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Hyperglycemia
Kinds of Hyperglycemia Selected AbstractsPOSTPRANDIAL HYPERGLYCEMIA IS AN INDEPENDENT RISK FOR RETINOPATHY IN ELDERLY PATIENTS WITH TYPE 2 DIABETES MELLITUS, ESPECIALLY IN THOSE WITH NEAR-NORMAL GLYCOSYLATED HEMOGLOBINJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2010Toru Aizawa PhD No abstract is available for this article. [source] INHIBITORY POTENTIAL OF WINE AND TEA AGAINST ,-AMYLASE AND ,-GLUCOSIDASE FOR MANAGEMENT OF HYPERGLYCEMIA LINKED TO TYPE 2 DIABETESJOURNAL OF FOOD BIOCHEMISTRY, Issue 1 2008YOUNG-IN KWON ABSTRACT Natural ,-amylase and ,-glucosidase inhibitors from food-grade plants offer an attractive strategy to manage postprandial hyperglycemia for type 2 diabetes management via control of starch breakdown and intestinal glucose absorption. In this study, four random sources of red and white wines as well as four types of teas were investigated for ,-amylase and ,-glucosidase inhibitory potential. Water extracts of black tea had the highest ,-glucosidase inhibitory activity, followed by white tea and oolong tea. All the randomly selected red wines had significant ,-glucosidase inhibitory activity compared to white wine. The ,-glucosidase inhibitory activity of the tea and wines correlated to the phenolic content, antioxidant activity and phenolic profile of the extracts. Further, these extracts had less or no ,-amylase inhibitory activity, indicating potential to overcome the side effects of undigested starch. This research has relevance for managing hyperglycemia and related oxidation-linked dysfunction and concurrently reducing problems of undigested starch. PRACTICAL APPLICATIONS In this study anti-diabetic-relevant potential of wines and teas were confirmed in four types of red and white wines as well as four types of commonly available teas using in vitro enzyme assays for alpha-glucosidase and alpha-amylase inhibitory activities. In vitro inhibitory activities of these enzymes provide a strong biochemical rationale for further in vivo studies and dietary management strategy for type 2 diabetes through the control of glucose absorption. Further this phenolic antioxidant-enriched dietary strategy using specific beverage combinations can generate a whole food profile that has the potential to reduce hyperglycemia-induced pathogenesis and also associated complications linked to cellular oxidation stress. [source] Diabetic embryopathy: Studies using a rat embryo culture system and an animal modelCONGENITAL ANOMALIES, Issue 3 2005Shoichi Akazawa ABSTRACT The mechanism of diabetic embryopathy was investigated using in vitro experiments in a rat embryo culture system and in streptozotocin-induced diabetic pregnant rats. The energy metabolism in embryos during early organogenesis was characterized by a high rate of glucose utilization and lactic acid production (anaerobic glycolysis). Embryos uninterruptedly underwent glycolysis. When embryos were cultured with hypoglycemic serum, such embryos showed malformations in association with a significant reduction in glycolysis. In a diabetic environment, hyperglycemia caused an increased glucose flux into embryonic cells without a down-regulation of GLUT1 and an increased metabolic overload on mitochondria, leading to an increased formation of reactive oxygen species (ROS). Activation of the hexamine pathway, subsequently occurring with increased protein carbonylation and increased lipid peroxidation, also contributed to the increased generation of ROS. Hyperglycemia also caused a myo-inositol deficiency with a competitive inhibition of ambient glucose, which might have been associated with a diminished phosphoinositide signal transduction. In the presence of low activity of the mitochondrial oxidative glucose metabolism, the ROS scavenging system in the embryo was not sufficiently developed. Diabetes further weakened the antioxidant system, especially, the enzyme for GSH synthesis, ,-GCS, thereby reducing the GSH concentration. GSH depletion also disturbed prostaglandin biosynthesis. An increased formation of ROS in a diminished GSH-dependent antioxidant system may, therefore, play an important role in the development of embryonic malformations in diabetes. [source] Admission Hyperglycemia and Length of Hospital Stay in Patients With Diabetes and Heart Failure: A Prospective Cohort StudyCONGESTIVE HEART FAILURE, Issue 3 2008Yohannes Gebreegziabher MD The authors assessed the relationship between glycemia and length of hospital stay (LOS) in a prospective cohort study of patients with diabetes mellitus and heart failure (HF). Of 212 patients with acute HF exacerbation, 119 (56%) also had diabetes. The mean age of the cohort was 63±0.87 years, and the mean body mass index was 29.3 kg/m2. Diabetic patients had significantly longer LOS compared with the nondiabetics (5.0±0.29 vs 3.4±0.19; P<.001). In patients with diabetes, the mean glycated hemoglobin A1c was 8.3%, admission blood glucose (BG) was 169±7.7 mg/dL, and average BG was 196±8.1 mg/dL. After adjusting for age, sex, weight, hypertension, renal function, and anemia, LOS was significantly correlated with admission BG (r=0.31; P<.001) and average BG (r=0.34; P=.001). In patients with acute HF exacerbation, diabetes significantly prolonged LOS. Hyperglycemia correlated with LOS. [source] High glucose activates pituitary proopiomelanocortin gene expression: possible role of free radical-sensitive transcription factorsDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2007Koichi Asaba Abstract Background Hyperglycemia is recognized as a metabolic stress, and indeed it is known to stimulate hypothalamo-pituitary-adrenal (HPA) axis, a representative anti-stress system, in patients with diabetes mellitus or in animal models of hyperglycemia. Thus, we tried to clarify the