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Sample records for adult onset diabetes

  1. Effects of diabetes mellitus on bone mass in juvenile and adult-onset diabetes.

    PubMed

    Levin, M E; Boisseau, V C; Avioli, L V

    1976-01-29

    To assess the influence of diabetes mellitus on bone metabolism, we measured skeletal mass in the forearms of 35 patients with juvenile diabetes on insulin and 101 stable patients with adult-onset diabetes, on diet alone, insulin, or oral hypoglycemic agents. There was a significant loss of bone mass in both juvenile and adult-onset diabetes (P less than 0.01) as compared to controls matched for age and sex. The decrease was already present in patients with diabetes of less than five years' duration. Bone loss and duration of the diabetes did not correlate; the greatest decrease in bone mass was observed in the patients receiving oral agents. These data are consistent with the hypothesis that the loss of skeletal tissue in diabetes reflects the underlying disease since it occurs early and is not related to severity as evidenced by the need for insulin, to duration, or to treatment with insulin or diet alone.

  2. Correlates of Age Onset of Type 2 Diabetes Among Relatively Young Black and White Adults in a Community

    PubMed Central

    Nguyen, Quoc Manh; Xu, Ji-Hua; Chen, Wei; Srinivasan, Sathanur R.; Berenson, Gerald S.

    2012-01-01

    OBJECTIVE The risk factors for middle-age onset of type 2 diabetes are well known. However, information is scant regarding the age onset of type 2 diabetes and its correlates in community-based black and white relatively young adults. RESEARCH DESIGN AND METHODS This prospective cohort study consisted of normoglycemic (n = 2,459) and type 2 diabetic (n = 144) adults aged 18–50 years who were followed for an average of 16 years. RESULTS The incidence rate of the onset of type 2 diabetes was 1.6, 4.3, 3.9, and 3.4 per 1,000 person-years for age-groups 18–29, 30–39, and 40–50 and total sample, respectively. Incidences of diabetes increased with age by race and sex groups (P for trend ≤0.01); higher in black females versus white females and blacks versus whites in total sample (P < 0.05). In a multivariable Cox model, baseline parental diabetes (hazard ratio [HR] 5.24) and plasma insulin were significantly associated with diabetes incidence at the youngest age (18–29 years); black race, BMI, and glucose at age 30–39 years; female sex, parental diabetes (HR 2.44), BMI, ratio of triglycerides and HDL cholesterol (TG/HDL-C ratio), and glucose at age 40–50 years; and black race, parental diabetes (HR 2.44), BMI, TG/HDL-C ratio, and glucose in whole cohort. Further, patients with diabetes, regardless of age onset, displayed a significantly higher prevalence of maternal history of diabetes at baseline (P < 0.01). CONCLUSIONS In relatively young adults, predictability of baseline cardiometabolic risk factors along with race, sex, and parental history of diabetes for the onset of type 2 diabetes varied by age-group. These findings have implications for early prevention and intervention in relatively young adults. PMID:22399694

  3. Lifestyle Risk Factors and New-Onset Diabetes Mellitus in Older Adults

    PubMed Central

    Mozaffarian, Dariush; Kamineni, Aruna; Carnethon, Mercedes; Djoussé, Luc; Mukamal, Kenneth J.; Siscovick, David

    2010-01-01

    Background The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults. Methods We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989–1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73[6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels. Results During 34 539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35% lower (relative risk, 0.65; 95% confidence interval, 0.59–0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes

  4. A new structural approach to genomic discovery of disease: example of adult-onset diabetes.

    PubMed

    Sirovich, Lawrence

    2016-12-01

    This paper reports on an investigation of disease discovery from genomic data, by methods which depart substantially from customary practices found in the investigation of genome-wide association studies. Such data in general are composed of the genomic content from two contrasting phenotypes, e.g., disease versus control populations, and the analysis proceeds under the hypothesis that populational dissimilarities might reveal disease risk alleles. The proposed suite of new methods is in part based on information theory (Shannon in Bell Syst Tech J 27:379-423, 1948a; Bell Syst Tech J 27:623-656, 1948b; Jaynes in Phys Rev 106:620-630, 1957), and strong evidence will be given of the effectiveness of this new approach. The methodology extends naturally and successfully to predicting genomic disposition to disease arising from large collections of weakly contributing genomic loci. Evidence will be advanced that the example of adult-onset diabetes ("type 2 diabetes") is such a candidate disease, and in this case, probably for the first time, it can be demonstrated that disease prediction is possible. Another novel element of this study is the search and identification of potential beneficial genomic loci that may counter a disease. The generality of the methodology suggests that it might extend to other diseases.

