Hyperglycemic Subjects Research Articles

Valsalva ratios and insulin sensitivity

The chronic metabolic disorders, obesity, diabetes, hypertension and heart disease are approaching epidemic proportions in the U.S. These disorders are more frequent, occur earlier and are often more severe in ethnic minorities. This ongoing study is designed to evaluate differences in the hormonal and cardiovascular status of African, Caucasian and Hispanic American adults in various states of health and disease. The study hopes to develop a database of less‐invasive methodologies to identify people most at‐risk for diabetes and heart disease early, before the diseases develop. The study also plans to evaluate whether cellular and humoral markers differ among ethnic groups. Estimated insulin sensitivity among the study population was as predicted for the general population. Relationships between blood glucose and insulin delineated healthy normals, diabetics and a transitional group of mildly hyperglycemic and euglycemic subjects with estimated insulin sensitivities very similar to that of diabetics. In approximately half of the subjects, glucagon declined sharply as expected during glycemic challenge. However, glucagon remained unchanged or was elevated in the remaining subjects. Autonomic reflex responses based on standardized valsalva ratios indicated approximately half of the subjects were below historical norms. The valsalva ratios correlated tightly with insulin sensitivity.

Glucose control, organ failure, and mortality in pediatric intensive care*

In ventilated children, to determine the prevalence of hyperglycemia, establish whether it is associated with organ failure, and document glycemic control practices in Australasian pediatric intensive care units (PICUs). Prospective inception cohort study. All nine specialist PICUs in Australia and New Zealand. Children ventilated > 12 hrs excluding those with diabetic ketoacidosis, on home ventilation, undergoing active cardiopulmonary resuscitation on admission, or with do-not-resuscitate orders. None. All blood glucose measurements for up to 14 days, clinical and laboratory values needed to calculate Paediatric Logistic Organ Dysfunction (PELOD) scores, and insulin use were recorded in 409 patients. Fifty percent of glucose measurements were > 6.1 mmol/L, with 89% of patients having peak values > 6.1 mmol/L. The median time to peak blood glucose was 7 hrs. Hyperglycemia was defined by area under the glucose-time curve > 6.1 mmol/L above the sample median. Thirteen percent of hyperglycemic subjects died vs. 3% of nonhyperglycemic subjects. There was an independent association between hyperglycemia and a PELOD score > or = 10 (odds ratio 3.41, 95% confidence interval 1.91-6.10) and death (odds ratio 3.31, 95% confidence interval 1.26-7.7). Early hyperglycemia, defined using only glucose data in the first 48 hrs, was also associated with these outcomes but not with PELOD > or = 10 after day 2 or with worsening PELOD after day 1. Five percent of patients received insulin. Hyperglycemia is common in PICUs, occurs early, and is independently associated with organ failure and death. However, early hyperglycemia is not associated with later or worsening organ failure. Australasian PICUs seldom use insulin.

Auditory acuity in type 2 diabetes mellitus

BACKGROUND AND OBJECTIVES:The relationship between diabetes and hearing loss has been debated for many years. Hyperglycemia appears to have an effect on hearing loss and the proposed mechanisms are microangiopathy, neuropathy or a combination of both. The objective of this study was to evaluate a cross section of hyperglycemic subjects with age- and sex-matched normoglycemic controls with pure tone audiometry and compare the differences.MATERIALS AND METHODS:Forty-one type 2 diabetes mellitus subjects and 41 age- and sex-matched normoglycemic controls were subjected to a pure tone audiometric assessment followed by evaluation of their glycemic status and degree of glycemic control. The resulting data was statistically analyzed.RESULTS:The auditory thresholds in hyperglycemic subjects were higher in all age groups in all the frequencies suggestive of sensorineural hearing loss. The hyperglycemic subjects with poor control of their blood sugar levels (HbA1C > 8%) had elevated auditory thresholds in all the test frequencies. The fasting blood sugar level in hyperglycemic subjects showed a trend towards significant difference at higher frequencies, the postprandial blood sugar levels showed significant differences at higher frequencies. There was no effect of duration of diabetes mellitus on the hearing thresholds in hyperglycemic subjects.CONCLUSION:Subjects with hyperglycemia have a sensorineural hearing loss when evaluated with a pure tone audiometer in all frequencies than a normoglycemic control group. The study showed that post prandial blood sugar levels and HbA1C levels had a direct bearing on the auditory acuity of the hyperglycemic subjects.