molecular mechanism of glucose-induced HPA axis activation. Methods We studied the effect of high glucose on the transcriptional regulation of proopiomelanocortin (POMC) gene that encodes adrenocorticotropic hormone, a central mediator of HPA axis, using AtT20 corticotroph cell line in vitro. Results We found that high glucose concentration (24 mM) significantly stimulated the 5,-promoter activity of POMC gene. The effect was promoter-specific, and was mimicked by nuclear factor-kappaB (NF-,B)- or AP1-responsive promoters but not by cAMP-responsive element or serum-response element-containing promoters. Furthermore, the stimulatory effect of high glucose on POMC gene was eliminated by NF-,B and AP1 inhibitors, suggesting the involvement of the transcriptional factors. The POMC 5,-promoter has the canonical NF-,B consensus sequence, and gel shift assay showed the binding of NF-,B to the element. Finally, the effect of high glucose was completely abolished by treatment with a radical quencher 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPOL). Conclusions Our data suggest that hyperglycemia activates POMC gene expression, at least partly, via NF-,B/AP1, and that high-glucose-induced free radical generation may mediate the activation of these transcription factors, which in turn stimulates the transcription of POMC gene. Copyright © 2006 John Wiley & Sons, Ltd. [source] Stroke in patients with diabetes mellitusDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 4 2004Boris N. Mankovsky Abstract The article's objective is to review the key advances in the scientific literature related to the association of stroke with diabetes mellitus and to summarize the current approaches to stroke prevention in diabetic patients. The key findings from the literature regarding stroke incidence in patients with diabetes, specific and nonspecific risk factors of stroke in the diabetic population, such as arterial hypertension, dyslipidemia, hyperglycemia, diabetes duration, diabetic complications, insulin resistance/hyperinsulinemia, course and outcome of stroke in subjects with diabetes and/or hyperglycemia, and the peculiarities of type, site and size of stroke in diabetic patients are discussed. The results of recent clinical trials aimed at correcting hyperglycemia, hypertension, and dyslipidemia, to prevent stroke in people with diabetes, are reviewed. The medical database Medline along with original articles from peer-reviewed journals were used for analysis. There is convincing evidence suggesting that diabetes mellitus represents a strong independent risk factor of stroke. The contribution of hyperglycemia to increased stroke risk is not proven. Data suggest an association of the full cluster of the insulin resistance syndrome and stroke. Diabetes is a risk factor mainly for ischemic stroke, while its association with hemorrhagic stroke remains controversial. Hyperglycemia is common in stroke patients, but it is not known whether it independently influences the course and outcome of stroke or merely reflects stroke severity and location. Aggressive control of arterial hypertension and dyslipidemia allows to decrease the risk of stroke in diabetic patients substantially, while the importance of glucose control for stroke prevention remains unproven. Copyright © 2004 John Wiley & Sons, Ltd. [source] Movement-Induced Focal Motor Seizures and Choreoathetosis As- sociated with Nonketotic Hyperglycemia: A Case ReportEPILEPSIA, Issue 2000Hisashi Tanaka Case Report: We report the case of a diabetic woman who developed right-sided reflex seizures and bilateral choreoathetosis during an episode of nonketotic hyperglycemia. The patient was a 67-year-old woman with a 14-year history of HCV-related liver cirrhosis who experienced polydipsia and polyuria in January 1998. She began to have episodes of abnormal hyperkinetic movements of the right upper extremity and tonic-clonic seizures in the right arm triggered by voluntary movements of right or bilateral arms in the beginning of March 1998. The seizures increased in frequency and consequently left her disabled. She was admitted to our hospital with complaints of these abnormal motor phenomena on March 9, 1998. Neurological examinations revealed that she was alert, well-oriented, and that cranial nerve functions were normal. Slight motor weakness of the right upper limb and deep tendon hyporeflexes were observed in all extremities. Sensations and cerebellar functions were intact. Choreic or athetotic involuntary movements were seen in the bilateral upper limbs and neck. These involuntary movements were increased by voluntary movement or posturing of the upper limbs. The focal tonic-clonic seizures were easily triggered by voluntary movements such as knotting a cord. This seizure suddenly began by tonic movements in the right upper limb and gradually progressed to the right hemi-face and neck without loss of consciousness. The average duration of seizures was about one minute. The laboratory data demonstrated mild leukocytopenia, thrombocytopenia, hepatic dysfunction, and hyperglycemia without ketosis. Fasting blood glucose was 41 I mg/dl, and HbAlc was 14.5%. Blood ammonia was within normal levels. Cranial CT revealed no abnormalities. Brain MRI on T I-weighted images demonstrated bilateral high signal intensity in the putamen. An interictal EEG revealed a symmetrical slow background activity of 7,8 Hz. An ictal EEG recording showed a 2.5 4 Hz irregular sharp and slow wave discharge in the bilateral frontal-central regions. Treatment with carbamazepine was ineffective for the seizures. However, the seizures completely disappeared after the administration of insulin on March 17. Under good control of the hyperglycemia, the abnormal involuntary movements decreased gradually and then completely disappeared; the patient