Effectiveness of the Lilly Connected Care Program in Improving Glycemic Management Among Patients With Type 2 Diabetes in China: Retrospective Real-world Study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a worldwide public health concern. Mobile health management platforms could be a potential way to achieve effective glycemic control. OBJECTIVE: This study aimed to evaluate the real-world effectiveness of the Lilly Connected Care Program (LCCP) platform in glycemic control among patients with T2DM in China. METHODS: This retrospective study included Chinese patients with T2DM (aged ≥18 years) from April 1, 2017, to January 31, 2020, for the LCCP group and from January 1, 2015, to January 31, 2020, for the non-LCCP group. Propensity score matching was used to match the LCCP and non-LCCP groups to reduce confounding, with covariates including age, sex, the duration of diabetes, baseline hemoglobin A1c (HbA1c), and the number of oral antidiabetic medication classes. HbA1c reduction over 4 months, the proportions of patients achieving an HbA1c reduction of ≥0.5% or ≥1%, and the proportions of patients reaching to target HbA1c level of ≤6.5% or <7% were compared between the LCCP and non-LCCP groups. Multivariate linear regression was used to assess factors associated with HbA1c reduction. RESULTS: A total of 923 patients were included, among whom 303 pairs of patients were well matched after propensity score matching. HbA1c reduction during the 4-month follow-up was significantly larger in the LCCP group than the non-LCCP group (mean 2.21%, SD 2.37% vs mean 1.65%, SD 2.29%; P=.003). The LCCP group had a higher proportion of patients with an HbA1c reduction of ≥1% (209/303, 69% vs 174/303, 57.4%; P=.003) and ≥0.5% (229/303, 75.6% vs 206/303, 68%; P=.04). The proportions of patients reaching the target HbA1c level of ≤6.5% were significantly different between the LCCP and non-LCCP groups (88/303, 29% vs 61/303, 20.1%; P=.01), whereas the difference in the proportions of patients reaching the target HbA1c level of <7% was not statistically significant (LCCP vs non-LCCP: 128/303, 42.2% vs 109/303, 36%; P=.11). LCCP participation and higher baseline HbA1c were associated with a larger HbA1c reduction, whereas older age, longer diabetes duration, and higher baseline dose of premixed insulin analogue were associated with a smaller HbA1c reduction. CONCLUSIONS: The LCCP mobile platform was effective in glycemic control among patients with T2DM in China in the real world.

Efficacy and safety of janagliflozin as add-on therapy to metformin in Chinese patients with type 2 diabetes inadequately controlled with metformin alone: A multicentre, randomized, double-blind, placebo-controlled, phase 3 trial.

AIM: To evaluate the efficacy and safety of janagliflozin in Chinese patients with type 2 diabetes (T2D) inadequately controlled with metformin monotherapy. MATERIALS AND METHODS: This multicentre phase 3 trial included a 24-week, randomized, double-blind, placebo-controlled period, followed by a 28-week extension period. Patients (N = 421) with HbA1c of 7.0% or higher and 10.5% or less were randomized (1:1:1) to receive once-daily placebo, janagliflozin 25 or 50 mg. After the 24-week treatment period, patients on placebo were re-randomized (1:1) to janagliflozin 25 or 50 mg for the additional 28-week treatment, whereas patients on janagliflozin maintained the same therapy. The primary endpoint was the change from baseline in HbA1c to week 24. RESULTS: At week 24, the placebo-adjusted least squares mean changes of HbA1c were -0.58% and -0.58% with janagliflozin 25 and 50 mg, respectively (P < .0001 for both). The proportion of patients achieving HbA1c less than 7.0% was higher with janagliflozin 25 and 50 mg compared with placebo (41.8%, 41.7% and 28.0%, respectively). Both janagliflozin doses provided significant reductions in fasting plasma glucose, 2-hour postprandial glucose, body weight and systolic blood pressure, and improvements in high-density lipoprotein cholesterol and insulin sensitivity compared with placebo (P < .05 for all). The trends in improvement of these variables were retained during the 28-week extension period. No severe hypoglycaemia occurred throughout the whole 52-week treatment. CONCLUSIONS: Janagliflozin 25 or 50 mg once-daily added to metformin therapy significantly improved glycaemic control, reduced body weight and systolic blood pressure, improved high-density lipoprotein cholesterol and insulin sensitivity, and was generally well-tolerated by Chinese T2D patients who had poor glycaemic control with metformin monotherapy.

