Identification of blood metabolic biomarkers associated with diabetic distal symmetric sensorimotor polyneuropathy in patients with type 2 diabetes mellitus.

BACKGROUND: Distal symmetric sensorimotor polyneuropathy (DSPN) is a common neurologic complication of type 2 diabetes mellitus (T2DM), but the underlying mechanisms and changes in serum metabolites remain largely undefined. This study aimed to characterize the plasma metabolite profiles of participants with T2DM using targeted metabolomics analysis and identify potential biomarkers for DSPN. METHODS: A combined liquid chromatography MS/MS and direct flow injection were used to quantify plasma metabolite obtained from 63 participants with T2DM, 81 with DSPN, and 33 nondiabetic control participants. A total of 130 metabolites, including amino acids, biogenic amines, sphingomyelins (SM), phosphatidylcholines, carnitines, and hexose, were analyzed. RESULTS: A total of 16 plasma metabolites and 3 cholesterol-related laboratory parameters were found to have variable importance in the projection score >1.0 and false discovery rate <5.0% between control, T2DM, and DSPN. Among these variables, five serum metabolites, including phenylalanine (AUC = 0.653), alanine (AUC = 0.630), lysine (AUC = 0.622) tryptophan (AUC = 0.620), and SM C16:0 (AUC = 0.630), are potential biomarkers (all p < .05) in distinguishing T2DM with DSPN from those without (AUC = 0.720). CONCLUSIONS: In this cross-sectional study, derangement of several metabolites in the plasma was observed in T2DM with and without DSPN, and these metabolites may be potential biomarkers for predicting DSPN. Longitudinal studies are warranted.

Evaluation of recurrence risk in patients with papillary thyroid cancer through tumor-node-metastasis staging: A single-center observational study in Taiwan.

BACKGROUND: Many patients with papillary thyroid cancer (PTC) demonstrate satisfactory outcomes. However, 8%-28% of patients with PTC show tumor recurrence, which may affect prognosis. Therefore, identifying factors associated with tumor recurrence in patients with PTC may be helpful to refine therapeutic strategies. METHODS: To identify factors associated with PTC recurrence, we retrospectively reviewed demographic features (sex and age), operation method, image character, serum thyroglobulin (Tg), accumulated radioactive iodine (I-131) therapeutic dose, I-131 uptake, and metastases at diagnosis in 829 patients with PTC. Patients were grouped into early (stage I and II; n = 698) and advanced (stage III and IV; n = 131) tumor-node-metastasis (TNM) stages. Recurrence rate, mortality rate, risk factors of recurrence, recurrent free survival and overall survival curve were compared between two groups. RESULTS: Patients in the early stage demonstrated a lower recurrence rate (7.2%) than did those in the advanced stage (28.2%, p < 0.05). The mortality rate of patients with recurrence in the advanced stage was higher than that of those in the early stage (51.4% vs. 12.0%). The major impact factors on tumor recurrence in early TNM stage were distant metastasis and lymph node metastasis, while in advanced TNM stage were distant metastasis, male gender, total thyroidectomy with limited lymph node dissection, and a high serum Tg level. CONCLUSIONS: Strategies to monitor tumor recurrence might be refined according to the TNM stages of PTC patients.

Association between serum bilirubin levels and progression of albuminuria in Taiwanese with type 2 diabetes mellitus.

BACKGROUND: To investigate the association between serum bilirubin (BIL) levels and the progression of albuminuria in type 2 diabetic Taiwanese. METHODS: Longitudinal data from January 2001 to June 2015 were retrospectively reviewed from Chang Gung Memorial Hospital in Taiwan. A total of 2877 type 2 diabetic patients with normal total BIL levels were divided into 4 groups according to BIL, with the highest BIL in the fourth group. The urinary albumin/creatinine ratio (UACR) trend and progression, as well as other laboratory measurements, were evaluated among the four groups. The cumulative incidence and Cox proportional hazard model analysis were performed to examine the relationship between BIL and the risk of albuminuria progression (AUPr). RESULTS: The mean duration of follow-up was 1.5 years (±1.37 years). The mean patient age, glycosylated hemoglobin level, and duration of diabetes were 62.52 years, 7.9%, and 3.94 years, respectively. A significant correlation was observed between BIL and both the UACR at baseline (P < 0.001) and the cumulative incidence of AUPr (log-rank test, P = 0.031). Hazard ratio (HR) analysis revealed that patients in the fourth BIL quartile had the lowest HR risk of AUPr among the four groups (adjusted HR = 0.70; 95% Confidence Interval = 0.56-0.89, P < 0.05). CONCLUSIONS: Higher serum BIL levels are associated with a lower risk of AUPr in type 2 diabetes patients in Taiwan.

