Higher Plasma Glucose Levels Research Articles

Large brachial artery diameter and diabetes in post-menopausal women

Vascular remodelling is one of the possible compensatory mechanisms in response to artery wall injury. It was demonstrated that post-menopausal women with carotid atherosclerosis had a larger brachial artery diameter (BAD) than women without carotid plaques. Therefore, it is possible to hypothesise that artery enlargement could be a marker of early atherosclerosis. To investigate the eventual association between carotid and brachial artery diameter and disease affecting the vascular wall, we performed a case-control study in post-menopausal women with or without type II diabetes mellitus. We enrolled 28 cases (with diabetes) and 56 controls (without diabetes) matched for age and carotid atherosclerosis presence and severity. On the t-test, women with diabetes showed significantly larger brachial and common carotid artery diameters and, as expected, higher plasma glucose level and homeostasis model assessment (HOMA) than women without diabetes. On the univariate analysis, only plasma glucose level results correlated to BAD in the whole sample. Multivariate analysis confirmed that diabetes was a good predictor of brachial and carotid artery diameter, while age, systolic blood pressure and triglycerides were correlated only to the carotid diameter. Our data confirm that vascular remodelling is a systemic process occurring in conditions related to atherosclerosis, such as type II diabetes. Indeed, artery diameter could be a marker of early response of vessel wall to injury.

The Isolation of the Receptor for Advanced Glycation End‐Products from Avian Vasculature

Accumulation of glucose in the plasma results in the formation of Advanced Glycation End Products (AGEs) by a non‐enzymatic reaction with albumin. These products bind to Receptors for AGEs (RAGE) on endothelial cells. This alters the basement membrane structure leading to accumulation of fluid in tissues as seen in Type II Diabetes. Humans normally maintain plasma glucose concentrations of 4.4 to 5.5mM/L whereas birds maintain concentrations of 16.6mM/L or greater. If plasma glucose concentrations in humans exceed 6.6mM/L for 4–6 weeks, symptoms of diabetes will begin to develop. Birds can serve as an animal model for the study of Type II diabetes due to their high plasma glucose levels and that they are insulin insensitive resisting the effects of these levels. In the present study, SDS PAGE and Western Blot analysis were used to isolate RAGE from the vasculature of Mourning Doves. RAGE N‐16 goat polyclonal IgG (Santa Cruz) was used as the primary anti‐body which detects the presence of RAGE in mice, rats, humans and cows increasing the likelihood of detecting RAGE in birds. Vascular tissue isolated from rats was used as a control. We hypothesized that birds lack RAGE as they do not suffer Type II Diabetic pathologies. Our data indicate a band at 55kda suggesting the presence of a RAGE in birds. The density of these receptors in the vasculature is to be determined by immunohistochemistry.E. Cousens was a recipient of an APS UGSRF.

High normal fasting glucose level in obese youth: a marker for insulin resistance and beta cell dysregulation

A high but normal fasting plasma glucose level in adults is a risk factor for future development of type 2 diabetes mellitus and cardiovascular disease. We investigated whether normal fasting plasma glucose levels (<5.60 mmol/l) are associated with decreases in insulin sensitivity and beta cell function, as well as an adverse cardiovascular profile in obese youth. We performed a cross-sectional analysis in a multiethnic sample of 1,020 obese youth (614 girls and 406 boys; mean age 12.9 years [CI 95% 12.7-13.1], BMI z score 2.34 [CI 95% 2.31-2.38]) with normal fasting plasma glucose. All participants had a standard OGTT, with calculation of indices of insulin sensitivity and beta cell function. For the analysis, prepubertal and pubertal participants were stratified into quartiles of normal fasting plasma glucose. We observed a significant increase in fasting insulin and AUC 2 h glucose across quartiles. Pronounced changes were observed in insulin sensitivity and secretion, particularly in the pubertal group. Moreover, the odds of presenting with impaired glucose tolerance increased by 4.5% with each 0.06 mmol/l increase in fasting plasma glucose. No significant differences in cardiovascular indices were seen across quartiles. These data suggest that in obese youth, independent of age, BMI z score, sex, family history and ethnicity, insulin sensitivity and secretion decline when moving from low to high normal fasting plasma glucose. The simple measure of fasting plasma glucose could assist clinicians in identifying children for targeted diabetes screening and subsequent lifestyle management.