became neurologically asymptomatic by March 30. The follow-tip EEG demonstrated 9-Hz alpha background activity without any epileptic discharges. Conclusions: Nonketotic hyperglycemia has been rarely reported to cause stimulus-induced seizures or hyperkinetic involuntary movements such as hemichorea-ballism. To our knowledge, this is the first reported case of both induced seizures and involuntary movements simultaneously caused by hyperglycemia. Movement-induced seizures and choreoathetoid movements in this patient can be considered to result from transiently-increased activity in the basal ganglia and/or cerebral cortex associated with metaholic disorders. [source] Diabetes hyperglycemia and recovery from strokeGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1-2 2001Christopher S Gray Strokeis a major cause of death and severe disability in older people. Despite the burden of disease, there is still no safe, simple and proven medical therapy for the treatment of acute stroke. Advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis), and attention is once again being directed towards physiological variables that may influence outcome. Both insulin-dependent and non-insulin-dependent diabetes mellitus are major risk factors for stroke. Diabetes mellitus has also been shown to be associated with increased mortality and reduced functional outcome after stroke. Hyperglycemia is a frequent finding following stroke and may reflect the metabolic stress of the acute event, so-called stress hyperglycemia, and/or underlying impaired glucose metabolism. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery. What is not clear is to what extent hyperglycemia is a ,normal' physiological response to stroke or whether hyperglycemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection. It remains to be determined whether lowering and maintaining ,normal' glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome. [source] Olanzapine associated weight gain, Hyperglycemia and Neuroleptic Malignant Syndrome: case reportINTERNATIONAL JOURNAL OF GERIATRIC PSYCHIATRY, Issue 4 2002Rhonda Malyuk Abstract We describe here a case of olanzapine associated weight gain, hyperglycemia and neuroleptic malignant syndrome in a 64 year-old woman with a significant medical history. Eighteen weeks after initiating olanzapine, Mrs X lost glycemic control, exhibited signs and symptoms consistent with neuroleptic malignant syndrome and gained 8.9 kg. We suggest that utilization of olanzapine in the less medically stable geriatric patient be implemented with vigilant monitoring for such complications mentioned above. Copyright © 2002 John Wiley & Sons, Ltd. [source] Hyperglycemia and glucosamine-induced mesangial cell cycle arrest and hypertrophy: Common or independent mechanisms?IUBMB LIFE, Issue 7 2006Elodie Masson Abstract The Hexosamine Pathway (HP) is one hypothesis proposed to explain glucose toxicity and the alterations observed during the course of diabetic microvascular complication development. Glucosamine is a precursor of UDP-N-Acetylglucosamine (UDP-GlcNAc), the main product of the HP that has often been used to mimic its activation. The transfer of a UDP-GlcNAc residue onto proteins (O-GlcNAc modification) represents the final step of the HP and is considered as a major mechanism by which this pathway exerts its signalling effects. While it is well accepted that the HP promotes extracellular matrix accumulation in the context of diabetic nephropathy, its involvement in the perturbations of cell cycle progression and hypertrophy of renal cells has been poorly investigated. Nevertheless, in a growing number of studies, the HP and O-GlcNAc modification are emerging as important regulators of cell cycle progression. This review will focus on the role of glucosamine and O-GlcNAc modification in cell cycle regulation in the context of diabetic nephropathy. Special emphasis will be given into the role of the HP as a potential mediator of the effects of high glucose on the perturbations of renal cell growth. iubmb Life, 58: 381-388, 2006 [source] Hyperglycemia as a Predictor of In-Hospital Mortality in Elderly Patients without Diabetes Mellitus Admitted to a Sub-Intensive Care UnitJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 6 2008Intissar Sleiman MD OBJECTIVES: To investigate the association between hyperglycemia and in-hospital and 45-day mortality in acutely ill elderly patients. DESIGN: Retrospective cohort. SETTING: Hospital medical patients admitted to a sub-intensive care unit (sub-ICU) for elderly patients, which is a level of care between ordinary wards and intensive care. PARTICIPANTS: One thousand two hundred twenty-nine patients (mean age 79.6±8.4) admitted to the sub-ICU from January 2003 to January 2006. Forty patients with acute myocardial infarction and 34 patients with extreme fasting glucose values (<60 or >500 mg/dL) were excluded. Eight hundred twenty-two patients without a history of diabetes mellitus (DM) and 333 patients with a diagnosis of DM were selected and subdivided into three categories according to serum fasting blood glucose: 60 to 126 mg/dL (Group A), 127 to 180 mg/dL (Group B), and 181 to 500 mg/dL (Group C). MEASUREMENTS: Age, sex, mental and functional status, Acute Physiology Score, comorbid conditions, serum albumin, serum cholesterol, fasting serum glucose, and length of stay. In-hospital mortality was the primary outcome, and 45-day mortality was the secondary outcome. RESULTS: Total in-hospital mortality was 14.5%. In patients with and without DM, mortality was 8.8% and 11.3%, respectively, in Group A; 13.6% and 17.3% in Group B, and 12.6% and 34.3% in Group C. After controlling for confounders, newly recognized hyperglycemia (>181 mg/dL) was independently associated with in-hospital mortality (adjusted odds ratio=2.7, 