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II Diabetes (ii + diabetes)
Kinds of II Diabetes Terms modified by II Diabetes Selected AbstractsSPIRONOLACTONE FURTHER REDUCES URINARY ALBUMIN EXCRETION AND PLASMA B-TYPE NATRIURETIC PEPTIDE LEVLES IN HYPERTENSIVE TYPE II DIABETES TREATED WITH ANGIOTENSIN-CONVERTING ENZYME INHIBITORCLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 5-6 2006Susumu Ogawa SUMMARY 1Over the course of treatment with angiotensin-converting enzyme inhibitor (ACEI), plasma levels of aldosterone have been shown to increase and this increase would blunt the effectiveness of the ACEI (aldosterone escape phenomenon). 2In the present study, we assessed a potential renal benefit of additional aldosterone blockade with spironolactone in hypertensive diabetic patients treated with ACEI showing the phase of aldosterone escape. 3The present clinical study was a randomized prospective study to assess difference between the clinical effects of spironolactone and furosemide. Thirty hypertensive type II diabetics (DM2) with a urinary alubumin : creatinine ratio (ACR) above 30 mg/g creatinine (showing albuminuria) and plasma B-type natriuretic peptide (BNP) levels above 100 pg/mL (showing mild heart failure) were treated with an ACEI (imidapril 5 mg/day) for 1 year and then randomly divided into two groups, one group receiving additional spironolactone (25 mg/day) treatment and the other receiving furosemide (20 mg/day) treatment. Blood pressure, ACR and plasma BNP levels were monitored in both groups. 4Treatment with the ACEI reduced ACR initially but, in 1 year, ACR tended to increase. Additional spironolactone treatment progressively reduced ACR, whereas furosemide treatment did not show any effect. Plasma BNP levels were reduced by ACEI and were further reduced by additional spironolactone treatment, but not furosemide treatment. Blood pressure levels in both groups were comparable. 5In conclusion, additional therapy with spironolactone in ACEI treatment exerts a renoprotective, as well as cardioprotective, effect in hypertensive diabetes. [source] AMP-activated protein kinase and cancerACTA PHYSIOLOGICA, Issue 1 2009W. Wang Abstract AMP-activated protein kinase (AMPK) is a cellular energy sensor that is conserved in eukaryotes. Elevated AMP/ATP ratio activates AMPK, which inhibits energy-consuming processes and activates energy-producing processes to restore the energy homeostasis inside the cell. AMPK activators, metformin and thiazolidinediones, are used for the treatment of type II diabetes. Recently, reports have indicated that AMPK may also be a beneficial target for cancer treatment. Cancer cells have characteristic metabolic changes different from normal cells and, being a key metabolic regulator, AMPK may regulate the switch. AMPK may act to inhibit tumorigenesis through regulation of cell growth, cell proliferation, autophagy, stress responses and cell polarity. [source] Which comes first: atypical antipsychotic treatment or cardiometabolic risk?ACTA PSYCHIATRICA SCANDINAVICA, Issue 3 2009S. M. Stahl Objective:, To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment. Method:, A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross-referenced with schizophrenia was performed on articles published between 1990 and May 2008. Results:, Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics. Conclusion:, Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic-related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death. [source] Inhibition of recombinant human maltase glucoamylase by salacinol and derivativesFEBS JOURNAL, Issue 12 2006Elena J. Rossi Inhibitors targeting pancreatic ,-amylase and intestinal ,-glucosidases delay glucose production following digestion and are currently used in the treatment of Type II diabetes. Maltase-glucoamylase (MGA), a family 31 glycoside hydrolase, is an ,-glucosidase anchored in the membrane of small intestinal epithelial cells responsible for the final step of mammalian starch digestion leading to the release of glucose. This paper reports the production and purification of active human recombinant MGA amino terminal catalytic domain (MGAnt) from two different eukaryotic cell culture systems. MGAnt overexpressed in Drosophila cells was of quality and quantity suitable for kinetic and inhibition studies as well as future structural studies. Inhibition of MGAnt was tested with a group of prospective ,-glucosidase inhibitors modeled after salacinol, a naturally occurring ,-glucosidase inhibitor, and acarbose, a currently prescribed