  5. Clinically Relevant Cognitive Impairment in Middle-Aged Adults With Childhood-Onset Type 1 Diabetes

    PubMed Central

    Nunley, Karen A.; Ryan, Christopher M.; Jennings, J. Richard; Aizenstein, Howard J.; Zgibor, Janice C.; Costacou, Tina; Boudreau, Robert M.; Miller, Rachel; Orchard, Trevor J.; Saxton, Judith A.

    2015-01-01

    OBJECTIVE The aim of this study was to investigate the presence and correlates of clinically relevant cognitive impairment in middle-aged adults with childhood-onset type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS During 2010–2013, 97 adults diagnosed with T1D and aged <18 years (age and duration 49 ± 7 and 41 ± 6 years, respectively; 51% female) and 138 similarly aged adults without T1D (age 49 ± 7 years; 55% female) completed extensive neuropsychological testing. Biomedical data on participants with T1D were collected periodically since 1986–1988. Cognitive impairment status was based on the number of test scores ≥1.5 SD worse than demographically appropriate published norms: none, mild (only one test), or clinically relevant (two or more tests). RESULTS The prevalence of clinically relevant cognitive impairment was five times higher among participants with than without T1D (28% vs. 5%; P < 0.0001), independent of education, age, or blood pressure. Effect sizes were large (Cohen d 0.6–0.9; P < 0.0001) for psychomotor speed and visuoconstruction tasks and were modest (d 0.3–0.6; P < 0.05) for measures of executive function. Among participants with T1D, prevalent cognitive impairment was related to 14-year average A1c >7.5% (58 mmol/mol) (odds ratio [OR] 3.0; P = 0.009), proliferative retinopathy (OR 2.8; P = 0.01), and distal symmetric polyneuropathy (OR 2.6; P = 0.03) measured 5 years earlier; higher BMI (OR 1.1; P = 0.03); and ankle-brachial index ≥1.3 (OR 4.2; P = 0.01) measured 20 years earlier, independent of education. CONCLUSIONS Clinically relevant cognitive impairment is highly prevalent among these middle-aged adults with childhood-onset T1D. In this aging cohort, chronic hyperglycemia and prevalent microvascular disease were associated with cognitive impairment, relationships shown previously in younger populations with T1D. Two additional potentially modifiable risk factors for T1D-related cognitive impairment, vascular health and BMI

  6. Trans-Palmitoleic Acid, Metabolic Risk Factors, and New-Onset Diabetes in US Adults

    PubMed Central

    Mozaffarian, Dariush; Cao, Haiming; King, Irena B.; Lemaitre, Rozenn N.; Song, Xiaoling; Siscovick, David S.; Hotamisligil, Gökhan S.

    2011-01-01

    Background Palmitoleic acid (cis-16:1n-7), produced by endogenous fat synthesis, has been linked to both beneficial and deleterious metabolic effects, potentially confounded by diverse determinants and tissue sources of endogenous production. Trans-palmitoleate (trans-16:1n-7) represents a distinctly exogenous source of 16:1n-7, unconfounded by endogenous synthesis or its determinants, that may be uniquely informative. Objective We investigated whether circulating trans-palmitoleate was independently related to lower metabolic risk and incident type2 diabetes. Design Prospective cohort study (1992–2006). Setting Four US communities. Patients 3,736 adults in the Cardiovascular Health Study. Measurements Plasma phospholipid fatty acids, anthropometry, blood lipids, inflammatory markers, and glucose-insulin levels were measured at baseline in 1992; and diet, 3 years earlier. In multivariable-adjusted models, we investigated how demographic, clinical, and lifestyle factors independently related to trans-palmitoleate; how trans-palmitoleate related to major metabolic risk factors; and how trans-palmitoleate related to new-onset diabetes (304 incident cases). We validated findings for metabolic risk factors in an independent cohort of 327 women. Results In multivariable-analyses, whole-fat dairy consumption was most strongly associated with higher trans-palmitoleate. Higher trans-palmitoleate was associated with slightly lower adiposity and, independently, higher high-density-lipoprotein(HDL)-cholesterol (across quintiles: +1.9%, P=0.04), lower triglycerides (−19.0%, P<0.001), lower total:HDL-cholesterol (−4.7%, P<0.001), lower C-reactive protein (−13.8%, P=0.05), and lower insulin resistance (−16.7%, P<0.001). Trans-palmitoleate was associated with substantially lower incidence of diabetes, with multivariable-hazard-ratios=0.41 (95%CI=0.27–0.64) and 0.38 (95%CI=0.24–0.62) in quintile-4 and quintile-5, versus quintile-1 (P-trend<0.001). Findings were

