Evaluation of 1, 5 -Anhydroglucitol as a Biomarker for Type 2 Diabetes Mellitus in Patients without Overt Nephropathy

1,5-Anhydroglucitol (1,5-AG) is a non-fasting glycemic marker that responds to hyperglycemia excursions. The reduction in serum levels of 1,5-AG is associated with an increase in postprandial glycemia and glycosuria, phenomena that increase the risk and severity of diabetic complications. The objective is to assess the ability of 1,5-AG to discriminate type 2 diabetes (T2D) patients without overt kidney disease, for screening or diagnostic purposes. The Human Research Ethics Committee of Universidade Federal do Paraná (UFPR) approved the project. Serum samples from 567 individuals classified as healthy subjects (n = 291) and T2D (n = 276) with moderate glycemic control (HbA1c of 7-8%), matched by gender, were analyzed. Serum 1,5-AG levels were measured using an automated enzymatic method (GlycoMark, Inc.). Receiver Operating Characteristic (ROC) curve analysis for 1,5-AG showed sensibility of 65.3% and specificity of 91.1% to detect T2D at cut-off point of 92 µmol/L. The results were similar to the groups' discrimination by glycemia (sensibility/specificity, 62.2%; 89.0%) at cut-off point of 6.3 mmol/L. HbA1c was the best discriminator (sensibility/specificity, 87.4%; 94.2%) at a cut-off point of 5.8% (40 mmol/mol). The serum 1,5-AG concentration was not able to discriminate T2D in the presence of moderate glycemic control with no overt nephropathy.

Impact of Weight Loss on Inflammation State and Endothelial Markers Among Individuals with Extreme Obesity After Gastric Bypass Surgery: a 2-Year Follow-up Study.

BACKGROUND: The medium-term impact of gastric bypass (GB) surgery on the inflammatory state and endothelial function of patients has yet to be confirmed. OBJECTIVE: This study aims to elucidate the inflammatory profile and endothelial dysfunction response of adults with obesity 6 and 24 months after undergoing GB surgery. METHODS: The anthropometric and biochemical markers of 32 adults with obesity (two men and 30 females) were collected preoperatively, and 6 and 24 months postoperatively. RESULTS: Body mass index (BMI) and excess weight had decreased by 15.79 ± 1.21 kg/m2 (p < 0.01) and 83.80 ± 24.50% respectively at 24 months. Leptin, C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1) levels, and the leptin/adiponectin ratio decreased significantly at both postoperative follow-up points compared with preoperative values (p < 0.01). IL-6 and ICAM-1 levels decreased between 6 and 24 months post-GB (p < 0.01). IL-6 and ICAM-1 levels decreased between 6- and 24-months post-GB (p < 0.01). Resistin levels were significantly decreased (p < 0.01) at 6-month follow-up. The levels of the anti-inflammatory biomarkers IL-10, adiponectin, and the adiponectin/leptin ratio significantly increased postoperatively. There was an improvement in metabolic disorders after surgery. CONCLUSION: Our results demonstrated that after GB there was an improvement in the inflammatory profile, identified by a reduction in pro-inflammatory markers (CRP, IL-6, leptin) and an increase in anti-inflammatory markers (adiponectin, IL-10). The decrease in PAI-1 and ICAM-1 levels may suggest improvement in endothelial function. These findings provide clear evidence of the medium-term impact of GB on inflammation state and a number of endothelial markers, and a consequent reduction in the risk of cardiovascular diseases.

Serum 1,5-Anhydroglucitol Concentration as a Biomarker for Type 1 Diabetes in Adults and Children.

BACKGROUND: Type 1 diabetes (T1D) is an autoimmune disease and the leading form of diabetes among young white people. 1,5-Anhydroglucitol (1,5-AG), a nontraditional biomarker of postprandial glycemic control (after 1 - 3 days to 2 weeks), may be useful in T1D screening. We studied serum 1,5-AG concentration as a potential biomarker for T1D screening and diagnosis in adults and children. METHODS: In this case-control study, adults (n = 121; age, 19 - 61 years) and children (n = 19; age, 8 - 14 years) with T1D were matched with healthy subjects (n = 242) according to gender and age. Serum 1,5-AG levels were measured enzymatically (GlycoMark Inc., NY, USA). RESULTS: Patients showed no symptoms of overt kidney disease, assessed by serum creatinine concentrations. The median (25th - 75th percentile) 1,5-AG concentrations for the control group compared with the T1D group were 155 (128 - 183) vs. 21 (14 - 34) µmol/L in adults and 190 (158 - 237) vs. 20 (12 - 30) µmol/L in children (p < 0.001 for both). Receiver operating characteristic curves showed that 1,5-AG cutoffs of ≤ 113 and ≤ 79 µmol/L for adult men and women, respectively, and ≤ 57 µmol/L for children of both genders had > 95% sensitivity and specificity for both groups. CONCLUSIONS: Our results suggest that serum 1,5-AG concentration may be useful as an adjunct measure of hyperglycemia for diagnosing T1D and has the potential to screen for T1D in high-risk subjects.

