Search

Insulin-induced severe hypoglycemia causes brain damage. The hypothesis to be tested was that diabetes portends to more extensive brain tissue damage following an episode of severe hypoglycemia. Nine-week-old male streptozotocin-diabetic (DIAB; n = 10) or vehicle-injected control (CONT; n = 7) Sprague-Dawley rats were subjected to hyperinsulinemic (0.2 U x [kg.sup.-1] x [min.sup.-1]) severe hypoglycemic (10-15 mg/dl) clamps while awake and unrestrained. Groups were precisely matched for depth and duration (1 h) of severe hypoglycemia (CONT 11 [+ or -] 0.5 and DIAB 12 [+ or -] 0.2 mg/dl, P = not significant). During severe hypoglycemia, an equal number of episodes of seizure-like activity were noted in both groups. One week later, histological analysis demonstrated extensive neuronal damage in regions of the hippocampus, especially in the dentate gyms and CA1 regions and less so in the CA3 region (P < 0.05), although total hippocampal damage was not different between groups. However, in the cortex, DIAB rats had significantly (2.3-fold) more dead neurons than CONT rats (P < 0.05). There was a strong correlation between neuronal damage and the occurrence of seizure-like activity ([r.sup.2] > 0.9). Separate studies conducted in groups of diabetic (n = 5) and nondiabetic (n = 5) rats not exposed to severe hypoglycemia showed no brain damage. In summary, under the conditions studied, severe hypoglycemia causes brain damage in the cortex and regions within the hippocampus, and the extent of damage is closely correlated to the presence of seizure-like activity in nonanesthetized rats. It is concluded that, in response to insulin-induced severe hypoglycemia, diabetes uniquely increases the vulnerability of specific brain areas to neuronal damage. Fluoro-Jade; insulin; seizure; streptezotocin

Objective: To compare changes in diagnosed diabetes prevalence and incidence among Status Aboriginal men and women living in urban and rural areas of Alberta. Methods: We compared trends in diabetes prevalence and incidence from 1995 to 2006 based on diagnostic codes from Alberta Health and Wellness (AHW) administrative records for adults aged 20 years and older. The AHW Registry file was used to determine registered Aboriginal status, as well as rural and urban residence (based on postal code). Multivariable logistic regression was used to compare diabetes rates over time, by sex and location of residence. Results: Age- and sex-adjusted diabetes prevalence increased 35% in rural Status Aboriginals, from 10.9 (10.4-11.5) per 100 in 1995 to 14.7 (14.215.2) per 100 in 2006. Rates in urban Status Aboriginals increased 22% in the same time period from 9.4 (8.5-10.3) per 100 in 1995 to 11.5 (10.912.1) per 100 in 2006. The increases in prevalence were greater (p Conclusions: Prevalence and incidence of diagnosed diabetes were highest in Status Aboriginal women, but these rates have increased faster in men over the past decade, regardless of their location of residence. Key words: Diabetes; epidemiology; rural health; Status Aboriginal Objectif : Comparer les changements de taux de prevalence et d&apos;incidence du diabete diagnostique chez les hommes et les femmes qui appartiennent a la population autochtone et qui resident dans les regions urbaines et rurales de l&apos;Alberta. Methodes : Nous avons compare les tendances des taux de prevalence et d&apos;incidence du diabete de 1995 a 2006, selon les codes de diagnostic des dossiers administratifs conserves par Alberta Health and Wellness (AHW) pour les adultes fges de 20 ans ou plus. Les fichiers du registre d&apos;AHW ont ete utilises pour determiner le statut de personne inscrite comme Autochtone, en plus de sa residence rurale ou urbaine (selon le code postal). Une analyse de regression logistique multidimensionnelle a ete utilisee pour comparer les taux de diabete au fil des ans, selon le sexe et le lieu de residence. Resultats : Le taux de prevalence du diabete, rajuste pour tenir compte de l&apos;fge et du sexe, a augmente de 35 % chez les Autochtones qui resident en milieu rural, de 10,9 (10,4 a 11,5) par 100 habitants en 1995 a 14,7 (14,2 a 15,2) par 100 habitants en 2006. Le taux de prevalence du diabete chez les Autochtones qui resident en milieu urbain a augmente de 22 % au cours de la meme periode, de 9,4 (8,5 a 10,3) par 100 habitants en 1995 a 11,5 (10,9 a 12,1) par 100 habitants en 2006. Les augmentations des taux de prevalence (p Conclusions : Les taux de prevalence et d&apos;incidence du diabete diagnostique etaient plus eleves chez les femmes autochtones, mais ces taux ont augmente plus rapidement chez les hommes autochtones au cours de la derniere decennie, peu importe le lieu de residence. Mots cles : diabete; epidemiologie; sante en milieu rural; personne appartenant a la population autochtone, Aboriginal Canadians, including First Nations, Metis and Inuit people, are recognized to be at increased risk for major health problems.1 The increasing prevalence and incidence of diabetes mellitus among Aboriginal [...]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2008.12.007 Byline: Abhinav Goyal (a)(b), Shamir R. Mehta (a)(c), Hertzel C. Gerstein (a)(c), Rafael Diaz (d), Rizwan Afzal (a), Denis Xavier (e), Jun Zhu (f), Prem Pais (e), Liu Lisheng (f), Khawar A. Kazmi (g), Mohammad Zubaid (h), Leopoldo S. Piegas (i), Petr Widimsky (j), Andrzej Budaj (k), Alvaro Avezum (i), Salim Yusuf (a)(c) Abstract: Both a history of diabetes mellitus and elevated inhospital glucose levels predict death after acute myocardial infarction (AMI). However, only diabetes history (and not glucose levels) is routinely considered in AMI risk assessment. Author Affiliation: (a) Population Health Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada (b) Emory Schools of Public Health and Medicine, Atlanta, GA (c) Department of Medicine, McMaster University, Hamilton, Ontario, Canada (d) Estudios Cardiologicos Latinoamerica, Rosario, Argentina (e) St. John's Medical College, Bangalore, India (f) Cardiovascular Institute and Fu Wai Hospital, Chinese Hypertension League Institute, Beijing, China (g) Aga Khan University, Karachi, Pakistan (h) Department of Medicine, Faculty of Medicine, Kuwait University, Kuwait City, Kuwait (i) Instituto Dante Pazzanese de Cardiologia, Sao Paulo, Brazil (j) Cardiocenter, Third Faculty of Medicine, Charles University, Prague, Czech Republic (k) Postgraduate Medical School, Department of Cardiology, Grochowski Hospital, Warsaw, Poland Article History: Received 23 September 2008; Accepted 6 December 2008

