Lipocalin-2 Levels, Insulin Resistance, and Urinary Albumin Excretion in Type 2 Diabetes Subgroups.

BACKGROUND: Lipocalin-2 (LCN2) level in type 2 diabetes mellitus (T2DM) subgroups has not been investigated. The aim of this study was to investigate LCN2 levels, insulin resistance, urinary albumin excretion, and inflammation status in T2DM subgroups. METHODS: A total of 251 patients with newly diagnosed T2DM were evaluated. LCN2, glycated hemoglobin (HbA1c), FPG, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) levels were measured. Patients with diabetes were categorized into three subgroups: patients diagnosed with fasting plasma glucose (FPG) alone (FPG-DM), those with isolated hemoglobin A1c (HbA1c) diabetes (A1c-DM), and those who met the criteria for both FPG and HbA1c (FPG/A1c-DM). The albumin-to-creatinine ratio (ACR), estimated glomerular filtration rate (eGFR), homeostasis model assessment of insulin resistance (HOMA-IR), and adjusted LCN2 values, such as the LCN2/inflammation index (LCN2/Inf) and LCN2/creatinine (LCN2/ Cr), were calculated. RESULTS: The ACR, HOMA-IR, and glycosuria prevalence were significantly higher in FPG-DM than in A1c-DM. In contrast, no significant difference was observed in LCN2, eGFR, and proinflammatory cytokine levels between the two groups. Patients with FPG/A1c-DM had significantly higher LCN2, TNF-α, IL-6, and hsCRP levels than those with A1c-DM or FPG-DM. The percent difference between LCN2 and LCN2/Inf was 3.2-fold greater than that between LCN2 and LCN2/Cr in FPG/A1c-DM. The presence of FPG-DM led to a 1.8-fold increase in the prevalence of proteinuria (odds ratio, 1.876; 95% CI, 1.014 - 3.295; p < 0.001). The ability of FPG to identify proteinuria outperformed that of HbA1c (area under the curve: 0.629, 95% CI, 0.553 - 0.706 versus 0.522, 95% CI, 0.436 - 0.605, p < 0.001). CONCLUSIONS: LCN2 elevation may be more largely due to inflammation than kidney function, particularly in FPG/A1c-DM. Patients with FPG-DM may be at a greater risk of diabetic nephropathy and insulin resistance than those with A1c-DM.

Lipocalin-2, Soluble Transferrin Receptor, and Erythropoietin in Anemia During Mild Renal Dysfunction.

Background: Mild renal dysfunction (MRD) is a common condition often associated with diabetes or inflammation and regarded as a risk factor for cardiovascular disease in patients with hypertension. Few studies have examined the role of lipocalin-2 (LCN2) as a regulator of iron and a contributor to anemia in MRD. The aim of this study was to investigate the relationship between LCN2, soluble transferrin receptor (sTfR), erythropoietin (EPO), reticulocyte production, and the prevalence of anemia in MRD. Methods: A total of 235 subjects with MRD were evaluated. LCN2, sTfR, EPO, and iron levels were measured. Reticulocyte maturity index (RMI) and corrected LCN2 (cLCN2) values were calculated using reticulocyte subpopulations and the inflammation index, respectively. Results: Subjects with LCN2 elevation had significantly higher sTfR and significantly lower RMI levels than those without LCN2 elevation. Compared to subjects without LCN2 elevation, those with LCN2 elevation exhibited significantly lower hemoglobin (12.9 ± 1.6 g/dL vs 14.0 ± 1.7 g/dL, p < 0.001) and more prevalent anemia (27.7% vs 13.3%, p = 0.008). Patients with anemia had significantly higher LCN2 and cLCN2 than those without anemia. LCN2 was positively correlated with sTfR and negatively correlated with RMI but not EPO. Elevated LCN2 led to a 1.3-fold increase in the prevalence of anemia (odds ratio: 1.302; 95% CI: 1.012-2.527; p < 0.001). Conclusion: LCN2 elevation may contribute to the development of anemia in MRD, particularly in conjunction with restricted iron availability and suppressed reticulocyte production.

