Exploring HbA1c variation between Australian diabetes centres: The impact of centre-level and patient-level factors.

BACKGROUND: Increasing global diabetes incidence has profound implications for health systems and for people living with diabetes. Guidelines have established clinical targets but there may be variation in clinical outcomes including HbA1c, based on location and practice size. Investigating this variation may help identify factors amenable to systemic improvement interventions. The aims of this study were to identify centre-specific and patient-specific factors associated with variation in HbA1c levels and to determine how these associations contribute to variation in performance across diabetes centres. METHODS: This cross-sectional study analysed data for 5,872 people with type 1 (n = 1,729) or type 2 (n = 4,143) diabetes mellitus collected through the Australian National Diabetes Audit (ANDA). A linear mixed-effects model examined centre-level and patient-level factors associated with variation in HbA1c levels. RESULTS: Mean age was: 43±17 years (type 1), 64±13 (type 2); median disease duration: 18 years (10,29) (type 1), 12 years (6,20) (type 2); female: 52% (type 1), 45% (type 2). For people with type 1 diabetes, volume of patients was associated with increases in HbA1c (p = 0.019). For people with type 2 diabetes, type of centre was associated with reduction in HbA1c (p <0.001), but location and patient volume were not. Associated patient-level factors associated with increases in HbA1c included past hyperglycaemic emergencies (type 1 and type 2, p<0.001) and Aboriginal and Torres Strait Islander status (type 2, p<0.001). Being a non-smoker was associated with reductions in HbA1c (type 1 and type 2, p<0.001). CONCLUSIONS: Centre-level and patient-level factors were associated with variation in HbA1c, but patient-level factors had greater impact. Interventions targeting patient-level factors conducted at a centre level including sick-day management, smoking cessation programs and culturally appropriate diabetes education for and Aboriginal and Torres Strait Islander peoples may be more important for improving glycaemic control than targeting factors related to the Centre itself.

Serum FGF21 levels are altered by various factors including lifestyle behaviors in male subjects.

Fibroblast growth factor (FGF) 21 has various functions, including glucose and lipid metabolism. This cross-sectional study aimed to investigate specific conditions that might influence the functions of FGF21. 398 men who underwent a health examination were enrolled in this study. Physical and biochemical parameters and information on several lifestyle behaviors were obtained from all subjects. FGF21 levels correlated with age, body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure (DBP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GTP), uric acid, total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLC), fasting plasma glucose (FPG), and HbA1c. Moreover, FGF21 levels were significantly associated with lifestyle behaviors, including smoking status and breakfast and alcohol consumption frequency. Multivariable regression analysis showed that age, ALT, γ-GTP, smoking status, and breakfast and alcohol consumption frequency were independent variables for FGF21 levels. Assessment among the non-obese and obese groups showed that FGF21 levels correlated with WC, SBP, and TC only in the non-obese group. Thus, serum FGF21 levels were affected by several factors, including lifestyle behaviors, age, and liver function. To assess the functions of FGF21 in individuals, considering these factors would be essential.

Estimation of inter-laboratory reference change values from external quality assessment data.

INTRODUCTION: It is common for patients to switch between several healthcare providers. In this context, the long-term follow-up of medical conditions based on laboratory test results obtained from different laboratories is a challenge. The measurement uncertainty in an inter-laboratory context should also be considered in data mining research based on routine results from randomly selected laboratories. As a proof-of-concept study, we aimed at estimating the inter-laboratory reference change value (IL-RCV) for exemplary analytes from publicly available data on external quality assessment (EQA) and biological variation. MATERIALS AND METHODS: External quality assessment data of the Reference Institute for Bioanalytics (RfB, Bonn, Germany) for serum creatinine, calcium, aldosterone, PSA, and of whole blood HbA1c from campaigns sent out in 2019 were analysed. The median CVs of all EQA participants were calculated based on 8 samples from 4 EQA campaigns per analyte. Using intra-individual biological variation data from the EFLM database, positive and negative IL-RCV were estimated with a formula based on log transformation under the assumption that the analytes under examination have a skewed distribution. RESULTS: We estimated IL-RCVs for all exemplary analytes, ranging from 13.3% to 203% for the positive IL-RCV and - 11.8% to - 67.0% for the negative IL-RCV (serum calcium - serum aldosterone), respectively. CONCLUSION: External quality assessment data together with data on the biological variation - both freely available - allow the estimation of inter-laboratory RCVs. These differ substantially between different analytes and can help to assess the boundaries of interoperability in laboratory medicine.