Loss of [beta]-cell function in type 1 and type 2 diabetes leads to metabolic dysregulation and inability to maintain normoglycemia. Noninvasive imaging of [beta]-cell function in vivo would therefore provide a valuable diagnostic and research tool for quantifying progression to diabetes and response to therapeutic intervention. Because manganese ([Mn.sup.2+]) is a longitudinal relaxation time (T1)-shortening magnetic resonance imaging (MRI) contrast agent that enters cells such as pancreatic [beta]-cells through voltage-gated calcium channels, we hypothesized that [Mn.sup.2+]-enhanced MRI of the pancreas after glucose infusion would allow for noninvasive detection of [beta]-cell function in vivo. To test this hypothesis, we administered glucose and saline challenges intravenously to normal mice and mice given high or low doses of streptozotocin (STZ) to induce diabetes. Serial inversion recovery MRI was subsequently performed after [Mn.sup.2+] injection to probe [Mn.sup.2+] accumulation in the pancreas. Time-intensity curves of the pancreas (normalized to the liver) fit to a sigmoid function showed a 51% increase in signal plateau height after glucose stimulation relative to saline (P < 0.01) in normal mice. In diabetic mice given a high dose of STZ, only a 9% increase in plateau signal intensity was observed after glucose challenge (P = not significant); in mice given a low dose of STZ, a 20% increase in plateau signal intensity was seen after glucose challenge (P = 0.02). Consistent with these imaging findings, the pancreatic insulin content of high- and low-dose STZ diabetic mice was reduced about 20-fold and 10-fold, respectively, compared with normal mice. We conclude that [Mn.sup.2+]-enhanced MRI demonstrates excellent potential as a means for noninvasively monitoring [beta]-cell function in vivo and may have the sensitivity to detect progressive decreases in function that occur in the diabetic disease process. diabetes; islet

Multiclass Mahalanobis-Taguchi system (MMTS), the extension of MTS, is developed for simultaneous multiclass classification and feature selection. In MMTS, the multiclass measurement scale is constructed by establishing an individual Mahalanobis space for each class. To increase the validity of the measurement scale, the Gram-Schmidt process is performed to mutually orthogonalize the features and eliminate the multicollinearity. The important features are identified using the orthogonal arrays and the signal-to-noise ratio, and are then used to construct a reduced model measurement scale. The contribution of each important feature to classification is also derived according to the effect gain to develop a weighted Mahalanobis distance which is finally used as the distance metric for the classification of MMTS. Using the reduced model measurement scale, an unknown example will be classified into the class with minimum weighted Mahalanobis distance considering only the important features. For evaluating the effectiveness of MMTS, a numerical experiment is implemented, and the results show that MMTS outperforms other well-known algorithms not only on classification accuracy but also on feature selection efficiency. Finally, a real case about gestational diabetes mellitus is studied, and the results indicate the practicality of MMTS in real-world applications. Index Terms--Classification, feature selection, multiclass problem, Mahalanobis-Taguchi system (MTS), weighted Mahalanobis distance, Gram-Schmidt orthogonalization process, gestational diabetes mellitus.

