Chinese Type 2 Diabetes Research Articles

Visceral fat area is more strongly associated with arterial stiffness than abdominal subcutaneous fat area in Chinese patients with type 2 diabetes

BackgroundFew studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D.MethodsIn this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression.ResultsThe baPWV was linked with VFA, waist circumference, and women’s SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men’s SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05).ConclusionsCompared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

Comparison of multiple linear regression and machine learning methods in predicting cognitive function in older Chinese type 2 diabetes patients.

The prevalence of type 2 diabetes (T2D) has increased dramatically in recent decades, and there are increasing indications that dementia is related to T2D. Previous attempts to analyze such relationships principally relied on traditional multiple linear regression (MLR). However, recently developed machine learning methods (Mach-L) outperform MLR in capturing non-linear relationships. The present study applied four different Mach-L methods to analyze the relationships between risk factors and cognitive function in older T2D patients, seeking to compare the accuracy between MLR and Mach-L in predicting cognitive function and to rank the importance of risks factors for impaired cognitive function in T2D. We recruited older T2D between 60-95years old without other major comorbidities. Demographic factors and biochemistry data were used as independent variables and cognitive function assessment (CFA) was conducted using the Montreal Cognitive Assessment as an independent variable. In addition to traditional MLR, we applied random forest (RF), stochastic gradient boosting (SGB), Naïve Byer's classifier (NB) and eXtreme gradient boosting (XGBoost). Totally, the test cohort consisted of 197 T2D (98 men and 99 women). Results showed that all ML methods outperformed MLR, with symmetric mean absolute percentage errors for MLR, RF, SGB, NB and XGBoost respectively of 0.61, 0.599, 0.606, 0.599 and 0.2139. Education level, age, frailty score, fasting plasma glucose and body mass index were identified as key factors in descending order of importance. In conclusion, our study demonstrated that RF, SGB, NB and XGBoost are more accurate than MLR for predicting CFA score, and identify education level, age, frailty score, fasting plasma glucose, body fat and body mass index as important risk factors in an older Chinese T2D cohort.

Plasma thrombin-activatable fibrinolysis inhibitor and the 1040C/T polymorphism are risk factors for diabetic kidney disease in Chinese patients with type 2 diabetes.

Inflammatory and hemostatic disorders in diabetic microangiopathy (DMA) can be linked to thrombin-activatable fibrinolysis inhibitor (TAFI) and its own gene polymorphisms. Thus, the study aimed to investigate the associations of plasma TAFI and gene polymorphisms with DMA in Chinese patients with type 2 diabetes (T2D). Plasma TAFI of 223 patients with T2D was measured, and the genotypes and alleles of the 1040C/T, 438G/A, and 505G/A polymorphisms of the TAFI gene were analyzed. A ROC curve was constructed to evaluate the identifying power of TAFI between patients with T2D and DMA, and logistic regression analysis was used to observe the correlation of plasma TAFI and gene polymorphisms with the risk for DMA. Plasma TAFI was higher in patients with DMA than in patients with only T2D (p < 0.05). TAFI exhibited the largest area under ROC in identifying diabetic kidney disease (DKD) from only T2D (0.763, 95% CI [0.674-0.853], p < 0.01), and adjusted multivariate analysis showed a high odds ratio (OR: 15.72, 95% CI [4.573-53.987], p < 0.001) for DKD. Higher frequencies of the CT genotype and T allele of the 1040C/T polymorphism were found in DKD compared with only T2D (respectively p < 0.05), and the CT genotype exhibited a high OR (1.623, 95% CI [1.173-2.710], p < 0.05) for DKD. DKD patients with the CT genotype had higher plasma TAFI levels, while T2D and DKD patients with CC/TT genotypes had lower plasma TAFI levels. Plasma TAFI and the CT genotype and T allele of the 1040C/T polymorphism are independent risk factors for DKD in Chinese T2D patients.

Identification of a Common Variant for Coronary Heart Disease at PDE1A Contributes to Individualized Treatment Goals and Risk Stratification of Cardiovascular Complications in Chinese Patients With Type 2 Diabetes.