  7. Sex-specific associations of low birth weight with adult-onset diabetes and measures of glucose homeostasis: Brazilian Longitudinal Study of Adult Health

    PubMed Central

    Yarmolinsky, James; Mueller, Noel T; Duncan, Bruce B; Chor, Dóra; Bensenor, Isabela M; Griep, Rosane H; Appel, Lawrence J; Barreto, Sandhi M; Schmidt, Maria Inês

    2016-01-01

    Emerging evidence suggests sex differences in the early origins of adult metabolic disease, but this has been little investigated in developing countries. We investigated sex-specific associations between low birth weight (LBW; <2.5 kg) and adult-onset diabetes in 12,525 participants from the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Diabetes was defined by self-reported information and laboratory measurements. In confounder-adjusted analyses, LBW (vs. 2.5–4 kg) was associated with higher prevalence of diabetes in women (Prevalence Ratio (PR) 1.54, 95% CI: 1.32–1.79), not in men (PR 1.06, 95% CI: 0.91–1.25; Pheterogeneity = 0.003). The association was stronger among participants with maternal diabetes (PR 1.60, 95% CI: 1.35–1.91), than those without (PR 1.15, 95% CI: 0.99–1.32; Pheterogeneity = 0.03). When jointly stratified by sex and maternal diabetes, the association was observed for women with (PR 1.77, 95% CI: 1.37–2.29) and without (PR 1.45, 95% CI: 1.20–1.75) maternal diabetes. In contrast, in men, LBW was associated with diabetes in participants with maternal diabetes (PR 1.45, 95% CI: 1.15–1.83), but not in those without (PR 0.92, 95% CI: 0.74–1.14). These sex-specific findings extended to continuous measures of glucose homeostasis. LBW was associated with higher diabetes prevalence in Brazilian women, and in men with maternal diabetes, suggesting sex-specific intrauterine effects on adult metabolic health. PMID:27845438

  8. Adult-onset type 1 diabetes patients display decreased IGRP-specific Tr1 cells in blood.

    PubMed

    Chujo, Daisuke; Nguyen, Thien-Son; Foucat, Emile; Blankenship, Derek; Banchereau, Jacques; Nepom, Gerald T; Chaussabel, Damien; Ueno, Hideki

    2015-12-01

    The breakdown of immune tolerance against islet antigens causes type 1 diabetes (T1D). The antigens associated with adult-onset T1D (AT1D) remain largely undefined. It is possible that AT1D patients display a unique type of CD4(+) T cells specific for a certain islet antigen. Here we analyzed the cytokine production profiles of CD4(+) helper T (Th) cells that are specific for three islet antigens; GAD65, preproinsulin, and IGRP in patients with AT1D, juvenile-onset T1D (JT1D), and age-, gender- and human leukocyte antigen (HLA)-matched control adults. While IGRP-specific Th cells in AT1D patients were dominantly Th1 cells, IGRP-specific Th cells in control adults and JT1D patients were dominantly Th2 and T regulatory type 1 (Tr1) cells. Notably, the frequency of IGRP-specific Tr1 cells was significantly lower in AT1D patients than in control adults and JT1D patients. In conclusion, our study suggests that IGRP-specific Th cells play a unique pathogenic role in AT1D.

  9. Identifying Early Onset of Hearing Loss in Young Adults With Diabetes Mellitus Type 2 Using High Frequency Audiometry.