The unifying hypothesis of diabetes maintains that reactive oxygen species (ROS) generated in the mitochondria of glucose-treated cells promote reactions leading to the development of diabetic complications. Although the unifying hypothesis attributes the generation of oxidants solely to impaired glucose and fatty acid metabolism, diabetes is also associated with a decline in the levels of the endogenous antioxidant taurine in a number of tissues, raising the possibility that changes in taurine status might also contribute to the severity of oxidant-mediated damage. There is overwhelming evidence that taurine blocks toxicity caused by oxidative stress, but the mechanism underlying the antioxidant activity remains unclear. One established antioxidant action of taurine is the detoxification of hypochlorous acid. However, not all of the antioxidant actions of taurine are related to hypochlorous acid because they are detected in isolated cell systems lacking neutrophils. There are a few studies showing that taurine either modulates the antioxidant defenses or blocks the actions of the oxidants, but other studies oppose this interpretation. Although taurine is incapable of directly scavenging the classic ROS, such as superoxide anion, hydroxyl radical, and hydrogen peroxide, there are numerous studies suggesting that it is an effective inhibitor of ROS generation. The present review introduces a novel antioxidant hypothesis, which takes into consideration the presence of taurine-conjugated tRNAs in the mitochondria. Because tRNA conjugation is required for normal translation of mitochondria]-encoded proteins, taurine deficiency reduces the expression of these respiratory chain components. As a result, flux through the electron transport chain decreases. The dysfunctional respiratory chain accumulates electron donors, which divert electrons from the respiratory chain to oxygen, forming superoxide anion in the process. Restoration of taurine levels increases the levels of conjugated tRNA, restores respiratory chain activity, and increases the synthesis of ATP at the expense of superoxide anion production. The importance of this and other actions of taurine in diabetes is discussed. Key words: taurine, oxidative stress, taurine chloramines, antiinflammatory activity, mitochondria, tRNA conjugation, diabetes. L'hypothese unificatrice du diabete maintient que les especes reactives a l'oxygene (ROS) produites dans les mitochondries des cellules traitees au glucose favorisent des reactions entrainant des complications diabetiques. Cette hypothese attribue la production d'oxydants uniquement a une anomalie du metabolisme du glucose et des acides gras; cependant, le diabete est aussi associe a une diminution des taux de l'antioxydant endogene, taurine, dans plusieurs tissus, ce qui souleve la possibilite que des modifications dans l'etat de la taurine pourraient aussi jouer un role dans la severite des anomalies induites par l'oxydant. Le blocage par la taurine de la toxicite causee par le stress oxydatif est largement admis, mais le mecanisme a l'origine de l'activite antioxydante demeure obscur. Une action antioxydante etablie de la taurine est la detoxification de l'acide hypochloreux. Toutefois, les actions antioxydantes de la taurine ne sont pas toutes reliees a l'acide hypochloreux, parce qu'elle sont detectees dans des systemes cellulaires isoles depourvus de neutrophiles. Quelques etudes montrent que la taurine module les defenses antioxydantes ou bloque les actions des oxydants, mais d'autres etudes contredisent cette interpretation. Bien que la taurine soit incapable de pieger directement les ROS classiques, tels l'anion superoxyde, le radical hydroxyl et le peroxyde d'hydrogene, elle serait, selon de nombreuses etudes, un inhibiteur efficace de la production des ROS. La presente synthese propose une nouvelle hypothese antioxydante qui tient compte de la presence d'ARNt conjugues a la taurine dans les mitochondries. Comme la conjugaison des ARNt est necessaire pour une translation normale des proteines mitochondriales encodees, un deficit en taurine diminue l'expression de ces composantes de la chaine respiratoire. Par consequent, le flux a travers la chaine de transport des electrons diminue. La chaine respiratoire dysfonctionnelle emmagasine des donneurs d'electrons, ce qui detourne les electrons de la chaine respiratoire vers l'oxygene, generant, dans le processus, l'anion superoxyde. La restauration des taux de taurine augmente les taux d'ARNt conjugues, retablit l'activite de la chaine respiratoire et augmente la synthese de l'ATP aux depens de la production d'anion superoxyde. Cette synthese parle de l'importance de cette action et d'autres actions de la taurine dans le diabete. Mots-cles : taurine, stress oxydatif, taurine chloramine, activite antiinflammatoire, mitochondrie, conjugaison de l'ARNt, diabete. [Traduit par la Redaction], Introduction Diabetes mellitus is a multifactorial disease associated with the development of retinopathy, nephropathy, neuropathy, cardiomyopathy, and severe vascular dysfunction. Since the complications of diabetes are caused by either insulin [...]

Diabetic kidney disease (DKD) occurs in 20% to 40% of patients with diabetes mellitus and is the leading cause of chronic kidney disease and end-stage renal disease in the United [...]