Fatty Acid Profiles and Their Association With Autoimmunity, Insulin Sensitivity and ß Cell Function in Latent Autoimmune Diabetes in Adults.

Background: The pathogenesis of the progressive loss of beta cell function latent autoimmune diabetes in adults (LADA) remains still elusive. We aim to study the fatty acid (FA) profile in LADA. Subjects and methods: Data from 116 patients with diabetes and GADA and 249 diabetes controls without GADA selected by Propensity Score Matching were collected. FA was analyzed with liquid chromatography-tandem mass spectrometry analysis. Results: Principal factor analysis found component 1 explains 82.6% of total variance contained fatty acids from a mixed of lard oil, seafood, and vegetable diet, followed by diet predominantly from vegetable oil, a diet of high fat diet, and a diet of seafood diet. The FA heatmap looked clearly different among the three groups with more similar type 1 (t1dm) and LADA fatty acid profile. n-3 α-linolenic acid (ALA), n-3 long chain polyunsaturated fatty acid (n-3 LC-PUFA), such as Eicosapentaenoic Acid and Docosapentaenoic Acid, n-3/n-6 ratio and triene/tetraene ratio were higher in patients with type 2 diabetes (t2dm) compared with LADA and t1dm. Saturated FAs were lower in t2dm than t1dm and LADA. Arachidic acid and n-6 LC-PUFAs were lower in t2dm than in t1dm and LADA. The characteristics of FAs in LADA were in between of classical t1dm and t2dm. Patients were classified into 6 clusters by FA clusters. Only cluster 2, 3, 5 contained enough patients to be analyzed. Cluster 5 showed an insulin deficient phenotype containing more than 60% of patients with t1dm and LADA and only 12.8% of t2dm. Cluster 2 and 3 were similar. ß cell function and glycemic control was better in cluster 3 homing 25% of t2dm. Cluster 2 held 28% of t1dm and LADA, in this cluster more than 60% of patients was t2dm. n-3 linolenic acid, n-3 LC-PUFAs, some n-6 LC-PUFAs, n-3/n-6 ratio and triene/tetraene ratio were negatively associated with GADA positivity while n-6 Arachidonic Acid was associated positively with GADA. Similar findings were found for insulin sensitivity and beta cell function. Conclusion: PUFA are associated with insulin sensitivity and beta cell function, and like other clinical features, FA profile distributed differently, but could not be used as makers to differentiate LADA from t1dm and t2dm. Ethics and Dissemination: This study has been approved by the Ethical Review Committee of Second Hospital of Dalian Medical University (approval number: 2021-005). Clinical Trial Registration: none.

Dorzagliatin in drug-naïve patients with type 2 diabetes: a randomized, double-blind, placebo-controlled phase 3 trial.

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.

Generation of an induced pluripotent stem cell (iPSC) line from a diabetic patient with glucagon receptor (GCGR) p.W83X mutation.

Induced pluripotent stem cell (iPSC) line, SJHi001-A, was generated from a diabetic patient carrying a heterozygous c.G248A mutation in GCGR gene that generated the p.W83X. The PBMCs from her father (no diabetes and no mutation site) were also prepared into iPSC (SJHi002-A) as a control. Both two cell lines had normal karyotype, expressed pluripotency markers and could differentiate into the three germ layers in vivo.

Artificial intelligence-enabled screening for diabetic retinopathy: a real-world, multicenter and prospective study.

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.

Evaluation of effectiveness of treatment paradigm for newly diagnosed type 2 diabetes patients in Chin: A nationwide prospective cohort study.