    PubMed

    Vignesh, S S; Jaya, V; Moses, Anand; Muraleedharan, A

    2015-09-01

    Diabetes mellitus (DM) is a metabolic disorder caused by hyperglycemia which leads to dysfunction of various organs. Hearing acuity is equally hindered by this disorder. Among individuals with DM audiological characteristics of DM type 1 are of great concern in the literature. This study aims at establishing high frequency audiometry (HFA) as a useful tool in identifying early onset of hearing loss in individuals with DM type 2. 20 non-diabetic participants and 20 individuals with DM type 2 in the age range of 20-40 years were considered for the study. Subjects in both groups underwent otoscopic examination, PTA at 0.25, 0.5, 1, 2, 4 and 8 kHz and HFA at 9, 10, 11.2, 12.5, 14 and 16 kHz. Results revealed statistically significant difference in thresholds of both PTA and HFA at all frequencies across the group, but the mean threshold difference between the diabetic and non-diabetic group was marked in HFA than in PTA. In the diabetic subjects the thresholds of PTA was within 25 dBHL at all frequencies when compared to the thresholds of HFA. Individuals with DM type 2 showed bilateral symmetrical mild hearing loss in HFA and the hearing loss increased with ascending test frequencies from 9,000 to 16,000 Hz. Mild hearing loss in HFA is an indicator for early onset of hearing loss in DM type 2. Hence this present study emphasis the clinical utility of HFA in young adults with DM type 2.

  10. Fractures associated with neuropathic arthropathy in adults who have juvenile-onset diabetes.

    PubMed

    Clohisy, D R; Thompson, R C

    1988-09-01

    Eighteen patients, twenty-five to fifty-two years old, who had juvenile-onset diabetes, had neuropathic arthropathy and fractures at the ankle or tarsus, most of which were bilateral. After a minimum follow-up of one year, four patients could not walk and fourteen were dependent on orthoses. In nine patients, the lesions produced fixed skeletal deformities that caused severe malum perforans, which in three patients was so severe that a below-the-knee amputation had to be done. In patients who had bilateral lesions, when the extremity that was initially involved was prevented from bearing weight, involvement of the contralateral limb became evident after an average of 4.5 months, compared with an average of twelve months in the patients who were allowed weight-bearing on the extremity that was initially involved. Our current treatment protocol is non-weight-bearing immobilization of the involved extremity, and we recommend prophylactic immobilization of the contralateral extremity with a protective cast or orthosis. All of the patients who had this treatment regimen could walk; in contrast, of the eleven patients who were not so treated, four could not walk.

  11. Adult onset retinoblastoma

    PubMed Central

    Sengupta, Sabyasachi; Pan, Utsab; Khetan, Vikas

    2016-01-01

    Retinoblastoma (RB) is the most common primary malignant intraocular tumor of childhood presenting usually before 5 years of age. RB in adults older than 20 years is extremely rare. A literature search using PubMed/PubMed Central, Scopus, Google Scholar, EMBASE, and Cochrane databases revealed only 45 cases till date. Over the past decade, there has been a significant increase in the number of such reports, indicating heightened level of suspicion among ophthalmologists. Compared to its pediatric counterpart, adult onset RB poses unique challenges in diagnosis and treatment. This article summarizes available literature on adult onset RB and its clinical and pathologic profile, genetics, association with retinocytoma, diagnostics, treatment, and outcomes. PMID:27609158

  12. Adult-onset Atopic Dermatitis

    PubMed Central

    Kanwar, Amrinder Jit

    2016-01-01

    Adult-onset atopic dermatitis is still an under recognized condition as there are only few studies regarding this entity. As compared to childhood onset atopic dermatitis, clinical features of adult onset atopic dermatitis are still not categorized. Adult atopic dermatitis can present for the first time in adult age with atypical morphology or may progress from childhood onset. This article reviews the characteristic clinical features of adult atopic dermatitis, associated risk factors and management. PMID:27904186

  13. [Early onset diabetes mellitus].

    PubMed

    Busiah, K; Vaivre-Douret, L; Yachi, C; Cavé, H; Polak, M

    2013-12-01

    Neonatal diabetes mellitus is a rare condition (1/90,000 to 1/260,000 live births) defined as mild-to-severe hyperglycemia within the first year of life. Permanent neonatal diabetes mellitus requires lifelong therapy, whereas transient form resolves early in life but may relapse later on. Two main physiopathological mechanisms may explain this disease: β cell functional impairment or absence (pancreas agenesis or β cells destruction). The main genetic causes of β cells impairment are 6q24 abnormalities and mutations in ABCC8 or KCNJ11 potassium channel (KATP channel) genes. Compared to the KATP subtype, the 6q24 subtype had specific features: developmental defects involving the heart, kidneys, or urinary tract, intrauterine growth restriction, and early diagnosis. Remission of neonatal diabetes mellitus occurred in 51% of probands at a median age of 17 weeks. Recurrence was common at pubertal age, with no difference between the 6q24 and KATP-channel groups (82% vs 86%, p=0.36, respectively). Patients with mutations in ABCC8 or KCNJ11 genes had developmental delay with or without epilepsy but also developmental coordination disorder (particularly visual-spatial dyspraxia) or attention deficits in all of those who underwent in-depth neuropsychomotor investigations.