This paper aims to elucidate the need for counseling services among clients with diabetes, clarify common adjustment and diabetes self-care issues, and suggest counseling strategies for this population. We suggest that counselors increase their competencies in diabetes counseling, and strive to help traditional members of the diabetes care team (e.g., physicians) to recognize the benefits of routinely including counseling in diabetes care. This paper also explains the medical, psychosocial, and vocational aspects and implications of diabetes., In the United States, 14.6 million people have been diagnosed with diabetes and an estimated 6.2 million more people have the disease but are undiagnosed. In addition, 54 million adults [...]

The advent of hyperpolarized [sup.13]C magnetic resonance (MR) has provided new potential for the real-time visualization of in vivo metabolic processes. The aim of this work was to use hyperpolarized [1-[sup.13]C]pyruvate as a metabolic tracer to assess noninvasively the flux through the mitochondrial enzyme complex pyruvate dehydrogenase (PDH) in the rat heart, by measuring the production of bicarbonate ([H.sup.13]C[O.sup.-.sub.3]), a byproduct of the PDH-catalyzed conversion of [1-[sup.13]C]pyruvate to acetyl-CoA. By noninvasively observing a 74% decrease in [H.sup.13]C[O.sup.-.sub.3] production in fasted rats compared with fed controls, we have demonstrated that hyperpolarized [sup.13]C MR is sensitive to physiological perturbations in PDH flux. Further, we evaluated the ability of the hyperpolarized [sup.13]C MR technique to monitor disease progression by examining PDH flux before and 5 days after streptozotocin induction of type 1 diabetes. We detected decreased [H.sup.13]C[O.sup.-.sub.3] production with the onset of diabetes that correlated with disease severity. These observations were supported by in vitro investigations of PDH activity as reported in the literature and provided evidence that flux through the PDH enzyme complex can be monitored noninvasively, in vivo, by using hyperpolarized [sup.13]C MR. cardiac metabolism | diabetes | fasting | DNP

Our objective was to determine whether defects underlying impaired fasting glucose (IFG) are maintained and additive when combined with impaired glucose tolerance (IGT) (representing a progressive form of prediabetes) or are distinct in IFG/IGT (reflecting a parallel form of prediabetes). Volunteers with IFG (n = 10), IFG/IGT (n = 14), or normal glucose tolerance (NGT; n = 15) were matched for demographics and anthropometry. Insulin secretion was assessed using the glucose step-up protocol and insulin action through the use of a two-stage hyperinsulinemic euglycemic clamp with infusion of [6,6[sup.2.][H.sub.2]glucose. Modeling of insulin secretory parameters revealed similar basal ([PHI].sub.b) but diminished dynamic ([PHI].sub.d]) components in both IFG and IFG/IGT (P = 0.05 vs. NGT for both). Basal glucose rate of appearance ([R.sub.a]) was higher in IFG compared with NGT (P < 0.01) and also, surprisingly, with IFG/IGT (P < 0.04). Moreover, glucose [R.sub.a] suppressed more during the low-dose insulin clamp in IFG (P < 0.01 vs. NGT, P = 0.08 vs. IFG/IGT). Insulin-stimulated glucose uptake [glucose rate of disappearance ([R.sub.d]) was similar in IFG, IFG/IGT, and NGT throughout the clamp. We conclude that nuances of [beta]-cell dysfunction observed in IFG were also noted in IFG/IGT. A trend for additional insulin secretory defects was observed in IFG/ IGT, possibly suggesting progression in [beta]-cell failure in this group. In contrast, basal glucose [R.sub.a] and its suppressability with insulin were higher in IFG, but not IFG/IGT, compared with NGT. Together, these data indicate that IFG/IGT may be a distinct prediabetic syndrome rather than progression from IFG. insulin resistance; isotopes; clamp