95% confidence interval=1.6,4.8). Forty-five-day mortality in newly recognized hyperglycemic patients was 17.5%, 25.7%, and 42% in Groups A, B, and C, respectively, whereas it was 21.2% in patients with DM. CONCLUSION: In elderly patients, newly recognized hyperglycemia was associated with a higher mortality rate than in those with a prior history of DM. These data suggest that further randomized clinical trials are needed to assess the efficacy and the risk of a target glucose of greater than 180 mg/dL. [source] Relevance of insulin-like growth factor 2 in the etiopathophysiology of diabetic nephropathy: Possible roles of phosphatase and tensin homolog on chromosome 10 and secreted protein acidic and rich in cysteine as regulators of repairJOURNAL OF DIABETES, Issue 2 2009Movva SIREESHA Abstract Background: Diabetic nephropathy (DN) is a devastating complication of diabetes, the exact molecular pathophysiology of which is not well established. Hyperglycemia increases insulin-like growth factors (IGFs), especially IGF2, which acts via the IGF1 receptor present on renal cells. Elevated glucose levels damage the kidney, which is repaired by modulators such as secreted protein acidic and rich in cysteine (SPARC). Hence, it was hypothesized that IGF2 and SPARC may have an important role in the etiology of DN. Methods: Human renal biopsies, histopathologically categorized as normal, early Type 2 diabetes mellitus (T2DM), or established DN, were analyzed for the localization and expression of IGF2, its negative regulator phosphatase and tensin homolog on chromosome 10 (PTEN), and SPARC. Results: Expression of IGF2, PTEN, and SPARC was increased in renal biopsies from T2DM patients compared with normal samples. Although IGF2 protein was increased in biopsies from DN patients, PTEN and SPARC levels were decreased. Real-time reverse transcription,polymerase chain reaction indicated that transcript levels of IGF2 and PTEN were greater than those of ,-actin in all human renal biopsy samples. Conclusion: The results suggest the following molecular etiopathophysiology of DN: (i) hyperglycemia upregulates IGF2, which initiates PTEN, a regulator of IGF2 signaling; (ii) loss of this IGF2,PTEN feedback loop causes changes that are characteristic of DN; and (iii) lowered expression of the repair modulator SPARC results in the development and/or progression of DN. Hence, targeting relevant modulators, such as like IGF2, PTEN, and SPARC, may be important in the management of DN. [source] REVIEW ARTICLE: Hyperglycemia: a prothrombotic factor?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 8 2010B. A. LEMKES Summary., Diabetes mellitus is characterized by a high risk of atherothrombotic events. What is more, venous thrombosis has also been found to occur more frequently in this patient group. This prothrombotic condition in diabetes is underpinned by laboratory findings of elevated coagulation factors and impaired fibrinolysis. Hyperglycemia plays an important role in the development of these hemostatic abnormalities, as is illustrated by the association with glycemic control and the improvement upon treatment of hyperglycemia. Interestingly, stress induced hyperglycemia, which is often transient, has also been associated with poor outcome in thrombotic disease. Similar laboratory findings suggest a common effect of acute vs. chronic hyperglycemia on the coagulation system. Many mechanisms have been proposed to explain this prothrombotic shift in hyperglycemia, such as a direct effect on gene transcription of coagulation factors caused by hyperglycemia-induced oxidative stress, loss of the endothelial glycocalyx layer, which harbours coagulation factors, and direct glycation of coagulation factors, altering their activity. In addition, both chronic and acute hyperglycemia are often accompanied by hyperinsulinemia, which has been shown to have prothrombotic effects as well. In conclusion, the laboratory evidence of the effects of both chronic and acute hyperglycemia suggests a prothrombotic shift. Additionally, hyperglycemia is associated with poor clinical outcome of thrombotic events. Whether intensive treatment of hyperglycemia can prevent hypercoagulability and improve clinical outcome remains to be investigated. [source] Incidence and Clinical Relevance of Hyperglycemia in Critically Ill DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2007Danna M. Torre Background: Hyperglycemia associated with critical illness in nondiabetic human patients is a common occurrence in the intensive care unit (ICU), with a reported incidence as high as 71%. Hypothesis: Hyperglycemia in critically ill dogs increases the risk of morbidity and mortality. Animals: Two hundred forty-five dogs hospitalized in the ICU over a 2-month period were evaluated. Methods: Prospective observational study was conducted over a 2-month period. All dogs in the ICU had their highest daily blood glucose concentration recorded. All dogs with diabetes were excluded from the study. Hyperglycemia was defined as a blood glucose concentration >120 mg/dL. Dogs with hyperglycemia were monitored for persistence and resolution of hyperglycemia. Results: During the study period, 245 dogs were evaluated, of which 38 (16%) were hyperglycemic. Twenty-six percent (10/ 38) developed hyperglycemia during hospitalization, whereas 74% (28/38) were hyperglycemic at presentation. Length of hospitalization (LOH) was shorter in dogs that presented with hyperglycemia compared with those that developed hyperglycemia during hospitalization (P= .001). Seventy-one percent (27/38) of dogs were discharged from the hospital, whereas the remaining 29% (11/38) died or were euthanatized. Nonsurvivors had significantly higher median glucose concentration (median, 176 mg/dL; range 122,310 mg/dL) than did survivors (median, 139 mg/dL; 