Download the Free Unbound MEDLINE PubMed App to your smartphone or tablet.
Available for iPhone, iPad, iPod touch, and Android.
- A comparison of cardiovascular risk factors for ten antipsychotic drugs in clinical practice. [Journal Article]
- Neuropsychiatr Dis Treat 2013.:371-7.
It is well known that abdominal obesity, dyslipidemia, and insulin resistance are highly prevalent in patients receiving maintenance treatment with antipsychotics, but there is limited knowledge about the association between cardiovascular risk factors and treatment with antipsychotic drugs. In this naturalistic study we investigated a sample of 809 antipsychotic-treated patients from Swedish psychosis outpatient teams. Cardiovascular risk factors (eg, metabolic syndrome, homeostasis model assessment of insulin resistance, and low-density lipoprotein values) were measured, and their associations to current antipsychotic pharmacotherapy were studied. Ten antipsychotic drugs were compared in a stepwise logistic regression model. For the patients, the presence of the components of metabolic syndrome ranged from 35% for hyperglycemia to 64% for elevated waist circumference. Hypertriglyceridemia was associated with clozapine (odds ratio [OR] = 1.81, 95% confidence interval [CI] 1.08-3.04), reduced high-density lipoprotein with both clozapine and olanzapine (OR = 1.73, 95% CI 1.01-2.97; and OR = 2.03, 95% CI 1.32-3.13), hypertension with perphenazine (OR = 2.00, 95% CI 1.21-3.59), and hyperglycemia inversely with ziprasidone (OR = 0.21, 95% CI 0.05-0.89) and positively with haloperidol (OR = 2.02, 95% CI 1.18-3.48). There were no significant relationships between any of the antipsychotic drugs and increased waist circumference, homeostasis model assessment of insulin resistance, or low-density lipoprotein levels. In conclusion, treatment with antipsychotic drugs is differentially associated with cardiovascular risk factors, even after adjusting for waist circumference, sex, age, and smoking.
- Practical approach to management of inpatient hyperglycemia in select patient populations. [Journal Article]
- Hosp Pract (1995) 2013 Apr; 41(2):45-53.
Hospitalized patients frequently transition between various levels of care and changing clinical situations. Optimal management of hospitalized patients with hyperglycemia includes awareness of situations that may significantly affect glucose and/or insulin metabolism. A review of published clinical trials reveals practical approaches to the management of hyperglycemia in select patient populations that may prove useful for the hospital clinician. We outline approaches to the management of hyperglycemia in hospitalized patients receiving glucocorticoids, patients with severe or end-stage renal disease undergoing hemo- or peritoneal dialysis, and patients receiving total parenteral or enteral feeding, in addition to patients transitioning from intravenous insulin infusion to subcutaneously administered insulin. Key considerations underlying these management methods include a proactive approach, frequent blood glucose monitoring, daily review of blood glucose patterns, and daily reassessment of the insulin regimen and associated orders.
- The orphan nuclear receptor small heterodimer partner negatively regulates pancreatic beta cell survival and hyperglycemia in multiple low-dose streptozotocin-induced type 1 diabetic mice. [JOURNAL ARTICLE]
- Int J Biochem Cell Biol 2013 May 13.