In this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. We performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases. We identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 × 10-8) and BP (β ± SE 0.130 ± 0.017; P = 4.1 × 10-14) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1 × 10-4). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 × 10-8 < P < 3.6 × 10-5), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 × 10-3). We discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated.

Elevated serum uric acid is not an independent risk factor for the occurrence of Type 2 diabetic kidney disease in Chinese populations

Previous studies suggested that increased serum uric acid (SUA) level is an independent risk factor for albuminuria in Type 2 diabetes (T2D) patients. However, the association between SUA and onset of Type 2 DKD (T2DKD) remained to be clarified. This was a cross-sectional clinical study in which 1210 Chinese T2D patients were enrolled. According to the urine albumin-to-creatinine ratio (UACR), the cohort was divided into normal-albuminuria (UACR < 30 mg/g), micro-albuminuria (UACR 30-300 mg/g) and macro-albuminuria (UACR > 300 mg/g). The micro- and macro-albuminuria groups were combined into albuminuria category. Results showed that T2D patients with macro-albuminuria have significantly higher SUA than the other 2 groups (P < .001). In the binary logistic regression model, the subjects with SUA higher than 420 μmol/L were associated with a 2-fold increase in the odds of albuminuria (odds ratio = 2.024, 95% confidence interval: 1.232-3.325, P = .005), as compared with those with SUA lower than 300 μmol/L. Moreover, the multinomial regression analysis revealed that the subjects with SUA higher than 420 μmol/L had about 3-fold increase in the odds of macro-albuminuria (odds ratio = 3.758, 95% confidence interval: 2.051-6.885, P < .001), as compared with those with SUA lower than 300 μmol/L. However, SUA was not significantly associated with the presence of micro-albuminuria. Although the SUAwas not independently risk factor for micro-albuminuria, it was closely correlated with the development of macro-albuminuria in Chinese T2DKD patients. Elevated SUA may be useful for predicting the occurrence of macro-albuminuria but not onset of micro-albuminuria at the early stage of T2DKD.

Risk prediction models for incident type 2 diabetes in Chinese people with intermediate hyperglycemia: a systematic literature review and external validation study

BackgroundPeople with intermediate hyperglycemia (IH), including impaired fasting glucose and/or impaired glucose tolerance, are at higher risk of developing type 2 diabetes (T2D) than those with normoglycemia. We aimed to evaluate the performance of published T2D risk prediction models in Chinese people with IH to inform them about the choice of primary diabetes prevention measures.MethodsA systematic literature search was conducted to identify Asian-derived T2D risk prediction models, which were eligible if they were built on a prospective cohort of Asian adults without diabetes at baseline and utilized routinely-available variables to predict future risk of T2D. These Asian-derived and five prespecified non-Asian derived T2D risk prediction models were divided into BASIC (clinical variables only) and EXTENDED (plus laboratory variables) versions, with validation performed on them in three prospective Chinese IH cohorts: ACE (n = 3241), Luzhou (n = 1333), and TCLSIH (n = 1702). Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer–Lemeshow test).ResultsForty-four Asian and five non-Asian studies comprising 21 BASIC and 46 EXTENDED T2D risk prediction models for validation were identified. The majority were at high (n = 43, 87.8%) or unclear (n = 3, 6.1%) risk of bias, while only three studies (6.1%) were scored at low risk of bias. BASIC models showed poor-to-moderate discrimination with C-statistics 0.52–0.60, 0.50–0.59, and 0.50–0.64 in the ACE, Luzhou, and TCLSIH cohorts respectively. EXTENDED models showed poor-to-acceptable discrimination with C-statistics 0.54–0.73, 0.52–0.67, and 0.59–0.78 respectively. Fifteen BASIC and 40 EXTENDED models showed poor calibration (P < 0.05), overpredicting or underestimating the observed diabetes risk. Most recalibrated models showed improved calibration but modestly-to-severely overestimated diabetes risk in the three cohorts. The NAVIGATOR model showed the best discrimination in the three cohorts but had poor calibration (P < 0.05).ConclusionsIn Chinese people with IH, previously published BASIC models to predict T2D did not exhibit good discrimination or calibration. Several EXTENDED models performed better, but a robust Chinese T2D risk prediction tool in people with IH remains a major unmet need.