Data for serum 1,5 anhydroglucitol concentration in different populations.

1,5 anhydroglucitol (1,5-AG), is a nonmetabolized 1-deoxy form of glucose, originate mainly from the diet. 1,5-AG is a biomarker to detect and magnify hyperglycemic excursions (postprandial hyperglycemia) in diabetic patients. Concentrations of 1,5-AG has been applied as supporting biomarker to diagnosis of the major forms of diabetes (type 1, type 2, and gestational). The serum 1,5-AG reference interval is relevant to the appropriate clinical application of this biomarker. This article contains data regards to serum concentration of the biomarker primarily for healthy subjects, capture from the literature, in different populations. Correlation analysis between 1,5-AG and markers associated with diabetes and its complication were presented. The data was complementary to the study "Reference intervals for serum 1,5-anhydroglucitol in children, adolescents, adults, and pregnant women" (Welter et al., 2018). The data present in this article improve the comparisons for 1,5-AG in different conditions and methodologies.

Reference intervals for serum 1,5-anhydroglucitol in children, adolescents, adults, and pregnant women.

BACKGROUND: 1,5-anhydroglucitol (1,5-AG) is a validated marker of short-term glycemic control. We determined the reference intervals of 1,5-AG in different age groups and during pregnancy. METHODS: Blood samples were collected from 2303 Euro-Brazilian healthy subjects: 580 children, 496 adolescents, 922 adults matched by age and sex, and 305 pregnant women in four gestational periods. Serum 1,5-AG was measured using an enzymatic reagent in an automated system. RESULTS: The calculated reference intervals (nonparametric, 2.5th-97.5th) for males and females were, respectively: children, 96-302 and 89-277 µmol/l; adolescents, 84-311 and 79-277 µmol/l; and adults, 80-260 and 62-241 µmol/l. Males consistently showed significantly higher concentrations than females. 1,5-AG reference intervals in pregnant women were 56-298 µmol/l at <23 weeks gestation (n = 110), 37-166 µmol/l at 24-28 weeks gestation (n = 106), 34-155 µmol/l at 29-32 weeks gestation (n = 52), and 33-246 µmol/l at >32 weeks gestation (n = 37). No significant differences in 1,5-AG concentration were observed between non-pregnant and pregnant women at <23 weeks of gestation. A negative correlation (r = -0.287; p < .001) between 1,5-AG concentration and age was observed. CONCLUSIONS: The reference intervals for 1,5-AG were affected by sex and age.

Early effects of Roux-en-Y gastric bypass on peptides and hormones involved in the control of energy balance.

INTRODUCTION: Body weight varies depending on the prevailing direction of environmental pressures; however, physiological factors also play a significant role in the control of body weight. The aim of the present study was to assess the impact of Roux-en-Y gastric bypass (RYGB) on hormones and peptides involved in the control of energy balance and their possible implications in appetite/satiety. METHODS: The sample included 39 individuals with extreme obesity (37 women and two men) who underwent RYGB. Anthropometric and biochemical markers were collected before surgery and 6 months after RYGB. RESULTS: The BMI decreased from 44.3±6.4 to 31.7±5.7 kg/m (P<0.001) at the sixth month. Percentage of excess weight lost was 63.2±25.0%. Leptin and glucose levels decreased significantly 6 months after RYGB (P<0.001). Interestingly, a significant correlation was confirmed between the anorexigenic gut hormone peptide YY (PYY) and the central anorexigenic mediator α-melanocyte-stimulating hormone after 6 months of RYGB (r=0.35, P=0.004). In contrast, PYY concentrations were correlated negatively with BMI (r=-0.34, P=0.002). CONCLUSION: In the present investigation, it was found that there is a relationship between α-melanocyte-stimulating hormone and PYY concentrations, and it supports the role of the PYY to POMC signal in appetite regulation after RYGB.