Efficacy of Semaglutide in a Subcutaneous and an Oral Formulation.

Despite the benefits of early and effective glycemic control in the management of type 2 diabetes (T2D), achieving glycated hemoglobin (HbA1c) targets is challenging in some patients. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) provide effective reductions in HbA1c and body weight. Semaglutide is the only GLP-1RA that is available in both an injectable and oral formulation. The efficacy of once-weekly subcutaneous semaglutide and once-daily oral semaglutide has been investigated in the global SUSTAIN and PIONEER phase III clinical trial programs in a range of clinical settings, including early T2D managed with diet and exercise only, more established T2D uncontrolled on one to three oral antidiabetic drugs, and advanced disease treated with insulin. Across the SUSTAIN program, once-weekly subcutaneous semaglutide 1.0 mg reduced HbA1c by 1.5-1.8% after 30-56 weeks, which was significantly more than sitagliptin, liraglutide, exenatide extended release, dulaglutide, canagliflozin, or insulin glargine. Across the PIONEER program, once-daily oral semaglutide 14 mg reduced HbA1c by 1.0-1.4%, significantly more than sitagliptin or empagliflozin, and to a similar extent as liraglutide after 26 weeks. In addition, subcutaneous semaglutide reduced body weight significantly more than all active comparators tested, while oral semaglutide reduced body weight more than sitagliptin and liraglutide, and to a similar extent as empagliflozin. Neither formulation of semaglutide has been associated with an increased risk of hypoglycemia and both improve various measures of health-related quality of life. Semaglutide offers the benefits of a highly effective GLP-1RA in both injectable and oral formulations. Selection of the most appropriate formulation can be made on an individual basis to best suit the patient's preferences and needs.

Identification of Novel Biomarkers for Pre-diabetic Diagnosis Using a Combinational Approach.

Reliable protein markers for pre-diabetes in humans are not clinically available. In order to identify novel and reliable protein markers for pre-diabetes in humans, healthy volunteers and patients diagnosed with pre-diabetes and stroke were recruited for blood collection. Blood samples were collected from healthy and pre-diabetic subjects 12 h after fasting. BMI was calculated from body weight and height. Fasting blood glucose (FBG), glycated hemoglobin (HbA1C), triglyceride (TG), total cholesterol, high-density lipoprotein, low-density lipoprotein (LDL), insulin and albumin were assayed by automated clinical laboratory methods. We used a quantitative proteomics approach to identify 1074 proteins from the sera of pre-diabetic and healthy subjects. Among them, 500 proteins were then selected using Mascot analysis scores. Further, 70 out of 500 proteins were selected via volcano plot analysis according to their statistical significance and average relative protein ratio. Eventually, 7 serum proteins were singled out as candidate markers for pre-diabetes due to their diabetic relevance and statistical significance. Immunoblotting data demonstrated that laminin subunit alpha 2 (LAMA2), mixed-lineage leukemia 4 (MLL4), and plexin domain containing 2 (PLXDC2) were expressed in pre-diabetic patients but not healthy volunteers. Receiver operating characteristic curve analysis indicated that the combination of the three proteins has greater diagnostic efficacy than any individual protein. Thus, LAMA2, MLL4 and PLXDC2 are novel and reliable serum protein markers for pre-diabetic diagnosis in humans.

Associations of Circulating Osteoglycin With Bone Parameters and Metabolic Markers in Patients With Diabetes.