Early-Life Exposure to the Chinese Famine of 1959-1961 and Type 2 Diabetes in Adulthood: A Systematic Review and Meta-Analysis.

Background: The fast-growing literature suggests that the Chinese famine of 1959–1961 drives current and future type 2 diabetes (T2D) epidemics in China. This conclusion may be premature, as many Chinese famine studies have major methodological problems. We examine these problems, demonstrate how they bias the study results, and formulate recommendations to improve the quality of future studies. Methods: We searched English and Chinese databases for studies that examined the relationship between prenatal exposure to the Chinese famine and adult T2D from inception to 8 February 2022. We extracted information on T2D cases and study populations of individuals born during the famine (famine births), before the famine (prefamine births), and after the famine (postfamine births). We used random-effects models to compare the odds of T2D in famine births to several control groups, including postfamine births, combined pre- and postfamine births, and prefamine births. We used meta-regressions to examine the impacts of age differences between comparison groups on famine effect estimates and the role of other characteristics, including participant sex, age, and T2D assessments; famine intensity; residence; and publication language. Potential sources of heterogeneity and study quality were also evaluated. Results: Twenty-three studies met our inclusion criteria. The sample sizes ranged from less than 300 to more than 360,000 participants. All studies defined the famine exposure based on the participants’ dates of birth, and 18 studies compared famine births and postfamine births to estimate famine effects on T2D. The famine and postfamine births had an age difference of three years or more in all studies. The estimates of the famine effect varied by the selection of controls. Using postfamine births as controls, the OR for T2D among famine births was 1.50 (95% CI 1.34–1.68); using combined pre- and postfamine births as controls, the OR was 1.12 (95% CI 1.02–1.24); using prefamine births as controls, the OR was 0.89 (95% CI 0.79–1.00). The meta-regressions further showed that the famine effect estimates increased by over 1.05 times with each one-year increase in ignored age differences between famine births and controls. Other newly identified methodological problems included the poorly assessed famine intensity, unsuitable study settings for famine research, and poor confounding adjustment. Interpretation: The current estimates of a positive relationship between prenatal exposure to the Chinese famine and adult T2D are mainly driven by uncontrolled age differences between famine births and postfamine births. Studies with more rigorous methods, including age-balanced controls and robust famine intensity measures, are needed to quantify to what extent the famine exposure is related to current T2D patterns in China.

IDF21-0179 Efficacy and Safety of Gla-100 vs premix insulin after SIT in Chinese T2D: BEYOND V sub-analysis by Screening HbA1c

Background: The randomized, open-label, parallel-group BEYOND V (NCT03359837) study demonstrated that compared with insulin aspart 70/30 (Asp 30), insulin glargine 100 U/ml (Gla-100) demonstrated similar glycemic control at a lower hypoglycemia risk in Chinese type 2 Diabetes (T2D) individuals who had undergone short-term intensive insulin treatment (SIT).

Genetic Risk Score for Plasma Uric Acid Levels Is Associated With Early Rapid Kidney Function Decline in Type 2 Diabetes.

Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.

Serum bile acid response to oral glucose is attenuated in patients with early type 2 diabetes and correlates with 2-hour plasma glucose in individuals without diabetes.

AimTo determine the serum bile acid (BA) response to 75‐g oral glucose in individuals without diabetes, and whether this is attenuated in patients with ‘early’ type 2 diabetes (T2D) and related to the glycaemic response at 2 hours in either group.MethodsForty newly diagnosed, treatment‐naïve Han Chinese T2D subjects and 40 age‐, gender‐, and body mass index‐matched controls without T2D ingested a 75‐g glucose drink after an overnight fast. Plasma glucose and serum concentrations of total and individual BAs, fibroblast growth factor‐19 (FGF‐19), total glucagon‐like peptide‐1 (GLP‐1), and insulin, were measured before and 2 hours after oral glucose.ResultsFasting total BA levels were higher in T2D than control subjects (P < .05). At 2 hours, the BA profile exhibited a shift from baseline in both groups, with increases in conjugated BAs and/or decreases in unconjugated BAs. There were increases in total BA and FGF‐19 levels in control (both P < .05), but not T2D, subjects. Plasma glucose concentrations at 2 hours related inversely to serum total BA levels in control subjects (r = −0.42, P = .006). Total GLP‐1 and the insulin/glucose ratio were increased at 2 hours in both groups, and the magnitude of the increase was greater in control subjects.ConclusionsThe serum BA response to a 75‐g oral glucose load is attenuated in patients with ‘early’ T2D, as is the secretion of FGF‐19 and GLP‐1, while in individuals without T2D it correlates with 2‐hour plasma glucose levels. These observations support a role for BAs in the regulation of postprandial glucose metabolism.