  14. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    SciTech Connect

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E.

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  15. Adult-onset food allergy.

    PubMed

    Kivity, Shmuel

    2012-01-01

    The prevalence of food allergy is increasing in both the pediatric and adult populations. While symptom onset occurs mostly during childhood, there are a considerable number of patients whose symptoms first begin to appear after the age of 18 years. The majority of patients with adult-onset food allergy suffer from the pollen-plant allergy syndromes. Many of them manifest their allergy after exercise and consuming food to which they are allergic. Eosinophilic esophagitis, an eosinophilic inflammation of the esophagus affecting individuals of all ages, recently emerged as another allergic manifestation, with both immediate and late response to the ingested food. This review provides a condensed update of the current data in the literature on adult-onset allergy.

  16. Adult-onset mitochondrial myopathy.

    PubMed Central

    Fernandez-Sola, J.; Casademont, J.; Grau, J. M.; Graus, F.; Cardellach, F.; Pedrol, E.; Urbano-Marquez, A.

    1992-01-01

    Mitochondrial diseases are polymorphic entities which may affect many organs and systems. Skeletal muscle involvement is frequent in the context of systemic mitochondrial disease, but adult-onset pure mitochondrial myopathy appears to be rare. We report 3 patients with progressive skeletal mitochondrial myopathy starting in adult age. In all cases, the proximal myopathy was the only clinical feature. Mitochondrial pathology was confirmed by evidence of ragged-red fibres in muscle histochemistry, an abnormal mitochondrial morphology in electron microscopy and by exclusion of other underlying diseases. No deletions of mitochondrial DNA were found. We emphasize the need to look for a mitochondrial disorder in some non-specific myopathies starting in adult life. Images Figure 1 Figure 2 PMID:1589382

  17. Specific Intellectual Deficits in Children with Early Onset Diabetes Mellitus.

    ERIC Educational Resources Information Center

    Rovet, Joanne F.; And Others

    1988-01-01

    Compares 27 children with early onset diabetes (EOD) with 24 children with late onset diabetes (LOD) and 30 sibling controls in performance on tests of intellectual functioning and school achievement. Results revealed that duration of illness, age of onset, and hypoglycemic convulsions significantly predicted spatial ability. (Author/RWB)

  18. [Adult-onset rare diseases].

    PubMed

    Pfliegler, György; Kovács, Erzsébet; Kovács, György; Urbán, Krisztián; Nagy, Valéria; Brúgós, Boglárka

    2014-03-02

    The present paper is focusing on rare diseases manifesting in late childhood or adulthood. A part of these syndromes are not of genetic origin, such as relatively or absolutely rare infections, autoimmune diseases, tumours, or diseases due to rare environmental toxic agents. In addition, even a large proportion of genetic disorders may develop in adulthood or may have adult forms as well, affecting are almost each medical specialization. Examples are storage disorders (e.g. adult form of Tay-Sachs disease, Gaucher-disease), enzyme deficiencies (e.g. ornithin-transcarbamylase deficiency of the urea cycle disorders), rare thrombophilias (e.g. homozygous factor V. Leiden mutation, antithrombin deficiency), or some rare monogenic disorders such as Huntington-chorea and many others. It is now generally accepted that at least half of the 6-8000 "rare diseases" belong either to the scope of adult-care (e.g. internal medicine, neurology), or to "age-neutral" specialities such as ophtalmology, dermatology etc.).

  19. Diabetes: Unique to Older Adults

    MedlinePlus

    ... Stroke Urinary Incontinence Related Documents PDF Choosing Wisely: Diabetes Tests and Treatments Download Related Video Join our e-newsletter! Aging & Health A to Z Diabetes Unique to Older Adults This section provides information ...

  20. Statins and Risk of New-Onset Diabetes Mellitus

    MedlinePlus

    ... Patient Page Statins and Risk of New-Onset Diabetes Mellitus Ravi V. Shah , Allison B. Goldfine Download ... initiation in at-risk patients. Can Statins Cause Diabetes Mellitus? Careful review of findings from many trials ...

