Ming-Xia Yuan

Evaluation for fasting and 2-hour glucose and HbA1c for diagnosing diabetes based on prevalence of retinopathy in a Chinese population.

Background The glycemic thresholds for diabetes diagnosis have long been at the forefront of discussion. However, no information about glycemic cutoff points has been made available for the Chinese population. The aim of the present study was to examine the association of fasting plasma glucose (FPG), 2-h plasma glucose (2-h PG) and HbA1c levels with diabetic retinopathy (DR) and determine the associated cutoff levels in a Chinese population. Methodology and Principal Findings In a cross-sectional population-based sample of 2551 Chinese (representing a population of 1,660,500 in a Beijing district) between 18–79 years of age, the three glycemic measures were measured in a 75 g oral glucose tolerance test, and DR was assessed by two 45° color digital retinal images. The prevalence of DR increased in the ninth decile of each variable, corresponding to an FPG of ≥7.2 mmol/l, a 2-h PG of ≥10.7 mmol/l, and HbA1c of ≥6.4%, according to the Joinpoint regression method. After excluding individuals receiving antihyperglycemic medication, the prevalence significantly increased at an FPG of ≥6.8 mmol/l, a 2-h PG of ≥12.0 mmol/l, and HbA1c of ≥6.7%. The area under the ROC curve for all three measures showed no significant differences for detecting DR. After excluding individuals receiving antihyperglycemic medication, the three measures also showed no significant differences. Conclusions and Significance A significant increase in retinopathy prevalence occurs among individuals with FPG ≥7.2 mmol/l, 2-h PG ≥10.5 mmol/and HbA1c ≥6.4%; and measuring FPG or HbA1c are equally reliable methods as measuring 2-h PG for the diagnosis of diabetes in the Chinese population.

Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis

The classical axis of renin-angiotensin system (RAS), angiotensin (Ang)-converting enzyme (ACE)/Ang II/AT1, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas) in hepatic steatosis is still unclear. Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2−/y) mice. Meanwhile, oxidative stress and inflammation were also aggravated in ACE2−/y mice. On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation-related genes were up-regulated. In vitro, Ang-(1–7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what’s more, Akt inhibitors reduced ACE2-mediated lipid metabolism. Furthermore, ACE2-mediated Akt activation could be attenuated by blockade of ATP/P2 receptor/Calmodulin (CaM) pathway. These results indicated that Ang-(1–7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. Our findings support the potential role of ACE2/Ang-(1–7)/Mas axis in prevention and treatment of hepatic lipid metabolism.

High prevalence of lower extremity peripheral artery disease in type 2 diabetes patients with proliferative diabetic retinopathy.

Little is known about the relationship between lower extremity peripheral arterial disease (PAD) and proliferative diabetic retinopathy (PDR) in type 2 diabetes (T2D). Here, we explored the relationship between sight-threatening PDR and PAD. We screened for diabetic retinopathy (DR) and PAD in hospitalized patients with T2D. Patients with a diabetic duration of more than 10 years, HbA1c ≥7.5%, eGFR ≥60mL/min/1.73m2 and with PDR or with no diabetic retinopathy (NDR) were eligible for this cross-sectional study. Severities of DR were graded by digital retinal photographs according to the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. We assessed PAD by measuring Ankle Brachial Index (ABI), Toe Brachial Index (TBI) and Doppler ultrasound. Statistical analyses were performed using SPSS 17.0 software. Of the 1544 patients, 169 patients with extreme eye (57 PDR and 112 NDR) phenotypes met the inclusion criteria. Patients with PDR had a significantly higher proportion of low ABI (≤0.99) and high ABI (≥1.3) than patients with NDR (28.1% and 15.8% vs. 14.3% and 6.2% respectively, P<0.05). PDR patients also had lower TBI than NDR patients (0.56±0.09 vs. 0.61±0.08, P<0.01). The proportion of patients with abnormal duplex ultrasound was higher in PDR than in NDR (21.1% vs. 9.8%, P<0.001). This showed that PDR associated with PAD could be defined in multiple ways: abnormal ABI (≤0.9) (OR = 3.61, 95% CI: 1.15–11.26), abnormal TBI (OR = 2.84, 95% CI: 1.19–6.64), abnormal duplex (OR = 3.28, 95% CI: 1.00–10.71), and critical limb ischemia (OR = 5.52, 95% CI: 2.14–14.26). Moreover, PDR was a stronger independent correlation factor for PAD than a diabetic duration of 10 years. In conclusion, PAD is more common in PDR than in NDR. It implies that PDR and PAD are mostly concomitant in T2D. We should focus on screening PAD in patients with PDR in clinical practice.

Low prevalence of diabetic retinopathy in a Chinese population.