Acetyl-coenzyme A carboxylase beta gene polymorphism does not predict cardiovascular risk susceptibility in Chinese type 2 diabetic individuals.

Type 2 diabetes (T2D) is associated with significant cardiovascular (CV) morbidity and mortality. A single-nucleotide polymorphism (SNP) in the acetyl-coenzyme A carboxylase beta (ACACB) gene, rs2268388, reproducibly associates with diabetic nephropathy (DN). ACACB regulates fatty-acid oxidation. As such, we assessed whether ACACB SNP rs2268388 was associated with CV disease in Chinese individuals with T2D. Chinese individuals with T2D were genotyped for SNP rs2268388. Baseline demographics were recorded and clinical data regarding coronary, carotid, and peripheral arterial disease and congestive heart failure were retrieved from electronic patient records. Statistical analyses were performed to detect associations between the rs2268388 T risk allele with CV outcomes in the cohort. A total of 596 Chinese individuals with T2D were genotyped. Their mean age was 66.8 ± 10.9 years at the time of data extraction. Genotyping revealed 59.7%, 33.2% and 7.1% of the study population were non-carriers, heterozygous and homozygous carriers of the rs2268388 T risk allele in ACACB. No statistically significant correlations of the risk allele were observed with CV outcomes. These results did not demonstrate association between rs2268388 SNP in ACACB with CV outcomes in Chinese T2D patients. The ACACB gene and its role in CV risk susceptibility, via alterations in fatty acid oxidation, remains an interesting postulate and studies with larger cohort sizes and in different ethnic groups remain warranted.

Cardiovascular risk profile and clinical characteristics of diabetic patients: a cross-sectional study in China.

Background:Cardiovascular (CV) disease is the leading cause of morbidity and mortality in adults with type 2 diabetes (T2D). The aim of this study was to determine the CV risk in Chinese patients with T2D based on the 2019 European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD) guidelines on diabetes, pre-diabetes, and CV diseases.Methods:A total of 25,411 patients with T2D, who participated in the study of China Cardiometabolic Registries 3B study, were included in our analysis. We assessed the proportions of patients in each CV risk category according to 2019 ESC/EASD guidelines.Results:Based on the 2019 ESC/EASD guidelines, 16,663 (65.6%), 1895 (7.5%), and 152 (0.6%) of patients were included in “very high risk,” “high risk,” and “moderate risk” categories, respectively. The proportions of patients in each category varied based on age, sex, body mass index, and duration. While 58.7% (9786/16,663) of elderly patients were classified to “very high risk” group, 89.6% (3732/4165) of patients with obesity were divided into “very high risk” group. Almost all patients with a duration of diabetes >10 years had “very high risk” or “high risk.” However, 6701 (26.4%) of Chinese T2D patients, who had shorter duration, and one or two risk factors, could not be included in any category (the “unclear risk” category).Conclusions:In China, most patients with T2D have “very high” or “high” CV risk based on 2019 ESC/EASD guidelines. However, the risk of patients in “unclear risk” group needs to be further classified.