antidiabetic agent. Four synthetic inhibitors that bind and inhibit MGAnt activity better than acarbose, and at comparable levels to salacinol, were found. The inhibitors are derivatives of salacinol that contain either a selenium atom in place of sulfur in the five-membered ring, or a longer polyhydroxylated, sulfated chain than salacinol. Six-membered ring derivatives of salacinol and compounds modeled after miglitol were much less effective as MGAnt inhibitors. These results provide information on the inhibitory profile of MGAnt that will guide the development of new compounds having antidiabetic activity. [source] Crystal structure of human Rad GTPase of the RGK-familyGENES TO CELLS, Issue 8 2006Arry Yanuar Rad (Ras associated with diabetes) is an RGK-family small GTPase that is over-expressed in the skeletal muscle of humans with type II diabetes. Unlike other small GTPases, RGK family members including Rad lack several conserved residues in the GTPase domain. Here, we report the crystal structure of the GTPase domain of human Rad in the GDP-bound form at 1.8 Å resolution. The structure revealed unexpected disordered structures of both switches I and II. We showed that the conformational flexibility of both switches is caused by non-conservative substitutions in the G2 and G3 motifs forming the switch cores together with other substitutions in the structural elements interacting with the switches. Glycine-rich sequences of the switches would also contribute to the flexibility. Switch I lacks the conserved phenylalanine that makes non-polar interactions with the guanine base in H-Ras. Instead, water-mediated hydrogen bonding interactions were observed in Rad. The GDP molecule is located at the same position as in H-Ras and adopts a similar conformation as that bound in H-Ras. This similarity seems to be endowed by the conserved hydrogen bonding interactions with the guanine base-recognition loops and the magnesium ion that has a typical octahedral coordination shell identical to that in H-Ras. [source] Brain structure and obesityHUMAN BRAIN MAPPING, Issue 3 2010Cyrus A. Raji Abstract Obesity is associated with increased risk for cardiovascular health problems including diabetes, hypertension, and stroke. These cardiovascular afflictions increase risk for cognitive decline and dementia, but it is unknown whether these factors, specifically obesity and Type II diabetes, are associated with specific patterns of brain atrophy. We used tensor-based morphometry (TBM) to examine gray matter (GM) and white matter (WM) volume differences in 94 elderly subjects who remained cognitively normal for at least 5 years after their scan. Bivariate analyses with corrections for multiple comparisons strongly linked body mass index (BMI), fasting plasma insulin (FPI) levels, and Type II Diabetes Mellitus (DM2) with atrophy in frontal, temporal, and subcortical brain regions. A multiple regression model, also correcting for multiple comparisons, revealed that BMI was still negatively correlated with brain atrophy (FDR <5%), while DM2 and FPI were no longer associated with any volume differences. In an Analysis of Covariance (ANCOVA) model controlling for age, gender, and race, obese subjects with a high BMI (BMI > 30) showed atrophy in the frontal lobes, anterior cingulate gyrus, hippocampus, and thalamus compared with individuals with a normal BMI (18.5,25). Overweight subjects (BMI: 25,30) had atrophy in the basal ganglia and corona radiata of the WM. Overall brain volume did not differ between overweight and obese persons. Higher BMI was associated with lower brain volumes in overweight and obese elderly subjects. Obesity is therefore associated with detectable brain volume deficits in cognitively normal elderly subjects. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. [source] Argyria associated with colloidal silver supplementationINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2003Jeffrey K. McKenna MD A 65-year-old male presented for skin examination and was incidentally noted to have discoloration of the fingernails. These findings were completely asymptomatic. The patient had been taking colloidal silver supplementation (SilverzoneÔ 140 p.p.m. silver Gifts of Nature, St. George, UT, USA) for 2 years as therapy for diabetes. He first noticed the onset of nail discoloration 1 year ago. His past medical history included type II diabetes and hypertension. His current medications were metformin, glyburide, and benazepril. Physical examination revealed slate-gray discoloration involving the lunulae of the fingernails (Fig. 1). The skin, mucous membranes, and sclerae were unaffected. Figure 1. Slate-blue pigmentation of the lunula of an affected nail [source] An integrative literature review of lifestyle interventions for the prevention of type II diabetes mellitusJOURNAL OF CLINICAL NURSING, Issue 17 2008Suzanne G Madden Aims and objectives., An integrative literature review was undertaken to determine what type II diabetes prevention programmes have been evaluated, what type of programme is the most effective and how adherent to lifestyle changes adults are after participating in a prevention programme. Background., Type II diabetes is important because the disease is affecting millions of people worldwide. Obesity and sedentary lifestyles are preventable risk factors for type II diabetes, leading many researchers from around the world to examine different programmes that are focussed on prevention of the disease. Design., Integrative literature review. Method., Search of electronic databases. Results., Diet, exercise, counselling and diet plus exercise were the types of prevention programmes, with the diet plus exercise being the most efficacious. Although many studies demonstrated excellent results initially, maintaining the effects of the lifestyle behaviour change proved to be difficult for participants, with only one study demonstrating the persistence of results after six years. Conclusion., Future research should focus on long-term maintenance programmes, rather than just short-term prevention programmes to determine the need for booster interventions or other means to ultimately decrease the incidence of type II diabetes. Relevance to clinical practice., As front-line healthcare providers working across a broad array of settings, nurses are particularly well-suited to play an integral part in future applications of diabetes prevention programmes. Lifestyle interventions are being delivered in a variety of settings and venues such as the workplace, the Internet and places of worship. In addition, at-risk populations also can be targeted, particularly overweight and obese persons, with at least one parent having type II diabetes or persons with gestational diabetes. [source] Association between body weight and periodontal infectionJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 4 2008Pekka Ylöstalo Abstract Background: Besides being a risk factor for cardiovascular diseases, certain cancers and type II diabetes, obesity has been suggested to be a risk factor for periodontitis. A number of epidemiological studies have studied the association between obesity and periodontitis, but the results have been partly inconclusive. The aim of this study was to examine the association of body weight with periodontal infection. Material and Methods: The association between body weight and periodontal infection was examined using a nationally representative Health 2000 Health Examination Survey. The study was based on a subpopulation of dentate non-diabetic subjects aged 30,49 (n=2841). Periodontal infection was measured by the number of teeth with periodontal pockets of 4 mm or deeper and 6 mm or deeper. Body weight was measured using body mass index (BMI). Results: We detected a weak exposure,response association of BMI with teeth with deepened periodontal pockets after controlling for smoking habits by restricting the sample to subjects who have never smoked and for other potential confounders by including them in the multivariate models. Conclusions: The results showed an association between body weight and periodontal infection among the non-diabetic, non-smoking population aged 30,49. Additional research is needed to determine the nature of this association. [source] Determinants of prescribing patterns for type II diabetes at Primary Care Trust levelJOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 4 2004D. C. E. F. Lloyd BA (Hons) MSc Dip Epidem Summary Objective:, To estimate the effect of demography, deprivation and ethnicity on variations in prescribing of oral antidiabetics at the Primary Care Trust level. Design:, Cross-sectional survey. Setting:, All Primary Care Trusts in England. Main outcome measures:, Percentage of variance explained. Results:, A model using measures of demography, ethnicity, deprivation and use of thiazolidinediones explained 59% of the variation in cost per registered patient although individual variables explained far less. Conclusions:, This study shows the importance of using a multivariate approach in modelling the drivers of cost. The high use of thiazolidinediones is