Diabetic Distal Symmetrical Polyneuropathy: Correlation of Clinical, Laboratory, and Electrophysiologic Studies in Patients with Type 2 Diabetes Mellitus.

This cross-sectional study is aimed at determining the prevalence of distal symmetrical polyneuropathy (DSPN) and diabetic peripheral neuropathic pain (DPNP) in participants with type 2 diabetes mellitus (T2DM); finding the risk factors for DSPN and DPNP via biochemical tests; and correlating DSPN and DPNP with the results of electrophysiologic studies, quantitative sensory tests, and neurologic examination. The 145 participants with T2DM enrolled were divided into the DSPN (abnormal nerve conduction studies (NCS) with signs of polyneuropathy), subclinical DSPN (abnormal NCS without signs of polyneuropathy), minimal DSPN (normal NCS with signs of polyneuropathy), and no DSPN groups. The biochemical risk factors of diabetic peripheral neuropathy were investigated. Neurologic examinations, laboratory tests, NCS, vibration threshold tests, and thermal threshold tests were conducted. The modified Michigan Neuropathy Screening Instrument (mMNSI) and Douleur Neuropathique 4 were used to evaluate the severity of DSPN and DPNP, respectively. In all, 30% of participants had DSPN and 11% had DPNP. DSPN correlated strongly with male gender and higher glycohaemoglobin levels; NCS abnormality correlated with higher glycohaemoglobin levels; DSPN severity correlated with NCS of each stimulating nerve. DPNP commonly occurred with clinical and electrophysiologic evidence of DSPN. Symptomatic diabetic polyneuropathy significantly correlated with longer disease duration, higher glycohaemoglobin levels, and abnormal vibration tests. The thermal threshold test combined with nerve conduction tests could detect most of the patients with DSPN, subclinical DSPN, and minimal DSPN. Poor diabetic control was independently associated with the development of DSPN. DPNP was associated with DSPN. The combination of thermal threshold tests with NCS can potentially provide the diagnosis of DSPN.

A comparison of different definitions of metabolic syndrome for the risks of atherosclerosis and diabetes.

BACKGROUND: The reported outcomes of the metabolic syndrome (MetS), containing atherosclerotic cardiovascular disease and diabetes, vary according to the definitions used. This study was designed to compare the performance of the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI) and International Diabetes Federation (IDF) criteria for the risks of atherosclerosis and diabetes. METHODS: We sifted subjects from a self-paid Health examination program from 1999 to 2015 in this cross-sectional population-based study. On the basis of the ATP III/AHA/NHLBI and IDF criteria, the MetS diagnosis and scores were concluded. A brachial-ankle pulse wave velocity (baPWV) more than or equal to 1400 cm/s indicated more severe arterial stiffness, and a high fasting glucose level more than or equal to 6.99 mmol/L or postprandial glucose level more than or equal to 11.10 mmol/L indicated diabetic-level hyperglycemia. Comparisons of the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores to correlate with a higher baPWV and diabetic-level hyperglycemia were evaluated. RESULTS: In the 26,735 enrolled subjects with an average age of 55 (± 12) years, 6633 and 7388 (24.8% vs. 27.6%, p < 0.001) were classified as having MetS on the basis of the ATP III/AHA/NHLBI and IDF criteria, respectively. The AUC-ROC for the ATP III/AHA/NHLBI-MetS score were higher than those for the IDF-MetS score (0.685 vs. 0.595 to correlate with a higher baPWV, p < 0.001; 0.791 vs. 0.665 to correlate with diabetic-level hyperglycemia, p < 0.001). CONCLUSIONS: To the best of our knowledge, this is the first study to demonstrate that through a holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of atherosclerosis and diabetes was superior to the IDF-MetS score for Asians.

Metabolic syndrome positively correlates with the risks of atherosclerosis and diabetes in a Chinese population.