Objective: Circulating osteoglycin may facilitate the crosstalk between bone and pancreas to empower adaptation of bone mass to whole body energy balance. We aimed to examine whether osteoglycin is associated with bone and metabolic parameters and if osteoglycin levels differ between patients with type 1 and 2 diabetes (T1D and T2D). Design and methods: A cross-sectional study of 190 patients with diabetes mellitus and stable hemoglobin A1c (HbA1c) (97 T1D and 93 T2D) was conducted. S-osteoglycin was analyzed by ELISA. Unpaired t-tests were performed to test differences between patients with T1D and T2D and linear regression analyses were performed to investigate associations between osteoglycin, glycemic markers, bone turnover markers and characteristics. Results: S-osteoglycin did not differ between patients with T1D and T2D (p=0.10). No associations were present between osteoglycin and age, gender, microvascular complications, HbA1c, or plasma glucose in T1D or T2D patients (p>0.05 for all). S-osteoglycin was not associated with levels of bone turnover markers (C-terminal cross-linked telopeptide of type-I collagen (CTX), P-procollagen type 1 amino terminal propeptide (P1NP), P-osteocalcin (OC), P-sclerostin, S-osteoprotegerin (OPG) or S-Receptor Activator of Nuclear factor Kappa beta Ligand (RANKL)) in neither T1D or T2D patients (p>0.05 for all). Conclusion: Osteoglycin levels were similar in T1D and T2D patients. Osteoglycin did not correlate with glucose, HbA1c or any other biochemical marker of bone turnover. Thus, we did not find evidence supporting the existence of an osteoglycin-bone-pancreas axis. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT01870557.

Efficacy and Safety of Stem Cell Therapy for T1DM: An Updated Systematic Review and Meta-Analysis.

BACKGROUND: The long-term insulin therapy for type 1 diabetes mellitus (T1DM) fails to achieve optimal glycemic control and avoid adverse events simultaneously. Stem cells have unique immunomodulatory capacities and have been considered as a promising interventional strategy for T1DM. Stem cell therapy in T1DM has been tried in many studies. However, the results were controversial. We thus performed a meta-analysis to update the efficacy and safety of stem cell therapy in patients with T1DM. METHODS: We systematically searched the Medline, EMBASE, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, Web of Science, Wan Fang Data, China National Knowledge Infrastructure, VIP database, and the Chinese Biomedical Literature Database (SinoMed) for relevant studies published before March 19, 2019. The outcomes included parameters for glycemic control (i.e., glycosylated hemoglobin (HbA1c) levels and insulin dosages), ß cell function (i.e., fasting C-peptide levels and area-under-curve of C-peptide concentration (AUCC)), and relative risk of adverse events. Statistical analysis was conducted by using RevMan 5.3 and Stata 12.0. RESULTS: Five randomized controlled trials (RCTs) and eight nonrandomized concurrent control trials (NRCCTs) with a total of 396 individuals were finally included into the meta-analysis. Among RCTs, stem cell therapy could significantly reduce HbA1c levels (MD = -1.20, 95% CI -1.91 to -0.49, P = 0.0009) and increase fasting C-peptide levels (MD = 0.25, 95% CI 0.04 to 0.45, P = 0.02) and AUCC (SMD = 0.66, 95% CI 0.13 to 1.18, P = 0.01). Stem cell therapy could also reduce insulin dosages (SMD = -2.65, 95% CI -4.86 to -0.45, P = 0.02) at 6 months after treatment. NRCCTs also had consistent results. Furthermore, RCTs showed stem cell therapy did not increase relative risk of gastrointestinal symptom (RR = 0.69, 95% CI 0.14 to 3.28, P = 0.64) and infection (RR = 0.97, 95% CI 0.40 to 2.34, P = 0.95). However, NRCCTs showed stem cell therapy increased relative risk of gastrointestinal symptom (RR = 44.49, 95% CI 9.20 to 215.18, P < 0.00001). CONCLUSION: Stem cell therapy for T1DM may improve glycemic control and ß cell function without increasing the risk of serious adverse events. Stem cell therapy may also have a short-term (3-6 months) effect on reducing insulin dosages.

Determining the Threshold for HbA1c as a Predictor for Adverse Outcomes After Total Joint Arthroplasty: A Multicenter, Retrospective Study.