Selection bias in a population survey with registry linkage: potential effect on socioeconomic gradient in cardiovascular risk

Non-participation in population studies is likely to be a source of bias in many types of epidemiologic studies, including those describing social disparities in health. The objective of this paper is to present a non-attendance analysis evaluating the possible impact of selection bias, when investigating the association between education level and cardiovascular risk factors. Data from the INTERGENE research programme including 3,610 randomly selected individuals aged 25-74 (1,908 women and 1,702 men), in West Sweden were used. Only 42% of the invited population participated. Non-attendance analyses were done by comparing data from official registries (Statistics Sweden) covering the entire invited study population. This analysis revealed that participants were more likely to be women, have university education, high income, be married and of Nordic origin compared to non-participants. Among participants, all health behaviours studied were significantly related to education. Physical activity, alcohol use and breakfast consumption were higher in the more educated group, while there were more smokers in the less educated group. Central obesity, obesity and hypertension were also significantly associated with lower education level. Weaker associations were observed for blood lipids, diabetes, high plasma glucose level and perceived stress. The socio-demographic differences between participants and non-participants indicated by the register analysis imply potential biases in epidemiological research. For instance, the positive association between education level and frequent alcohol consumption, may, in part be explained by participation bias. For other risk factors studied, an underestimation of the importance of low socioeconomic status may be more likely.

262 Are Zucker Obese Rats a Useful Model for Cardiovascular Complications in Metabolic Syndrome? Physical, Biochemical and Oxidative Stress Considerations

We wondered if Zucker obese (ZO) rats would be a good experimental model to evaluate cardiovascular complications of Metabolic Syndrome (MS). ZO rats were compared with both their littermate controls, Zucker lean (ZL) rats and to Wistar rats (reference strain). We designed this work 1) to measure certain physical and biochemical characteristics of MS 2) to evaluate coronary and cardiac function in isolated conditions and after ischemia 3) to study plasma and heart tissue oxidative stress markers. In vivo, ZO rats had higher levels of plasma glucose, cholesterol and triglycerides than their ZL littermates, but there was no difference between the groups for systolic arterial blood pressure and heart rate. In vitro, coronary endothelial function was notably impaired in ZO and ZL rats. After global ischemia, the worse ventricular recovery in ZO and ZL rats was associated with arrhythmias during reperfusion. We detected similar levels of plasma ascorbyl free radical, Oxygen Radical Absorbance Capacity and vitamin C concentrations in the three groups. DHE staining showed higher superoxide production in the coronary vessels of ZO rats than in ZL and Wistar rats. Our results show that ZO might only correspond to early-stage cardiovascular complications associated with MS.

Neuro-endocrine basis for altered plasma glucose homeostasis in the Fragile X mouse.