of concern in the light of NICE guidance. [source] Evaluation of gut motility in type II diabetes by the radiopaque marker methodJOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 4 2000Motoyuki Iida Abstract Background: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms. Methods: After administration of a Sitzmark capsule®, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan's methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R-R intervals on the electrocardiograms (CVR-R) was measured to evaluate parasympathetic autonomic function. Results: In the diabetics, the average (± SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 ± 8.3 vs 9.9 ± 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 ± 20.9 and 57.9 ± 22.3 h, respectively) compared with control subjects (23.3 ± 8.5 and 33.2 ± 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CVR-R. Conclusions: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts. [source] Dietary habits and health status of African-Caribbean adultsJOURNAL OF HUMAN NUTRITION & DIETETICS, Issue 3 2010J. Earland Abstract Background:, Although African-Caribbeans in the UK are more likely to suffer from a number of diet-related health conditions, including obesity, hypertension and type II diabetes, there have been few dietary studies on this group. The present study is based on a small survey of food and nutrient intakes and traditional dietary habits of African-Caribbean adults living in Staffordshire. Methods:, A questionnaire, designed to collect demographic data and information on medical status, physical activities, dietary, cooking and food shopping habits was administered to a convenience sample of 39 adults. Detailed information on food intakes was gathered using a modified existing Food Frequency Questionnaire with 169 items. Height and weight were measured for the calculation of body mass index. Results:, The average age of the subjects was 47 years (range 19,65 years). The prevalence of obesity was 39% and one-third of subjects reported having at least one health condition. Physical activities, outside of work, were undertaken by 95% of the sample. Traditional foods were used by 92% of respondents, including fruit and vegetables purchased at markets outside of their local area. A wide variety of foods were consumed and the percentages of energy provided by fats and carbohydrates (30% and 53%, respectively) appeared to be meeting government recommendations. However, absolute energy intakes were high and salt consumption, often in the form of commercial seasonings, exceeded government recommendations. Conclusions:, The positive aspects of the diets of this population need to be encouraged. Interventions need to focus on ways of reducing total energy intakes, as well as levels of salt consumption. [source] Type 2 diabetes and periodontal indicators: epidemiology in France 2002,2003JOURNAL OF PERIODONTAL RESEARCH, Issue 4 2006C. Mattout Background and Objective:, ,Diabetes and periodontal disease have been associated in the literature. In the present study, the periodontal heath of noninsulin-dependent diabetic adults was compared with that of a general population of nondiabetic patients. Material and Methods:, In France, 2144 adults (age: 35,65 years) were examined for life habits (tobacco, alcohol), biological diagnosis (type II diabetes, arterial hypertension), biometry (weight, size) and biochemistry. Dental and periodontal data included plaque index, gingival index, probing depth, and clinical attachment loss. Results:, Descriptive and multifactorial analysis evidenced a more severe periodontal disease in diabetic patients. Moreover, when the plaque index was held constant, the gingival index was more elevated in diabetics. In nondiabetics, age, gender, glycemia, alcohol, and tobacco smoking were identified as significant risk factors for periodontal disease. In contrast, in diabetic subjects, only tobacco smoking was a significant risk factor. Conclusion:, In type II diabetics, the diabetes factor is probably more significant than periodontal risk factors, age, and gender. [source] Analysis of haemochromatosis gene mutations in a population from the Mediterranean BasinLIVER INTERNATIONAL, Issue 4 2001Salvatore Campo Abstract:Background/Aims: The C282Y mutation in the haemochromatosis gene (HFE) located on chromosome 6 has been identified as the main genetic basis of hereditary haemochromatosis (HH). Two more mutations of that gene, H63D and S65C, appear to be associated with milder forms of HH. A high allele frequency for C282Y and H63D mutations