BACKGROUND: Although HbA1c is commonly used for assessing glycemic control before surgery, there is no consensus regarding its role and the appropriate threshold in predicting adverse outcomes. This study was designed to evaluate the potential link between HbA1c and subsequent periprosthetic joint infection (PJI), with the intention of determining the optimal threshold for HbA1c. METHODS: This is a multicenter retrospective study, which identified 1645 diabetic patients who underwent primary total joint arthroplasty (1004 knees and 641 hips) between 2001 and 2015. All patients had an HbA1c measured within 3 months of surgery. The primary outcome of interest was a PJI at 1 year based on the Musculoskeletal Infection Society criteria. Secondary outcomes included orthopedic (wound and mechanical complications) and nonorthopedic complications (sepsis, thromboembolism, genitourinary, and cardiovascular complications). A regression analysis was performed to determine the independent influence of HbA1c for predicting PJI. RESULTS: Overall 22 cases of PJI occurred at 1 year (1.3%). HbA1c at a threshold of 7.7 was distinct for predicting PJI (area under the curve, 0.65; 95% confidence interval, 0.51-0.78). Using this threshold, PJI rates increased from 0.8% (11 of 1441) to 5.4% (11 of 204). In the stepwise logistic regression analysis, PJI remained the only variable associated with higher HbA1c (odds ratio, 1.5; confidence interval, 1.2-2.0; P = .0001). There was no association between high HbA1c levels and other complications assessed. CONCLUSION: High HbA1c levels are associated with an increased risk for PJI. A threshold of 7.7% seems to be more indicative of infection than the commonly used 7% and should perhaps be the goal in preoperative patient optimization.

Circulating sortilin level as a potential biomarker for coronary atherosclerosis and diabetes mellitus.

CONTEXT: A previous genome-wide association study showed that a genetic variant of sortilin was associated with the risk of coronary artery disease (CAD). However, the role of circulating sortilin is still unknown. We investigated the potential role of plasma sortilin as a biomarker for CAD and diabetes mellitus. METHODS: We enrolled statin-naïve subjects with CAD (n = 31) who underwent coronary artery bypass surgery and control subjects (n = 116) who were free from CAD as evaluated by coronary CT angiography. The presence of diabetes mellitus was evaluated and plasma sortilin levels were measured with a commercial ELISA kit. RESULTS: Plasma sortilin levels were higher in subjects with CAD and subjects with diabetes mellitus than in those without CAD or diabetes mellitus. Subjects in the highest sortilin tertile group were older and had higher glucose and HbA1c levels, but lipid profiles in the three tertile groups were comparable. Multivariable logistic regression analysis revealed that sortilin levels were independently associated with CAD. In addition, the receiver operating characteristic curve analysis showed that plasma sortilin levels could identify the presence of CAD or diabetes mellitus. CONCLUSIONS: Elevated circulating sortilin levels are associated with CAD and diabetes mellitus and can be used as a biomarker of both diseases in statin-naïve subjects.

Site-specific fatty chain-modified exenatide analogs with balanced glucoregulatory activity and prolonged in vivo activity.

The therapeutic utility of exenatide (Ex-4) is limited due to short plasma half-life of 2.4h and thus numerous approaches have been used to obtain a longer action time. However, such strategies often attend to one thing and lose another. The study aimed to identify a candidate with balanced glucoregulatory activity and prolonged in vivo activity. A series of fatty chain conjugates of Ex-4 were designed and synthesized. First, thirteen cysteine modified peptides (1-13) were prepared. Peptides 1, 10, and 13 showed improved glucagon-like peptide-1 (GLP-1) receptor activate potency and were thus selected for second step modifications to yield conjugates I-1-I-9. All conjugates retained significant GLP-1 receptor activate potency and more importantly exerted enhanced albumin-binding properties and in vitro plasma stability. The protracted antidiabetic effects of the most stable I-3 were further confirmed by both multiple intraperitoneal glucose tolerance test and hypoglycemic efficacies test in vivo. Furthermore, once daily injection of I-3 to streptozotocin (STZ) induced diabetic mice achieved long-term beneficial effects on hemoglobin A1C (HbA1C) lowering and glucose tolerance. Once daily injection of I-3 to diet induced obesity (DIO) mice also achieved favorable effects on food intake, body weight, and blood chemistry. Our results suggested that I-3 was a promising agent deserving further investigation to treat obesity patients with diabetes.