  1. Onset of autoimmune type 1 diabetes during pregnancy: Prevalence and outcomes.

    PubMed

    Wucher, Hélène; Lepercq, Jacques; Timsit, José

    2010-08-01

    Although this has been recently challenged, gestational diabetes mellitus (gestational diabetes) is still defined as an "impairment of glucose tolerance with onset or first recognition during pregnancy". According to this definition, all pathophysiological conditions leading to beta cell deficiency may reveal as gestational diabetes, due to the physiological insulin resistance associated with pregnancy. In rare patients, gestational diabetes is associated with the presence of islet autoantibodies and with a high risk of progression to overt type 1 diabetes after delivery. This condition has often been compared to the Latent Autoimmune Diabetes in Adults. The frequency of islet autoantibodies in gestational diabetes has been assessed in many studies, but data about the clinical presentation of this subtype and about its prognosis are few. We review these studies and discuss the links of autoimmune gestational diabetes with type 1 diabetes mellitus.

  2. Adult-onset opsoclonus-myoclonus syndrome.

    PubMed

    Klaas, James P; Ahlskog, J Eric; Pittock, Sean J; Matsumoto, Joseph Y; Aksamit, Allen J; Bartleson, J D; Kumar, Rajeev; McEvoy, Kathleen F; McKeon, Andrew

    2012-12-01

    BACKGROUND Little is known about adult-onset opsoclonus-myoclonus syndrome (OMS) outside of individual case reports. OBJECTIVE To describe adult-onset OMS. DESIGN Review of medical records (January 1, 1990, through December 31, 2011), prospective telephone surveillance, and literature review (January 1, 1967, through December 31, 2011). SETTING Department of Neurology, Mayo Clinic, Rochester, Minnesota. PATIENTS Twenty-one Mayo Clinic patients and 116 previously reported patients with adult-onset OMS. MAIN OUTCOME MEASURES Clinical course and longitudinal outcomes. RESULTS The median age at onset of the 21 OMS patients at the Mayo Clinic was 47 years (range, 27-78 years); 11 were women. Symptoms reported at the first visit included dizziness, 14 patients; balance difficulties, 14; nausea and/or vomiting, 10; vision abnormalities, 6; tremor/tremulousness, 4; and altered speech, 2. Myoclonus distribution was extremities, 15 patients; craniocervical, 8; and trunk, 4. Cancer was detected in 3 patients (breast adenocarcinoma, 2; and small cell lung carcinoma, 1); a parainfectious cause was assumed in the remainder of the patients. Follow-up of 1 month or more was available for 19 patients (median, 43 months; range, 1-187 months). Treatment (median, 6 weeks) consisted of immunotherapy and symptomatic therapy in 16 patients, immunotherapy alone for 2, and clonazepam alone for 1. Of these 19 patients, OMS remitted in 13 and improved in 3; 3 patients died (neurologic decline, 1; cancer, 1; and myocardial infarction, 1). The cause of death was of paraneoplastic origin in 60 of 116 literature review patients, with the most common carcinomas being lung (33 patients) and breast (7); the most common antibody was antineuronal nuclear antibody type 2 (anti-Ri, 15). Other causes were idiopathic in origin, 38 patients; parainfectious, 15 (human immunodeficiency virus, 7); toxic/metabolic, 2; and other autoimmune, 1. Both patients with N -methyl-D-aspartate receptor antibody had

  3. Early onset type 2 diabetes in Jamaica and in Mexico. Opportunities derived from an interethnic study.

    PubMed

    Irving, Rachael; Tusié-Luna, Ma Teresa; Mills, James; Wright-Pascoe, Rosemarie; McLaughlin, Wayne; Aguilar-Salinas, Carlos A

    2011-01-01

    Populations with Amerindian or African heritages are the one with the highest prevalence of diabetes worldwide. A large percentage of these individuals survived famine. However, the survival effect has become detrimental to their descendents living in an environment of caloric surplus. In countries, like Mexico and Jamaica, in which diabetes is highly prevalent, the onset of the disease happens at earlier ages. Our objective is to summarize diabetes data from Mexico and Jamaica and to discuss the opportunities that can result from an interethnic study. On one hand, the prevalence of diabetes in Jamaica is 17.9% in the 15+ age group. Jamaican researchers have built a cohort of families with early onset type 2 diabetes. In this population, this form of the disease is unrelated to MODY genes. On the other hand, the prevalence of diabetes in adult Mexicans is 14.4%. The group in which the greater percentual changes have occurred is the adults who are below the age of 40. More than two thirds of the early onset cases studied have a body mass index that is >25 kg/m2 and the clinical characteristics of metabolic syndrome. A minority of them has mutations in the MODY genes. The joint study of Mexican and Jamaican cohorts of early onset type 2 diabetes cases will be useful to identify new genetic and environmental players in the pathogenesis of this entity.