Glucose metabolism in lymphoid and inflammatory cells and tissues

To examine the role of glucose as a fuel for immune cells and the influence of glucose supply on immune-cell functional responses. Immune cells express the insulin receptor and a range of glucose-transporter isoforms. Glucose transporters are responsive to both immune stimulation and insulin. The pattern of glucose-transporter upregulation differs among different types of immune cell. In-vitro studies reveal that both hypo- and hyperglycaemia impair immune-cell functions and promote inflammatory responses. Clamp studies have revealed proinflammatory effects of hyperglycaemia and antiinflammatory and immune-promoting effects of insulin. Glucose is readily utilized by cells of the immune system and is used to generate energy and biosynthetic precursors. Activation of immune cells is associated with increased glucose utilization and this is facilitated, in part, by increased expression of glucose transporters. Immune cells express the insulin receptor and respond to insulin. Both hypo- and hyperglycaemia impair immune-cell functions and promote inflammatory responses. Insulin therapy in hyperglycaemic subjects may be of benefit through effects of both insulin itself and lowered glucose concentration. Excessive lowering of blood glucose concentration may also be harmful to the immune response.

Short- and long-term glycaemic control and the state of the renin system in type 1 diabetes mellitus

Renin system blockade in diabetes exerts a strong positive influence on complications, especially nephropathy. In hyperglycaemic diabetic subjects, however, blockade of the renin-angiotensin system with angiotensin-converting enzyme inhibitors results in a marked rise in plasma renin. We investigated whether glycaemic fluctuations measured in hours, or those measured in weeks by Haemoglobin A(1C) (HbA(1C)) , influenced the plasma renin response to captopril. Fifty-four type 1 diabetic subjects were studied in high-salt balance. After an all night fast and in the supine position, baseline serum glucose level was drawn. Iv. glucose and insulin were then administered to keep serum glucose between 100 and 150 mg/dL (target). When target was reached, captopril 25 mg pre os was administered and plasma renin activity (PRA) and finger stick glucose were drawn, then serially every 45 minutes for 225 minutes. Baseline glucose and baseline PRA were drawn hours apart. Peak PRA corresponded to the renin level at peak captopril effect, 90' after administration. Renin response (RR) = peak PRA - baseline PRA. Correlation of baseline glucose with baseline PRA was weak (r=0.3, p=0.02), but strong with peak PRA (r=0.65; p=0.002). Drop in glucose had a weak, negative correlation with baseline PRA (r=-0.3, p=0.03) but a much stronger one with peak PRA (r=-0.7, p<0.0001). After adjustment for baseline PRA and baseline glucose, mean RR correlated strongly with mean drop in glucose (r=-0.72; p=0.008). Conversely, HbA1C correlated with none of the measures of renin system activation (r=0.05;p=0.7). In type 1 diabetic subjects, short-term hyperglycaemia, but not long-term glycaemic control, enhanced the RR to captopril.

Cell Biology Assessment of Glucokinase Mutations V62M and G72R in Pancreatic β-Cells

Mutations in the glucokinase (GK) gene cause defects in blood glucose homeostasis. In some cases (V62M and G72R), the phenotype cannot be explained by altered enzyme kinetics or protein instability. We used transient and stable expression of green fluorescent protein (GFP) GK chimaeras in MIN6 beta-cells to study the phenotype defect of V62M and G72R. GK activity in lysates of MIN6 cell lines stably expressing wild-type or mutant GFP GK showed the expected affinity for glucose and response to pharmacological activators, indicating the expression of catalytically active enzymes. MIN6 cells stably expressing GFP V62M or GFP G72R had a lower GK activity-to-GK immunoreactivity ratio and GK activity-to-GK mRNA ratio but not GK immunoreactivity-to-GK mRNA ratio than wild-type GFP GK. Heterologous expression of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FDP2) in cell lines increased GK activity for wild-type GK and V62M but not for G72R, whereas expression of liver GK regulatory protein (GKRP) increased GK activity for wild type but not V62M or G72R. Lack of interaction of these mutants with GKRP was also evident in hepatocyte transfections from the lack of nuclear accumulation. These results suggest that cellular loss of GK catalytic activity rather than impaired translation or enhanced protein degradation may account for the hyperglycemia in subjects with V62M and G72R mutations.