The small heterodimer partner (SHP; NR0B2) regulates the transcription of a variety of target genes and controls a variety of physiological functions in various tissues. However, the role of SHP in beta cell has not been fully determined yet. We used SHP knockout (SHP KO) mice to investigate the role of SHP in multiple low-dose streptozotocin (MLDS)-induced diabetes. Blood glucose and insulin levels were measured until 20 days, and intraperitoneal glucose tolerance and glucose-stimulated insulin secretion tests were performed. The expression of apoptotic genes and beta cell markers were detected by quantitative realtime-polymerase chain reaction, immunostaining and western blot analysis. SHP KO mice showed significantly lower blood glucose, higher insulin levels, and enhanced glucose tolerance compared with wild type (WT) mice after MLDS treatment. Moreover, beta cell mass and pancreatic insulin content were remarkably increased in SHP KO mice. In the response to glucose stimulation, islets of SHP KO showed increased insulin secretion via up-regulation of beta cell enriched transcription factors compared to WT mice after streptozotocin (STZ) treatment. In quantification for beta cell apoptosis at day 1 post STZ treatment, the SHP KO mice showed significantly increased anti-apoptotic gene expression and decreased release of apoptotic markers cytochrome c, smac/diablo, and only a few apoptotic beta cells were found in SHP KO pancreas through inactivation of caspase-3, compared to those of WT. These data demonstrate that SHP deficiency ameliorates hyperglycemia and preserves islet function by inhibiting apoptosis of pancreatic beta cells and up-regulating of their enriched transcriptional factors.
- Prevalence and risk factors of microalbuminuria in type 2 diabetes mellitus outpatients at University Sains Malaysia Hospital. [Journal Article]
- Diabetes Metab Syndr 2013 Apr-Jun; 7(2):64-7.
Microalbuminuria is early stage of diabetic nephropathy as well as a marker of cardiovascular disease. The objective of this study is to determine the prevalence of microalbuminuria and associated risk factors among type 2 diabetic outpatients, attending a diabetic clinic in University Sains Malaysia Hospital (HUSM).Prospective study design was used in the data collection process. The study sample consists of 1066 type 2 diabetes mellitus outpatients who fit the inclusion criteria. All the patients were recruited from the diabetic outpatient clinics from HUSM. The study period was from January till December 2008. Microalbuminuria was diagnosed if the urinary albumin excretion more than 30mg/g of creatinine.A total of 1661 patients were included in this study. Microalbuminuria was diagnosed in 273 (25.4%) patients. Multivariate logistic regression analysis indicated that microalbuminuria was positively associated with duration of hypertension (P=0.044), HbA1c (P=0.004), systolic blood pressure (<0.001), creatinine clearance (P=0.007) and the presence of neuropathy (P=0.004).High prevalence of microalbuminuria was in type 2 diabetic outpatients. Predictive factors for microalbuminuria were duration of hypertension, HbA1c, systolic blood pressure, creatinine clearance and the presence of neuropathy. The study suggests the need to screen for microalbuminuria early and the active management of modifiable risk factors in particular, hyperglycemia, hypertension and creatinine clearance, to reduce the burden of end-stage renal disease in the future.
- Hyperglycemia as a risk factor for the development of retinopathy of prematurity. [JOURNAL ARTICLE]
- BMC Pediatr 2013 May 16; 13(1):78.
BACKGROUND:Hyperglycemia has recently been described as a risk factor for the development of retinopathy of prematurity (ROP), a proliferative vascular disease of the retina that primarily affects premature infants. This study was to evaluate the relationship of hyperglycemia and the development of ROP in premature infants less than 32 weeks gestation.
METHODS:This was a retrospective cohort study of all infants less than 32 weeks gestation from 2003--2007 who survived to discharge in our NICU. Demographic data including birthweight, gestational age, Apgar scores, method of delivery, antenatal steroid use, neonatal steroid use, and size for gestational age was collected for each infant. Episodes of sepsis, grade of intraventricular hemorrhage, presence of a patent ductus arteriosus, number of days on the ventilator, and stage of necrotizing enterocolitis were assessed as well as days of hyperglycemia, defined as number of days with whole blood glucose > 150 mg/dl. In addition, the highest stage of ROP was recorded for each infant. A Student's two tailed t-test or Fisher's exact test was performed to identify significant clinical risk factors associated with the development of ROP. From this univariate analysis, a multiple logistic regression was performed to determine the effect of hyperglycemia on the development of ROP, adjusting for significant clinical risk factors. Statistical analysis was performed using SAS v.9.2.