Influence of iron deficiency anemia on hemoglobin A1c levels in diabetic individuals with controlled plasma glucose levels.

INTRODUCTION: Hemoglobin A1C (HbA1c) reflects patient's glycemic status over the previous 3 months. Previous studies have reported that iron deficiency may elevate A1C concentrations, independent of glycemia. This study is aimed to analyze the effect of iron deficiency anemia on HbA1c levels in diabetic population having plasma glucose levels in control. METHODS: Totally, 120 diabetic, iron-deficient anemic individuals (70 females and 50 males) having controlled plasma glucose levels with same number of iron-sufficient non-anemic individuals were streamlined for the study. Their data of HbA1c (Bio-Rad D-10 HPLC analyzer), ferritin (cobas e411 ECLIA hormone analyzer), fasting plasma glucose (FPG, Roche Hitachi P800/917 chemistry analyzer), hemoglobin (Beckman Coulter LH780), peripheral smear examination, red cell indices, and medical history were recorded. Statistical analysis was carried out by student's t-test, Chi-square test, and Pearson's coefficient of regression. RESULTS: We found elevated HbA1c (6.8 ± 1.4%) in iron-deficient individuals as compared to controls, and elevation was more in women (7.02 ± 1.58%). On further classification on the basis of FPG levels, A1C was elevated more in group having fasting glucose levels between 100-126 mg/dl (7.33 ± 1.55%) compared to the those with normal plasma glucose levels (<100 mg/dl). No significant correlation was found between HbA1c and ferritin and hemoglobin. CONCLUSION: This study found a positive correlation between iron deficiency anemia and increased A1C levels, especially in the controlled diabetic women and individuals having FPG between 100-126 mg/dl. Hence, before altering the treatment regimen for diabetic patient, presence of iron deficiency anemia should be considered.

Effect of bile acid sequestrants on glucose metabolism, hepatic de novo lipogenesis, and cholesterol and bile acid kinetics in type 2 diabetes: a randomised controlled study.

AIMS/HYPOTHESIS: The primary aim of this completed multicentre randomised, parallel, double-blind placebo-controlled study was to elucidate the mechanisms of glucose-lowering with colesevelam and secondarily to investigate its effects on lipid metabolism (hepatic de novo lipogenesis, cholesterol and bile acid synthesis). METHODS: Participants with type 2 diabetes (HbA(1c) 6.7-10.0% [50-86 mmol/mol], fasting glucose <16.7 mmol/l, fasting triacylglycerols <3.9 mmol/l and LDL-cholesterol >1.55 mmol/l) treated with diet and exercise, sulfonylurea, metformin or a combination thereof, were randomised by a central coordinator to either 3.75 g/day colesevelam (n = 30) or placebo (n = 30) for 12 weeks at three clinical sites in the USA. The primary measure was the change from baseline in glucose kinetics with colesevelam compared to placebo treatment. Fasting and postprandial glucose, lipid and bile acid pathways were measured at baseline and post-treatment using stable isotope techniques. Plasma glucose, insulin, total glucagon-like peptide-1 (GLP-1), total glucose-dependent insulinotropic polypeptide (GIP), glucagon and fibroblast growth factor-19 (FGF-19) concentrations were measured during the fasting state and following a meal tolerance test. Data was collected by people blinded to treatment. RESULTS: Compared with placebo, colesevelam improved HbA(1c) (mean change from baseline of 0.3 [SD 1.1]% for placebo [n = 28] and -0.3 [1.1]% for colesevelam [n = 26]), glucose concentrations, fasting plasma glucose clearance and glycolytic disposal of oral glucose. Colesevelam did not affect gluconeogenesis or appearance rate (absorption) of oral glucose. Fasting endogenous glucose production and glycogenolysis significantly increased with placebo but were unchanged with colesevelam (treatment effect did not reach statistical significance). Compared with placebo, colesevelam increased total GLP-1 and GIP concentrations and improved HOMA-beta cell function while insulin, glucagon and HOMA-insulin resistance were unchanged. Colesevelam increased cholesterol and bile acid synthesis and decreased FGF-19 concentrations. However, no effect was seen on fractional hepatic de novo lipogenesis. CONCLUSIONS/INTERPRETATION: Colesevelam, a non-absorbed bile acid sequestrant, increased circulating incretins and improved tissue glucose metabolism in both the fasting and postprandial states in a manner different from other approved oral agents. TRIAL REGISTRATION: ClinicalTrials.gov NCT00596427 FUNDING: The study was funded by Daiichi Sankyo.