Paired values of serum fructosamine and blood glucose for the screening of gestational diabetes mellitus: A retrospective study of 165 Saudi pregnant women

This study reports the utilization of serum fructosamine and blood glucose for the screening of gestational diabetes mellitus (GDM). Blood samples from 165 pregnant women were analyzed for fasting blood glucose (FBG), random blood glucose (RBG) and serum fructosamine. The actual fructosamine levels were corrected for serum protein (c-Fruct) for more precise presentation. Two cut-off values of FBG (>5.3 mmol/L and >7.0 mmol/L) and RBG (>7.8 mmol/L and >11.0 mmol/L) were used to classify hyperglycemic subjects for subsequent evaluation. The average values±standard deviations for FBG, RBG and cFruct were 5.865±1.95, 7.767±3.21 and 2.387±0.47 mmol/L, respectively. FBG levels were significantly correlated with RBG (Pearson correlation=0.597, P<0.001). Significant correlations were also observed between cFruct and FBG (Pearson correlation=0.673, P<0.001) or RBG (Pearson correlation=0.641, P<0.001). Out of 165 subjects, 24 (14.5%) cases were classified as hyperglycemic on the basis of FBG>7.0 mmol/L or RBG>11.0 mmol/L; use of lower cut-off values resulted higher frequencies of hyperglycemia. Whereas, a combined criteria of FBG>5.3 mmol/L and cFruct >2.5 mmol/L predicted 35 patients as the most probable hyperglycemic as compared to 32 patients identified using the criteria of RBG >7.8 mmol/L and cFruct >2.5 mmol/L. These criteria were associated with 4.8% and 3.6% false-positivity at the expense of 3.6% and 3.0% false-negative outcomes, respectively. The levels of FBG, RBG and cFruct were significantly higher in hyperglycemic groups (irrespective of grouping criteria) as compared to the respective normal groups. In conclusion, these findings clearly indicate that the paired values of cFruct with FBG or RBG could help in filtering high-risk individuals for OGTT and therefore avoiding a unnecessary OGTT.

Close Relationship Between Sympathetic Activation and Coronary Microvascular Dysfunction During Acute Hyperglycemia in Subjects With Atherosclerotic Risk Factors

The effect of acute hyperglycemia (AHG) during the oral glucose tolerance test (OGTT) on coronary microvascular function was evaluated, as well as the associations among the changes in coronary microvascular function, oxidative stress, and sympathetic tone. Transthoracic Doppler echocardiography and OGTT were performed in 24 subjects with atherosclerotic risk factors (61+/-9 years). The coronary flow velocity before and during the infusion of adenosine (CFV(hyp)), plasma levels of thiobarbituric acid-reactive substances (TBARS), and the low-frequency/high-frequency power (LF/HF) ratio yielded by power spectral analysis of heart rate variability were measured before and at 1 h during 75-g OGTT. AHG significantly decreased the CFV(hyp), and increased the TBARS and LF/HF. Multiple linear regression analysis revealed that the percent changes in the CFV(hyp) were significantly associated with the percent changes in the LF/HF ratio (beta=-0.43, p<0.05). In subjects with atherosclerotic risk factors who may be considered likely to have atherosclerotic arterial damage, AHG seems to induce concomitant coronary microvascular dysfunction, increased oxidative stress, and sympathetic activation. Coronary microvascular dysfunction, therefore, appears to be closely related to sympathetic activation.