Sensitive and high-resolution chromatographic-driven metabonomomics studies experienced major growth with the aid of new analytical technologies and bioinformatics software packages. Hence, data collections by LC--MS and data analyses by multivariate statistical methods are by far the most straightforward steps, and the detection of biomarker candidates can easily be achieved. However, the unequivocal identification of the detected metabolite candidates, including isomer elucidation, is still a crux of current metabonomics studies. Here we present a comprehensive analytical strategy for the elucidation of the molecular structure of metabolite biomarkers detected in a metabonomics study, exemplified analyzing spot urine of a cohort of healthy, insulin sensitive subjects and clinically well characterized prediabetic, insulin resistant individuals. An integrated approach of LC--MS fingerprinting, multivariate statistic analysis, LC--[MS.sup.n] experiments, micro preparation, FTICR-MS, GC retention index, database search, and generation of an isotope labeled standard was applied. Overall, we could demonstrate the efficiency of our analytical approach by the unambiguous elucidation of the molecular structure of an isomeric biomarker candidate detected in a complex human biofluid. The proposed strategy is a powerful new analytical tool, which will allow the definite identification of physiologically important molecules in metabonomics studies from basic biochemistry to clinical biomarker discovery.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.07.028 Byline: Marije M. Vis (a), Krischan D. Sjauw (a), Rene J. van der Schaaf (a), Jan Baan (a), Karel T. Koch (a), J. Hans DeVries (b), Jan G.P. Tijssen (a), Robbert J. de Winter (a), Jan J. Piek (a), Jose P.S. Henriques (a) Abstract: Primary percutaneous coronary intervention (PCI) reduces mortality in patients with ST-segment elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). Despite PCI, mortality in CS is still approximately 50%. Admission glucose concentration is an independent predictor of mortality in patients with STEMI and is associated with the occurrence of CS. Whether admission glucose is also a predictor of mortality in CS patients treated with primary PCI is unexplored. We therefore assessed the relation between admission glucose concentration and 1-year mortality in patients with STEMI with CS without a prior diagnosis of diabetes on admission and treated with PCI. Author Affiliation: (a) Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands (b) Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands Article History: Received 5 February 2007; Accepted 23 July 2007

We report 10 heterozygous mutations in the human insulin gene in 16 probands with neonatal diabetes. A combination of linkage and a candidate gene approach in a family with four diabetic members led to the identification of the initial INS gene mutation. The mutations are inherited in an autosomal dominant manner in this and two other small families whereas the mutations in the other 13 patients are de novo. Diabetes presented in probands at a median age of 9 weeks, usually with diabetic ketoacidosis or marked hyperglycemia, was not associated with [beta] cell autoantibodies, and was treated from diagnosis with insulin. The mutations are in critical regions of the preproinsulin molecule, and we predict that they prevent normal folding and progression of proinsulin in the insulin secretory pathway. The abnormally folded proinsulin molecule may induce the unfolded protein response and undergo degradation in the endoplasmic reticulum, leading to severe endoplasmic reticulum stress and potentially [beta] cell death by apoptosis. This process has been described in both the Akita and Munich mouse models that have dominant-acting missense mutations in the Ins2 gene, leading to loss of [beta] cell function and mass. One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder. endoplasmic reticulum stress | insulin biosynthesis | disulfide bonds | unfolded protein response

This paper investigates levels in diabetes prevalence patterns across key socioeconomic status indicators and how they changed over time. The investigation spans both the conventional concept of diagnosed diabetes and a more comprehensive measure that includes those whose diabetes is undiagnosed. By doing so, I separate the distinct impact of covariates on trends over time in disease onset and the probability of disease diagnosis. The principal force leading to higher diabetes prevalence over time is excessive weight and obesity, which was only partially offset by improvements in the education of the population over time. Undiagnosed diabetes remains an important health problem, but much less so than 25 years ago. Although race and ethnic differentials in undiagnosed diabetes were eliminated over the last 25 years, the disparities became larger across other measures of disadvantage, such as education. diagnosed

High ambient glucose activates intracellular signaling pathways to induce the expression of extracellular matrix and cytokines such as connective tissue growth factor (CTGF). Cell responses to CTGF in already glucose-stressed cells may act to transform the mesangial cell phenotype leading to the development of glomerulosclerosis. We analyzed cell signaling downstream of CTGF in high glucose-stressed mesangial cells to model signaling in the diabetic milieu. The addition of CTGF to primary human mesangial cells activates cell migration which is associated with a PKC-[zeta]-GSK313 signaling axis. In high ambient glucose basal PKC-[zeta] and GSK3[beta] phosphorylation levels are selectively increased and CTGF-stimulated PKC-[zeta] and GSK3[beta] phosphorylation was impaired. These effects were not induced by osmotic changes. CTGF-driven profibrotic cell signaling as determined by p42/44 MAPK and Akt phosphorylation was unaffected by high glucose. Nonresponsiveness of the PKC-[zeta]-GSK3[beta] signaling axis suppressed effective remodeling of the microtubule network necessary to support cell migration. However, interestingly the cells remain plastic: modulation of glucose-induced PKC-[beta] activity in human mesangial cells reversed some of the pathological effects of glucose damage in these cells. We show that inhibition of PKC-[beta] with LY379196 and PKC-[beta] siRNA reduced basal PKC-[zeta] and GSK3[beta] phosphorylation in human mesangial cells exposed to high glucose. CTGF stimulation under these conditions again resulted in PKC-[zeta] phosphorylation and human mesangial cell migration. Regulation of PKC-[zeta] by PKC-[beta] in this instance may establish PKC-[zeta] as a target for constraining the progression of mesangial cell dysfunction in the pathogenesis of diabetic nephropathy. GSK3[beta]; PKC-[zeta]; migration; diabetic nephropathy doi:10.1152/ajprenal.00342.2006.