BackgroundThe fragile X mouse model shows an increase in seizure susceptibility, indicating an involvement of the GABAergic system via an alteration in cellular excitability. In the brain, we have previously described a reduction in GABAA receptor expression as a likely basis for this susceptibility. In the brains of fragile X mice, this reduction in receptor expression culminates with a concomitant increase in the expression of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis. Further, voltage-sensitive calcium channel expression is reduced in the pancreas of the fragile X mouse. Since there are considerable similarities in the GABAergic system in the brain and pancreas, we evaluated the protective role of taurine in pancreatic islet development in both wild type (WT) and fragile X mice (KO).MethodsOne-month-old FVB/NJ males or age-matched fmr1-knockout (KO) mice were supplemented with taurine in drinking water (0.05% w/v) for four weeks. Age-matched controls were fed water only for the same duration. At four weeks, mice were sacrificed and pancreases processed for histology and immunohistochemical studies on changes of insulin, glucagon and somatostatin expression. Additional mice were subjected to a glucose tolerance test.ResultsTaurine treatment resulted in a significant increase in the number and size of islets. WT taurine-fed mice, slightly hypoglycemic prior to glucose injection, showed significantly reduced plasma glucose at 30 min post-injection when compared to control mice. KO mice had normal baseline plasma glucose concentration; however, following glucose injection they had higher plasma glucose levels at 30 min when compared to controls. Supplementation of taurine to KO mice resulted in reduced baseline levels of plasma glucose. After glucose injection, the taurine-fed KO mice had reduced plasma glucose at 30 min compared to KO. Concomitant with the increased islets size and glucose tolerance observed in taurine-fed mice there was an increase in insulin, glucagon and somatostatin immunoreactivity in the islets of WT mice. In the KO mice however, insulin levels were not affected whereas glucagon and somatostatin levels were reduced. Exocytosis of these hormones is calcium-dependent, therefore any exacerbation of calcium homeostasis could affect hormone release. We found the expression of the voltage sensitive calcium channels (VSCC) is drastically reduced in the pancreas of fragile X mice.ConclusionsDuring early development, the VSCC play an important role in calcium-dependent gene expression. Since these channels are also involved in depolarization and calcium-mediated vesicular release of neurotransmitters and pancreatic hormones, alterations in the expression of VSCC not only will affect calcium-mediated gene expression but also hormonal and neurotransmitter release creating therefore a neuroendocrine perturbation in the fragile X that may potentially affect other organ systems. We find that in the fragile X mouse, taurine treatment may partially restore functionality of the neuro-endocrine pancreas.

The Effects of Oenanthe javanica Extracts on Hepatic Fat Accumulation and Plasma Biochemical Profiles in a Nonalcoholic Fatty Liver Disease Model

We tested the effects of Oenanthe javanica (OJ) on hepatic fat accumulation and plasma biochemical profiles in a nonalcoholic fatty liver disease model (NAFLD). Rats were divided 5 groups and fed the following diets for 6 weeks: normal rat chow diet (CHOW), high-fat highcholesterol diet (HFCD), HFCD with the water extract of OJ (HFCD+W), HFCD with the nbutanol extract of OJ (HFCD+B), and HFCD with metadoxine (HFCD+M). Metadoxine (pyridoxine-pyrrolidone-carboxylate) is being used to treat alcoholic fatty liver and has been suggested that it can be effective for treating NAFLD. The HFCD gained significantly more body weight and visceral fat mass and had significantly higher levels of plasma glucose, triglyceride, cholesterol, and liver triglyceride content than the CHOW. The water- and n-butanol extracts of OJ improved the elevated plasma triglyceride and glucose levels induced by high-fat highcholesterol diet and lowered triglyceride content in the liver. Similarly, the treatment with metadoxine reversed the increased plasma glucose and triglyceride and showed a tendency to decrease hepatic fat accumulation. However, these supplements did not change body weight or visceral fat mass. These results indicate that OJ extracts improve changes in hepatic fat accumulation, plasma glucose, and lipid profiles induced by high-fat high-cholesterol diet but did not affect visceral obesity. In conclusion, the water- and n-butanol extracts of OJ and metadoxine improved hepatic fat accumulation, hyperglycemia, and dyslipidemia induced by high-fat highcholesterol diet although the effect of metadoxine on fatty liver was not significant, suggesting their potential use for the prevention and treatment of NAFLD.