BACKGROUND: Published studies seldom tested the weight of different waist circumference (WC) cut-off values for the diagnosis of metabolic syndrome (MetS) in predicting clinical outcomes, including cardiovascular disease and diabetes. METHODS: This is a Chinese population-based cross-sectional study screening subjects from a Health Examination Program since 1999 to 2015. The MetS identification and scores were determined either according to the Adult Treatment Panel III/American Heart Association/National Heart, Lung, and Blood Institute (ATP III/AHA/NHLBI)- or Asian-WC cut-off points. The developments of a higher brachial-ankle pulse wave velocity (baPWV), defined as ≥1400 cm/s, and diabetic-level hyperglycemia, defined as a high fasting glucose level ≥6.99 mmol/L or postprandial glucose level ≧11.10 mmol/L, were surveyed by comparing the areas under receiver operating characteristic curves (AUC-ROC) for both MetS scores. RESULTS: According to the ATP III/AHA/NHLBI- vs Asian-MetS criteria, 6633 vs 9133 (24.8% vs 34.2%, p < 0.001) subjects were diagnosed as the MetS among 26,735 study subjects with a mean age of 55 ±â€¯12 years. The stepwise increases in baPWV and prevalence of diabetic-level hyperglycemia were associated with both MetS scores after adjusting for age and sex. Both MetS scores yielded similar results for correlation with a higher baPWV (AUC-ROC = 0.685 for ATP III/AHA/HLBI- vs 0.680 for Asian-MetS, p = 0.271) and diabetic-level hyperglycemia (AUC-ROC = 0.791 for ATP III/AHA/HLBI- vs 0.784 for Asian-MetS, p = 0.546). CONCLUSIONS: In a stepwise manner, both ATP III/AHA/NHLBI- or Asian-MetS scores were strong risk factors for arterial stiffness and diabetes. Through a novel and holistic approach, the performance of the ATP III/AHA/NHLBI-MetS score for the risks of arterial stiffness and diabetes was comparable to the Asian-MetS score among a Chinese population.

Linagliptin and cardiovascular outcomes in type 2 diabetes after acute coronary syndrome or acute ischemic stroke.

BACKGROUND: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS. METHODS: An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database. A total of 1203 patients with T2DM after ACS or AIS were selected as the study cohort. Cardiovascular safety and efficacy of linagliptin were evaluated by comparing outcomes of 401 subjects receiving linagliptin after ACS or AIS to 802 matched control subjects not receiving any incretin-based therapy after ACS or AIS. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. RESULTS: The primary composite outcome after 15-month follow-up was 7% (28 patients) in the linagliptin group compared with 6.1% (49 patients) in the control group [hazard ratio (HR) 1.06; 95% confidence interval (CI) .66-1.68]. The linagliptin group also had similar risks of all-cause mortality, hospitalization for heart failure, percutaneous coronary intervention and coronary artery bypass grafting compared to the control group in terms of the secondary outcomes. CONCLUSIONS: In T2DM patients after ACS or AIS, treatment with linagliptin was not associated with increased risks of cardiovascular death, non-fatal myocardial infarction, or non-fatal ischemic stroke.

Moderate- to high-intensity statins for secondary prevention in patients with type 2 diabetes mellitus on dialysis after acute myocardial infarction.

BACKGROUND: Evidences support the benefits of moderate- to high-intensity statins for patients with acute myocardial infarction (AMI) except for those with type 2 diabetes mellitus (T2DM) on dialysis after AMI. This study was aimed to investigate the safety and efficacy of secondary prevention of cardiovascular diseases using moderate- to high-intensity statins in T2DM patients on dialysis after AMI. METHODS: A simulated prospective cohort study was conducted between January 1st, 2001 and December 31st, 2013 utilizing data from the Taiwan National Health Insurance Research Database. A total of 882 patients with T2DM on dialysis after AMI were selected as the study cohort. Cardiovascular efficacy and safety of moderate- to high-intensity statins were evaluated by comparing outcomes of 441 subjects receiving statins after AMI to 441 matched subjects not receiving statins after AMI. The primary composite outcome included cardiovascular death, non-fatal myocardial infarction and non-fatal ischemic stroke. RESULTS: The Kaplan-Meier event rate for the primary composite outcomes at 8 years was 30.2% (133 patients) in the statin group compared with 25.2% (111 patients) in the non-statin group (hazard ratio [HR], .98; 95% confidence interval [CI] .76-1.27). Significantly lower risks of non-fatal ischemic stroke (HR, .58; 95% CI .35-.98) and all-cause mortality (HR, .70; 95% CI .59-.84) were found in the statin group. CONCLUSIONS: In T2DM patients on dialysis after AMI, the use of moderate- to high-intensity statins has neutral effects on composite cardiovascular events but may reduce risks of non-fatal ischemic stroke and all-cause mortality.

Vital roles of age and metabolic syndrome-associated risk factors in sex-specific arterial stiffness across nearly lifelong ages: Possible implication of menopause and andropause.

