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Diabetes poses severe global public health problems and places heavy burdens on the medical and economic systems of society. Type 2 diabetes (T2D) accounts for 90% of these cases. Diabetes also often accompanies serious complications that threaten multiple organs such as the brain, eyes, kidneys, and the cardiovascular system. MicroRNAs (miRNAs) carried by extracellular vesicles (EV-miRNAs) are considered to mediate cross-organ and cross-cellular communication and have a vital role in the pathophysiology of T2D. They also offer promising sources of diabetes-related biomarkers and serve as effective therapeutic targets. Here, we briefly reviewed studies of EV-miRNAs in T2D and related complications. Specially, we innovatively explore the targeting nature of miRNA action due to the target specificity of vesicle binding, aiding mechanism understanding as well as the detection and treatment of diseases.

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BACKGROUND: The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with UACR in the Chinese community population. METHODS: This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR. RESULTS: Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01-1.34) and triglyceride (OR: 1.18, 95% CI: 1.04-1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02-1.50), WC (OR: 1.21, 95% CI 1.00-1.48), and triglycerides (OR: 1.18, 95% CI 0.97-1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG) <7.0 or 7.8 ≤ post-load blood glucose (PBG) <11.1 mmol/L, FBG ≥7.0 or PBG ≥11.1, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. CONCLUSIONS: In the Chinese general population, CVAI and UACR were significantly associated in both genders. At higher CVAI levels, the population with prediabetes, diabetes, and hypertension has a more significant association between CVAI and UACR.

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BACKGROUND: Patients with normoalbuminuria and a reduced estimated glomerular filtration rate (eGFR) account for a considerable proportion of type 2 diabetes patients. The aim of this research was to investigate the epidemiological and clinical characteristics of normoalbuminuric kidney disease in a Chinese population. METHODS: We included 8131 diabetic patients from a multicenter prospective study in China. Based on eGFR and urinary albumin-to-creatinine ratio (UACR), participants were stratified into four groups-normal albuminuria, albuminuria, normoalbuminuria with eGFR < 60 mL/min/1.73 m2 , and albuminuria with eGFR < 60 mL/min/1.73 m2 . Clinical parameters and characteristics of patients with normoalbuminuria and eGFR < 60 mL/min/1.73 m2 were retrospectively analyzed. RESULTS: A total of 1060 out of 8131 individuals with diabetes had decreased eGFR (<60 mL/min/1.73 m2 ). Normoalbuminuria accounted for 63.3% of participants with eGFR < 60 mL/min/1.73 m2 , and microalbuminuria and macroalbuminuria accounted for 30.1% and 6.3%, respectively. Patients with normoalbuminuria and reduced eGFR were more frequently male, older, and had higher levels of triglycerides than patients with normal albuminuria and eGFR. We also detected a correlation between lower extremity arterial disease, newly diagnosed diabetes, and normoalbuminuria-reduced eGFR. Compared with participants with both albuminuria and eGFR decline, those with normoalbuminuria had better metabolic indicators, including systolic blood pressure and glycosylated hemoglobin, and shorter diabetes duration. Even in the normal range, UACR has a significant correlation with the risk of eGFR insufficiency. CONCLUSIONS: Normoalbuminuric renal insufficiency, characterized by male sex, older age, a higher level of triglyceride levels, and a higher risk of lower extremity arterial disease, accounted for a dominant proportion of diabetic patients with eGFR decline.

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BACKGROUND: Fluid imbalance is associated with various clinical conditions, but the association between elevated extracellular-water to total-body-water (ECW/TBW) ratio, an indicator of fluid balance, and cognitive impairment is unknown. We aimed to investigate relationship between ECW/TBW ratio and cognitive function in type 2 diabetes mellitus. METHODS: This study was a cross-sectional design, comparing 1233 patients aged 61.4 ± 8.0 years from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) cohort. ECW/TBW was measured using bioelectrical impedance method. Cognitive function was assessed with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine association between ECW/TBW and RBANS scores, adjusting for demographics, education, clinical covariates, and apolipoprotein E allele. RESULTS: In unadjusted analyses, there was an inverse dose-dependent association between ECW/TBW and RBANS total score. The associations persisted in fully adjusted model with ß = -1.18 (95% confidence interval [CI] -2.19 to -0.17; P = 0.022) for slight edema and -2.33 (-3.99 to -0.67; P = 0.006) for edema. Slight edema and edema were significantly associated with reduced cognitive function in delayed memory and attention. There was significant association between edema but not slight edema, with reduced cognitive function in language. Pulse pressure accounted for 16.8% of association between ECW/TBW and RBANS total score. CONCLUSIONS: Our novel finding of an independent association between higher ECW/TBW and poorer cognitive function highlights the potential importance of maintaining body fluid balance in the management of cognitive impairment.