RESULTS:Univariate analysis demonstrated that infants with ROP were of lower birthweight and gestational age, and were affected by a patent ductus arteriosus, neonatal sepsis, intraventricular hemorrhage, have significant lung disease and received postnatal glucocorticoid therapy. Infants with ROP experienced more days with hyperglycemia (7 vs. 2, p = < 0.0001). Using multiple logistic regression analysis to compare no ROP vs. all stages of ROP, gestational age (OR 0.745, 95% CI [0.634, 0.877], p = 0.0004), mean days of hyperglycemia (OR 1.073, 95% CI [1.004, 1.146], p = 0.04), and mean days receiving mechanical ventilation (OR 1.012, 95% CI [1.000, 1.025], p = 0.05) remained significantly associated with ROP after adjusting for other risk factors.
CONCLUSION:Our data suggests that hyperglycemia is associated with the development of ROP in premature infants.
- The role of epidermal growth factor receptor in diabetes-induced cardiac dysfunction. [Journal Article]
- Bioimpacts 2013; 3(1):5-9.
The incidence of diabetes mellitus is increasing rapidly and set to reach near epidemic proportions with the latest estimates suggesting that by 2030 there will be over 550 million people with this debilitating disease. Cardiovascular complications and dysfunctions are three- to eight-folds more likely in diabetic patients and are major causes of increased mortality. The exact underlying mechanisms for the development of complications of the diabetic heart are poorly understood and may involve multiple signaling pathways that are affected by hyperglycemia. This focused article reviews the recent evidence for a possible dual role of epidermal growth factor receptor signaling in diabetes-induced cardiac dysfunction.
- ADAM17 mediates Nox4 expression and NADPH oxidase activity in the kidney cortex of OVE26 mice. [JOURNAL ARTICLE]
- Am J Physiol Renal Physiol 2013 May 15.
Matrix protein accumulation is a prominent feature of diabetic nephropathy that contributes to renal fibrosis and decline in renal function. The pathogenic mechanisms of matrix accumulation are incompletely characterized. We investigated if the matrix metalloprotease A Disintegrin And Metalloprotease17 (ADAM17), known to cleave growth factors and cytokines, is activated in the kidney cortex of OVE26 type 1 diabetic mice and potential mechanisms by which ADAM17 mediates extracellular matrix accumulation. Protein expression and activity of ADAM17 were increased in OVE26 kidney cortex. Using a pharmacological inhibitor to ADAM17, TMI-005, we determined that ADAM17 activation results in increased type IV collagen, Nox4, and NADPH oxidase activity in the kidney cortex of diabetic mice. In cultured mouse proximal tubular epithelial cells (MCTs), high glucose increases ADAM17 activity, Nox4 and fibronectin expression, cellular collagen content, and NADPH oxidase activity. These effects of glucose were inhibited when cells were pretreated with TMI-005 and/or transfected with siADAM17. Collectively, these data indicate a novel mechanism whereby hyperglycemia in diabetes increases extracellular matrix protein expression in the kidney cortex through activation of ADAM17 and enhanced oxidative stress through Nox enzyme activation. Additionally, our study is the first to provide evidence that Nox4 is downstream of ADAM17.
- The Antioxidant Activity of Copper(II) (3,5-Diisopropyl Salicylate)4 and Its Protective Effect Against Streptozotocin-Induced Diabetes Mellitus in Rats. [JOURNAL ARTICLE]
- Biol Trace Elem Res 2013 May 17.