121,191 mg/dL; P= .021). Conclusions and Clinical Importance: The incidence of hyperglycemia in this population of dogs was 16%. Dogs that developed hyperglycemia had longer LOH and nonsurvivors had more pronounced hyperglycemia than did survivors. [source] Editorial: Stress Hyperglycemia and Diabetes Mellitus in CatsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2002Richard Nelson DVM No abstract is available for this article. [source] Acute Stress Hyperglycemia in Cats Is Associated with Struggling and Increased Concentrations of Lactate and NorepinephrineJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 2 2002Jacqueline S. Rand We characterized the changes in blood glucose concentrations in healthy cats exposed to a short stressor and determined the associations between glucose concentrations, behavioral indicators of stress, and blood variables implicated in stress hyperglycemia (plasma glucose, lactate, insulin, glucagon, cortisol, epinephrine, and norepinephrine concentrations). Twenty healthy adult cats with normal glucose tolerance had a 5-minute spray bath. Struggling and vocalization were the most frequent behavioral responses. There was a strong relationship between struggling and concentrations of glucose and lactate. Glucose and lactate concentrations increased rapidly and significantly in all cats in response to bathing, with peak concentrations occurring at the end of the bath (glucose baseline 83 mg/dL, mean peak 162 mg/dL; lactate baseline 6.3 mg/dL, mean peak 64.0 mg/dL). Glucose response resolved within 90 minutes in 12 of the 20 cats. Changes in mean glucose concentrations were strongly correlated with changes in mean lactate (r= .84; P <.001) and mean norepinephrine concentrations (r= .81; P < .001). There was no significant correlation between changes in mean glucose concentrations and changes in mean insulin, glucagon, cortisol, or epinephrine concentrations. Struggling and lactate concentrations were predictive of hyperglycemia. Gluconeogenesis stimulated by lactate release is the likely mechanism for hyperglycemia in healthy cats in this model of acute stress. Careful handling techniques that minimize struggling associated with blood collection may reduce the incidence of stress hyperglycemia in cats. [source] Hyperglycemia Stimulates a Sustained Increase in Hydraulic Conductivity In Vivo without Any Change in Reflection CoefficientMICROCIRCULATION, Issue 7 2007RACHEL M. PERRIN ABSTRACT Objective: Increased microvascular permeability contributes to the development of diabetic microvascular complications and diabetic vasculopathy is correlated with blood glucose levels. The mechanisms underlying increased permeability, however, are poorly understood. Methods: The Landis-Michel technique was used to measure water permeability (hydraulic conductivity, Lp) and macromolecular permeability (reflection coefficient, ,) of exchange capillaries in frogs and rats. Results: Dialysed normoglycemic plasma from diabetic patients had no effect on Lp. The same plasma with 20 mM glucose increased hydraulic conductivity from (mean ± SEM × 10,7 cm · s,1· cm H2O,1) 5.73 ± 2.01 to 13.09 ± 2.67 (P < .01). Nondiabetic control plasma did not affect Lp, but addition of 20 mM glucose increased Lp to a similar degree. The effect of glucose alone was examined. Glucose at 20 mM increased Lp, from 2.82 ± 0.61 to 4.71 ± 1.35 × 10, 7 cm · s, 1· cm H2O,1 (P = .002, n = 13). A similar increase was seen in rat mesenteric microvessels, from 1.04 ± 0.40 in control perfusions to 2.18 ± 0.56, P < .05. The microvascular macromolecular reflection coefficient in all the above experiments was unaltered. The use of specific inhibitors indicated that the glucose-induced increased Lp did not appear to be mediated through protein kinase C (PKC), free radical generation, glucose metabolism, or albumin glycation. Conclusions: These data suggest that hyperglycemia induced increased apparent protein permeability may be secondary to a glucose-mediated change in macromolecular convective flux rather than any change in protein permeability per se. The authors speculate that the increased microvascular permeability to water in vivo is mediated by direct interaction of glucose with the endothelial cells (perhaps with the glycocalyx). [source] Hyperglycemia not hypoglycemia alters neuronal dendrites and impairs spatial memoryPEDIATRIC DIABETES, Issue 6 2008John I Malone Background/Objective:, We previously reported that chronic hyperglycemia, but not hypoglycemia, was associated with the reduction of neuronal size in the rat brain. We hypothesized that hyperglycemia-induced changes in neuronal structure would have negative consequences, such as impaired learning and memory. We therefore assessed the effects of hyperglycemia and hypoglycemia on neuronal dendritic structure and cognitive functioning in young rats. Design/Methods:, Experimental manipulations were conducted on male Wistar rats for 8 wk, beginning at 4 wk of age. At the completion of the treatments, all rats were trained in the radial-arm water maze, a spatial (hippocampus-dependent) learning and memory task. Three groups of rats were tested: an untreated control group, a streptozotocin-induced diabetic (STZ-D) group, and an intermittent hypoglycemic group. Following behavioral training, the brains of all animals were examined with histologic and biochemical measurements. Results:, Peripheral hyperglycemia was associated with significant increases in brain sorbitol (7.5 ± 1.6 vs. 5.84 ± 1.0 ,M/mg) and inositol (9.6 ± 1.4 vs. 7.1 ± 1.1 ,M/mg) and reduced taurine (0.65 ± 0.1 vs. 1.3 ± 0.1 mg/mg). Histologic evaluation revealed neurons with reduced dendritic branching and spine density in STZ-D rats but not in control or hypoglycemic animals. In addition, the STZ-D group exhibited impaired performance on the water