Diabetes treatment with insulin glargine and risk of malignancy: methodological pitfalls and ethical issues

Diabetes treatment with insulin glargine and risk of malignancy: methodological pitfalls and ethical issues

Preserved Inhibitory Potency of GLP-1 on Glucagon Secretion in Type 2 Diabetes Mellitus

Glucagon-like peptide-1 (GLP-1) is insulinotropic, but its effect on the alpha-cell is less clear. We investigated the dose-response relationship for GLP-1-induced glucagon suppression in patients with type 2 diabetes (T2DM) and healthy controls. Ten patients with T2DM (duration of DM, 4 +/- 1 yr; glycosylated hemoglobin, 7.1 +/- 0.3%) were studied on 2 d, with stepwise increasing GLP-1 infusions (0.25, 0.5, 1.0, and 2.0 pmol x kg(-1) x min(-1)) (d 1) or saline (d 2) with plasma glucose (PG) clamped at fasting level. On d 3, patient PG was normalized overnight using a variable insulin infusion, followed by a 3-h GLP-1 infusion as on d 1. Ten healthy subjects were examined with the same protocol on d 1 and 2. We observed similar dose-dependent stepwise suppression of glucagon secretion in both patients and controls. Significant suppression was observed at a GLP-1 infusion rate of 0.25 pmol x kg(-1) x min(-1) (resulting in physiological plasma concentrations) as early as time 15 min in healthy controls and time 30 min in patients (d 1 and d 3). AUC for glucagon was significantly reduced on d 1 and 3 (1096 +/- 109 and 1116 +/- 108 3h x pmol/liter; P = NS) as compared to d 2 (1733 +/- 193 3h x pmol/liter; P < 0.01) in patients with T2DM. A similar reduction in AUC for glucagon was observed in healthy controls [1122 +/- 186 (d 1) vs. 1733 +/- 312 3h x pmol/liter (d 2); P < 0.001]. The diabetic alpha-cell appears to be highly sensitive to the inhibitory action of GLP-1 both during high and near-normalized PG levels, but responds with a short, nevertheless significant delay.

Significance of chronic marked hyperglycemia on FDG-PET: is it really problematic for clinical oncologic imaging?

The purpose of this study was to evaluate the adverse effects of chronic marked hyperglycemia on clinical diagnostic performance of positron emission tomography (PET) using (18)F-fuorodeoxyglucose (FDG). Fifty-seven scans of 54 patients, who received FDG-PET for the diagnosis of various cancer(s), and who showed high plasma glucose level of more than 200 mg/dl at the time of administration of FDG in spite of at least 4-h fasting, were retrospectively analyzed. In the clinical follow-up, this high plasma glucose was confirmed as chronic hyperglycemia derived from uncontrolled diabetes (n = 32) and untreated diabetes (n = 25). Based on the final diagnosis of malignancy obtained by histopathology or clinical follow-up for at least 6 months, the diagnostic performance of visual PET analysis was evaluated. Excluding nine scans of nine patients without sufficient follow-up, final diagnosis was obtained in 48 scans of 45 patients. In 36 scans of 36 patients, at least one malignant lesion was finally confirmed, and true-positive and false-negative results were obtained in 30 and six cases, respectively. Six cases showed false-negative results due to low FDG-avid pathological characteristics (hepatocellular carcinoma, etc.), chemotherapeutic effect or small tumor size. Overall, the patient-based sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy were 83, 83, 94, 63 and 83%, respectively. In lesion-based diagnosis, 56 of 75 lesions (74%) were depicted by PET, while 19 lesions were negative on PET, also due to low FDG-avid characteristics or small size (less than 15 mm). At the time of chronic hyperglycemia (not acute hyperglycemia), the adverse effect caused by high plasma glucose level was minimum. The FDG uptake of the tumor maintained a sufficiently high level for visual clinical diagnosis in most cases, except in the cases of low FDG-avid tumors or small lesions (15 mm in size).