Two genes encoding cardiac myosin heavy chain (MHC) isoforms, [beta] and [alpha], are arranged in tandem 4.5 kb apart. We examined pre-mRNA and mature mRNA levels of [beta] and ct genes in control, diabetic (streptozotocin), hypothyroid (propylthiouracil), and hyperthyroid rat hearts and analyzed the naturally occurring antisense (AS) [beta] RNA species that starts in the middle of the 4.5-kb intergenic region and extends upstream to the [beta]-gene promoter. The [beta] and [alpha] genes are expressed antithetically in control, diabetic, hypothyroid, and hyperthyroid hearts. Expression of AS [beta]-RNA was positively correlated with [alpha]-mRNA and negatively correlated with sense [beta] mRNA. These results support the novel idea of common promoter-regulatory elements situated in the intergenic region that likely control transcription of both sense [alpha] and AS [beta] genes and that AS [beta] transcription negatively regulates [beta]-MHC gene expression. To test whether an intergenic promoter drives transcription of AS [beta] RNA, a 1340-bp sequence of the intergenic region was inserted into a luciferase plasmid in the 3'-to-5' AS direction and was injected into rat ventricle. This promoter was activated in control heart and decreased greatly in response to propylthiouracil and streptozotocin and increased in hyperthyroid rats, similar in pattern to the endogenous AS [beta] RNA. When a putative retinoic acid receptor (RAR) site (a known thyroid hormone receptor cofactor) in this promoter was mutated, the reporter activity was almost abolished in control, propylthiouracil, and streptozotocin hearts. We conclude that there is an intergenic promoter that is active in the AS direction and that the putative RAR element is a vital regulatory site. mRNA; hyperthyroidism; in vivo gene injection; retinoic acid receptor; peroxisome proliferator-activated receptor doi: 10.1152/ajpheart.01224.2006.

There is concern among Aboriginal communities in Canada that conventional approaches to the treatment of diabetes are ineffective in part because they fail to recognize the local Aboriginal perspective on the causal determinants of diabetes. While this shortcoming has been recognized, there have been no explicit attempts to practically define these perspectives and prescribe how conventional health management might be altered to incorporate them. In part, this may be due to difficulties in communicating Aboriginal perspectives in a manner which permits incorporation into conventional science-based frameworks. Here we use fuzzy cognitive mapping (FCM) as a technique to represent and compare Canadian Aboriginal and conventional science perspectives on the determinants of diabetes as contained in published articles drawn from a search of Medline and PubMed (1966-2005). The FCM allows for a detailed description of the complex system of culture, spirituality and balance at the root of the Aboriginal view. It also highlights how, for these less tangible factors, it is possible to identify more concrete stressors and outcomes which are amenable to management and monitoring. This preliminary comparison of conventional and Aboriginal views also demonstrates the potential for FCM as a technique to extract, compare and integrate perspectives of different knowledge systems into health management and policy development. Keywords: Canada; Aboriginal health; Diabetes determinants; Fuzzy cognitive map; Traditional knowledge

OBJECTIVE. The goal was to determine the rates of diabetes screening and the prevalence of screening abnormalities in overweight and nonoverweight individuals in an urban primary care clinic. METHODS. This study was a retrospective chart review conducted in a hospital-based urban primary care setting. Deidentified data for patients who were 10 to 19 years of age and had [greater than or equal to] 1 BMI measurement between September 1, 2002, and September 1, 2004, were extracted from the hospital electronic health record. RESULTS. A total of 7710 patients met the study criteria. Patients were 73.0% black or Hispanic and 47.0% female; 42.0% of children exceeded normal weight, with 18.2% at risk for overweight and 23.8% overweight. On the basis of BMI, family history, and race, 8.7% of patients met American Diabetes Association criteria for type 2 diabetes mellitus screening, and 2452 screening tests were performed for 1642 patients. Female gender, older age group, and family history of diabetes were associated with screening. Increasing BMI percentile was associated with screening, exhibiting a dose-response relationship. Screening rates were significantly higher (45.4% vs 19.0%) for patients who met the American Diabetes Association criteria; however, less than one half of adolescents who should have been screened were screened. Abnormal glucose metabolism was seen for 9.2% of patients screened. CONCLUSIONS. This study shows that, although pediatricians are screening for diabetes mellitus, screening is not being conducted according to the American Diabetes Association consensus statement. Point-of-care delivery of consensus recommendations could increase provider awareness of current recommendations, possibly improving rates of systematic screening and subsequent identification of children with laboratory evidence of abnormal glucose metabolism. www.pediatrics.org/cgi/doi/10.15421 peds.2006-0121 doi:10.1542/peds.2006-0121 Key Words type 2 diabetes mellitus, screening, childhood obesity Abbreviations T2DM--type 2 diabetes mellitus ADA--American Diabetes Association FPG--fasting plasma glucose OGTT---oral glucose tolerance test RPG--random plasma glucose PPCC--pediatric primary care center EHR--electronic health record HbA1c--hemoglobin Arc CI--confidence interval, ALTHOUGH PREVIOUSLY CONSIDERED an adult disease, type 2 diabetes mellitus (T2DM) is increasing in US children (1-3) and children around the world. (4,5) T2DM now accounts for up to 45% [...]