Cardiometabolic effects of rosiglitazone in patients with type 2 diabetes and coronary artery bypass grafts: A randomized placebo-controlled clinical trial.

OBJECTIVES: To assess the efficacy and safety of rosiglitazone on saphenous vein graft (SVG) atherosclerosis prevention and on modification of the global cardiometabolic risk profile. METHODS AND RESULTS: This was a double-blind, randomized, placebo-controlled, multicenter trial which enrolled 193 post-CABG patients with type 2 diabetes. Atherosclerosis changes in one SVG were assessed with intravascular ultrasound at baseline and at 12 months. Serial cardiometabolic assessments were performed. At baseline, both groups had mean HbA(1C)<7%, LDL-cholesterol (LDL-C)<2.3 mmol/l, HDL-cholesterol (HDL-C)>1.0 mmol/l and blood pressure<130/75 mmHg. After 12 months, plaque volume in SVG had increased (median [interquartile range]) by 7.7 mm(3) (-17.2 to 37.9) in the placebo group and decreased by 0.3mm(3) (-19.1 to 22.3) in the rosiglitazone group (P=0.22). Compared to placebo, rosiglitazone treated patients had a higher (mean + or - SD) body weight (89 + or - 15 kg vs. 84 + or - 15 kg, P=0.02) at the end of the study, mostly related to an increment in subcutaneous adipose tissue. Rosiglitazone treated patients also displayed further improvements in glycemic control compared to placebo (HbA(1C): 6.4 + or - 0.7% vs. 7.0 + or - 0.9%, P<0.001) as well as in several cardiometabolic parameters such as lipids (HDL-C: 1.16 + or - 0.28 mmol/l vs. 1.06 + or - 0.23 mmol/l, P=0.003), inflammatory profile (C-reactive protein: 0.92 mg/l [0.51-1.56] vs. 1.37 mg/l [0.79-3.08], P=0.02), and adiponectin levels (11.1 microg/ml [8.19-17.9] vs. 4.65 microg/ml [3.27-7.15], P<0.001). There was no significant difference in the incidence of serious adverse cardiovascular events. However, more patients in the rosiglitazone group had peripheral oedema (33% vs. 18%, P=0.0019). CONCLUSION: After a 12-month follow-up, we found no evidence for a statistically significant effect of rosiglitazone on SVG atherosclerosis whereas significant effects on glycemic control and on the cardiometabolic risk profile appeared to be modulated in part by changes in subcutaneous adiposity.

High-fat feeding period affects gene expression in rat white adipose tissue.

The expression of 76 sequences, previously isolated as differentially expressed in visceral white adipose tissue (WAT) of female rats, fed with a high-fat diet for 11 days (Lopez et al., Biochem Biophys Res Comm 318: 234-239, 2004), was analyzed in epidydimal WAT of male rats after a feeding period of 65 days with the same diet, using microarray technology. After Northern blot validation of the results, only three genes appeared upregulated (caveolin-2, the alpha-1 chain of haemoglobin and rat mammary tumor-7) and two downregulated (adiponectin and dystroglycan). We have also analyzed caveolin-1 gene expression and found that follows the opposite pattern of caveolin-2, indicating that they are inversely regulated. Our results suggest that if feeding with a high-fat diet is prolonged, many of the initial changes in gene expression, probably aimed to consume the energy surplus and prevent excessive fat deposition, are not maintained, and adaptation to an increased lipid storage is developed.