Cardiac impairment in rabbits fed a high-fat diet is counteracted by dehydroepiandrosterone supplementation

Aims The biochemical and structural cardiac oxidative-dependent damage induced by high-fat (HF) diet was examined in a rabbit model, together with the role of dehydroepiandrosterone (DHEA) in contrasting tissue damage. Main methods New Zealand white rabbits fed a HF diet supplemented or not with DHEA (0.02%) were utilized for 12 weeks. Oxidative stress, inflammatory and necrosis parameters, fatty deposition, heavy-chain myosin isoforms (MHC) expression and papillary muscle functionality were examined in the left ventricle of rabbits. Key findings Rabbits fed a HF diet that showed hyperglycemia, insulin resistance and dyslipidemia together with increase of oxidative stress and of advanced end-glycation product levels have been observed. Concerning pro-inflammatory insults, there was increased p65-NFkB activation and increased tumor necrosis factor-alpha and C-reactive protein expressions. Cellular damage induced by the HF diet was detected through the switch of expression of MHC isoforms, indicating impairment of cardiac contractility, confirmed by altered of basal parameters of papillary muscle functionality. Rabbits fed the HF diet supplemented with DHEA showed a partial reduction of oxidative stress and the inflammatory state. Cardiac necrosis, the shift of MHC isoforms, and cardiac functionality, were also partially counteracted. Significance Rabbits fed with a HF diet showed a beneficial effect when low-dose DHEA was added to the diet. The steroid, without affecting high plasma glucose level or insulin resistance, restored oxidative balance, lowered lipid levels and inflammation insults, preventing cellular and functional alterations of cardiac tissue and thus delaying the onset of cardiac damage.

The amelioration of streptozotocin diabetes-induced renal damage by Wu-Ling-San (Hoelen Five Herb Formula), a traditional Chinese prescription

Ethnopharmacological relevance Wu-Ling-San (Hoelen Five Herb Formula) is a Chinese prescription used to promote water metabolism. Aim of the study The present study was undertaken to characterize the effects of Wu-Ling-San on diabetic nephropathy. Materials and methods Streptozotocin (STZ)-diabetic rats were orally administrated with Wu-Ling-San (0.5, 1.5, 2.5 g/(kg day)) once a day for 10 weeks. Changes in the renal function related parameters in plasma and urine were analyzed at the end of 10-week administration. Kidney was isolated for pathology histology, immunohistochemistry staining and Western blot analyses. Results Wu-Ling-San (2.5 g/(kg day)) partially decreased the high plasma glucose level in diabetic rats. Diabetic-dependent alterations in urinary albumin, 24-h urinary albumin excretion rate, creatinine clearance, and glomerular mesangial matrix expansion were ameliorated by Wu-Ling-San. The increased expression of nuclear factor-kB as well as transforming growth factor-β 1 and the progressive accumulation of fibronectin in kidney of diabetic rats were attenuated by Wu-Ling-San. Not only the elevated levels of advanced glycation end products (AGEs) and mitochondrial thiobarbituric acid-reactive substance, but also the higher levels of N ɛ-(carboxymethyl)lysine and receptor for AGEs in kidney of diabetic rats were ameliorated by Wu-Ling-San. Conclusions : Wu-Ling-San posses an anti-diabetic property with plasma glucose lowering action accompanied with amelioration of glycation-mediated renal damage.

Hypertension and diabetes as predictors of early death after spontaneous intracerebral hemorrhage

Previous investigators have suggested that a high mean arterial blood pressure (MABP) and an elevated plasma glucose level at admission are associated with a poor outcome after hemorrhagic stroke. It remains unclear, however, whether hypertension and diabetes are responsible for this effect. High admission MABP and plasma glucose levels may also be markers of other factors such as stroke severity. The authors retrospectively investigated the role of a high admission MABP and plasma glucose level together with other predictors of early death among 379 nonsurgical patients with spontaneous intracerebral hemorrhages (ICHs) who were admitted to the stroke unit of Oulu University Hospital. The 3-month mortality rate was 28%. The patients who died within 3 months of ICH had significantly higher plasma glucose levels and MABPs at admission (p < 0.001). After adjustments for patient sex, age, size and location of hematoma, Glasgow Coma Scale score at admission, presence of intraventricular hemorrhage, history of cardiac disease, and previous use of warfarin, history of diabetes (relative risk 1.61, 95% CI 1.03-2.53, p < 0.05) and high MABP at admission (relative risk 1.01 per mm Hg, 95% CI 1.00-1.02, p < 0.05) remained independent predictors of death 3 months after ICH. A high admission plasma glucose level and history of hypertension were not independent predictors of death. A high MABP at admission was found to be an independent predictor of early death in patients with ICH. History of hypertension was not responsible for the effect. Admission hyperglycemia appeared to be a stress response to the severity of the bleeding, whereas diabetes predicted early death.