721-P: Efficacy and Safety of Basal-First Titration Order in Patients with Type 2 Diabetes (T2D) Receiving Short-Term Intensive Insulin Therapy (SIT)

To titrate basal and bolus insulin sequentially or simultaneously during SIT remains controversial. Here we report an easy titration order verified in a 7-10 day SIT period. Insulin naive Chinese T2D adults receiving stable doses of metformin and 1-2 oral antihyperglycemic drugs with HbA1c 7.5%-11.0% were treated with once-daily insulin glargine 100 U/mL (Gla-100) and thrice-daily insulin glulisine (Glu) for 7-10 days titrated to achieve a fasting blood glucose (FBG) In conclusion, when starting basal-bolus regimen in SIT, basal-first titration order was effective, fast to target and well tolerated in Chinese T2D patients. Disclosure L. Guo: Consultant; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., BD, Eli Lilly and Company, Merck & Co., Inc., Merck Sharp & Dohme Corp., Novartis AG, Novo Nordisk, Sanofi China. J. Liu: Employee; Self; Sanofi China. X. Zhang: None. N. Cui: Employee; Self; Sanofi China. H. Yin: None. Y. Mu: Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim Pharmaceuticals, Inc., Lilly Diabetes, Novo Nordisk Inc., Sanofi-Aventis. H. Wan: None. J. Wang: None. B. Xu: None. G. Wang: None. C. Jiang: None. L. Liang: None. W. Feng: Employee; Self; Sanofi China. Funding Sanofi China (NCT03359837)

A Two-Stage Study Identifies Two Novel Polymorphisms in PRKAG2 Affecting Metformin Response in Chinese Type 2 Diabetes Patients.

ObjectiveIndividual differences in glycemic response to metformin in antidiabetic treatment exist widely. Although some associated genetic variations have been discovered, they still cannot accurately predict metformin response. In the current study, we set out to investigate novel genetic variants affecting metformin response in Chinese type 2 diabetes (T2D) patients.MethodsA two-stage study enrolled 500 T2D patients who received metformin, glibenclamide or a combination of both were recruited from 2009 to 2012 in China. Change of HbA1c, adjusted by clinical covariates, was used to evaluate glycemic response to metformin. Selected single nucleotide polymorphisms (SNPs) were genotyped using the Infinium iSelect and/or Illumina GoldenGate genotyping platform. A linear regression model was used to evaluate the association between SNPs and response.ResultsA total of 3739 SNPs were screened in Stage 1, of which 50 were associated with drug response. Except for one genetic variant preferred to affect glibenclamide, the remaining SNPs were subsequently verified in Stage 2, and two SNPs were successfully validated. These were PRKAG2 rs2727528 (discovery group: β=−0.212, P=0.046; validation group: β=−0.269, P=0.028) and PRKAG2 rs1105842 (discovery group: β=0.205, P=0.048; validation group: β=0.273, P=0.025). C allele carriers of rs2727528 and C allele carriers of rs1105842 would have a larger difference of HbA1c level when using metformin.ConclusionTwo variants rs2727528 and rs1105842 in PRKAG2, encoding γ2 subunit of AMP-activated protein kinase (AMPK), were found to be associated with metformin response in Chinese T2D patients. These findings may provide some novel information for personalized pharmacotherapy of metformin in China.

1071-P: Long-Term Renin-Angiotensin System Inhibitor Use and Risk of Pneumonia and Pneumonia-Related Death in Type 2 Diabetes

Introduction: Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) are renin angiotensin system inhibitors (RASi) which can reduce the proinflammatory-vasoconstricting activity of ACE/angiotensin II and enhance the anti-inflammatory-vasodilatory activity of ACE2/angiotensin 1-7. These drugs may be protective across a range of respiratory infections including bacterial and viral pneumonias. We examined long-term use of ACEi/ARBs on the risk of first pneumonia hospitalization and pneumonia-related death in Chinese patients with type 2 diabetes (T2D). Methods: Prospective analysis of 16,285 Chinese T2D patients with new RASi use observed between 2001 and 2019. Overlap weighting was performed to balance baseline characteristics. We used time-dependent Cox model to estimate the hazard ratio (HR) of outcomes while adjusting for the time-varying covariates. Results: There were 6,379 (39.2%) ACEi-users only, 4,065 (25.0%) ARBs-users and 5,841 (35.9%) non RASi-users. During a median observation of 7.6 years, 6.1% had first pneumonia hospitalization, 1.3% died during or within one month of pneumonia hospitalization and 17.6% died from other causes. No association was observed between RASi use and first pneumonia hospitalization. However, RASi-users had lower risk for pneumonia-related death (HR 0.51, 95% CI 0.35-0.76) than non-users [ACEi-users only: HR 0.53 (0.34-0.81); ARBs-users: HR 0.58 (0.32-1.04)]. We also noted reduced risk for all-cause death in RASi-users (HR 0.60, 95% CI 0.54-0.67) [ACEi-users only: HR 0.61 (0.54-0.69); ARBs-users: HR 0.67 (0.57-0.79)]. Conclusions: Long-term use of RASi was associated with reduced risk of pneumonia-related death and all-cause death, but not first pneumonia hospitalization, in Chinese patients with T2D. Relevance to other respiratory infections such as coronavirus-disease 2019 (COVID-19) merits further investigation. Disclosure M. Shi: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. Yang: None. E. S. H. Lau: None. H. Wu: None. B. Fan: None. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. A. Luk: None. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA.

Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naïve Chinese Type 2 Diabetes Patients.

IntroductionTo compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM).MethodsThis was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (n = 23) versus NPH (n = 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4–6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24.ResultsHbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c < 7% without confirmed hypoglycemia. There were no differences in anytime glucose SD at week 24 (LS mean difference − 0.08 mmol/l, 95% CI [− 0.42–0.26], p = 0.63). Anytime %TIRs (3.9–10.0 mmol/l) at week 24 were similar (p = 0.91). Nocturnal % time below range < 3.9 mmol/l was significantly lower in the Gla-300 group (least squares (LS) mean difference – 5.03% [− 9.92 to − 0.14], p = 0.04) with lower % coefficient of variation (LS mean difference − 4.5% [− 8.1 to − 0.8], p = 0.018). Diurnal TIR was higher in Gla-300 patients at week 11 but there were no differences at week 24.ConclusionsOnce-daily bedtime Gla-300 was associated with lower nocturnal GV, time below range and self-reported hypoglycemia in insulin-naïve Chinese T2D patients over a 24-week study period, as compared with NPH insulin.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT03389490.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01046-6.

Validation of the Simplified Chinese Version of the Brief Diabetes Quality of Life (DQoL) Questionnaire Based on a Cross-Sectional Study.

(1) Objective: To assess the reliability and validity of the simplified Chinese version of the brief Diabetes Quality of Life (DQoL) questionnaire in measuring health-related quality of life (HRQoL) in Chinese type 2 diabetes (T2D) patients. (2) Methods: A cross-sectional validation study including 277 patients was conducted at a tertiary hospital in Shanghai, China during April–May, 2018. The English brief DQoL was forward and back-translated into simplified Chinese. The expert interview, exploratory factor analysis (EFA), and Spearman correlation with the 5-level version of EuroQoL-5 (EQ-5D-5L) were employed to establish its validity. The internal reliability was assessed by Cronbach’s alpha. Participants were also stratified into subgroups to evaluate if the Chinese brief DQoL had more test effectiveness in a specific subpopulation. (3) Results: No items were removed from the original English brief DQoL based on the results of factor analysis and expert interview. The Spearman coefficient revealed a low-moderate inverse correlation between DQoL and EQ-5D-5L index and visual analogue scale (VAS), respectively (ρ1 = −0.364, p < 0.0001; ρ2 = −0.514, p < 0.0001). The Cronbach’s alpha coefficient of the final scale was 0.731. (4) Conclusions: The simplified Chinese version of the brief DQoL questionnaire showed reasonable reliability and validity, suggesting its potential appropriateness for evaluating quality of life in Chinese T2D patients. More future efforts should be made to generalize the application of the findings.

Serum Adiponectin Levels Are Positively Associated With Diabetic Peripheral Neuropathy in Chinese Patients With Type 2 Diabetes.