Oxidative stress has been suggested as a potential contributor to the development of diabetic complications. In this study, we investigated the protective effect of a strong antioxidant copper complex against streptozotocin (STZ)-induced diabetes in animals. Out of four copper complexes used, copper(II) (3,5-diisopropyl salicylate)4 (Cu(II)DIPS) was found to be the most potent antioxidant-copper complex. Pretreatment with Cu(II)DIPS (5 mg/kg) twice a week prior to the injection of streptozotocin (50 mg/kg) has reduced the level of hyperglycemia by 34 % and the mortality rate by 29 %. Injection of the same dosage of the ligand 3,5-diisopropyl salicylate has no effect on streptozotocin-induced hyperglycemia. The same copper complex has neither hypoglycemic activity when injected in normal rats nor antidiabetic activity when injected in STZ-induced diabetic rats. The protective effect of Cu(II)DIPS could be related to its strong antioxidant activity compared to other copper complexes median effective concentration (MEC) = 23.84 μg/ml and to Trolox MEC = 29.30 μg/ml. In addition, it reduced serum 8-hydroxy-2'-deoxyguanosine, a biomarker of oxidative DNA damage, by 29 %. This effect may explain why it was not effective against diabetic rats, when β Langerhans cells were already destroyed. Similar protective activities were reported by other antioxidants like Trolox.
- Chronic resveratrol administration improves diabetic cardiomyopathy in part by reducing oxidative stress. [JOURNAL ARTICLE]
- Cardiol J 2013 May 15.
BACKGROUND:Based on the key role of hyperglycemia-mediated oxidative stress in the pathogenesis of diabetic cardiomyopathy, increasing antioxidant defense would represent novel therapeutic approach for management of diabetic cardiomyopathy. This study was designed to seek the effectiveness of chronic treatment with resveratrol, a potent natural antioxidant, on streptozotocin-nicotinamide experimental model of type 2 diabetic hearts.
METHODS:Male rats randomized into four groups (n =12): control, diabetic, control + resveratrol, and diabetic + resveratrol.
RESULTS:Four-month oral resveratrol administration to diabetic rats (5 mg/kg/day) alleviated the reduction of cardiac antioxidant enzymes activities (3.88 ± 0.48 vs. 1.49 ± 0.43 U, p < 0.05 for superoxide dismutase, and 2.72 ± 0.26 vs. 1.18 ± 0.19 nmol/min/ml, p < 0.05 for catalase) and the enhancement of cardiac oxidative markers (5.01 ± 0.37 vs. 7.23 ± 0.51 ng, p < 0.05 for 8-isoprostane, 6.03 ± 0.87 vs. 8.49 ± 0.52 µmol, p < 0.05 for nitrite/nitrate, and 0.44 ± 0.03 vs. 0.59 ± 0.04, p < 0.05 for oxidized/reduced glutathione ratio), nuclear factor kappa B activity (0.37 ± 0.09 vs. 0.60 ± 0.11, p < 0.05) and apoptosis rate (0.98 ± 0.28 vs. 1.63 ± 0.16, p < 0.05). Moreover, it improved left ventricular developed pressure (72.46 ± 8.16 vs. 52.01 ± 11.32 mmHg, p < 0.05) and coronary flow (14.08 ± 1.09 vs. 11.75 ± 1.43 ml/min × g, p < 0.05).
CONCLUSION:These beneficial cardioprotective observations suggest that treatment with resveratrol can potentially delay or attenuate the progression of diabetic-related cardiac complications.
- [A new physiopathological classification of diabetic neuropathy]. [English Abstract, Journal Article]
- Rev Med Chil 2012 Dec; 140(12):1593-605.
Nowadays, Diabetic Neuropathy (DN) is considered the most common cause of peripheral neuropathy in clinical practice. It can affect sensitive, motor or autonomic nerve fibers, with symmetric, asymmetric, acute or chronic presentations. Due to this variability, with multiple physiopathologic mechanisms involved, a complex clinical classification has been used until recently. The aim of this review is to present a new classification of diabetic neuropathy, based on its physiopathology. It is divided in metabolic microvascular and hypoxic, autoimmune and inflammatory, compressive, secondary to complications ofdiabetes and related to treatment. It must be understood that DN is notjust a functional disease, but a complication of diabetes with molecular and pathological substrates caused by hyperglycemia. Therefore, normalization of blood glucose is a fundamental step towards the successful prevention and treatment of DN.