Objective: To determine inner city American Indians' perceptions of diebetes; find out how they manage their disease; and identify what health care improvements may be necessary for this population. Design: Eight focus group discussions conducted with diabetic inner city American Indian adults. Setting: Focus group discussions led by moderator using open-ended questions with prompts. Participants: Eligibility criteria include age ([greater than or equal to] 18 years), a self-reported diagnosis of diabetes, and self-identification as inner city American Indian. Participants were screened by telephone to ensure all criteria were met. Forty inner city American Indian men and women participated in 8 focus groups. Phenomenon of Inlerest: American Indians' perception of diabetes, its treatment, and how they manage the disease. Analysis: Focus group discussions were tape recorded and transcribed verbatim. Transcripts were analyzed by coding responses and identifying common themes according to content analysis procedures. Quantitative data from self-administered demographic forms were analyzed. Results: Participants could verbalize information regarding treatment and management of diabetes, but few could apply this information to their own lives. Some participants were homeless or without insurance, which makes successful disease management difficult. Perceptions of the health care system varied; a majority felt the system was meeting their needs, whereas others said it was not adequate. Implications for Research and Practice: The study identified the need for health care workers to develop a better understanding of how this population lives; doing so could improve patient compliance to treatment. The results may provide direction for the development of culturally specific diabetes education appropriate for low-income patients focusing on the diabetic diet and exercise, and suggesting ways that the patient can move from knowing the information to implementing behavior change. Key Words: American Indians, diabetes mellitus, health care, weight loss, diet, physical activity, disease management

The pancreas is an elongated gland, light tan or pinkish in color, nestled alongside the small intestine and adjacent to the stomach. The organ is composed of two functionally separate [...]

Objective: To investigate patterns of membership and barriers to service use in the Christchurch Diabetes Society. Methods: A socio-economic profile of the Christchurch Diabetes Society's membership was constructed by examining the residential locations of society members in Christchurch City. Rates of membership by deprivation decile were calculated by comparing the membership data to the population of people diagnosed with diabetes. Results: Persons living in deprived areas, in particular Maori and Pacific people, are under-represented in society membership. However, there is evidence that the relationship between ethnicity and membership rates is stronger in more deprived areas. Conclusions: This study provides further insights in understanding barriers to care and the role of NGOs. Given that groups in the community most likely to be affected by diabetes are least likely to be members of the society and to have access to the society's services, the results raise questions about the most appropriate role for local diabetes societies within a decentralised health system.

Diffuse photon density wave (DPDW) methodology at Near Infrared frequencies has been used to calculate absorption and scattering from wounds of healthy and diabetic rats. The diffusion equation for senti-infinite media is being used for calculating the absorption and scattering coefficients based on measurements of phase and amplitude with a frequency domain device. Differences observed during the course of healing in the two populations can be correlated to the delayed healing observed in diabetics. These results are encouraging and further work will focus on the implementation of this device to the clinical setting as a monitoring tool in chronic diabetic wounds. Index Terms--Diabetic wounds, diffuse photon density wave, near infrared spectroscopy (NIRS).

Several studies have shown that patients suffering from Diabetes Mellitus can significantly delay the onset and slow down the progression of diabetes micro-and macro-angiopathic complications through intensive monitoring and treatment. In general, intensive treatments imply a careful blood glucose level (BGL) self-monitoring. The analysis of BGL measurements is one of the most important tasks in order to assess the glucose metabolic control and to revise the therapeutic protocol. Recent clinical studies have shown the correlation between the glucose variability and the long-term diabetes related complications. In this paper, we propose a stochastic model to extract the time course of such variability from the self-monitoring BGL time series. This information can be conveniently combined with other analysis to evaluate the adequacy of the therapeutic protocol and to highlight periods characterized by an increasing glucose instability. The method here proposed has been validated on two simulated data sets and tested with success in the retrospective analysis of three patients' data sets. Index Terms--Bayesian estimation, blood glucose level time series analysis, blood glucose variability, diabetes long-term complications, diabetic patients home monitoring, Markov chain Monte Carlo methods, risk index, stochastic volatility models.