  4. Infantile onset diabetes mellitus in developing countries - India.

    PubMed

    Varadarajan, Poovazhagi

    2016-03-25

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India.

  5. Infantile onset diabetes mellitus in developing countries - India

    PubMed Central

    Varadarajan, Poovazhagi

    2016-01-01

    Infantile onset diabetes mellitus (IODM) is an uncommon metabolic disorder in children. Infants with onset of diabetes mellitus (DM) at age less than one year are likely to have transient or permanent neonatal DM or rarely type 1 diabetes. Diabetes with onset below 6 mo is a heterogeneous disease caused by single gene mutations. Literature on IODM is scanty in India. Nearly 83% of IODM cases present with diabetic keto acidosis at the onset. Missed diagnosis was common in infants with diabetes (67%). Potassium channel mutation with sulphonylurea responsiveness is the common type in the non-syndromic IODM and Wolcott Rallison syndrome is the common type in syndromic diabetes. Developmental delay and seizures were the associated co-morbid states. Genetic diagnosis has made a phenomenal change in the management of IODM. Switching from subcutaneous insulin to oral hypoglycemic drugs is a major clinical breakthrough in the management of certain types of monogenic diabetes. Mortality in neonatal diabetes is 32.5% during follow-up from Indian studies. This article is a review of neonatal diabetes and available literature on IODM from India. PMID:27022444

  6. Type 2 Diabetes Widespread in Adults

    MedlinePlus

    ... version of this page please turn Javascript on. Type 2 Diabetes Widespread in Adults Past Issues / Fall 2006 Table ... pre-diabetes have an increased risk for developing type 2 diabetes, the most common form of diabetes, and for ...

  7. Osteoporosis in juvenile-onset diabetes mellitus: morphometric and comparative studies.

    PubMed

    Soejima, K; Landing, B H

    1986-01-01

    Ribs and vertebrae of 8 children and young adults aged from 17 months to 24 years with juvenile-onset diabetes mellitus, 4 with diabetes secondary to cystic fibrosis and 2 with diabetes secondary to thalassemia major, were analyzed for osteoporosis by a point-count morphometric method. The mean ratio of bone spicule to marrow space in cancellous bone of ribs of patients with juvenile-onset diabetes mellitus or with diabetes mellitus secondary to cystic fibrosis or thalassemia was 55% that of 10 control patients. The lengths of the zones of proliferating and mature cartilage cells in costal epiphyses of patients with juvenile-onset diabetes mellitus were also below normal. The ratio of bone spicule to marrow space of vertebrae of the diabetic patients was not significantly different from control values. The data confirm clinical reports that osteoporosis is a regular feature of juvenile-onset diabetes mellitus and suggest that the degree of bone matrix and mineral deficiency in such patients is greater than is usually considered.

  8. Vaccinations for Adults with Diabetes

    MedlinePlus

    Vaccinations for Adults with Diabetes The table below shows which vaccinations you should have to protect your health if ... sure you and your healthcare provider keep your vaccinations up to date. Vaccine Do you need it? ...