maze memory test. Conclusions:, Hyperglycemia, but not hypoglycemia, was associated with adverse effects on the brain polyol pathway activity, neuronal structural changes, and impaired long-term spatial memory. This finding suggests that the hyperglycemic component of diabetes mellitus has a greater adverse effect on brain functioning than does intermittent hypoglycemia. [source] Hyperglycemia, glycoxidation and receptor for advanced glycation endproducts: potential mechanisms underlying diabetic complications, including diabetes-associated periodontitisPERIODONTOLOGY 2000, Issue 1 2000EVANTHIA LALLA First page of article [source] Proteomic analysis of human proximal tubular cells exposed to high glucose concentrationsPROTEOMICS - CLINICAL APPLICATIONS, Issue 7-8 2008Eun-Jeong So Abstract Hyperglycemia is a major key factor in the pathogenesis of microvascular complications of diabetes, including diabetic nephropathy (DN). Most studies to date have focused on the glomerular abnormalities found in DN. However, nephromegaly in the early stages of diabetes and the correlation of tubulointerstitial pathology rather than glomerular pathology with declining renal function in DN suggests the involvement of the tubulointerstitium. The etiology of the tubulointerstitial pathology in DN, however, is not fully understood. In this study, to understand the DN pathways, we constructed an initial 2-DE reference map for primitively cultured human proximal tubule (HK-2) cell in the presence of 5,mM and 25,mM glucose, which correspond to blood glucose concentrations during the normal and hyperglycemia conditions, respectively. Differentially expressed HK-2 cell cellular proteins at the high glucose concentration were identified via ESI-Q-TOF MS/MS and confirmed by Western blotting; enolase 1 (up-regulated) and lactate dehydrogenase (down-regulated). The regulation of these proteins will help in understanding DN mechanism through the glycolysis metabolic pathways in high glucose stimulated HK-2 cells. [source] Disturbed morphogenesis of cardiac outflow tract and increased rate of aortic arch anomalies in the offspring of diabetic ratsBIRTH DEFECTS RESEARCH, Issue 12 2004Daniėl G.M. Molin Abstract BACKGROUND Maternal diabetes (MD) is a risk factor for offspring to develop cardiovascular anomalies; this is of growing clinical concern since the number of women in childbearing age with compromised glucose homeostasis is increasing. Hyperglycemia abrogates cardiovascular development in vitro; however, a link to cardiovascular defects in diabetic offspring remains to be investigated. METHODS We have studied cardiovascular development in offspring of MD rats by examining serial histological sections of GD 12.0,18.0 offspring. Development of pharyngeal arch artery malformations was analyzed and related to intracardiac anomalies. RESULTS Pharyngeal arch artery and intracardiac defects were present in 27 of 37 MD GD 13.0,18.0 offspring. Early sixth arch arteries showed abrogated arteriogenesis, whereas fourth arch artery defects developed as a result of abnormal remodeling. Morphometrical analysis showed increased apoptosis in regressing artery segments and reduced apoptosis in persisting artery segments. Double outlet right ventricle with infundibular stenosis (tetralogy of Fallot) was predominantly found in combination with sixth artery defects and pulmonary atresia. As confirmed by morphometric analysis and three-dimensional (3D)-reconstructions, outflow tract defects coincided with endocardial cushion hypoplasia. Cases with teratology of Fallot additionally showed a shorter outflow tract. No relation with apoptosis or disturbed neural crest cell migration was found. CONCLUSIONS Our data uniquely demonstrate mechanistic differences involved in the development of sixth and fourth artery anomalies. Whereas increased apoptosis induces fourth artery anomalies, pulmonary outflow obstruction abrogates sixth artery differentiation independent of apoptosis. The model presented allows analysis of diabetic conditions on cardiovascular development in vivo, essential for elucidating this teratology. Birth Defects Research (Part A), 2004. © 2004 Wiley-Liss, Inc. [source] Oxidative Stress as the Leading Cause of Acute Myocardial Infarction in DiabeticsCARDIOVASCULAR THERAPEUTICS, Issue 2 2006Clara Di Filippo ABSTRACT The risk factors, such as hypertension and metabolic syndrome, tend to promote heart pathology. These risk factors can aggravate concomitant heart insults as well. Diabetes mellitus represents one of the most important risk factors for the development of heart pathology. By itself it represents a source of vascular and heart dysfunction through formation of reactive oxygen species (ROS) and can compromise the recovery from cardiovascular diseases. This review focuses on the evidence that cellular oxidative stress is the leading cause of the worst outcome of myocardial infarction (MI) in diabetics. Hyperglycemia is viewed in this article as the primary mediator of a cascade of heart damaging events, starting from ROS formation and leading to myocardial ischemia, inflammation and death of myocytes. This article also provides insights into why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress and inflammation, can impede or delay the onset of complications of myocardial infarction in diabetic patients. [source] The role of HIF-1 alfa in apoptosis and proliferative retinopathyACTA OPHTHALMOLOGICA, Issue 2009R FERNANDES Purpose In diabetic retinal capillaries, the earlier morphological changes include pericyte loss and acellular capillary formation. These processes are regulated by interactions among a number of pro- and antiangiogenic factors, including vascular endothelial growth factor (VEGF) and Angiopoietin-2 (Ang-2). We hypothesize that increased levels of methylglyoxal (MGO) in RPE cells disrupts the balance of VEGF/Ang-2 promoting endothelial cell death and vessel regression. Methods Rats with moderate T2D, and retinal cell lines of epithelium (RPE) and endothelium (EC) were used. MGO levels were determined by HPLC. Immunohistochemical analysis was performed in retinas stained for VEGF and Ang-2. RPE cells were incubated with MGO in hypoxic conditions and the level of VEGF and Ang-2 was assessed by ELISA. EC were subsequently treated with the pre-conditioned media of the RPE cells. Cell death was determined by WB against Bax and Bcl-2, while EC proliferation was assessed by BrdU-incorporation and fibrin gel angiogenic assays. Results Hyperglycemia increases the levels of MGO in retinas and RPE cells. MGO increases the levels of Ang-2 and strongly decreases the levels of VEGF in response to hypoxia. VEGF downregulation appears to result both from increased HIF-1, degradation and low HIF-1 transcriptional activity. The MGO-induced imbalance in the VEGF/Ang-2 significantly increases the expression of Bax and decreases the levels of Bcl-2. Consistently, this imbalance leads to decreased proliferation of the EC. Conclusion In diabetic retinopathy, accumulation of MGO may play a role in VEGF/Ang-2 imbalance, triggering the activation of the apoptotic cascade which induces decreased proliferation of retinal endothelial cells and as a consequence vessels regression [source] Non surgical approach in diabetic macular edema : the future ?ACTA OPHTHALMOLOGICA, Issue 2009C CHIQUET Purpose To present the different non surgical therapeutical options of diabetic macular edema Methods The pathogenesis of diabetic macular edema is multifactorial. Hyperglycemia and poor systemic factor balance are major risk factors. Laser treatemnts and antiagiogenic treatments represent the main non surgical options to treat macular edema. Results Focal macular edema remains the best indication of laser treatment. Laser remains also the standard of care of diffuse macular edema but some edemas remain resistant. Several therapeutic options have been proposed : Steroid intravitreal injection and antiVEGF therapy (either PKC inhibitors, VEGF aptamers or VEGF antibodies) represent the future alternative treatments as well as their potential combination. Conclusion Laser remains the main treatment of diabetic macular edema. However, steroids and antiangiogenic agents either isolated or combined represent the main alternative treatment for non responding diffuse macular edema. [source] Heart changes in 17-day-old fetuses of diabetic ICR (Institute of Cancer Research) mothers: Improvement with maternal immune stimulationCONGENITAL ANOMALIES, Issue 1 2009Juan Claudio Gutierrez ABSTRACT Maternal diabetes mellitus is associated with increased fetal teratogenesis, including cardiovascular defects. Non-specific maternal immune stimulation with Freund's complete adjuvant (FCA) or interferon gamma (IFN,) has been associated with protection against birth malformations. Using a diabetic mouse model, late-gestation fetal heart and great vessel morphology were analyzed. Four groups of mice were used: non-diabetic females as a control group, hyperglycemic females induced by streptozotocin as a diabetic group, and diabetic females injected either with FCA or IFN,. At day 17 of gestation, females were euthanized and one fetus was arbitrarily selected per litter for fixation and sectioning. Treatment-induced changes in cardiac development were assessed from digital images of serial sections taken at standardized levels in the thorax. One-way parametric and non-parametric ANOVA and ordinal logistic regression were performed to compare the difference among groups (P < 0.05). Maternal hyperglycemia altered morphology of the late-gestation fetal mouse heart by causing ventricular chamber dilation, sectional myocardial reduction, and an increase in transversal aortic area. FCA protected the fetal heart from cavitary dilation in diabetic mothers. FCA and IFN, protected the fetal heart against reduction of myocardial area, and ascending thoracic aorta dilation. Consequences of late gestation heart chamber dilation and myocardial reduction are not yet known. Maternal immune stimulation partially protected against these developmental defects by mechanisms that remain unclear. [source] Diabetic embryopathy: Studies using a rat embryo culture system and an animal modelCONGENITAL ANOMALIES, Issue 3 2005Shoichi Akazawa ABSTRACT The mechanism of diabetic embryopathy was investigated using in vitro experiments in a rat embryo culture system and in streptozotocin-induced diabetic pregnant rats. The energy metabolism in embryos during early organogenesis was characterized by a high rate of glucose utilization and lactic acid production (anaerobic glycolysis). Embryos uninterruptedly underwent glycolysis. When embryos were cultured with hypoglycemic serum, such embryos showed malformations in association with a significant reduction in glycolysis. In a diabetic environment, hyperglycemia caused an increased glucose flux into embryonic cells without a down-regulation of GLUT1 and an increased metabolic overload on mitochondria, leading to an increased formation of reactive oxygen species (ROS). Activation of the hexamine pathway, subsequently occurring with increased protein carbonylation and increased lipid peroxidation, also contributed to the increased generation of ROS. Hyperglycemia also caused a myo-inositol deficiency with a competitive inhibition of ambient glucose, which might have been associated with a diminished phosphoinositide signal transduction. In the presence of low activity of the mitochondrial oxidative glucose metabolism, the ROS scavenging system in the embryo was not sufficiently developed. Diabetes further weakened the antioxidant system, especially, the enzyme for