was reported in populations from North Europe, while incomplete information is available for individuals from the Mediterranean Basin where C282Y homozygotes comprise a smaller percentage of HH cases. In this study we investigated the allele frequency of HFE mutations and the association between HFE mutations and cases of HH in a population from the South of Italy (Sicily and Calabria). In addition, we evaluated a possible association between HFE mutations and either chronic liver disease or type II diabetes. Patients and Methods: Three hundred and twenty-seven individuals (654 chromosomes) were tested for C282Y, H63D and S65C mutations of the HFE gene by restriction fragment length polymorphism. Four had HH, 23 had hepatocellular carcinoma, 100 had chronic liver disease, 100 had type II diabetes, and 100 were healthy controls. Results: Both C282Y and S65C mutations were each detected in one of the 654 chromosomes analysed (allele frequency=0.15%), while H63D change was found in 122 chromosomes (allele frequency=18.6%) and was equally distributed in all the categories examined. One healthy individual had compound heterozygosity for C282Y and H63D mutations. The frequency of C282Y in this Southern Italian sample was the lowest yet reported for a population of European origin. None of the four HH patients was either homozygous or heterozygous for C282Y. Conclusions: In Mediterranean populations from Southern Italy the C282Y mutation occurs sporadically and HFE polymorphisms seem to have little diagnostic relevance. [source] Cover Picture , Mol.MOLECULAR NUTRITION & FOOD RESEARCH (FORMERLY NAHRUNG/FOOD), Issue 12 2008Nutr. Selected topics of issue 12 are: Procyanidin effects on oesophageal adenocarcinoma cells strongly depend on flavan-3-ol degree of polymerization Daily Intake of thiamine correlates with the circulating level of endothelial progenitor cells and the endothelial function in patients with type II diabetes Fungal siderophores function as protective agents of LDL oxidation and are promising anti-atherosclerotic metabolites in functional food Identification of four IgE-reactive proteins in raspberry (Rubus ideaeus L.) [source] Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program,PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, Issue 1 2005Robert J. Cluxton Jr PharmD Abstract Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n,=,7226) or rosiglitazone (n,=,1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two ,Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth ,Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright © 2004 John Wiley & Sons, Ltd. [source] The efficacy of Silybum marianum (L.) Gaertn. (silymarin) in the treatment of type II diabetes: a randomized, double-blind, placebo-controlled, clinical trialPHYTOTHERAPY RESEARCH, Issue 12 2006H. Fallah Huseini Abstract Oxidative stresses are increasingly implicated in the pathogenesis of diabetic complications which may either cause direct pancreatic , -cell damage or lead to metabolic abnormalities that can induce or aggravate diabetes. The valuable effect of antioxidant nutrients on the glycemic control of diabetic patients has been reported in experimental and clinical studies. The present study was designed to investigate the effects of the herbal medicine, Silybum marianum seed extract (silymarin), which is known to have antioxidant properties on the glycemic profile in diabetic patients. A 4-month randomized double-blind clinical trial was conducted in 51 type II diabetic patients in two well-matched groups. The first group (n = 25) received a silymarin (200 mg) tablet 3 times a day plus conventional therapy. The second group (n = 26) received the same therapy but a placebo tablet instead of silymarin. The patients were visited monthly and glycosylated hemoglobin (HbA1c), fasting blood glucose (FBS), insulin, total cholesterol, LDL and HDL, triglyceride, SGOT and SGPT levels were determined at the beginning and the end of the study. The results showed a significant decrease in HbA1c, FBS, total cholesterol, LDL, triglyceride SGOT and SGPT levels in silymarin treated patients compared with placebo as well as with values at the beginning of the study in each group. In conclusion, silymarin treatment in type II diabetic patients for 4 months has a beneficial effect on improving the glycemic profile. Copyright © 2006 John Wiley & Sons, Ltd. [source] Use of herbal remedies by diabetic Hispanic women in The southwestern United StatesPHYTOTHERAPY RESEARCH, Issue 4 2006Lane Johnson Abstract Objective: The primary purpose