AIMS/INTRODUCTION: Data of nationwide glycemic control and hypoglycemic treatment patterns in newly diagnosed type 2 diabetes patients in China are absent. The aim of this study was to assess the evolution of treatment patterns for newly diagnosed type 2 diabetes patients and the clinical outcomes during 12-month follow up. MATERIALS AND METHODS: This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes for <6 months were enrolled. Glycated hemoglobin A1c (HbA1c) levels and hypoglycemic treatment patterns were collected at baseline and at every 3 months of follow up. RESULTS: A total of 79 hospitals were recruited, consisting of 5,770 participants. The mean HbA1c was 8.4 ± 2.5% at baseline, and decreased to 6.7 ± 1.2% at 12 months with 68.5% of patients achieving HbA1c <7%. At baseline, 44.6% of the patients were without hypoglycemic medications, 37.7% had oral hypoglycemic agents and 17.7% received insulin treatment. Determinants of change in HbA1c were treatment patterns, comorbidities, baseline characteristics such as obesity and smoking, regions, and tiers of hospitals. Associated factors with treatment alterations were time of follow up, treatment patterns, patient-reported reasons such as the economic factors and poor efficacy. CONCLUSIONS: In newly diagnosed type 2 diabetes patients, compared with patients without medications, patients with one oral hypoglycemic agent had higher possibilities of reaching glycemic control, whereas patients using insulin had lower possibilities of reaching the target. Factors associated with change in HbA1c and treatment alterations were also revealed.

The risk factors of glycemic control, blood pressure control, lipid control in Chinese patients with newly diagnosed type 2 diabetes _ A nationwide prospective cohort study.

Nationwide data on glycemic control, blood pressure (BP) control and lipid control in patients with newly diagnosed type 2 diabetes were vacant in China. The aim of this study was to assess the clinical outcomes for these patients. This is an observational prospective cohort study with 12 months of follow up. Patients with a diagnosis of type 2 diabetes less than 6 months were enrolled. Hemoglobin A1c (HbA1c) levels, BP levels and lipid levels were collected at baseline and the follow-ups. This study was registered at www.clinicaltrials.gov (NCT01525693). A total of 5770 participants from 79 hospitals across six geographic regions of China were recruited. After 12 months of treatment, 68.5% of these patients achieved HbA1c <7.0%; 83.7% reached BP <140/90 mmHg; 48.2% met low density lipoprotein cholesterol (LDL-c) <2.6 mmol/L; and 29.5% of patients reached the combined three therapeutic targets. Compared to those patients with baseline HbA1c <7.0%, patients with baseline HbA1c ≥7.0% had higher failure rate to reach glycemic control (relative risk (RR) = 2.04, p < 0.001), BP control (RR = 1.21, p < 0.001) and LDL-c control (RR = 1.11, p < 0.001). Obese patients had higher possibilities of failure in glucose control (RR = 1.05, p = 0.004), BP control (RR = 1.62, p < 0.001) and lipid control (RR = 1.09, p = 0.001) than patients with normal weight. The active smokers were more likely to fail in glycemic control than non-smokers (RR = 1.06, p = 0.002), and patients with physical activities were less likely to fail in lipid control than patients without exercises (RR = 0.93, p = 0.008). This study outlined the burdens of glycemic control, blood pressure control, lipid control in newly diagnosed type 2 diabetic patients in China, identified gaps in the quality of care and risk-factor control and revealed the factors influencing these gaps.

Recent Advances in the Development of Vaccines for Diabetes, Hypertension, and Atherosclerosis.

Vaccines are commonly used in the prevention of infectious diseases. The basic principle of vaccination is to use specific antigens, endogenous or exogenous to stimulate immunity against the specific antigens or cells producing them. Autoantigen or oligo vaccination has been used for disease animal models. More recently humanized monoclonal antibodies have been successfully used for the treatment of neoplastic disorders or familial hypercholesterolemia. Humanized monoclonal antibody therapy needs repeated injection, and the therapy is expensive. Therapeutic vaccination can lead to persistent immunized or immune tolerant against the therapeutic molecule(s) or site. However, immunization against those endogenous substances may also elicit persistent autoimmune reaction or destruction that do harm to health. Therefore, rigorous studies are needed before any clinical application. In this review, we briefly reviewed vaccines used in protection against common metabolic diseases including atherosclerosis, hypertension, and diabetes mellitus.