Insulin Resistance and Microalbuminuria in Patients with Impaired Fasting Glucose versus Hemoglobin A1c-Defined Prediabetes.

OBJECTIVE: This study investigated differences among patients with impaired fasting glucose (IFG) and hemoglobin A1c (HbA1c)-defined prediabetes (A1c-PDM); we compared insulin resistance and the prevalence of microalbuminuria (MAU) in these individuals. METHODS: A total of 982 patients with newly diagnosed PDM and 455 non-PDM healthy individuals were evaluated. Serum insulin, HbA1c, fasting plasma glucose (FPG), and urine albumin excretion (UAE) levels were measured. The homeostasis model assessment of ß-cell function (HOMA-B) and insulin resistance (HOMA-IR) was calculated. RESULTS: MAU was more prevalent in patients with IFG than in those with A1c-PDM (13.2% versus 6.4%, p=0.003). Patients with MAU had significantly higher FPG than those with normoalbuminuria (99.8 mg/dL versus 97.1 mg/dL, p=0.008). However, there was no significant difference in HbA1c levels between the two groups. Patients with IFG had significantly higher HOMA-IR values than those with A1c-PDM (2.31 versus 2.04, p=0.009). In contrast, there was no significant difference in the HOMA-B between the two groups. After adjusting for potential confounders, UAE was significantly correlated with FPG, but not with HbA1c. An elevated FPG level ≥113 mg/dL led to a 2.1-fold increase in the prevalence of MAU (odds ratio, 2.107; 95% confidence interval, 1.010-4.193; p=0.015). However, an elevated HbA1c level ≥6.1% was not significantly associated with the prevalence of MAU. CONCLUSIONS: Patients with IFG may be at a greater risk of insulin resistance and possible progression to diabetic nephropathy than patients with A1c-PDM.

Relationship between Neutrophil Gelatinase-Associated Lipocalin, Eosinophil Cationic Protein, Cytokines, and Atopic Sensitization in Patients with Allergic Diseases.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on eosinophil activation, atopic sensitization, and systemic inflammation in allergic diseases has rarely been investigated. This study aimed to investigate the relationship between NGAL, eosinophil cationic protein (ECP), cytokines, and allergen-specific immunoglobulin E (sIgE) in allergic diseases. A total of 136 patients with allergies and 58 healthy individuals were evaluated. The concentrations of NGAL, ECP, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), sIgE, total IgE (tIgE), and high-sensitivity C-reactive protein (hsCRP) were measured. The transforming growth factor-ß1 (TGF-ß1) level was measured as a profibrotic marker of bronchial asthma. Allergic patients had significantly higher NGAL, ECP, and hsCRP levels than healthy individuals. However, there was no significant difference in NGAL levels between patients with positive and negative ECP tests and those with high and low sIgE scores. Asthmatic patients with elevated NGAL exhibited a significantly higher TGF-ß1 level than those without elevated NGAL. However, no significant difference was observed in the ECP, IL-5, and sIgE levels between the two groups. Among the patients with a positive ECP test, subjects with elevated hsCRP had two times higher NGAL levels than those without elevated hsCRP. NGAL was positively correlated with TNF-α, TGF-ß1, and hsCRP, but not with ECP, IL-5, tIgE, and sIgE. An elevated NGAL level led to a 1.3-fold increase in the prevalence of high TGF-ß1 (odds ratio: 1.31; 95% CI: 1.04-2.58; P < 0.001). In conclusion, NGAL elevation may be more closely linked to allergic inflammation and a possible fibrotic change in the airways than to the severity of eosinophil activation and atopic sensitization.

Association between Neutrophil Gelatinase-Associated Lipocalin and Fetal Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus.