P38 Mitogen-Activated Protein Kinase: A Critical Node Linking Insulin Resistance and Cardiovascular Diseases in Type 2 Diabetes Mellitus

Type 2 diabetes is associated with insulin resistance, endothelial dysfunction and accelerated atherosclerotic diseases. Though underlying mechanisms remain to be unraveled, p38 mitogen-activated protein kinase (MAPK) appears to play important roles in their pathogenesis. As a member of the MAPK family, it regulates the activities of many transcription factors and proteins/enzymes and thus has a wide-spectrum of biological effects. Patients with insulin resistance and/or type 2 diabetes have high levels of plasma free fatty acids, inflammatory cytokines, and/or glucose, and over-activation of the cardiovascular renin-angiotensin system, all are capable of activating p38 MAPK. p38 MAPK plays a central role in hepatic glucose and lipid metabolism, leading to increased hepatic glucose production and decreased hepatic lipogenesis. The roles of p38 MAPK in insulin-mediated glucose uptake in skeletal muscle and adipose tissue remain controversial. p38 MAPK also mediates inflammatory processes and cell apoptosis. Recent evidence suggests that p38 MAPK may be the key node linking cardiovascular insulin resistance, endothelial dysfunction and the pathogenesis of atherosclerotic diseases through its influences on monocytes/macrophages, vascular endothelial cells, and vascular smooth muscle cells in type 2 diabetes. In addition, p38 MAPK also contributes significantly to cardiac injury during ischemia-reperfusion.

Are Zucker obese rats a useful model for cardiovascular complications in metabolic syndrome? Physical, biochemical and oxidative stress considerations

We wondered if Zucker obese (ZO) rats would be a good experimental model to evaluate cardiovascular complications of metabolic syndrome (MS). ZO rats were compared with both their littermate controls, Zucker lean (ZL) rats and to Wistar rats (reference strain). We designed this work:(i) to measure certain physical and biochemical characteristics of MS; (ii) to evaluate coronary and cardiac function in isolated conditions and after ischemia; and (iii) to study plasma and heart tissue oxidative stress markers. In vivo, ZO rats had higher levels of plasma glucose, cholesterol and triglycerides than their ZL littermates, but there was no difference between the groups for systolic arterial blood pressure and heart rate. In vitro, coronary endothelial function was notably impaired in ZO and ZL rats. After global ischemia, the worse ventricular recovery in ZO and ZL rats was associated with arrhythmias during reperfusion. We detected similar levels of plasma ascorbyle free radical, oxygen radical absorbance capacity and vitamin C concentrations in the three groups. Dihydroethidium staining showed higher superoxide production in the coronary vessels of ZO rats than in ZL and Wistar rats. Our results show that ZO might only correspond to early-stage cardiovascular complications associated with MS.

Body mass index for predicting hyperglycemia and serum lipid changes in Brazilian adolescents