Pioglitazone Use and Risk of Bladder Cancer: an In Vitro Study.

Aims: Whether pioglitazone (PIO), a peroxisome proliferator-activated receptor-gamma agonist, increases the risk of developing bladder cancer has been debated for several years. The aim of this study was to investigate the in vitro effects of PIO on normal urothelial transitional epithelium (NUTE) cells and bladder cancer (J82) cells to further evaluate the risk. Methods: NUTE cells were obtained from Sprague-Dawley rats. NUTE and J82 cells were treated with different concentrations of PIO for various time periods. Cell proliferation was tested by the MTT assay. Cell apoptosis was evaluated by flow cytometry. The expressions of p53, cyclin D1, Bcl-2, and Bax were determined by qRT-PCR and western blots. Results: After 24 hours, the treatment of NUTE cells with 10 µmol/L PIO led to morphological changes, without changes in J82 cells. Moreover, PIO inhibited the proliferation and induced apoptosis of NUTE cells, but not J82 cells, in a time- and dose-dependent manner. However, PIO did not alter the growth of cells from other tissues. In addition, treatment with PIO for up to 72 hours did not result in changes in the expressions of p53, cyclin D1, Bcl-2, and Bax in NUTE cells and J82 cells. Interestingly, PIO significantly downregulated the protein levels of p53 and cyclin D1 in J82 cells, but not NUTE cells after more than 192 hours of treatment. Conclusions: PIO did not promote malignant alterations of NUTE cells or stimulate proliferation of J82 cells. PIO decreased the expression of p53 and cyclin D1 in J82 cells after long-term culture, which suggested that PIO may be helpful for diabetic patients with bladder cancer.

Gender Disparities in Lipid Goal Attainment among Type 2 Diabetes Outpatients with Coronary Heart Disease: Results from the CCMR-3B Study.

Our study was aimed to investigate the gender disparities in lipid goal attainment among type 2 diabetes outpatients with concomitant coronary heart disease (CHD) and explore potential risk factors. We performed the present analysis using data from a nationally representative epidemiologic study. The therapeutic goal was defined as achieving a low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L. A total of 1721 male and 2072 female type 2 diabetes outpatients with established CHD were identified. Compared with men, women had higher levels of total cholesterol (4.98 vs. 4.46 mmol/L; p < 0.001), LDL-C (2.82 vs. 2.54 mmol/L; p < 0.001), and triglycerides (2.02 vs. 1.79 mmol/L; p < 0.001), but not hemoglobin A1c (7.47% vs. 7.50%; p = 0.597). The proportion of women received lipid-lowering therapy was lower (38.1% vs. 48.2%; p < 0.001). The percentages of patients who achieved the LDL-C goal were higher among men. Multivariable regression analysis indicated that the odds ratio for lipid goal attainment due to the gender difference was 0.61 after adjusting confounders. The inability to achieve LDL-C goals in women with type 2 diabetes and CHD is apparently greater than that in men. This finding underscores the importance of initiatives to establish a more aggressive lipid management strategy for women to overcome gender imbalances.

Evaluation of Epicardial Adipose Tissue in Patients of Type 2 Diabetes Mellitus by Echocardiography and its Correlation with Intimal Medial Thickness of Carotid Artery.

The present study aimed to evaluate the diagnostic value of echocardiography in measuring the thickness of epicardial adipose tissue (EAT) of the patients of type 2 diabetes mellitus (T2DM) and its correlation with the intimal-medial thickness of the carotid artery (cIMT) to investigate the relationship between EAT and cIMT. 68 patients of T2DM were enrolled and were divided into 2 groups: group of T2DM with duration≤10 years (35 cases) and group of T2DM with duration>10 years (33 cases). And 30 healthy subjects were enrolled as the control group. The thickness of EAT and cIMT were measured by echocardiography and high-frequency ultrasonography. The thickness of EAT and IMT of the carotid artery of 2 type 2 diabetic groups (duration≤10 years and>10 years) were significantly higher than that of the control group (all p<0.05), and the thickness of EAT and cIMT of the group of T2DM with duration>10 years were significantly higher than that of the group of T2DM with duration≤10 years (p<0.05). In univariate analysis, the thickness of EAT was positively and significantly associated with age (r=0.412, p<0.05), BMI (r=0.566, p<0.05), waist circumference (r=0.475, p<0.05), LDL (r=0.425, p<0.05), TG (r=0.496, p<0.05), duration of diabetes (r=0.384, p<0.05) and cIMT (r=0.456, p<0.05). In multiple stepwise regression analyses, age, BMI and IMT of carotid artery were appeared to be significantly associated with EAT (p<0.05 for all). In conclusion, routine screening of EAT and cIMT by ultrasonography in type 2 diabetic patients helps us to predict cardiovascular risks and prevent further development of cardiovascular complications.

Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide, Cross-Sectional 3B Study.

BACKGROUND: There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. METHODS: Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24-27.9 kg/m2 and ≥28.0 kg/m2. Central obesity was defined as a waist circumference ≥80 cm in women and ≥85 cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90 mmHg and LDL-C<2.6 mmol/L. RESULTS: Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and 10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. CONCLUSIONS: Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients.

Positive hepatitis B surface antibody is associated with reduced risk of diabetes mellitus in retired female Chinese workers.

BACKGROUND: To study the relationship between positivity for hepatitis B surface antibody (HBsAb) and the risk of diabetes mellitus in the retired Chinese population. METHODS: A cross-sectional analysis was conducted in 900 retired Chinese workers attending a health check-up program. HBsAb, hepatitis B surface antigen, oral glucose tolerance test (OGTT), fasting plasma glucose (FBG), 2-h plasma glucose 2hBG, and insulin levels were collected. RESULTS: Participants positive for HBsAb were younger, with lower blood pressure, lower FBG and 2hBG serum uric acid, and glutamic pyruvic transaminase than those who were HbsAb negative. There were 306 subjects with impaired glucose tolerance and 121 with type 2 diabetes (T2D) in the present cohort. Using Chi-squared analysis to assess the risk of diabetes, women positive for HBsAb had a lower prevalence of T2D than those negative for HBsAb (15.7% vs 26.5%, respectively; P < 0.01). Multivariate analysis revealed family history of diabetes, age, and waist circumference were independently associated with a higher prevalence of diabetes, and that HBsAb positivity was independently associated with a lower prevalence of diabetes (odds ratio 0.579; 95% confidence interval 0.388-0.918) when adjusted for sex, family history of hypertension and dyslipidemia, and body mass index. CONCLUSIONS: An HBsAb-positive status is associated with a low rate of diabetes and better metabolic status. A prospective study of patients with known vaccination records is needed to investigate whether hepatitis B virus vaccination could protect against the development of diabetes.

Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study.

BACKGROUND: The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China. METHODS: We did a cross-sectional survey using data from the China National HbA1c Surveillance System (CNHSS), including 222,773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis. FINDINGS: Of 222,773 patients recruited from April 1, 2012, to June 30, 2012, 24,316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11·1% vs 4·9%; p<0·0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1·91, 95% CI 1·81-2·02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1·13, 1·06-1·20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes. INTERPRETATION: Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes. FUNDING: Novo Nordisk China (for the China National HbA1c Surveillance System [CNHSS]) and Merck Sharp & Dohme China (for the 3B study).

Plasma metabolomic profiling of patients with diabetes-associated cognitive decline.

Diabetes related cognitive dysfunction (DACD), one of the chronic complications of diabetes, seriously affect the quality of life in patients and increase family burden. Although the initial stage of DACD can lead to metabolic alterations or potential pathological changes, DACD is difficult to diagnose accurately. Moreover, the details of the molecular mechanism of DACD remain somewhat elusive. To understand the pathophysiological changes that underpin the development and progression of DACD, we carried out a global analysis of metabolic alterations in response to DACD. The metabolic alterations associated with DACD were first investigated in humans, using plasma metabonomics based on high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis. The related pathway of each metabolite of interest was searched in database online. The network diagrams were established KEGGSOAP software package. Receiver operating characteristic (ROC) analysis was used to evaluate diagnostic accuracy of metabolites. This is the first report of reliable biomarkers of DACD, which were identified using an integrated strategy. The identified biomarkers give new insights into the pathophysiological changes and molecular mechanisms of DACD. The disorders of sphingolipids metabolism, bile acids metabolism, and uric acid metabolism pathway were found in T2DM and DACD. On the other hand, differentially expressed plasma metabolites offer unique metabolic signatures for T2DM and DACD patients. These are potential biomarkers for disease monitoring and personalized medication complementary to the existing clinical modalities.