The effect of neutrophil gelatinase-associated lipocalin (NGAL) on fetal hemoglobin (HbF) levels in diabetic patients is rarely investigated. This study is aimed at investigating the possible association between NGAL and HbF levels in type 2 diabetes mellitus (T2DM). A total of 160 patients with T2DM and 61 healthy individuals were evaluated. NGAL, HbF, tumor necrosis factor-α (TNF-α), interleukin-5 (IL-5), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and urine albumin levels were measured. HbF levels were significantly higher in patients with elevated NGAL than in those without elevated NGAL (1.44% versus 0.94%, P = 0.001). High HbF was 2.3 times more prevalent in patients with elevated NGAL than in those without elevated NGAL. In addition, NGAL, TNF-α, and IL-5 levels were significantly higher in patients with high HbF than in those with low HbF; however, there was no significant difference in HbA1c and FPG levels between the two groups. HbF was positively correlated with NGAL (r = 0.275, P < 0.001), TNF-α (r = 0.256, P < 0.001), and IL-5 (r = 0.212, P < 0.001), but not with HbA1c and FPG. An elevated NGAL level led to a 1.27-fold increase in the prevalence of high HbF (odds ratio: 1.27, 95% CI: 1.03-2.51, and P < 0.001). The diagnostic efficacy of NGAL to identify an elevated HbF level was superior to that of HbA1c (area under the curve: 0.697, 95% CI: 0.609-0.786 versus 0.584, 95% CI: 0.488-0.681, and P = 0.022). In conclusion, enhanced NGAL production may be closely linked to elevated HbF in conjunction with proinflammatory cytokines in patients with T2DM.

Association of a Tobacco-specific Nitrosamine Carcinogen with Urinary Cotinine, Urinary Sodium Excretion, and Total Energy Intake in Adolescents and Children.

This study investigated the association of a tobacco-specific nitrosamine carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) with urinary cotinine (uCot), urinary sodium (uNa) excretion, systolic blood pressure (sBP), and total energy intake in adolescents and children in relation to the subjects' age. A total of 790 subjects aged 6-19 years were evaluated. NNAL, uCot, corrected NNAL (cNNAL), the NNAL/uCot ratio, uNa, sBP, and nutrient intake were measured. A strong association between uCot and cNNAL was observed in children who were 11 years of age (r=0.881, P<0.001); however, no significant association was noted in adolescents who were 19 years of age. The uNa level was significantly higher (133.9 mmol/L vs. 107.8 mmol/L, P<0.001) and sBP was significantly lower (105.3 mmHg vs. 110.6 mmHg, P=0.012) in adolescents with elevated NNAL than in those without elevated NNAL. NNAL was significantly higher in subjects with increased uNa excretion than in those without increased uNa excretion. NNAL was positively correlated with uNa (r=0.183, P<0.001) and negatively correlated with sBP (r=-0.142, P<0.001). Non-smokers with elevated NNAL/uCot ratios had significantly lower total energy intake than those without elevated NNAL/uCot ratios (1729.0 kcal/day vs. 1911.0 kcal/day, P=0.008). The relationship between NNAL and uCot varied according to the subjects' age. NNAL seems to play a role in decreasing sBP by enhancing uNa excretion. Insufficient nutrient intake may contribute to endogenous formation of NNAL in non-smoking adolescents and children.

A Novel de novo Mutation in ANK1 Gene Identified through Targeted Next-Generation Sequencing in a Neonate with Hereditary Spherocytosis.

Hereditary spherocytosis (HS) is a congenital disorder of the red blood cell membrane and is characterized by hemolytic anemia, variable jaundice, and splenomegaly. In neonates, the diagnosis of HS can be difficult in the absence of family history. Herein, we describe clinical and molecular genetic findings in a Korean neonate with HS. A one-month-old girl presented with severe anemia and jaundice. Spherocytes were frequently observed on peripheral blood smear, but the erythrocyte osmotic fragility test result was normal. Targeted next-generation sequencing (NGS) revealed the patient was heterozygous for a novel frameshift mutation, c.191_194del (p.Leu64Argfs*7), in exon 3 of ANK1 gene. Family study was performed by direct sequencing, and neither of her parents carried this mutation. The patient also harbored the UGT1A1*6 allele. To the best of our knowledge, this ANK1 mutation identified by targeted NGS has not been reported previously.

The Prevalence of Low Plasma Neutrophil Gelatinase-Associated Lipocalin Level in Systemic Inflammation and its Relationship with Proinflammatory Cytokines, Procalcitonin, Nutritional Status, and Leukocyte Profiles.