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BACKGROUND: Patients with type 1 diabetes (T1D) are at risk for other autoimmune diseases (ie, polyautoimmunity). The prevalence and risk factors of this phenomenon have been underreported in adults and ethnic minorities, and data are lacking regarding non-endocrine autoimmune diseases. METHODS: Study population data were gathered from HealthFacts, a deidentified patient database compiled from electronic medical records systems in the US. Patients with an International Classification of Diseases diagnosis code specifying T1D were included in the study, whereas those with a diagnosis of type 2 diabetes were excluded. RESULTS: The cross-sectional study cohort comprised 158 865 adults with T1D (mean [±SD] age 51.4 ± 18.9 years, 52.5% female). The most common autoimmune diseases were thyroid disease (20.1%), systemic rheumatic diseases (3.4%), rheumatoid arthritis specifically (2.0%), and gastrointestinal autoimmune diseases (1.4%). Most of the autoimmune diseases were more common in women (eg hypothyroidism, hyperthyroidism, celiac disease, rheumatoid arthritis, lupus, and Sjögren syndrome). Caucasians were more likely than other ethnicities to have an additional autoimmune disease. The prevalence of autoimmune diseases increased with increasing age, significantly in women, such that 38.5% of women over 80 years of age had an additional autoimmune disease, compared with 17.9% of women aged ≤29 years. CONCLUSIONS: Additional autoimmunity represents a significant comorbidity in patients with T1D. Autoimmune diseases are more common in Caucasians and in women, and increase with age. Clinicians treating patients with T1D should be aware of the risk factors for additional autoimmune diseases.

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BACKGROUND: Studies on racial differences in diabetic complications are very limited. The aim of this study was to investigate the race and sex differences in diabetic complications between African Americans and Whites with type 2 diabetes (T2D) in Louisiana. METHODS: A prospective cohort study was performed of 27 113 African Americans and 40 431 Whites with T2D who were 35 to 95 years of age from three healthcare systems located in south Louisiana. Four major diabetic complications were assessed: coronary heart disease (CHD), heart failure, stroke, and end-stage renal disease (ESRD). RESULTS: The age- and sex-adjusted incident rates per 1000 person-years and 95% confidence intervals (CI) for CHD, heart failure, stroke, and ESRD for African Americans with diabetes were 43.1 (95% CI 41.6-44.6), 36.6 (95% CI 35.2-37.9), 29.6 (95% CI 28.4-30.8), and 38.3 (95% CI 36.9-39.7), respectively. Cox regression models showed that African American women had a higher risk than White women for heart failure (hazard ratio (HR) 1.26; 95% CI 1.18-1.34), stroke (HR 1.15; 95% CI 1.08-1.22), and ESRD (HR 1.32; 95% CI 1.24-1.40), whereas African American men had higher risks than White men for heart failure (HR 1.33; 95% CI 1.25-1.43) and ESRD (HR 1.47; 95% CI 1.37-1.57) but a lower risk of CHD (HR 0.88; 95% CI 0.83-0.94). CONCLUSIONS: The incidence of major diabetic complications varied among difference race and sex groups. More race- or sex-specific studies on complications in patients with diabetes are needed to see whether incident rates are changing over time.

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BACKGROUND: The aim of the present study was to investigate hospitalization costs, diabetes complications, and their relationships using a large dataset in Beijing, China. METHODS: Data for 2006-10 from the 38 top-ranked (Grade 3 A) hospitals in Beijing, obtained from electronic Hospitalization Summary Reports (HSRs), were analyzed for hospitalization costs and diabetic complications. Patient demographics, types of costs, and length of hospital stay (LOS) were also evaluated. RESULTS: During the period evaluated, 62 523 patients with diabetes were hospitalized, of which 41 875 (67.0 %) had diabetes-associated complications. The median cost of hospitalization for diabetic patients was 7996.11 RMB. Prescribed drugs and laboratory tests were two major contributors to hospitalization costs, accounting for 36.2 % and 22.4 %, respectively. Hospitalization costs were significantly associated with LOS, number of complications, age, year of admission, admission status, sex, and medical insurance (P < 0.001). Both hospitalization costs and LOS increased substantially with an increase in the number of complications (P < 0.001). The highest hospitalization costs were seen in those diabetic patients with foot complications. CONCLUSION: Diabetic complications have a significant effect on increases in hospitalization costs and LOS in patients with type 2 diabetes mellitus.

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BACKGROUND: Insulin resistance (IR) is present in type 1 diabetes mellitus (T1DM) and is suggested to be related to chronic diabetic complications. The primary aim of our study was to assess IR in T1DM patients with and without chronic complications. A secondary aim was to evaluate the possible association between IR and chronic diabetic complications. METHODS: This cross-sectional study enrolled 272 patients with T1DM. Insulin resistance was quantified using the estimated glucose disposal rate (eGDR). Associations between eGDR and each diabetes complication were first evaluated using binary logistic regression, then multiparametric logistic regression with stepwise selection of covariates. The discriminative value of eGDR was assessed by receiver operating characteristic (ROC) curve analysis. RESULTS: Estimated GDR was lower in patients with chronic diabetic complications (6.1 vs. 6.9 mg/kg per min [P = 0.02] for retinopathy; 6.3 vs. 7.3 mg/kg per min [P < 0.01] for nephropathy; 6.5 vs. 7.6 mg/kg per min [P < 0.01] for neuropathy; and 5.2 vs. 7.5 mg/kg per min [P < 0.01] for cardiovascular complications). In univariate analysis eGDR was associated all diabetic complications. These associations remained significant after adjustment for different variables in the final regression models. In addition, eGDR was a good discriminator for each diabetic complication, with an area under the curve between 0.609 and 0.759. CONCLUSIONS: Patients with chronic diabetic complications are more insulin resistant than those without complications. Moreover, IR was independently associated with the presence of each chronic diabetic complication, and seems to be a good discriminator for them all.