Prevalence of microvascular diseases among tertiary care Chinese with early versus late onset of type 2 diabetes.

AIMS: This study aimed to investigate the impact of early-onset diabetes on the risk of microvascular diseases in Chinese with type 2 diabetes mellitus (T2DM). METHODS: A cross sectional survey of 29,442 patients with T2DM in 77 tertiary hospitals in China was conducted in 2011. Early-onset diabetes was defined as diagnosis of diabetes before 40years of age. Microvascular complications and risk factors were documented. Prevalence of microvascular disease was standardized to the Chinese population in 2010. Logistic regression analysis was performed to obtain odds ratios (OR) for early versus late onset of T2DM. RESULTS: A total of 1,303 (4.4%) patients had nephropathy, 2,137 (7.3%) had retinopathy and 3,012 (10.2%) had either of them. Early-onset diabetes greatly increased the prevalence of microvascular diseases compared with late-onset diabetes (nephropathy: 5.1% vs. 1.5%; retinopathy: 7.1% vs. 2.7%; either: 9.7% vs. 3.6%), especially among patients from 45 to 59years of age. After adjusting for age and sex, patients with early-onset T2DM were at 1.69-fold (95% CI 1.46-1.95) higher risk of microvascular diseases than those with late-onset T2DM. However, this was not significant after adjusting for traditional risk factors and disease duration (p=0.162). CONCLUSION: Chinese patients with early-onset T2DM are at a marked increased risk of microvascular diseases.

Acarbose treatment affects the serum levels of inflammatory cytokines and the gut content of bifidobacteria in Chinese patients with type 2 diabetes mellitus.

BACKGROUND: The effects of acarbose add-on therapy on gut microbiota and inflammatory cytokines were investigated in Chinese patients with type 2 diabetes mellitus (DM). METHODS: Ninety-five DM patients were randomly allocated to two groups: 59 to Group A who received antidiabetic treatment that included acarbose 150 mg/day, and 36 to Group B who received similar treatment to Group A but without acarbose. Forty-five healthy volunteers were selected as a control group. Serum concentrations of inflammatory cytokines were determined by ELISA, and the contents of 16S rDNA of gut bacteria were determined by real-time quantitative polymerase chain reaction. General linear analysis for repeated measurements was used to analyze trend differences between the two diabetic groups. RESULTS: After 4 weeks of antidiabetic treatment, the gut contents of Bifidobacterium longum and Enterococcus faecalis were significantly increased in both diabetes groups. The increase of Bifidobacterium longum (P = 0.004) and the decrease of lipopolysaccharides (LPS) (P < 0.001) and prothrombin activator inhibitor-1 (P = 0.003) were more significant in Group A. Decreases of monocyte chemoattractant protein-1 and LPS were more significant in patients whose HbA1c decrease was ≥1%, but there were no significant differences in the changes of other cytokines and gut bacteria between patients with HbA1c <7% and ≥7%. Pearson correlation analysis showed that changes of Enterococcus faecalis were negatively correlated with LPS, while multiple linear regression analysis showed a positive correlation of Bifidobacterium longum with acarbose treatment and the high-density lipoprotein cholesterol concentration. CONCLUSIONS: Acarbose treatment can increase the content of gut Bifidobacterium longum in type 2 diabetes mellitus patients and decrease some inflammatory cytokines independently of its antihyperglycemic effects.

Weight-neutral effect of once-daily insulin detemir in Chinese type 2 diabetes patients: subgroup analysis of the SOLVE study.