BACKGROUND: The significance of low plasma neutrophil gelatinase-associated lipocalin (NGAL) level in systemic inflammation has not been investigated. The aim of this study was to investigate low plasma NGAL level in systemic inflammation and its relationship with proinflammatory cytokines, procalcitonin (PCT), leukocyte profiles, nutritional status, and kidney function. METHODS: Patients with systemic inflammation were evaluated by measuring NGAL, PCT, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), serum creatinine (sCr), and clinical scores. RESULTS: Of 191 patients, 30 (15.7%) had low NGAL levels (< 68 ng/mL), and 102 (53.4%) had elevated NGAL levels (> 150 ng/mL). Among the 30 patients with low NGAL levels, 26 (86.7%) had normal kidney function and 24 (80.0%) had low-grade inflammation. In comparison with healthy individuals, patients with low NGAL levels had higher levels of TNF-α, IL-6, PCT, and hsCRP but not absolute neutrophil count (ANC). Neutropenia was more often observed in subjects with low NGAL levels than in those with elevated NGAL levels (16.7% versus 1.9%, p < 0.001). In the low NGAL group, plasma NGAL was significantly associated with ANC (r = 0.312, p < 0.001) but not cytokines, sCr, nutritional parameters, and clinical scores. Receiver operating characteristic (ROC) curve analysis demonstrated that the diagnostic ability of the ANC for identifying low NGAL levels was superior to that of PCT and TNF-α [0.82 (95% CI, 0.75 - 0.89) versus 0.67 (95% CI, 0.56 - 0.79) and 0.66 (95% CI, 0.54 - 0.78), respectively, p < 0.001]. CONCLUSIONS: Low plasma NGAL level in systemic inflammation was more closely linked to the non-increment of the ANC than proinflammatory cytokines, PCT, and nutritional status, particularly in patients with low-grade inflammation who had preserved kidney function.

Fas and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Are Closely Linked to the Levels of Glycated and Fetal Hemoglobin in Patients with Diabetes Mellitus.

BACKGROUND: The aim of this study was to investigate the relationships between apoptotic markers and the levels of glycated and fetal hemoglobin (HbA1c and HbF) in diabetes. METHODS: The levels of Fas, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), HbF, and HbA1c were measured in 112 patients with type 2 diabetes. RESULTS: Diabetic patients with microalbuminuria had an elevated Fas level and a decreased TRAIL level, compared to healthy controls. Elevated HbF level was more often observed in patients with decreased TRAIL level than in those with increased TRAIL level (33.9% versus 12.5%, p < 0.05). Fas was positively correlated with HbA1c (r = 0.31, p < 0.001), but TRAIL was inversely correlated with HbA1c and HbF (r = -0.30 and r = -0.32, respectively; p < 0.001). In a multivariate logistic regression analysis, decreased TRAIL level was significantly associated with enhanced HbF production after adjusting for potential confounders [odds ratio, 1.35 (95% CI, 1.09 - 2.87), p = 0.004]. The diagnostic ability of TRAIL to identify an elevated HbF > 1.0% was significantly higher than that of the Fas [0.760 (95% CI, 0.638 - 0.882) versus 0.589 (95% CI, 0.457 - 0.721), p < 0.001]. CONCLUSIONS: Fas is closely associated with long-term hyperglycemia, while TRAIL plays certain roles in enhancing HbF production in type 2 diabetes.

Elevated Plasma Neutrophil Gelatinase-Associated Lipocalin Level as a Risk Factor for Anemia in Patients with Systemic Inflammation.

Studies on neutrophil gelatinase-associated lipocalin (NGAL) as an iron-regulatory protein are limited. This study investigated the relationships between plasma NGAL levels and indices of anemia in 187 patients with systemic inflammation. Plasma NGAL levels were significantly higher in patients with anemia versus in patients without anemia (185 ng/mL versus 98 ng/mL; P < 0.001). Serum iron levels were lower in patients with NGAL > 156 ng/mL than in those with NGAL ≤ 156 ng/mL (27.4 ± 25.3 µg/dL versus 58.1 ± 43.5 µg/dL; P < 0.001). In a receiver operating characteristic curve, the diagnostic ability of NGAL to identify anemia was superior to that of high-sensitivity C-reactive protein [0.712 (95% CI, 0.618-0.787) versus 0.649 (95% CI, 0.573-0.744); P < 0.01]. In a multivariate logistic regression analysis, the elevated NGAL level was significantly associated with the presence of anemia after adjusting for potential confounders [odds ratio, 1.30 (95% CI, 1.07-2.58); P = 0.010]. In conclusion, enhanced NGAL production may contribute to the development of anemia in patients with systemic inflammation.