of this study was to examine the use and documentation of herbal remedies used by Hispanic women with Type II diabetes enrolled in two Community Health Centers in the Southwest USA. A secondary purpose was to review the literature on identified herbs to assess their likely effects on diabetes. Design: Open-ended structured interviews were conducted on a convenience sample (n = 23) of participants. Medical and medication charts were reviewed for the interviewed participants, and for a random sample of enrolled Hispanic diabetic patients (n = 81) who were not interviewed. Setting: Two Community Health Centers in the Southwest USA. Participants: Enrolled patient, Hispanic females with Type II diabetes. Intervention: Subjects were interviewed about their use of herbal therapies and supplements. Information collected from medical and pharmaceutical charts included documented use of herbal remedies; standard therapies prescribed and diabetes control (hemoglobin A1C values). For those herbal remedies reported, literature reviews were conducted to determine if there was supporting evidence of harm or efficacy for the stated condition. Main Outcome Measures: Reports of herbal use, and types of remedies used. Results: Among the interviewed participants, 21 of 23 (91%) reported using one or more herbal remedies. Among a random sample of patient medical charts, seven (6.7%) contained documentation of diabetes-specific herbs, and 16 (15.4%) had documented general herb use. A total of 77 different herbal remedies were identified, most of which were contained as part of commercial preparations, and appeared to supplement, rather than replace standard medical therapy for diabetes. Conclusion: Use of herbal therapies is not uncommon among diabetic patients. Many of the herbs reported have potential efficacy in treating diabetes or may result in adverse effects or interactions. In practical use, however, the herbs reported in this study are unlikely to have a significant effect on clinical outcomes in diabetes, either positively or negatively. Copyright © 2006 John Wiley & Sons, Ltd. [source] The detection of phenotypic differences in the metabolic plasma profile of three strains of Zucker rats at 20 weeks of age using ultra-performance liquid chromatography/orthogonal acceleration time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 19 2006Robert S. Plumb Analysis of biological fluids using ultra-performance liquid chromatography/mass spectrometry (UPLC/MS) (metabonomics) can allow new insights to be gained into disease processes, with advances in chromatographic techniques enabling the detection of thousands of metabolites. In this work metabonomics has been used to investigate the metabolic processes involved in type II diabetes in the Zucker obese rat. Plasma was analyzed from three different strains, the Zucker (fa/fa) obese, Zucker lean and the lean/(fa) obese cross. Using UPLC/MS, ca. 10,000 ions were detected due to the narrow peak widths and excellent peak shapes achieved with this technology. Confidence in the chromatographic performance was demonstrated by the use of quality control standards. The positive and negative ion total ion chromatograms obtained from the three strains were readily distinguishable using multivariate statistical analysis. The greatest difference was observed between the Zucker lean and Zucker lean/(fa) rats compared to the Zucker (fa/fa) obese rats. Positive ions m/z 220 (4.36,min), 282(3.78,min), 359 (5.33,min) and 405 (7.77,min) were elevated in the plasma derived from Zucker lean rats whilst ions m/z 385 (6.80,min) and 646 (4.36,min) were at a lower concentration compared to the plasma from the Zucker (fa/fa) obese animals. Negative ions elevated in the Zucker lean rats included m/z 212 (2.30,min), 514 (2.85,min), 295 (4.39,min), 329 (3.11,min), 343 (2.86,min) and 512 (2.86,min) with ions m/z 538 (4.18,min), 568 (4.18,min), 568 (5.09,min) and 612 (4.30,min) being raised in the samples derived from Zucker (fa/fa) obese animals. The ion m/z 514 (3.85,min) was found to correspond to taurocholate, providing further support for an involvement of taurine metabolism in diabetes. Copyright © 2006 John Wiley & Sons, Ltd. [source] High-fiber diet promotes weight loss and affects maternal behavior in vervet monkeysAMERICAN JOURNAL OF PRIMATOLOGY, Issue 3 2010Lynn A. Fairbanks Abstract The dramatic increase in obesity in western societies has shifted the emphasis in nutrition research from the problems of undernutrition to the adverse consequences of being overweight. As with humans, Old World