ObjectiveTo investigate the association between serum adiponectin levels and diabetic peripheral neuropathy (DPN) in Chinese type 2 diabetes (T2D) patients.Design and MethodsTwo hundred nineteen T2D patients aged 40–79 years were divided into two groups according to whether they had DPN. The systemic levels of five biomarkers were measured using a human adipokine multiplexed bead-based immunoassay. Diabetic peripheral neuropathy diagnostic criteria included both common DPN symptoms and neurological screening tests.ResultsMost features of DPN (n=98) and non-DPN patients (n=121) are similar, but the DPN patients were slightly older, had longer diabetes duration, higher hemoglobin (Hb) A1c, lower estimated glomerular filtration rates (eGFR), less exercise, and used lipid-lowering drugs more often. Serum adiponectin levels of DPN patients were higher than that of non-DPN patients (8.13 vs. 9.63 mg/ml, P = 0.004). Serum adiponectin levels were positively associated with DPN after adjusting for age, gender, body mass index, hypertension, HbA1c, alcohol intake, smoking status, physical activity, log-transformed low density lipoprotein cholesterol, lipid-lowering drug usage, eGFR, and diabetes duration {odds ratio (OR) 1.72 [95% confidence interval (CI) 1.02-2.89], P = 0.041}. The OR refers to a doubling in biomarkers.ConclusionsSerum adiponectin levels were higher in DPN patients compared to non‑DPN patients in this Chinese T2D population. Serum adiponectin levels were positively associated with DPN presence, independent of multiple confounders.

Health utility of type 2 diabetes patients using basal insulin in China: results from the BEYOND II study.

To derive the health utility scores of type 2 diabetes (T2D) patients using basal insulin (BI) with diverse characteristics in China. The study used the data of insulin-using T2D patients on BI treatment enrolled in the BEYOND II study, which is a multi-center, observational study from 78 hospitals nationwide. The 3-level EQ-5D (EQ-5D-3L) questionnaire was administered to each patient to derive their health utility scores using the EQ-5D-3L value set for China. Patients' clinical and sociodemographic information were retrieved from their electronic case report form (eCRF). Ordinary least-square models with different specifications were explored to identify the best-fitting model to predict the utility scores. The sample (n = 12,583) achieved a mean (standard deviation) EQ-5D-3L utility score of 0.936 (0.120). According to the model, a Chinese male who was younger than 59years, not underweight, diagnosed with T2D shorter than 10years, with controlled plasma glucose and free of diabetes complications/comorbidities, would have a mean utility of 0.993. Being female, older age, underweight, and higher plasma glucose, longer diabetes duration was negatively related to EQ-5D-3L scores. Comorbidities and seven of eleven complications were associated with utility decrement. Interactions between some complications were also discovered. The derived health utility scores for diabetes complications could facilitate the assessment of the cost-effectiveness of health interventions for Chinese insulin-using T2D patients.

Soluble Tumor Necrosis Factor Receptor Type 1 Levels Exhibit A Stronger Association With Renal Outcomes Than Traditional Risk Factors in Chinese Subjects With Type 2 Diabetes Mellitus

Objective: Associations between albuminuria and renal outcomes are inconsistent in patients with type 2 diabetes (T2D). Soluble tumor necrosis factor receptor type 1 (sTNFR1) is involved in declined kidney function and poor renal outcomes but this has not been confirmed among Chinese T2D patients. This study aimed to examine the association of sTNFR1 and renal outcomes in a cohort of these patients.Methods: Two hundred and eighty-three Chinese T2D patients were enrolled in a prospective observational study which excluded individuals with estimated glomerular filtration rates (eGFR) <30 mL/min/1.73m2. Composite renal outcomes included either or both a >30% decline in eGFR and worsening albuminuria from consecutive tests of blood/urine during a 3.5-year follow-up.Results: Higher sTNFR1 levels were associated with impaired renal outcomes. sTNFR1 levels of ≥979 pg/mL yielded the most sensitivity and specific predictions of renal outcomes according to the receiver operating curve (area under the curve 0.68, P<.001; sensitivity 78.3%, specificity 48.9%). Renal events occurred more frequently in subjects with sTNFR1 ≥979 pg/mL than in others (sTNFR1 <979 pg/mL; 29% versus 10%; P<.001 by log-rank test). The association between sTNFR1 ≥979 pg/mL and renal outcomes remained significant after adjustment for relevant covariates (adjusted hazard ratio 2.43, 95% confidence interval 1.18 to 5.02; P = .01) and consistent across subgroups stratified by age, sex, blood pressure, eGFR, albuminuria, and the use of renin-angiotensin system inhibitors.Conclusion: Increased sTNFR1 levels were associated with renal outcomes in Chinese T2D subjects, making sTNFR1 a potential biomarker in diabetic kidney disease.