Clinical Studies on Chromium Picolinate Supplementation in Diabetes Mellitus—A Review

Chromium (Cr) picolinate (CrPic) is a widely used nutritional supplement for optimal insulin function. A relationship among Cr status, diabetes, and associated pathologies has been established. Virtually all trials using CrPic supplementation for subjects with diabetes have demonstrated beneficial effects. Thirteen of 15 clinical studies (including 11 randomized, controlled studies) involving a total of 1,690 subjects (1,505 in CrPic group) reported significant improvement in at least one outcome of glycemic control. All 15 studies showed salutary effects in at least one parameter of diabetes management, including dyslipidemia. Positive outcomes from CrPic supplementation included reduced blood glucose, insulin, cholesterol, and triglyceride levels and reduced requirements for hypoglycemic medication. The greater bioavailability of CrPic compared with other forms of Cr (e.g., niacin-bound Cr or CrCl(3)) may explain its comparatively superior efficacy in glycemic and lipidemic control. The pooled data from studies using CrPic supplementation for type 2 diabetes mellitus subjects show substantial reductions in hyperglycemia and hyperinsulinemia, which equate to a reduced risk for disease complications. Collectively, the data support the safety and therapeutic value of CrPic for the management of cholesterolemia and hyperglycemia in subjects with diabetes.

Glucagon receptor knockout mice are resistant to diet-induced obesity and streptozotocin-mediated beta cell loss and hyperglycaemia

Under normal physiological conditions, glucagon signalling is important in glucose homeostasis. Hyperglucagonaemia or altered insulin:glucagon ratio plays a role in maintaining hyperglycaemia in subjects with type 2 diabetes. It has been reported that glucagon receptor knockout (Gcgr (-/-)) mice develop normally and have lower plasma glucose on a normal diet. The goal of the current research was to further investigate the role of glucagon signalling in metabolic control and glucose homeostasis. Gcgr (-/-) mice were challenged with a high-fat diet (HFD) and with streptozotocin, which induces beta cell damage. They were then analysed for whole-body and serum metabolic phenotypes as well as pancreatic islet morphology. In comparison with wild-type mice, Gcgr (-/-) mice exhibited decreased body weight and food intake, reduced plasma glucose levels, and improved oral and intraperitoneal glucose tolerance. Elevated glucagon-like peptide-1 levels and reduced gastric emptying were also observed in Gcgr (-/-) mice, which also had reduced HFD-induced hyperinsulinaemia and hyperleptinaemia, and were resistant to the development of hepatic steatosis. In addition, Gcgr (-/-) mice were resistant to STZ-induced hyperglycaemia and pancreatic beta cell destruction. This study demonstrates that blocking glucagon signalling by targeted Gcgr gene deletion leads to an improvement in metabolic control in this mouse model.

Brain lactate responses during visual stimulation in fasting and hyperglycemic subjects: A proton magnetic resonance spectroscopy study at 1.5 Tesla

Proton magnetic resonance spectroscopy ( 1H-MRS) studies showing increased lactate during neural activation support a broader role for lactate in brain energy metabolism than was traditionally recognized. Proton MRS measures of brain lactate responses have been used to study regional brain metabolism in clinical populations. This study examined whether variations in blood glucose influence the lactate response to visual stimulation in the visual cortex. Six subjects were scanned twice, receiving either saline or 21% glucose intravenously. Using 1H-MRS at 1.5 Tesla with a long echo time (TE = 288 ms), the lactate doublet was visible at 1.32 ppm in the visual cortex of all subjects. Lactate increased significantly from resting to visual stimulation. Hyperglycemia had no effect on this increase. The order of the slice-selective gradients for defining the spectroscopy voxel had a pronounced effect on the extent of contamination by signal originating outside the voxel. The results of this preliminary study demonstrate a method for observing a consistent activity-stimulated increase in brain lactate at 1.5 T and show that variations in blood glucose across the normal range have little effect on this response.

The Effects of Lifestyle Changing Program on Plasma and Body Compositions of Hyperglycemic Subjects

The Effects of Lifestyle Changing Program on Plasma and Body Compositions of Hyperglycemic Subjects

Serum carotenoid concentrations are inversely associated with serum aminotransferases in hyperglycemic subjects