As a typical microvascular complication and a leading cause of blindness in working-age individuals, diabetic retinopathy (DR) is a serious threat to the quality of life for millions worldwide. The prevalence of diabetic retinopathy is 22–37% in individuals with known diabetes (1,2) and 6–13% in individuals with newly diagnosed diabetes (3). However, current estimates of the prevalence and risk factors for DR are mostly derived from studies of Western populations. Population-based data on DR in Asians remain limited. It has been hypothesized that ethnic differences may result in varying susceptibilities to diabetic microvascular complications (4). For example, Greek ethnicity may confer some protection against DR (5). From July 2010 through March 2011, the 2010 Health Examination Survey in Beijing, a …

High Prevalence of Diabetic Retinopathy in Diabetic Patients Concomitant with Metabolic Syndrome

Objective To evaluate the relationship between metabolic syndrome (MetS) and the prevalence of diabetic retinopathy (DR). Research Design and Methods We conducted a case-controlled study, with data obtained from 2,551 Chinese participants between 18–79 years of age (representing a population of 1,660,500 in a district of Beijing). 74 cases of DR were found following data assessment by two 45° digital retinal images. Subjects without DR (NDR group) selected from the remaining 2,477 subjects were matched 1:1 to the DR group by HbA1c. MetS was defined by incorporating diagnostic criteria of the American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). Results There were no statistical differences between the DR group and NDR group in a number of biological or laboratory tests. However, the percentage of patients with DR increased vs. patients without DR with the number of MetS components from 1 to 5 (14.3% vs. 85.7%, 38.9% vs. 61.1%, 49.1% vs. 50.9%, 61.4% vs. 38.6% and 83.3% vs. 16.7%, respectively) (Pearson χ2 = 9.938, P = 0.037). The trend to develop DR with MetS was significantly higher than that without MetS (NMetS) (χ2 = 5.540, P = 0.019). MetS was an independent statistical indicator of the presence of DR after adjusting for age and sex [odds ratio (95% CI): 2.701(1.248–5.849), P = 0.012], which is still the case with an additional adjustment for WC, SBP, TC, HbA1c and duration of diabetes [odds ratio (95% CI): 2.948(1.134–7.664), P = 0.027]. Conclusion DR is one of the diabetic microvascular complications. Apart from poor glycemic control, the concomitance of other metabolic factors can also influence DR. MetS, defined as a cluster of metabolic risk factors, is a strong and independent indicator of DR, even to the same extent as glycemic control.

Angiotensin-converting enzyme 2 regulates mitochondrial function in pancreatic β-cells

Mitochondrial metabolism plays an essential role in the regulation of insulin release and glucose homeostasis. Evidence demonstrated that the angiotensin-converting enzyme 2 (ACE2) participates in the regulation of glucose metabolism, however, its role in mitochondrial metabolism remains unclear. The purpose of our study was to determine if ACE2 can regulate mitochondrial function in pancreatic β-cells. We found that ACE2 over-expression restored glucose-stimulated insulin secretion (GSIS) and mitochondrial membrane potential (MMP) in the presence of H2O2 in INS-1 cells. PCR array demonstrated that ACE2 over-expression up-regulated 67 mitochondria-related genes in INS-1 cells. In pancreatic islets, ACE2 ablation attenuated intracellular calcium influx with a decrease in GSIS. Ace2-/y mice islets exhibited impaired mitochondrial respiration and lower production of ATP, along with decreased expression of genes involved in mitochondrial oxidation. In islets from db/db mice, ACE2 over-expression increased intracellular calcium influx and restored impaired mitochondrial oxidation, potentially causing an increase in GSIS. These results shed light on the potential roles of ACE2 in mitochondrial metabolism, moreover, may improve our understanding of diabetes.

The effects of AER and eGFR on outcomes of CVD in patients with T2DM in an urban community over 8 years of multifactorial treatment: the Beijing Communities Diabetes Study 18

Objective It is well known that diabetic kidney disease is a risk factor for cardiovascular diseases (CVD) in patients with type 2 diabetes mellitus (T2DM). In this study, the effects of urine albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR) on CVD outcomes were analyzed in a population of T2DM. Methods The study was carried out using recorded information of a cohort study. A total of 1,914 patients with T2DM with no prevalent CVD were enrolled in an 8 years prospective study and received multifactorial intervention. The risk of CVD outcomes was assessed according to chronic kidney disease staging, which was categorized using AER (mg/d) and eGFR (mL/min/1.73 m2). The effects of AER and eGFR on risk of CVD onset were also analyzed. Results During the follow-up period (median 6.8 years), 71 CVD events occurred. At baseline, those with AER ≥300 mg/d and coexisting eGFR 60–89 mL/min/1.73 m2 or <60 mL/min/1.73 m2 showed increased risk for CVD outcomes when compared with “no chronic kidney disease” (AER <30 mg/d and eGFR ≥90 mL/min/1.73 m2). The increased CVD risk was observed in patients who progressed to AER ≥30 mg/d during the follow-up period, whereas patients who progressed to eGFR <90 mL/min/1.73 m2 alone showed no increased CVD risk. During the follow-up period, after multifactorial intervention, 8.7% patients with microalbuminuria and 1.8% patients with overt nephropathy reversed to normoalbuminuria or microalbuminuria. Conclusion AER is a more sensitive predictor than eGFR for CVD outcomes in T2DM patients. Overt nephropathy can be reversed after multifactorial intervention.