BACKGROUND: The present subanalysis of the Study of Once Daily Levemir (SOLVE) study was to evaluate the safety and efficacy of once-daily insulin detemir as add-on to oral antidiabetic drugs (OADs) in Chinese type 2 diabetes patients according to body mass index in a real-life setting. METHODS: In all, 3272 eligible patients who were treated with diet, exercise, and one or more OAD were prescribed once-daily insulin detemir by their physician according to routine clinical practice and were followed-up for 24 weeks. The incidence of serious adverse reactions (SADRs), including major hypoglycemia, was the primary endpoint. Subanalyses were performed on patients in the following BMI groups: normal weight (BMI < 25 kg/m2); overweight (25 ≤ BMI < 30 kg/m2); and obese (BMI ≥ 30 kg/m2). RESULTS: No SADRs were reported during the study. Significant improvements in glycemic levels were observed in all subgroups. For normal weight, overweight, and obese patients, the mean change in HbA1c (%/[mmol/mol]) was -1.26/-14, -1.09/-12, and -1.06/-12, respectively. The mean change in fasting plasma glucose in normal weight, overweight, and obese patients was -2.77, -2.57, and -2.71 mmol/L, respectively. Slight weight gain (0.25 kg), slight weight loss (-0.36 kg), and weight loss (-1.32 kg) were observed in the normal weight, overweight, and obese patients, respectively (P < 0.001). Linear regression analysis revealed a negative relationship between weight change and baseline BMI (slope = -0.16; P < 0.001). CONCLUSIONS: Once-daily insulin detemir as add-on to OADs in Chinese patients with type 2 diabetes showed effective glycemic control and a low risk of hypoglycemia. Weight-neutral effects were observed in different BMI subgroups.

[Lower grade chronic inflammation is associated with obstructive sleep apnea syndrome in type 2 diabetes mellitus].

OBJECTIVE: To investigate whether the existence of obstructive sleep apnea syndrome (OSAS) in patients with type 2 diabetes (T2DM) is associated with low grade chronic inflammation. METHODS: Fifty-four patients hospitalized for poor glycemic control from 12/2008 to 12/2009 were divided into 2 groups, OSAS group (T2DM with OSAS, 27 cases) and NOSAS group (T2DM without OSAS, 27 cases). The control group consisted of 26 people from a health check-up program without diabetes and OSAS. Biochemical indexes were analyzed in central laboratory of the hospital. Serum tumor necrosis factor-α(TNF-α), lipopolysaccharides (LPS), monocyte chemoattractant protein-1 (MCP), and plasminogen activator inhibitor-1 (PAI) levels were determined with commercial ELISA kits. Apnea hypopnea index (AHI), the lowest pulse oxygen saturation (LSpO2) at night were measured with a portable home sleep monitor. RESULTS: Homeostasis model assessment insulin resistance index (HOMA-IR), AHI in OSAS group were higher than those in NOSAS group and control group [for HOMA-IR, 2.7 ± 1.5 vs 1.7 ± 0.9 vs 1.2 ± 0.7, and for AHI, (17.0 ± 13.0) vs (3.4 ± 1.3) vs (3.2 ± 1.2) per hour], and LSpO2 was lower than that in NOSAS group and control group [(78 ± 11)% vs (87 ± 4)% vs (89 ± 6)%]. Compared with normal control, levels of TNF-α [(0.73 ± 0.19) vs (1.97 ± 0.13) vs (1.09 ± 0.29) ng/ml], LPS [(50 ± 11) vs (303 ± 70) vs (171 ± 49) pg/ml], MCP [(302 ± 41) vs (514 ± 122) vs (473 ± 134) pg/ml] and PAI [(0.89 ± 0.25) vs (2.27 ± 0.85) vs (1.59 ± 0.13) ng/ml] in patients with OSAS and with NOSAS group increased significantly. Pearson univariate correlation analysis revealed that TNF-α and PAI were both positively associated with HOMA-IR, FBG and AHI, and negatively with LSpO2, LPS, MCP were both associated positively with FBG and AHI, and negatively with LSpO2. Multiple linear regression stepwise analysis found that TNF-α and LPS were independently associated with AHI and FBG, MCP with LSpO2, PAI with both AHI and HOMA-IR. CONCLUSIONS: Patients with diabetes and OSAS show raised level of chronic inflammatory activity.