BACKGROUND AND AIMS: Postmenopausal status is correlated with increased metabolic syndrome (MetS) and cardiovascular risks. However, the vital roles of age and MetS-associated risk factors in sex-specific arterial stiffness remain unclear. METHODS: In this population-based cross-sectional study of the general population, we enrolled in our Health Examination Program 9812 adult participants who were measured for brachial-ankle pulse wave velocity (baPWV) to assess arterial stiffness. Piecewise linear regression models were used to survey pre-defined ages associated with menopause and andropause in relation to arterial stiffness. Multivariate linear regression analyses were used to evaluate independent determinants. RESULTS: Across gender, stepwise increases in baPWV corresponded to increased MetS-associated risk scores (MetSRS) and aging (all p for trend < 0.001), while a turning point was found at 50 years of age (50age). The incremental ratios of baPWV presented inverse U curves with aging, whereas the highest R2 values and incremental ratios of baPWV were found at 50age across gender. Comparing men with women, a 1.4-fold higher incremental ratio of baPWV was observed before 50age, compared to a 1.3-fold after 50age, respectively. MetS risk group and over 50age were associated with stepwise increased baPWV across gender (both p for trend < 0.001). Before 50age, the determinants did not include hs-CRP for women compared with men, while MetSRS was lost as a determinant across gender. In contrast with men, in women after 50age, HDL-C was an additional determinant and triglyceride was not, while MetSRS remained a determinant across gender. CONCLUSIONS: Arterial stiffness increased with aging across nearly lifelong ages more in women than in men. While menopause and andropause may both play a role, 50age was the most critical factor across gender. The sex-specific differences in determinants of arterial stiffness may remind us of sex-specific targets for further interventional studies associated with arterial stiffness.

Metabolic Syndrome-Associated Risk Factors and High-Sensitivity C-Reactive Protein Independently Predict Arterial stiffness in 9903 Subjects With and Without Chronic Kidney Disease.

Metabolic syndrome (MS), high-sensitivity C-reactive protein (hs-CRP), and chronic kidney disease (CKD) are related to cardiovascular diseases. Although MS is common in CKD subjects, the contribution of MS-associated risk factors and hs-CRP to arterial stiffness in CKD has not been well studied.In this cross-sectional cohort study, we enrolled 9903 subjects who underwent brachial-ankle pulse wave velocity (baPWV) measurements from our database of Health Care Center. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m. Comparing those grouped with and without CKD, multivariate linear regression analyses were used.Overall, baPWV was found to have an inverse relationship with eGFR (P for trend <0.001), which increased progressively with the presence of CKD, increasing number of MS-associated risk factors and hs-CRP (P for trend <0.001). In the non-CKD group, age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting glucose, triglyceride, high-density lipoprotein cholesterol, and hs-CRP independently predicted baPWV, whereas in CKD, eGFR, age, gender, body mass index, SBP, DBP, and fasting glucose remained predictors.The number of MS-associated risk factors and hs-CRP remains a determinant of arterial stiffness in both CKD and non-CKD groups. The decline of renal function contributes to arterial stiffness only in CKD but not in non-CKD. Our findings suggest that for CKD subjects, renal function, BP, and glycemic control are potential targets for further interventional studies of arterial stiffness.

Characteristics of Klebsiella pneumoniae bacteremia in community-acquired and nosocomial infections in diabetic patients.

BACKGROUND: Although diabetes mellitus is known as a major risk factor for Klebsiella pneumoniae infection, the differences in clinical characteristics between community-acquired and nosocomial K. pneumoniae bacteremia in diabetic patients have been rarely reported. METHODS: This retrospective analysis enrolled 193 adult diabetic patients with K. pneumoniae bacteremia hospitalized between January 2005 and December 2006. The chi-squared test, analysis of variance (ANOVA), Student's t test, Fisher exact test, and Cox regression model were used for statistical analysis. RESULTS: Of the enrolled patients, 147 had community-acquired infections and 46 had nosocomial infections. Compared with the community group, the nosocomial group had higher rates of in-hospital mortality (41.3% vs. 18.4%, p=0.001), malignancy (50.0% vs. 19.0%, p<0.001), and leukopenia (21.7% vs. 5.4%, p=0.001) but had lower levels of serum C-reactive protein (124.3 mg/L vs. 188.7 mg/L, p=0.018) and HbA1c (8.1% vs. 9.5%, p=0.025). The rate of infection with the extended-spectrum ß-lactamase-producing strain (ESBL infection) in the nosocomial group was 11 times higher than that in the community group (45.7% vs. 4.1%, p<0.001). ESBL infection accounted for 53% of mortality in the nosocomial group. Pneumonia was more common in the nosocomial group, while local abscess was more common in the community group. The risk factors for mortality were pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio (creatinine level at admission/baseline). CONCLUSIONS: The nosocomial group had more ESBL infections which might account for the higher mortality. The HbA1c level during the course of infection did not affect the outcome. Pneumonia, leukopenia, cirrhosis, and a high serum creatinine ratio at admission were the risk factors for poor outcome.