OBJECTIVE: To determine the best cut-offs of body mass index for identifying alterations of blood lipids and glucose in adolescents. METHODS: A probabilistic sample including 577 adolescent students aged 12-19 years in 2003 (210 males and 367 females) from state public schools in the city of Niterói, Southeastern Brazil, was studied. The Receiver Operating Characteristic curve was used to identify the best age-adjusted BMI cut-off for predicting high levels of serum total cholesterol (&gt;150mg/dL), LDL-C (&gt;100mg/dL), serum triglycerides (&gt;100mg/dL), plasma glucose (&gt;100mg/dL) and low levels of HDL-C (&lt; 45mg/dL). Four references were used to calculate sensitivity and specificity of BMI cut-offs: one Brazilian, one international and two American. RESULTS: The most prevalent metabolic alterations (&gt;50%) were: high total cholesterol and low HDL-C. BMI predicted high levels of triglycerides in males, high LDL-C in females, and high total cholesterol and the occurrence of three or more metabolic alterations in both males and females (areas under the curve range: 0.59 to 0.67), with low sensitivity (57%-66%) and low specificity (58%-66%). The best BMI cut-offs for this sample (20.3 kg/m² to 21.0 kg/m²) were lower than those proposed in the references studied. CONCLUSIONS: Although BMI values lower than the International cut-offs were better predictor of some metabolic abnormalities in Brazilian adolescents, overall BMI is not a good predictor of these abnormalities in this population.

The progression of type 2 diabetes: Partly caused by deficiency of ASP-C5L2 pathway?

Type 2 diabetes is characterized by insulin resistance and β-cell dysfunction. The pathway of acylation-stimulating protein (ASP) and its specific receptor, C5a-like receptor 2 (C5L2), involves in the effective clearance of plasma glucose and free fat acid. Abnormal ASP-C5L2 pathway may induce insulin resistance, as well as cause hyperglycemia and elevated plasma free fat acid. High levels of plasma glucose and free fat acid induce β-cell apoptosis and dysfunction. We proposed that the abnormality of ASP-C5L2 pathway contributes to progression of type 2 diabetes.

L’hémolyse : une cause d’erreur dans l’interprétation de l’hémoglobine glycosylée

Hemoglobin A1c (HbA1c), measured regularly in the patients with diabetes, is the major form of stable glycated hemoglobin and has to be maintained below 6.5% to prevent or decrease the risk of chronic complications. HbA1c reflects mean blood glucose levels of the previous 3 months. We report the case of a particularly low HbA1c in a diabetic patient despite high plasma glucose levels, that was induced by auto-immune hemolysis related to an Evans syndrome. All hemolytic disorders can be responsible for falsely reassuring HbA1c values. Clinicians must be aware that hematologic status has to be considered for the correct interpretation of HbA1c results.

Insulin signaling in chicken liver and muscle

This review addresses the control exerted by insulin through its receptor on the general metabolism and gene expression in chicken liver and muscle. Compared with mammals, chickens have similar concentrations of circulating insulin, but still maintain high plasma glucose levels. This may be a consequence of the low sensitivity of the chicken to exogenous insulin. In order to determine whether this low sensitivity is the result of differences in insulin receptor signaling between mammals and birds, insulin receptors have been characterized in several chicken tissues and two insulin receptor substrates (IRS-1 and Shc) have been described in liver and muscle. Compared with mammals current knowledge of insulin signaling in birds is incomplete. This is particularly evident when considering the number of isoforms of the components involved in the insulin cascade (IRSs, AKT, ERK and others) many of which may have not been characterized in the chicken. Despite these shortfalls in available data, it appears that insulin signaling in chicken liver is similar to that in mammals, but is unlike that in mammals in muscle. In leg muscle, chickens differ from mammals in the early steps of the insulin signaling cascade (IR, IRS-1 and PI3K) where PI3K activity is about 30-fold greater in the chicken than in the rat. This “constitutive” hyperactivity of PI3K in chicken muscle may over-stimulate a feedback inhibitory pathway described in mammals thereby desensitizing chicken muscle to insulin.

Symptoms of diabetes can be missed in older people.

Diabetes is often missed in older people because its presenting symptoms may be non-specific (for example, low energy levels, falls, dizziness, confusion and chronic infection in the genito-urinary tract, skin or mouth) and normal ageing is associated with lower levels of blood insulin. Diabetes in older people may not be accompanied by the very high plasma glucose levels that cause the classic symptoms of thirst and increased hunger. These undiagnosed older people are, however, still at risk of death and disease from vascular complications.