The effects of cardiovascular risk factor combined anti-platelet therapy and the risk of cerebrovascular events in patients with T2DM in an urban community over 96-months follow-up: The Beijing communities diabetes study 19

OBJECTIVE We investigated the prognostic significance of metabolic risk scores and aspirin with respect to cerebrovascular events. METHODS A total of 25 communities of diabetic patients were enrolled in Beijing Community Diabetes Study (BCDS) from 2008. 3413 patients with T2DM in BCDS have complete screening data, including blood glucose, blood pressure, lipid profiles and anti-platelet therapy, which were assigned metabolic score (MS) and add up to the total metabolic score (TMS). According to the total metabolic score (TMS), the patients were divided into four equal groups: Group 1 (24 < TMS < 40), Group 2 (40 < TMS < 47), Group 3 (47 < TMS < 55) and Group 4 (55 < TMS < 87). After 96 months, patients were followed-up to assess the long-term effects of the multifactorial interventions. RESULTS During 96-months follow-up, a total of 91 cerebrovascular events occurred, including acute cerebral infarction, acute cerebral hemorrhage and transient ischemic attack (TIA). The incidence of cerebrovascular events was higher in the Group 4 than in the Group 1. In Cox multivariate analyses, there are significant differences in incidences of cerebral infarction events among the four groups during the 96-months follow-up. Cox proportional hazards analysis revealed that, HbA1c (p ≤ 0.001), systolic pressure (p ≤ 0.001), aspirin free treatment (P = 0.0023) are independent predictor for cerebrovascular events in diabetic patients. CONCLUSIONS This study indicates that total metabolic score (TMS) influences the incidence of cerebrovascular events in diabetic patients. In addition to good control of blood glucose, blood pressure and lipid profiles, anti-platelet therapy is important for the prevention of cerebrovascular events in T2DM. TRIAL REGISTRATION ChiCTR-TRC-13003978, ChiCTR-OOC-15006090.

The Status of Maculopathy in Diabetes and Prediabetes Patients in a Population-Based Study Detected by Optical Coherence Tomography: The 2011 Health Examination Survey in Beijing

Objective The aim of the study was to investigate the prevalence and the risk factors of maculopathy detected by optical coherence tomography (OCT) in a Chinese population with diabetes or prediabetes. Methods. 8,155 people were randomly selected to participate in the 2011 annual Health Examination Survey in Beijing. A 75 g oral glucose tolerance test (OGTT) was tested in 3760 subjects with fasting plasma glucose (FPG) ≥ 5.6 mmol/L. Of 3,760 subjects, 583 were also randomly selected to take OCT. Results In this study population, 21 (3.95%) patients had maculopathy. Eight patients had diabetes macular edema (DME) and the prevalence was 6.72% in diabetes patients and 1.51% in all subjects. Eleven patients had age-related macular degeneration (AMD) and the prevalence was 3.36% in diabetes patients and 2.07% in all subjects. Logistic regression model confirmed that elevated HbA1c (p < 0.001) and systolic pressure (p < 0.05) made significant contributions to DME. Stepwise regression analysis revealed that HbA1c and blood creatinine were significantly independent influence factors for central subfield thickness (CST) (p = 0.01, p < 0.001). Conclusions High prevalence of maculopathy was found in patients with diabetes in a Chinese population. Maculopathy poses a significant public health problem in China with rapid rising trend of diabetes.

Prevalence and associated factors of diabetic retinopathy in Beijing, China: a cross-sectional study

Objectives The study aimed to determine the exact risk factors for diabetic retinopathy (DR) in the Chinese population using a cohort of 17  985 individuals from Beijing, China. Design Cross-sectional study. Setting A hospital. Participants 17  985 individuals from Beijing, China. Primary and secondary outcome measures This was a cross-sectional study of permanent residents from the Changping area (Beijing, China) recruited from July 2010 to March 2011 and from March 2014 to February 2015 during a routine health examination at the Tongren Hospital of Beijing. Eye examinations were conducted by experienced ophthalmologists. Medical history, height, weight, body mass index (BMI) and blood pressure were recorded. Routine laboratory examinations were performed. Results The prevalence of DR was 1.5% in the general study population and 8.1% among individuals with diabetes. Compared with the non-DR group, individuals in the DR group in the diabetes population had longer disease duration, higher systolic blood pressure (SBP), fasting plasma glucose (FPG) and uric acid (UA) (in men) and lower UA (in women) (all p<0.05). The multivariate analysis showed that disease duration (p<0.001), BMI (p=0.046), SBP (p=0.012), creatinine clearance rate (CCR) (p=0.014), UA (p=0.018) and FPG (p<0.001) were independently associated with DR in patients with diabetes. Conclusion The prevalence of DR was 8.1% among patients with diabetes. Disease duration, BMI, SBP, CCR, UA and FPG were independently associated with DR.