Hyperglycemia increases the generation of free radicals by glucose auto-oxidation, and the increment of free radicals may lead to liver cell damage. In this study, we tested the hypothesis that hyperglycemia-induced increases of serum liver enzymes among its physiological concentration would be inversely associated with serum antioxidant carotenoid level. Study subjects were 857 male and female Japanese who had received health examinations in 2003. Those with a history of liver disease and excessive alcohol drinkers were excluded. The associations of serum six-carotenoid concentrations with serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) stratified by glucose tolerance status were evaluated cross-sectionally. Serum AST and ALT concentrations in the groups of impaired fasting glucose (IFG) and diabetes were significantly higher than those in the normal group. The multivariate-adjusted means of the serum AST and ALT concentrations in IFG and diabetes group were significantly low in accordance with the tertiles of the serum β-cryptoxanthin and β-carotene concentrations. The most inverse association of serum liver enzyme and carotenoid concentration was observed in β-cryptoxanthin. Antioxidant carotenoid, especially β-cryptoxanthin, may act a deterrent substance against increasing the serum aminotransferase in the earlier pathogenesis of liver dysfunction among hyperglycemic subjects.

Nutritional, Dietary and Postprandial Oxidative Stress

Nutritional, or dietary oxidative stress denotes a disturbance of the redox state resulting from excess oxidative load or from inadequate nutrient supply favoring prooxidant reactions. Low intake or impaired availability of dietary antioxidants including vitamins E and C, carotenoids, polyphenols, and other micronutrients (e.g., selenium) weakens the antioxidant network. Postprandial oxidative stress, as a subform of nutritional oxidative stress, ensues from sustained postprandial hyperlipidemia and/or hyperglycemia and is associated with a higher risk for atherosclerosis, diabetes, and obesity. In Western societies, a significant part of the day is spent in the postprandial state. Unsaturated fatty acids incorporated into LDL and oxidized LDL are an atherogenic factor. Lipid hydroperoxides present in the diet are absorbed, contributing to the prooxidant load. In hyperlipidemic and hyperglycemic subjects, endothelium-dependent vasodilation is impaired in the postprandial state, making postprandial oxidative stress an important factor modulating cardiovascular risk. Postprandial oxidative stress is attenuated when dietary antioxidants are supplied together with a meal rich in oxidized or oxidizable lipids. Ingestion of dietary polyphenols, e.g., from wine, cocoa, or tea, improves endothelial dysfunction and lowers the susceptibility of LDL lipids to oxidation. Polyphenols affect endothelial function not solely as antioxidants but also as modulatory signaling molecules.

Comparison of Keratinocyte Proliferation in Diabetic and Non‐Diabetic Inflamed Gingiva

Keratinocytes are chiefly cells of the epidermis but also constitute 90% of the gingival cells. The molecular mechanisms of proliferative activity in keratinization whereby diabetes alters periodontal physiology have not been elucidated. In this study, we aimed to investigate the role of gingival keratinocytes in hyperglycemic subjects by examining their mitotic activities. We tested 30 patients with periodontitis, of whom 15 were type II diabetics and the remainder systemically healthy. Biopsies were obtained from the bottom of the deepest pocket in each subject by reverse beveled incision. Formalin-fixed and paraffin-embedded specimens were then processed for periodic acid-Schiff (PAS)-diastase histochemistry and proliferating cell nuclear antigen (PCNA) (P10). Immunohistochemical studies were employed to determine the presence of PCNA and were used to detect the proliferating potential of keratinocytes needed in synthesizing DNA. The expression of PCNA was evaluated using an immunoperoxidase technique and PC10 monoclonal antibody to PCNA. Mitotic index was calculated from basal cells. Statistical analysis employed the chi-square test. No significant difference between the diabetic and non-diabetic patients was found in the mitotic index of the oral-gingival epithelium. Although the mitotic index in patients with diabetes was slightly lower, keratinization in the gingival tissues for both groups was essentially identical.

Both relative insulin resistance and defective islet beta-cell processing of proinsulin are responsible for transient hyperglycemia in extremely preterm infants.