Possible link between glycated hemoglobin and lipid peroxidation in hyperthyroidism.

BACKGROUND: Glycated hemoglobin (HbA1C) levels are enhanced by elevated glucose concentrations. Glycation of hemoglobin is also modulated by lipid peroxides, ascorbic acid and reduced glutathione (GSH). We determined the strength of the relationships among these variables in a group of hyperthyroid patients. METHODS: Twenty-two untreated hyperthyroid patients and 17 healthy controls were recruited for the study. Whole blood GSH, HbA1C, plasma lipid peroxides, ascorbic acid and fasting glucose were analyzed in both the groups. Direct and partial correlation analysis was performed to explore the possible relationships between these variables. RESULTS: In hyperthyroid patients, HbA1C and lipid peroxides levels were found to be significantly increased than the controls. Ascorbic acid and GSH were decreased significantly in the test group when compared with the healthy control group. With partial correlation analysis, fasting glucose and lipid peroxides were found to have a significant positive correlation with HbA1C. Ascorbic acid and GSH showed no significant association with HbA1C levels. CONCLUSION: These data suggest that HbA1C levels are closely associated with fasting glucose and lipid peroxides in hyperthyroid patients. Therefore, serum lipid peroxides level should be kept in mind while interpreting HbA1C as a long-term glycemic index in hyperthyroid cases.

[Maternal serum tumor necrosis factor-alpha concentration and correlation with insulin resistance in gestational diabetes].

OBJECTIVE: To investigate serum concentration of tumor necrosis factor (TNF)-alpha and its correlation with insulin resistance in pregnant women with gestational diabetes mellitus (GDM). METHODS: Enzyme-linked immunosorbent assay was used to measure the fasting serum TNF-alpha levels of 42 women with GDM (28 approximately 39 gestational weeks), and 40 cases of normal pregnant women in the third trimester. Fasting plasma glucose, insulin, C-peptide and glycosylated hemoglobin (HbA1c) were also measured at the same time. Insulin sensitive index (ISI) was calculated. RESULTS: (1) Significantly elevated serum TNF-alpha was found in the women with GDM (5.2 +/- 1.6) ng/L as compared with the healthy pregnant women in third trimester (4.5 +/- 0.5) ng/L (P < 0.01); ISI between the two groups was significantly different, (-4.3 +/- 0.5) and (...3.8 +/- 0.3) (P < 0.01). (2) fasting plasma glucose, insulin, C-peptide, HbA1c in GDM group were (5.5 +/- 0.7) mmol/L, (13.4 +/- 3.8) mU/L, (1.6 +/- 0.4) nmol/L, (5.6 +/- 0.5)%, being significantly higher than those in the normal pregnant women (P < 0.01 or P < 0.05). (3) Significant negative linear correlation was revealed between TNF-alpha and ISI (r = -0.703, P < 0.01), and positive linear correlations between TNF-alpha and plasma glucose, C-peptide, and HbA1c were found (r = 0.512, 0.629, 0.386); but no correlation between TNF-alpha and insulin was found in GDM group. In normal group the correlation between ISI and TNF-alpha was also found (r = -0.390, P < 0.05), but less significant than that in the GDM group. CONCLUSIONS: Fasting plasma TNF-alpha levels in pregnant women with GDM is significantly higher than in normal pregnant women. A negative relationship between TNF-alpha and insulin sensitivity index is found in GDM, suggesting increased TNF-alpha may contribute to insulin resistance in pregnant women with gestational diabetes.