monkeys are at increased risk for type II diabetes and other chronic diseases when they gain excessive weight. To prevent overweight and obesity, promote animal health, and provide a more natural level of fiber in the diet, the standard commercial monkey chow diet at a vervet monkey breeding colony was changed to a higher fiber formulation in 2004. The new diet was also higher in protein and lower in carbohydrate and energy density than the standard diet. Because maternal behavior is known to be sensitive to differences in resource availability, data on weight and mother,infant interactions for 147 mothers with 279 infants born from 2000 through 2006 were assessed for effects of the diet change. The results showed that, even though food was provided ad libitum, the mean body weight of breeding females was 10% lower after the transition to the high-fiber diet. Behaviorally, mothers on the high-fiber diet were significantly more rejecting to their infants, and their infants had to play a greater role in maintaining ventral contact in the first few months of their lives. The effects of the diet change on maternal rejection were significantly related to the mother's body weight, with lower-weight mothers scoring higher in maternal rejection. These results demonstrate that maternal behavior is responsive to changes in maternal condition, and that beneficial changes in the diet may have unintended consequences on behavior. Am. J. Primatol. 72:234,241, 2010. © 2009 Wiley-Liss, Inc. [source] HNF1B and JAZF1 genes, diabetes, and prostate cancer risk,THE PROSTATE, Issue 6 2010Victoria L. Stevens Abstract BACKGROUND Epidemiologic studies have shown that men with type II diabetes have a lower risk of prostate cancer than non-diabetic men. Recently, common variants in two genes, HNF1B and JAZF1, were found to be associated with both of these diseases. METHODS We examined whether the relationship between HNF1B and JAZF1 variants and decreased prostate cancer risk may potentially be mediated through diabetes in two large prospective studies, the Cancer Prevention Study II Nutrition Cohort and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. RESULTS Three HNF1B SNPS, rs11649743, rs4430796, and rs7501939, were associated with decreased risk of prostate cancer and were also associated, with marginal statistical significance, with increased risk of diabetes. The JAZF1 SNPs rs6968704 and rs10486567 were associated with decreased risk of prostate cancer but were not associated with diabetes. All five SNP,prostate cancer relationships did not substantially differ when the analyses were stratified by diabetic status or when diabetic status was controlled for in the model. Furthermore, the association of diabetes with prostate cancer was not altered when the SNPs were included in the logistic model. CONCLUSIONS These findings indicate that the HNF1B variants are directly associated with both diabetes and prostate cancer, that diabetes does not mediate these gene variant,prostate cancer relationships, and the relationship between these diseases is not mediated through these gene variants. Prostate 70: 601,607, 2010. © 2009 Wiley-Liss, Inc. [source] The inhibitory effects of berry polyphenols on digestive enzymesBIOFACTORS, Issue 4 2005Gordon J. Mcdougall Abstract The evidence for the effect of polyphenol components of berries on digestive enzymes is reviewed. Anthocyanins inhibit ,-glucosidase activity and can reduce blood glucose levels after starch-rich meals, a proven clinical therapy for controlling type II diabetes. Ellagitannins inhibit ,-amylase activity and there is potential for synergistic effects on starch degradation after ingestion of berries such as raspberries and strawberries, which contain substantial amounts of ellagitannins and anthocyanins. A range of berry polyphenols (e.g. flavonols, anthocyanidins, ellagitannins and proanthocyanidins) can inhibit protease activities at levels which could affect protein digestion in the gastrointestinal tract. In contrast, potential for the inhibition of gastrointestinal lipase activity, a proven therapeutic target for the control of obesity through reduced fat digestion, may be limited to proanthocyanidins. Taking into account the manifold possible synergies for inhibition of starch, protein and/or lipid digestion by the spectrum of polyphenol components present within berry species, the inhibition of digestive enzymes by dietary polyphenols may represent an under-reported mechanism for delivering some of the health benefits attributed to a diet rich in fruit and