GSH synthesis, ,-GCS, thereby reducing the GSH concentration. GSH depletion also disturbed prostaglandin biosynthesis. An increased formation of ROS in a diminished GSH-dependent antioxidant system may, therefore, play an important role in the development of embryonic malformations in diabetes. [source] A quantitative study of the optic nerve in diabetic mutant, Otsuka Long-Evans Tokushima Fatty (OLETF) ratsCONGENITAL ANOMALIES, Issue 4 2001Kazuhiko Sawada ABSTRACT, Optic nerves of the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of non-insulin dependent diabetes mellitus, were examined using quantitative stereological procedures. At 67 weeks of age, OLETF rats showed a mild hyperglycemia: their blood glucose level was 196 ± 93 mg/dl, significantly higher than that of non-diabetic control Long-Evans Tokushima Otsuka (LETO) rats (110 ± 24 mg/dl). However, there were no differences in the cross sectional area of optic nerves (the mean minimum diameter), the total number and mean diameter of both myelinated and non-myelinated fibers, or the thickness of the myelin sheath between OLETF and LETO rats. The results suggested that a mild hyperglycemia in OLETF rats could not cause any morphological changes in the optic nerve. [source] Acupuncture: is it effective for treatment of insulin resistance?DIABETES OBESITY & METABOLISM, Issue 7 2010F. Liang Insulin resistance (IR) is closely associated with obesity, type 2 diabetes mellitus (T2DM), hypertension, polycystic ovary syndrome (PCOS), non-alcohol fatty liver diseases (NAFLD) and metabolic syndrome and is also a risk factor for serious diseases such as cardiovascular diseases. Pharmacological treatments available for IR are limited by drug adverse effects. Because acupuncture has been practiced for thousands of years in China, it has been increasingly used worldwide for IR-related diseases. This review analyses 234 English publications listed on the PubMed database between 1979 and 2009 on the effectiveness of acupuncture as a treatment for IR. These publications provide clinical evidence, although limited, in support of the effectiveness of acupuncture in IR. At this stage, well-designed, evidence-based clinical randomized controlled trial studies are therefore needed to confirm the effects of acupuncture on IR. Numerous experimental studies have demonstrated that acupuncture can correct various metabolic disorders such as hyperglycemia, overweight, hyperphagia, hyperlipidemia, inflammation, altered activity of the sympathetic nervous system and insulin signal defect, all of which contribute to the development of IR. In addition, acupuncture has the potential to improve insulin sensitivity. The evidence has revealed the mechanisms responsible for the beneficial effects of acupuncture, though further investigations are warranted. [source] Cognitive dysfunction in patients with type 2 diabetesDIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 7 2010Yael D. Reijmer Abstract People with diabetes mellitus are at increased risk of cognitive dysfunction and dementia. This review explores the nature and severity of cognitive changes in patients with type 2 diabetes. Possible risk factors such as hypo- and hyperglycemia, vascular risk factors, micro- and macrovascular complications, depression and genetic factors will be examined, as well as findings from brain imaging and autopsy studies. We will show that type 2 diabetes is associated with modest cognitive decrements in non-demented patients that evolve only slowly over time, but also with an increased risk of more severe cognitive deficits and dementia. There is a dissociation between these two ,types' of cognitive dysfunction with regard to affected age groups and course of development. Therefore, we hypothesize that the mild and severe cognitive deficits observed in patients with type 2 diabetes reflect separate processes, possibly with different risk factors and aetiologies. Copyright © 2010 John Wiley & Sons, Ltd. [source] Acetaminophen prevents aging-associated hyperglycemia in aged rats: effect of aging-associated hyperactivation of p38-MAPK and ERK1/2DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 3 2009Miaozong Wu Abstract Background Aging-related hyperglycemia is associated with increased oxidative stress and diminished muscle glucose transporter-4 (Glut4) that may be regulated, at least in part, by the mitogen-activated protein kinases (MAPK). Methods To test the possibility that aging-related hyperglycemia can be prevented by pharmacological manipulation of MAPK hyperactivation, aged (27-month old) Fischer 344/NNiaHSD × Brown Norway/BiNia F1 (F344BN) rats were administered acetaminophen (30 mg/kg body weight/day) for 6 months in drinking water. Results Hepatic histopathology, serum aspartate aminotransferase and alanine aminotransferase analyses suggested that chronic acetaminophen did not cause hepatotoxicity. Compared with adult (6-month) and aged (27-month) rats, very aged rats (33-month) had higher levels of blood glucose, phosphorylation of soleus p38-MAPK and extracellular-regulated kinase 1/2 (ERK1/2), superoxide and oxidatively modified proteins (p < 0.05), and these changes were associated with decreased soleus Glut4 protein abundance (p < 0.05). Chronic acetaminophen treatment attenuated age-associated increase in blood glucose by 61.3% (p < 0.05) and increased soleus Glut4 protein by 157.2% (p < 0.05). These changes were accompanied by diminished superoxide levels, decrease in oxidatively modified proteins (,60.8%; p < 0.05) and reduced p38-MAPK and ERK1/2 hyperactivation (,50.4% and , 35.4%, respectively; p < 0.05). Conclusions These results suggest that acetaminophen may be useful for the treatment of age-associated hyperglycemia. Copyright © 2009 John Wiley & Sons, Ltd. [source] | |||||||||||||||||||||||||||||||||||||