Significance of Neutrophil Gelatinase-Associated Lipocalin Level-to-Serum Creatinine Ratio for Assessing Severity of Inflammation in Patients with Renal Dysfunction.

The aim of this study was to assess the significance of the neutrophil gelatinase-associated lipocalin/serum creatinine ratio (NGAL/sCr ratio) in patients with renal dysfunction. The percent difference between plasma NGAL level and the NGAL/sCr ratio was 36.7% (95% CI, 18.4-83.7%) in patients with sCr level ≥ 1.2 mg/dL. In a multivariate analysis, high sensitivity C-reactive protein (hsCRP) was significantly associated with the NGAL/sCr ratio and plasma NGAL level (r = 0.526 and r = 0.453, resp., P < 0.001). In a receiver operating characteristics curve, the diagnostic ability of the NGAL/sCr ratio to identify hsCRP > 4.0 mg/dL was superior to that of NGAL [0.783 (95% CI, 0.674-0.892) versus 0.733 (95% CI, 0.615-0.852), P = 0.032]. The area under the curve of the NGAL/sCr ratio was larger than that of hsCRP to detect corrected erythrocyte sedimentation rate > 25 mm/h and the neutrophil-to-lymphocyte ratio >4.5 in renal dysfunction. In short, the NGAL/sCr ratio may offer useful information when screening patients with both systemic inflammation and renal dysfunction.

Corrected Neutrophil Gelatinase-Associated Lipocalin (NGAL) Level Adjusted by the Scoring System of an Inflammation Index for Screening Renal Dysfunction in Patients with Systemic Inflammation.

This study investigated the use of corrected neutrophil gelatinase-associated lipocalin (cNGAL) values to screen renal dysfunction in patients with systemic inflammation. Plasma NGAL concentrations were measured using a fluorescent immunoassay in 259 patients with inflammatory diseases. An inflammation index was calculated using a scoring system based on high-sensitivity C-reactive protein (hsCRP) and corrected erythrocyte sedimentation rates. The uncorrected NGAL (uNGAL) concentration increased with the inflammation index, but cNGAL increased in parallel with serum creatinine (sCr) levels. After adjustment with the inflammation index, increased uNGAL concentrations returned to a level not significantly different from the control value. In a multivariate regression analysis, hsCRP was more closely associated with uNGAL than cNGAL [r=0.513 (p<0.001) vs. r=0.201 (p=0.017)], but the sCr level was more strongly linked to cNGAL than uNGAL (r=0.692 vs. r=0.583, respectively, p<0.001). In a receiver operating characteristics (ROC) curve analysis, the diagnostic accuracy of cNGAL, which identifies an increase of sCr ≥0.3 mg/dL within 48 hours, was found to be superior to that of uNGAL [0.72 (95% CI, 0.61-0.84) vs. 0.67 (95% CI, 0.56-0.81), p=0.038]. In conclusion, cNGAL more accurately reflects renal dysfunction than uNGAL under inflammatory conditions. A measurement of cNGAL may provide helpful information for assessing patients with renal impairment, particularly in association with systemic inflammation.

Association of the urine homocysteine/creatinine ratio to proinflammatory cytokine, natural anticoagulant, and nitric oxide levels in cerebrovascular disease.