Many extremely preterm infants develop hyperglycemia in the first week of life during continuous glucose infusion. The objective of this study was to determine whether defective insulin secretion or resistance to insulin was the primary factor involved in transient hyperglycemia of extremely preterm infants. A prospective comparative study was conducted in appropriate-for-gestational-age preterm infants <30 weeks of gestational age with the aim specifically to evaluate the serum levels of proinsulin, insulin, and C-peptide secreted during transient hyperglycemia by specific immunoassays. Three groups of infants were investigated hyperglycemic (n = 15) and normoglycemic preterm neonates (n = 12) and normal, term neonates (n = 21). In addition, the changes in beta-cell peptide levels were analyzed during and after intravenous insulin infusion in the hyperglycemic group. Data were analyzed using analysis of variance and analysis of variance for repeated measures. At inclusion, insulin and C-peptide levels did not differ in hyperglycemic subjects and in preterm controls. Proinsulin concentration was significantly higher in the hyperglycemic group (36.5 +/- 3.9 vs 23.2 +/- 0.9 pmol/L). Compared with term neonates, proinsulin and C-peptide levels were higher in normoglycemic preterm infants (23.2 +/- 0.9 vs 18.9 +/- 2.71 pmol/L and 1.67 +/- 0.3 vs 0.62 +/- 0.12 nmol/L, respectively). During and after insulin infusion in hyperglycemic neonates, plasma glucose concentration fell and proinsulin and C-peptide levels were lowered (18.4 +/- 7.6 and 20.7 +/- 4.5 pmol/L, respectively). These data suggest that 1) preterm neonates are sensitive to changes in plasma glucose concentration, but proinsulin processing to insulin is partially defective in hyperglycemic preterm neonates; 2) hyperglycemic neonates are relatively resistant to insulin because higher insulin levels are needed to achieve euglycemia in this group compared with normoglycemic neonates. These results also show that insulin infusion is beneficial in extremely preterm infants with transient hyperglycemia.

Markers of endothelial dysfunction in hyperglycaemic Asian Indian subjects

Objective: The aims of this study were the following: (1) to determine the levels of endothelin-1(ET1), soluble adhesion molecules like intracellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in different stages of glucose intolerance and to identify a suitable marker of endothelial dysfunction and (2) to determine the possible association of these biochemical parameters with diabetic complications and with impaired glucose tolerance (IGT). Research Design and Methods: In this cross-sectional study, plasma ET1, sICAM-1, and sVCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) in 20 nondiabetic subjects, in 15 subjects with IGT, in 21 Type 2 diabetic subjects without any complication, and in 21 Type 2 diabetic patients with nephropathy and retinopathy. Results: Median ET1 levels were significantly elevated ( P=.004) in IGT subjects (0.31 fmol/ml) when compared with the nondiabetic subjects (0.11 fmol/ml). Subjects with nephropathy (0.50 fmol/ml) had significantly higher ( P=.002) ET1 values when compared with those without complications (0.40 fmol/ml). The levels of sICAM-1 and sVCAM-1 did not show any significant difference among the groups. ET1 showed correlation with age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), 2 h post glucose (2hPG), waist-to-hip ratio (WHR), total white blood corpuscles count, glycosylated haemoglobin (HbA1c), triglycerides (TG), very-low-density lipoprotein cholesterol (VLDLc), and hypertension (HTN). In the multiple linear regression analysis, plasma ET1 was significantly associated with the presence of Type 2 diabetes either with or without complications ( P<.0001 and P=.0098, respectively), WHR ( P=.0063), and sVCAM-1 ( P=.0051). The total variance explained by the above-mentioned parameters was 55%. Conclusion: Elevated levels of ET1 were present in subjects with IGT and in Type 2 diabetic subjects. Such associations with sICAM-1 or sVCAM-1 in these subjects were not seen. ET1 could be an early marker of endothelial dysfunction, which appeared to occur even in the subclinical stages of hyperglycaemia.

The N363S polymorphism in the glucocorticoid receptor gene is associated with overweight in subjects with type 2 diabetes mellitus.