vegetables. [source] The assessment of human regional drug absorption of free acid and sodium salt forms of Acipimox, in healthy volunteers, to direct modified release formulation strategyBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 9 2009Rajeev Menon Abstract Acipimox is an analog of nicotinic acid and is indicated for the treatment of dyslipidemia. It is also believed to improve glucose control by enhancing insulin sensitivity. The purpose of this study was to direct modified release (MR) formulation strategy by comparing the bioavailability of two forms of acipimox (free acid and sodium salt) from the distal small bowel (DSB) and colon with an immediate release formulation. Two parallel groups of healthy volunteers completed an open label, non-randomized, three-way crossover study. The rate and extent of acipimox absorption was highest following administration of the immediate release capsules, and was not influenced by the form of the drug administered. Following administration to the DSB, the relative bioavailability was approximately 52% and 30% for the salt form and free acid form, respectively. Following administration to the colon, the extent of absorption was further reduced. The data indicate that bioavailability from the DSB was limited by the solubility of the drug coupled with an absorption window, whilst absorption from the colon was limited by permeability. The study provided detailed information to support and guide the formulation strategy for a MR form of acipimox, which may improve the treatment of adult patients with type II diabetes and dyslipidemia. Copyright © 2009 John Wiley & Sons, Ltd. [source] Crystallization of the glycogen-binding domain of the AMP-activated protein kinase , subunit and preliminary X-ray analysisACTA CRYSTALLOGRAPHICA SECTION F (ELECTRONIC), Issue 1 2005Galina Polekhina AMP-activated protein kinase (AMPK) is an intracellular energy sensor that regulates metabolism in response to energy demand and supply by adjusting the ATP-generating and ATP-consuming pathways. AMPK potentially plays a critical role in diabetes and obesity as it is known to be activated by metforin and rosiglitazone, drugs used for the treatment of type II diabetes. AMPK is a heterotrimer composed of a catalytic , subunit and two regulatory subunits, , and ,. Mutations in the , subunit are known to cause glycogen accumulation, leading to cardiac arrhythmias. Recently, a functional glycogen-binding domain (GBD) has been identified in the , subunit. Here, the crystallization of GBD in the presence of ,-cyclodextrin is reported together with preliminary X-ray data analysis allowing the determination of the structure by single isomorphous replacement and threefold averaging using in-house X-ray data collected from a selenomethionine-substituted protein. [source] Comparison of chromatic macular ERG and multifocal ERG in diabetic macular edemaACTA OPHTHALMOLOGICA, Issue 2007MA ARAKELYAN Purpose: To evaluate the degree of macular function disturbances in patients with diabetes mellitus and high glycosylated haemoglobin (HbA1c). Methods: 11 patients with type II diabetes were included in our study. In 6 patients a clinically significant macular edema was detected; other 5 patients showed slight vascular changes and absence of macular pathology. All patients had much too high (8-10%) or extremely high (above 10%) levels of HbA1c and underwent a chromatic macular ERG test to red, green and blue stimuli (MBN, Russia). A RETIScan system for multifocal ERG was also used (Roland Consult, Germany). Results: Patients with macular edema and long duration of the disease had significant reduction of a- and b-wave amplitudes of macular ERG, whereas those with short duration of diabetes showed slight decrease of macular ERG amplitude. The density of photoreceptors in multifocal ERG and amplitudes of N1 and P1 components were analyzed in area of 15° of visual angle: the mean of 3 central rings' values was calculated. Correlation between mf-ERG data and macular ERG amplitudes were found. In patients without macular edema and duration of the disease from 7 to 10 years who had background diabetic retinopathy no significant changes of function testing of the macula were revealed. The amplitude values were close to lower normal data. Conclusions: Macular function in diabetic patients is mainly safe in spite of high levels of glycosylated haemoglobin. The complexity of pathogenetic mechanisms of diabetic retinopathy along with functional tests is still the subject of an investigation. [source] | ||||||||||||||||||||||||||||