Determinación colorimétrica de proteínas glicadas en sangre entera. Recolección de muestras en papel de filtro. Valores de referencia en niños / Colorimetric determination of glycated whole blood protein collection of samples on filter paper. Reference values on children

Las proteínas glicadas en sangre entera (PGSE) constituyen un parámetro que permite el seguimiento del control glucémico en pacientes con Diabetes mellitus, ofreciendo información de la glucemia promedio en los dos a tres meses previos. En el presente trabajo se llevó a cabo la puesta a punto del método colorimétrico del ácido 2-tiobarbitúrico (ATB) para medir PGSE, recolectada en papel de filtro. El fundamento del método consiste en la conversión del glúcido unido a la proteína a 5-hidroximetilfurfural (5-HMF) por calentamiento a 100 C en presencia de ácido oxálico. Por reacción entre 5-HMF y ATB se forma un compuesto coloreado que puede cuantificarse a 443 nm. Se estableció una comparación de los resultados de PGSE con HbA, medida por cromatografía de intercambio iónico (r=0,505) y por método colorimétrico del ATB (r=o,948). Este último estudio comparativo permite demostrar que las PGSE están constituidas en un 70-90% por HbA1, correspondiendo el porcentaje restante a proteínas séricas glicadas. También se estudió una población infantil normal obteniéndose un intervalo de referencia para PGSE de 41-87 nmol fructuosa/10mg proteínas; y una población infantil diabética, tipo I, observándose que el método en estudio permite diferenciar claramente los pacientes diabéticos compensados de aquellos no compensados. Los C.V.% intra e interensayo para estándares fueron inferiores a 4,3 y 5,3% respectivamente, en tanto para muestras fueron de 4,5 y 6,5% respectivamente. Además se observó que el método es sensible, barato y presenta ventajas respecto de otros métodos, ya que elimina la interferencia de hemoglobinopatías, aductos de Hb no glicadas y forma aldimina inestable; y no es influido por el pH y la temperatura

[Glucose and its protein environment in vivo]. / Le glucose et son environnement protéique in vivo.

The non-enzyme reaction by which glucose can combine with free amines has been known since the beginning of the century: in 1912, Mallard reported the combination of glucose with amino acids. This reaction results in the formation of cetoamine or fructosamine as well as often complex sub-products responsible for a change in the color of the medium that turns brown. This process, which food chemists are well-familiar with, was not observed in vivo until three-quarters of a century later. In 1975, hemoglobin A was shown to combine with glucose by means of a non-enzyme reaction, producing hemoglobin A1c. HbA1c is now believed to be a "black box", i.e. a cumulative reflection of all the hyperglycemic episodes that occurred over the last hundred days. This discovery was followed by an impressive number of similar observations: nearly all the available amines seem able to participate in this kind of reaction. Plasma proteins, membrane proteins, structural proteins such as collagen, the apolipoproteins of circulating lipoproteins, intracellular tubulines, and even nucleic acids seem capable of undergoing glycation. A great number of bioclinica uses of this phenomenon have already been developed. Diabetes mellitus has benefited most from these investigations and, from a broader viewpoint, studies in this field are unquestionably central to our understanding of atherosclerosis, inflammation, and cancer. Furthermore, the entire spectrum of these observations are related to ageing.

Nonenzymatically glycosylated proteins.

Nonenzymatic glycosylation takes place in all proteins with a free-reacting lysine or valine in the presence of glucose. The formation of glycosylated plasma albumin, hemoglobin (Hb A1c), and skin collagen provides a diagnostic index of short- to long-term time-concentration of glucose in vivo. A wide range of assay methods are available, with affinity chromatographic, isoelectric focusing, and spectrophotometric methods providing the best accuracy and versatility. Glycosylated hemoglobin assays indicate glucose pressure over the previous 2 to 3 months and are of diagnostic value in general diabetic control, while glycosylated plasma albumin determinations are preferable in acute episodes in the life of a diabetic (e.g., pregnancy, infection, stress, trauma, surgery), since they provide an overview of changing blood glucose values of the previous 2 to 4 weeks. Glycosylated collagen estimations reflect tissue aging and are relevant in healing processes. Glycosylation alters the biologic activity of proteins, and these may relate to the manifold complications concomitant on the lifelong elevation of blood and tissue glucose in the diabetic (C6a). Assays for glycosylated hemoglobin have been routinely performed in clinical chemistry laboratories for a decade, and convenient determination for other nonenzymatically glycosylated proteins is proceeding apace.