A single nucleotide polymorphism (A1220G; N363S) in exon 2 of the glucocorticoid receptor gene (NR3C1), associated with increased sensitivity to glucocorticoids, was shown to be associated with obesity in nondiabetic subjects. Here, we investigated the impact of this variant on traits related to obesity and hyperglycaemia in subjects with type 2 diabetes mellitus. The N363S variant was screened by restriction fragment length polymorphism technique following DNA amplification by polymerase chain reaction in 369 French Caucasians with type 2 diabetes mellitus. Twenty subjects were found to be heterozygous for the variant (AG genotype frequency 0.0542). The prevalence of overweight [body mass index (BMI) > 25 kg/m2] was higher in AG carriers than in AA carriers (100%vs. 73%, P = 0.003). Moreover, the mean body weight and the BMI were higher in AG as compared to AA carriers, although only the body weight was significantly different between groups. However, when only the men were considered, a significantly higher BMI was observed in AG as compared to AA carriers: 30.0 +/- 4.8 vs. 27.3 +/- 4.6 kg/m2 (BMI Z-score 1.28 +/- 1.38 vs. 0.55 +/- 1.17; P = 0.035). No evidence was found for an association of the N363S variant with parameters related to the severity of hyperglycaemia. The 363S allele of the N363S variant of NR3C1 is associated with the susceptibility to overweight in subjects with type 2 diabetes mellitus.

Hyperglycemia exacerbates muscle protein catabolism in burn-injured patients.

The purpose of this study was to assess if hyperglycemia influences energy expenditure or the extent of muscle protein catabolism in severely burned adults. Retrospective study. Burn intensive care unit at a university hospital. Adults with burns on >/=40% of their body surface area. Simultaneous measurement of indirect calorimetry and leg net balance of phenylalanine (as an index of muscle protein catabolism). Patients were stratified by plasma glucose values at the time of metabolic measurements (i.e., normal, glucose at </=130 mg/dL; mild hyperglycemia, glucose at 130-200 mg/dL; severe hyperglycemia, glucose at >200 mg/dL). Normal (n = 9; plasma glucose, 109 +/- 13 mg/dL [mean +/- sd]), mildly hyperglycemic (n = 13l plasma glucose, 156 +/- 17 mg/dL), and severely hyperglycemic subjects (n = 7, glucose 231 +/- 32 mg/dL) were similar in age, body weight, extent of burn area, and daily caloric intake. Severe hyperglycemia was associated with significantly higher arterial concentrations of phenylalanine (normal, 0.079 +/- 0.027 micromol/L; severe hyperglycemia, 0.116 +/- 0.028; p <.05) and a significantly greater net efflux of phenylalanine from the leg (normal, -0.067 +/- 0.072 micromol.min(-1).100 mL(-1) leg volume; severe hyperglycemia, -0.151 +/- 0.080 micromol.min(-1).100 mL(-1) leg volume; p <.05). Resting energy expenditure and respiratory quotient were similar between patient groups. These findings demonstrate an association between hyperglycemia and an increased rate of muscle protein catabolism in severely burned patients. This suggests a possible link between resistance of muscle to the action of insulin for both glucose clearance and muscle protein catabolism.

INCREASED URINARY EXCRETION OF N-ACETYLGLUCOSAMINIDASE IN SUBJECTS WITH IMPAIRED GLUCOSE TOLERANCE

N-acetylglucosaminidase (NAG) is a lysosomal enzyme produced by renal proximal tubular cells and has been widely used as a marker, which indicates a degree of renal tubular damage. An increase in urinary NAG excretion is thought to result from the renal tubular damage. The aim of this study was to evaluate whether even mild hyperglycemia causes an increase in urinary excretion of NAG, which is a renal tubular protein. We examined urinary NAG excretion in overnight urine in 22 Japanese men with impaired glucose tolerance (IGT) for more than two years (IGT group) and 41 healthy control subjects matched in age, gender, BMI and blood pressure (control group). Urinary NAG excretion levels of IGT group and control group were 2.89 (1.23–7.97) and 2.22 (0.60–4.93) U/g creatinine, median (range), respectively. The IGT group showed significantly higher urinary excretion of NAG compared to the control group (p<0.01). Several studies have indicated that plasma proteins filtered through the glomerular capillary may have intrinsic renal toxicity. Recently, we have reported that urinary excretion of plasma proteins (ceruloplasmin, IgG4 and IgG) with molecular radii of approximately 45–55 Å is increased in subjects with IGT compared to healthy control subjects with normal glucose tolerance. Considering the present result together with our recent finding, we suggest that increased urinary excretion of NAG in the mildly hyperglycemic subjects may be due to the adverse effects of the plasma proteins highly filtered through the glomerular capillary on tubular cells.