This study investigated the relationship between the urine homocysteine/creatinine (uHcy/Cr) ratio and the levels of natural anticoagulants, proinflammatory cytokines, and nitric oxide (NOx) metabolites in cerebrovascular diseases. No significant differences were observed in protein C, protein S, and antithrombin III levels among subjects with serum Hcy (sHcy) >15.0 µmol/L and ≤15.0 µmol/L. However, subjects with a uHcy/Cr ratio >14.8 µmol/g Cr showed significant differences in the levels of the corresponding parameters than those with uHcy/Cr ratio ≤14.8 µmol/g Cr. The sensitivity and specificity of the sHcy level at a cutoff of 15.0 µmol/L were 32.6% and 85.7%, respectively, with a positive predictive value of 69.5%. In contrast, those values for the uHcy/Cr ratio at a cutoff of 14.8 µmol/g Cr were 55.1% and 91.4% with a positive predictive value of 86.5%. The uHcy/Cr ratio correlated more closely with protein C, antithrombin III, TNF-α, and NOx levels than did sHcy concentrations. In short, the uHcy/Cr ratio has a significant relationship with anticoagulation- and inflammation-related parameters. A measurement of the uHcy/Cr ratio may provide helpful information for assessing patients with cerebrovascular diseases.

The ratio of estimated average glucose to fasting plasma glucose level is superior to glycated albumin, hemoglobin A1c, fructosamine, and GA/A1c ratio for assessing ß-cell function in childhood diabetes.

OBJECTIVE: This study investigated the use of the estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to screen for ß-cell function in pediatric diabetes. METHODS: Glycated hemoglobin (HbA1c), glycated albumin (GA), fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c (GA/A1c ratio) was calculated, and the homeostasis model assessment of ß-cell function (HOMA-ß) was determined. RESULTS: Median values of C-peptide, insulin, and HOMA-ß levels were significantly higher in patients with an increased eAG/fPG ratio than in those with a decreased eAG/fPG ratio. C-peptide and HOMA-ß levels were more closely correlated with the eAG/fPG ratio than with GA, HbA1c, the GA/A1c ratio, and fructosamine. In contrast, body mass index was significantly associated with GA, GA/A1c ratio, and fructosamine, but not with the eAG/fPG ratio and HbA1c levels. To test the diagnostic accuracies of the eAG/fPG ratio for identifying HOMA-ß>30.0% in patients with type 2 diabetes, the area under the ROC curve of the eAG/fPG ratio was significantly larger than that of the GA/A1c ratio [0.877 (95% CI, 0.780-0.942) versus 0.775 (95% CI, 0.664-0.865), P=0.039]. CONCLUSIONS: A measurement of the eAG/fPG ratio may provide helpful information for assessing ß-cell function in pediatric patients with diabetes.

Klebsiella pneumoniae associated extreme plasmacytosis.

Infection-associated plasmacytosis is not uncommon; however, marked plasmacytosis in both peripheral blood and bone marrow that mimicks plasma cell leukemia is a very rare condition. We encountered a case of extreme plasmacytosis associated with Klebsiella pneumoniae sepsis in an aplastic anemia patient. A 42-year-old man presented with high fever of 5 days' duration. Hematological analysis revealed severe neutropenia and thrombocytopenia; his white blood cell count was 900/mm(3), with 26% of plasma and plasmacytoid cells in peripheral blood. Bone marrow biopsy and aspiration showed 25% cellularity with marked plasmacytosis (80%), highly suggestive of plasma cell leukemia. On the eighth hospital day, K. pneumoniae was identified in blood and sputum cultures. Fever improved after switching antibiotics, although his hematological condition worsened. His bone marrow cellularity (plasma cell proportion) progressively decreased: the values were 25% (80%), 10% (26%), 10% (11%), and < 10% (< 4%) on the 8th, 30th, 60th, and 90th hospital day, respectively. His plasmacytosis was extremely severe but was confirmed to be reactive with polyclonality. The present case represents the first report of strong suspicion of K. pneumoniae sepsis-associated marked plasmacytosis in an aplastic anemia patient.

Serum glycated albumin as a new glycemic marker in pediatric diabetes.