Objective: To evaluate for Indigenous Australians the agreement between a fasting plasma glucose (FPG) criterion of 7.0 mmol/L and diabetes test results using a two-hour oral glucose tolerance test (OGTT), comparing relationships between test agreement and prevalence to similar studies. Methods: Screening was undertaken in 25 remote settlements. Agreement between FPG and OGTT results was evaluated using the kappa coefficient (chance-corrected agreement). Results: Participants (n=3,249) ranged from 15-94 years. Kappa ranged from 0.70-0.77 for diabetes prevalence of 5-30%, with overall agreement of 0.76. In comparison studies, the relationship between kappa and diabetes prevalence was similar, but with kappa 0.21-0.48. Conclusions and Implications: A FPG test with a 7.0 mmol/L cut-off is a reliable screening method, relative to the OGTT, for remote Indigenous settlements. The level of agreement between the FPG test and the OGTT for the Indigenous population surveyed is superior by far to agreement reported for non-Indigenous samples.

Abstract The severity of lung disease in cystic fibrosis may be related to the genetic propensity of the host to produce tumor necrosis fector [alpha] (TNF-[alpha]). A polymorphism in the [...]

It has been reported that mixed meals are used in clinics in developing and developed countries in screening and diagnosis of diabetes. Thus, we aimed to determine the differences in 2-h plasma glucose values after non-diabetic subjects ingested 75 g pure glucose and its equivalent content in frequently consumed carbohydrate foods in Caribbean subjects. Twenty-seven apparently healthy non-diabetic subjects (nine males, 18 females) consumed 75 g pure glucose and its carbohydrate equivalent in three ethnic test foods (bread, rice and roti) at 7 days apart. Plasma glucose and insulin levels were determined in blood samples collected before and after 60, 90, 120 and 150 min of ingestion of these foods. In comparison with each of the test foods, the postprandial 1-h and 2-h plasma glucose values and the 60, 90, 120 and 150 min incremental glucose concentrations after oral glucose load were significantly higher than the corresponding values for each of the test foods (all P 0.05). However, the test food, roti, tended to stimulate higher absolute and incremental insulin secretions than pure glucose or any other test food (all P >0.05). Generally, the correlation between 2-h plasma glucose value after the ingestion of the pure glucose and each of the test foods was significant (all correlation coefficients were greater than 0.70, P Keywords: Diagnosis of diabetes, carbohydrate foods, postprandial glucose, ethnic foods

Abstract. The endothelial function of children with and without vascular disease, consisting of 41 controls, 24 with Kawasaki disease (KD), and 46 with diabetes mellitus (DM), was examined. Age at [...]

A study is carried out to summarize the current state of evidence comparing the effectiveness and safety of c. The results conclude that the mortality advantage and decreased rates of revascularization seen with CABG in subgroups from early trials may not be applicable in the era of drug-eluting stents, glycoprotein IIb/IIIa inhibitors, and the latest medical therapies as of March 2005.

A study is done to examine the relationship between HIV-associated dementia (HAD) and diabetes among patients with HIV-1 infection. Within the Hawaii aging with HIV cohort, a longitudinal study enriched with older HIV-1-infected individuals, concluded that diabetes is associated with prevalent dementia.

Byline: Peter Holmquist (1), Sture Sjoblad (1), Ole Torffvit (2) Keywords: Albuminuria; Diabetes; Immunoglobulins; Glycosaminoglycans; Selectivity index Abstract: The urinary albumin excretion rate is increased at the time of diagnosis of diabetes. We investigated whether this is caused by change in pore size or charge selectivity in the glomerular basement membrane. Urine excretion of immunoglobulins (IgG2, IgG4), glycosaminoglycans (GAG), and albumin was analyzed during the first 20 days after diagnosis of diabetes in children aged 4--15 years 36 diabetic and 24 age-matched apparently healthy children were included. The excretion of albumin was significantly increased on day 1 in the diabetic children. Between day 1 and 20 the excretion of IgG2 and IgG4 decreased significantly from normal to a level below normal. GAG excretion was not affected. The GAG/creatinine index (GAGCI) was normal. IgG2CI was significantly below normal on days 4--20. IgG4CI was below normal on days 2--20. The albumin creatinine index decreased significantly from day 1 to normal levels on day 4--20. A charge selectivity index, expressed as the ratio between the neutrally charged IgG2 and the negatively charged IgG4, was significantly below the normal level on days 16 and 20. In conclusion, an increased albumin excretion rate in urine did not seem to be caused by a change in charge selectivity. Other explanations such as change in the small pore radius or tubular reabsorption are suggested. Author Affiliation: (1) Department of Pediatrics, University Hospital, 221 85 Lund, Sweden (2) Department of Medicine, University Hospital Lund, Sweden Article History: Registration Date: 21/07/2004 Received Date: 03/12/2003 Accepted Date: 22/06/2004 Online Date: 22/10/2004

Introduction The importance of psychosocial issues that affect people with diabetes has become more prominent since the publication of the National Service Framework (NSF) for Diabetes: Standards in 2003. NSF [...]

With the growing number of individuals having diabetes, it is likely that most dental practitioners will see patients with this disease more frequently. Therefore, it is not unlikely that in [...]