Roux-en-Y gastric bypass decreases pro-inflammatory and thrombotic biomarkers in individuals with extreme obesity.

BACKGROUND: The low-grade inflammatory state in obesity leads to insulin resistance and endothelial dysfunction, which promote cardiovascular diseases in individuals with obesity. The purpose of this study was to evaluate the early effects of weight loss achieved through bariatric surgery on the inflammatory and prothrombotic states. This study also aimed to identify the role of hyperleptinemia on the prothrombotic state. METHODS: The sample was composed of 41 extremely obese who underwent Roux-en-Y gastric bypass (RYGB). Anthropometric and clinical data, and biochemical markers of inflammation were collected prior to surgery and 6 months post-RYGB. RESULTS: It was found that plasminogen activator inhibitor-1 (PAI-1) concentrations were higher among extremely obese individuals with hyperleptinemia than in those without hyperleptinemia (p < 0.01).In relation to the baseline, post-surgery body mass index (BMI) was reduced by 12.9 kg/m(2), corresponding to 63.50 % of excess weight loss. Additionally, waist circumference was found to decrease significantly from 126.2 to 101.4 cm. Plasma total cholesterol (p < 0.01), LDL cholesterol (p = 0.02), triglycerides (p < 0.01), and glucose (p = 0.01) were also found to decrease. Pro-inflammatory biomarkers were observed to decrease: PAI-1 by 55.9 ± 6.0 % (p < 0.01), C-reactive protein (CRP) by 18.8 ± 3.4 % (p < 0.01), intercellular adhesion molecule-1 (ICAM-1) by 89.9 ± 5.7 % (p < 0.01), leptin by 27.9 ± 3.2 % (p < 0.01), and resistin by 69.3 ± 5.8 % (p < 0.01). Additionally, significant decreases of tumor necrosis factor alpha (TNF-α) and leptin/adiponectin ratio were observed. Anti-inflammatory cytokines adiponectin and interleukin-10 (IL-10) were significantly increased (170.7 ± 82.5 %, p < 0.01; 122.7 ± 55.1 %, p = 0.02). CRP levels were predictive of ICAM-1 (p = 0.04), and changes in leptin concentrations were associated with decreased PAI-1 levels (p = 0.03). CONCLUSIONS: We observed that individuals with obesity that have hyperleptinemia have higher circulating PAI-1 levels, which could indicate increased risk for cardiovascular disease. The biomarkers of inflammation and thrombosis measured in this study decreased after RYGB, suggesting that the surgery may be effective in reducing pro-inflammatory and thrombotic risk in individuals with extreme obesity.

Quantification of cerebrospinal fluid lactic acid in the differential diagnosis between HIV chronic meningitis and opportunistic meningitis.

BACKGROUND: Approximately 40% of HIV infected patients have chronic meningitis at various stages during the infection, 59% are asymptomatic. This is a diagnosis of exclusion and a confounding factor in cerebrospinal fluid (CSF) analysis, any other causes of chronic meningitis by opportunistic or co-infection must be ruled out. The aim of this study was to analyze CSF lactic acid (LA) as an adjuvant biomarker in chronic meningitis due to HIV. METHODS: CSF LA was quantified in 223 CSF samples by the Dimension AR (Dade Behring, Deerfield, IL, USA), distributed into nine groups: 1) HIV positive with an increase in CSF WBCs (n=17); 2) HIV positive with normal CSF (n=20); 3) enterovirus meningitis (n=33); 4) Herpesviridae meningoencephalitis (n=30); 5) fungal meningitis (n=25); 6) tuberculosis (TB) meningitis (n=17); 7) toxoplasmosis (n=18); 8) neurosyphilis (n=6); 9) control group (n=57). RESULTS: CSF LA (median; IQR) was higher in samples with TB meningitis (5.5; 2.9-7.5 mmol/L) and Cryptococcus neoformans meningitis (3.9; 2.7-5.8 mmol/L) compated with samples with HIV chronic meningitis (1.7; 1.4-1.9 mmol/L) and other groups (p ≤ 0.0001). For the diagnosis of HIV chronic meningitis, using a cut-off of 3.5 mmol/L, CSF LA showed high sensitivity and negative predictive value, although low specificity. CONCLUSIONS: CSF LA helps to discriminate between C. neoformans or TB meningitis and HIV chronic meningitis: CSF LA can be included with the methods currently used to identify these specific pathogens, though it does not replace them. It is rapid, inexpensive and easy to perform, and can be used in developing countries.