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BACKGROUND: The effects of diabetes on the respiratory system were investigated with arterial blood gas, sleep quality index and respiratory functions tests. METHODS: Fifty-three patients with type II diabetes and 41 healthy cases were included. Their biochemical data, demographic characteristics, anthropometric measurements and echocardiographic findings were collected from polyclinic records. Respiratory function tests were performed for all subjects and Pittsburgh Sleep Quality Index questionnaire was conducted. Aforementioned data were compared between these two groups. RESULTS: The age, body weight and body mass index were similar but oxygen pressure, oxygen saturation, forced vital capacity (FVC; %), and sleep quality were decreased in patients with diabetes. Sleep quality was correlated with the presence of diabetes and hypertension, duration of diabetes, fasting and postprandial blood glucose levels, homeostasis model of assessment-insulin resistance, Glycosylated hemoglobin levels, and FVC. Half of the diabetic patients exhibited respiratory failure during sleep. Especially diabetic patients with autonomic neuropathy, experienced a more severe and prolonged decrease in oxygen saturation. CONCLUSIONS: Blood gas, respiratory functions and sleep quality, which need to be evaluated as a whole, were affected in patients with diabetes. Assessment of sleep and its quality requires special attention in patients with diabetes.

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BACKGROUND: There is growing evidence suggesting a deleterious effect of type 2 diabetes on lung function and sleep breathing. The aim of this case-control study was to evaluate whether or not an improvement in glycemic control could arrest or ameliorate nocturnal hypoxemia in type 2 diabetes. METHODS: Thirty patients with type 2 diabetes with HbA1c ≥8% (cases) and 10 non-diabetic subjects were analyzed. Controls were closely matched to cases by age, gender, body mass index, and neck circumference. The nocturnal oxygen desaturation index (ODI) was calculated at baseline and 5 days after blood glucose improvement with pharmacological intervention. Four different oxygen desaturation thresholds (reductions in SaO2 ≥ 3%, 4%, 6%, and 8%) as indicators of hypoxemia severity (ODI-3%, ODI-4%, ODI-6%, ODI-8%) were used. RESULTS: At baseline, patients with diabetes showed a higher number of ODI-3%, ODI-4%, and ODI-6% in comparison with controls. A significant reduction in ODI-3% (29.7 [4.8-107.9] events per hour at baseline versus 24.6 [3.1-97.7] e/h at discharge, P < 0.001), ODI-4% (21.7 [1.6-79.3] versus 14.7 [0.3- 79.4], P = 0.003), ODI-6% (9.3 [0.3-71.8] versus 4.0 [0.0-73.7], P = 0.001), and ODI-8% (4.1 [0.0-64.3] versus 1.1 [0.0-69.8], P = 0.033) was observed in patients with diabetes after 5 days of follow-up. However, no changes in ODI events were observed in non-diabetic patients after the same period. No significant changes in weight were observed in either group. CONCLUSIONS: Glycemic control improvement significantly reduces the increased number of nocturnal oxygen desaturations that exist in type 2 diabetes. Although the mechanisms are not yet fully understood, the rapid effect without changes in body weight suggests a central mechanism involving respiratory center output.

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BACKGROUND: Patients with type 2 diabetes (T2D) are at a high risk of developing microvascular complications, such as diabetic retinopathy (DR). Previous studies have shown that low serum bilirubin concentrations in T2D patients may increase the risk of diabetic complications. Thus, the aim of the present was to investigate the association between the prevalence of DR and serum concentrations of total bilirubin in a Chinese population. METHODS: The present study was a population-based cross-sectional study on 1761 T2D patients aged ≥40 years from the Jiading district of Shanghai, China. Fundus photographs were taken to confirm the presence and severity of DR. Subjects were assigned to quartiles based on serum total bilirubin concentrations (Quartile (Q) 1 <0.60 mg/dL; Q2 0.60-0.76 mg/dL; Q3 0.77-0.99 mg/dL; Q4 >0.99 mg/dL). Logistic regression models were used to explore the association between bilirubin concentrations and the prevalence of DR. RESULTS: The prevalence of DR in the entire study population was 9.6%. The prevalence of DR was significantly lower in Q4 compared with the other three quartiles (Ptrend = 0.004). After adjustment for multiple confounding factors, T2D patients in Q4 (i.e. serum bilirubin >0.99 mg/dL) were less likely (odds ratio 0.55; 95% confidence interval 0.33-0.91) to suffer from DR than patients in Q1 (i.e. serum bilirubin <0.60 mg/dL). CONCLUSION: Serum bilirubin concentrations were inversely associated with DR in an elderly Chinese population, independent of traditional risk factors for microvascular complications.

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