therapy. Additionally, the high frequency of BG self-monitoring was associated with better glycemic control.
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http://dx.doi.org/10.1155/2020/7249782DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7671790PMC
November 2020

Response to Letter to the Editor from Knobler et al: "Validation of the Swedish Diabetes Regrouping Scheme in Adult-Onset Diabetes in China".

J Clin Endocrinol Metab 2021 Jan;106(2):e1068-e1069

Department of Metabolism & Endocrinology, The Second Xiangya Hospital, Central South University, Changsha, China.

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http://dx.doi.org/10.1210/clinem/dgaa828DOI Listing
January 2021

SUMOylation of Pdia3 exacerbates proinsulin misfolding and ER stress in pancreatic beta cells.

J Mol Med (Berl) 2020 12 7;98(12):1795-1807. Epub 2020 Nov 7.

The Center for Biomedical Research, Tongji Hospital Research Building, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, China.

SUMOylation has long been recognized to regulate multiple biological processes in pancreatic beta cells, but its impact on proinsulin disulfide maturation and endoplasmic reticulum (ER) stress remains elusive. Herein, we conducted comparative proteomic analyses of SUMOylated proteins in primary mouse/human islets following proinflammatory cytokine stimulation. Cytokine challenge rendered beta cells to undergo a SUMOylation turnover manifested by the changes of SUMOylation substrates and SUMOylation levels for multiple substrates. Our data support that SUMOylation may play a crucial role to regulate proinsulin misfolding and ER stress at least by targeting Protein Disulfide Isomerase a3 (Pdia3). SUMOylation regulates Pdia3 enzymatic activity, subcellular localization, and protein binding ability. Furthermore, SUMOylation of Pdia3 exacerbated proinsulin misfolding and ER stress, and repressed Stat3 activation. In contrast, disruption of Pdia3 SUMOylation markedly rescued the outcomes. Collectively, our study expands the understanding how SUMOylation regulates ER stress in beta cells, which shed light on developing potential strategies against beta cell dysfunction.
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http://dx.doi.org/10.1007/s00109-020-02006-6DOI Listing
December 2020