PURPOSE: Serum glycated albumin (GA) has been recently used as another glycemic marker that reflects shorter term glycemic control than glycated hemoglobin (HbA1c). Insulin secretory function and glycemic fluctuation might be correlated with the ratio of GA to HbA1c (GA/HbA1c) in diabetic adult patients. This study investigated the association of GA and GA/HbA1c ratio with the levels of fasting C-peptide, fasting plasma glucose in type 1 and type 2 pediatric diabetes. METHODS: Total 50 cases from 42 patients were included. The subjects were classified into type 1 diabetes mellitus (T1DM) (n=30) and type 2 diabetes mellitus (T2DM) (n=20) group. The associations among HbA1c, GA, and GA/HbA1c ratio were examined. The relationship between the three glycemic indices and fasting glucose, fasting C-peptide were analyzed. RESULTS: Mean values of GA, the GA/HbA1c ratio were significantly higher in T1DM than T2DM. GA (r=0.532, P=0.001), HbA1c (r=0.519, P=0.002) and the GA/HbA1c ratio (r=0.409, P=0.016) were correlated with the fasting plasma glucose. Fasting C-peptide level arranged 4.22±3.22 ng/mL in T2DM, which was significantly above the values in T1DM (0.26±0.49 ng/mL). There were no significant correlation between HbA1c and fasting C-peptide level. However, GA and the GA/HbA1c ratio exhibited inverse correlations with fasting C-peptide level (r=-0.214, P=0.002; r=-0.516, P<0.001). CONCLUSION: GA seems to more accurately reflects fasting plasma glucose level than HbA1c. GA, GA/HbA1c ratio appear to reflect insulin secretory function.

Relationships of Fetal-Type Erythropoiesis versus Nitric Oxide Production and Glycated Hemoglobin Levels in Diabetics.

This study investigated the potential contribution of nitric oxide (NOx) production to enhanced fetal hemoglobin (HbF) synthesis in patients with diabetes. Glycated hemoglobin (HbA1c), HbF, high sensitivity C-reactive protein (hsCRP), plasma glucose levels, and serum NOx concentrations were measured in 350 diabetics and 125 healthy subjects. There were no significant correlations between HbF and HbA1c levels, nor between HbF and plasma glucose levels. However, serum NOx concentrations in patients with HbF >1.0% (76.2 ± 32.4 µmol/L) were significantly higher than those with HbF ≤ 1.0% (47.3 ± 29.8 µmol/L, p <0.05). Inversely, patients with moderately increased serum NOx levels >98.1 µmol/L (75th percentile of patients) exhibited significantly higher HbF levels than those with decreased serum NOx levels <34.2 µmol/L (25th percentile of patients) (1.16 ± 0.41 vs. 0.62 ± 0.28%, p <0.05). After excluding the subjects with high NOx levels, elevated HbF concentrations returned to a level not significantly different from the control value. Serum NOx concentrations were significantly correlated with HbF (r = 0.32, p <0.05) and hsCRP levels (r = 0.35, p <0.05) in diabetic patients. In conclusion, long-term glycemic control does not contribute to fetal-type erythropoiesis, but increased NOx production seems to play an important role in the enhanced HbF synthesis of diabetics.

Thrombin-antithrombin III complex, proinflammatory cytokines, and fibrinolytic indices for assessing the severity of inflammation in pleural effusions.

This study investigated coagulation-related variables, proinflammatory cytokines, and fibrinolytic indices to assess the severity of inflammation in patients with pleural effusions. Tuberculous pleural fluids revealed significantly higher concentrations of tumor necrosis factor-α (TNF-α) and plasminogen activator inhibitor type I (PAI-1) than did malignant and pneumonic pleural fluids. Among the coagulation-related variables, thrombin-antithrombin III complex (TAT) exhibited the largest difference in mean values between pleural fluids and blood samples (125.4 ± 45.1 vs 14.3 ± 20.3 ng/ml, p <0.05). Inflammatory parameters were more closely associated with TAT than tissue type plasminogen activator (tPA), PAI-1, and D-dimers. TAT levels in the severe inflammation group (153.8 ± 45.6 ng/ml) were significantly above those in the mild inflammation group (105.6 ± 38.5 ng/ml, p <0.05); however, no significant differences were observed in PAI-1 and D-dimers levels between the two groups. In conclusion, TNF-α and PAI-1 are important indicators in patients with tuberculous pleural effusions, and measurement of TAT is useful for assessing the severity of inflammation in pleural fluids.