  9. Phenotypes, Risk Factors, and Mechanisms of Adult-Onset Asthma

    PubMed Central

    Ilmarinen, Pinja; Tuomisto, Leena E.; Kankaanranta, Hannu

    2015-01-01

    Asthma is a heterogeneous disease with many phenotypes, and age at disease onset is an important factor in separating the phenotypes. Genetic factors, atopy, and early respiratory tract infections are well-recognized factors predisposing to childhood-onset asthma. Adult-onset asthma is more often associated with obesity, smoking, depression, or other life-style or environmental factors, even though genetic factors and respiratory tract infections may also play a role in adult-onset disease. Adult-onset asthma is characterized by absence of atopy and is often severe requiring treatment with high dose of inhaled and/or oral steroids. Variety of risk factors and nonatopic nature of adult-onset disease suggest that variety of mechanisms is involved in the disease pathogenesis and that these mechanisms differ from the pathobiology of childhood-onset asthma with prevailing Th2 airway inflammation. Recognition of the mechanisms and mediators that drive the adult-onset disease helps to develop novel strategies for the treatment. The aim of this review was to summarize the current knowledge on the pathogenesis of adult-onset asthma and to concentrate on the mechanisms and mediators involved in establishing adult-onset asthma in response to specific risk factors. We also discuss the involvement of these mechanisms in the currently recognized phenotypes of adult-onset asthma. PMID:26538828

  10. Psychological Conditions in Adults With Diabetes

    PubMed Central

    de Groot, Mary; Golden, Sherita Hill; Wagner, Julie

    2016-01-01

    Type 1 (T1D) and Type 2 diabetes (T2D) represent a demanding set of biopsychosocial challenges for patients and their families, whether the age of disease onset occurs in childhood, adolescence, or adulthood. Psychological conditions, defined as syndromes, disorders, and diabetes-specific psychological issues affect a larger proportion of individuals with T1D and T2D compared to the general population. In this review, we summarize the prevalence, impact and psychological treatments associated with the primary categories of psychological conditions that affect adults with T1D and T2D: depressive symptoms and syndromes, anxiety disorders, eating behaviors and disorders and serious mental illness. The implications of the literature for psychologists are discussed, and priorities for future research to advance the science of psychological conditions for adults with T1D and T2D are identified. PMID:27690484

  11. Age at Transition from Pediatric to Adult Care Has No Relationship with Mortality for Childhood-Onset Type 1 Diabetes in Japan: Diabetes Epidemiology Research International (DERI) Mortality Study

    PubMed Central

    Onda, Yoshiko; Nishimura, Rimei; Morimoto, Aya; Sano, Hironari; Utsunomiya, Kazunori; Tajima, Naoko

    2016-01-01

    Objective To follow up Japanese patients with type 1 diabetes for a maximum of 40 years to examine when they transitioned from pediatric care to adult care and to explore whether the attending physician, i.e., pediatrician or internist, was associated with prognosis. Methods Participants consisted of 1,299 patients who had been diagnosed as having type 1 diabetes at less than 15 years old between 1965 and 1979 identified through two nationwide surveys. Patients were classified as having received either pediatric care or adult care at the age of 15 and 30, and were compared for differences in mortality associated with the attending physician. Results The attending physicians were confirmed for a total of 1,093 patients at the age of 15. Of these patients, 43.8% and 40.3% received pediatric care and adult care, respectively. Of the 569 patients receiving pediatric care, 74.2%, 56.6%, 53.4%, and 51.3% continued with pediatric care at 20, 30, 40, and 50 years old, respectively. The attending physicians (pediatrician or internist) at the age of 15 and 30 had no significant impact on their survival (P = 0. 892, 0.411, respectively). Conclusions More than half of the patients who had received pediatric care at the age of 15 continued to receive pediatric care even after the age of 30, suggesting that their transition was far from smooth, while the attending physician at the age of both 15 and 30 was not a prognostic factor for mortality. Thus, the timing for transition to adult care in these patients has no relationship with mortality in Japan. PMID:26937952

  12. Refractory Coats’ Disease of Adult Onset

    PubMed Central

    Beselga, D.; Campos, A.; Mendes, S.; Carvalheira, F.; Castro, M.; Castanheira, D.

    2012-01-01

    Purpose We present the case of an 18-year-old Caucasian male with a unilateral macular star and retinal vascular anomalies compatible with adult onset Coats’ disease. Methods Diagnosis was based on fundoscopic, fluorescein angiography and optical coherence tomography findings. Results The patient presented to our emergency department with complaints of low vision in his left eye (LE) detected 10 days before. The best-corrected visual acuity in the LE was 20/50. Fundoscopy of the LE evidenced a complete macular star. Optical coherence tomography showed increased retinal thickness, infiltration of the retinal wall, and detachment of the neuroepithelium. Angiography revealed no appreciable diffusion in the macula. Above the superior temporal (ST) arcade, anomalies in the retinal vasculature were found, with interruption of the peripheral vessels and vessels which were ‘sausage’-like. After 1 month, the LE vision evolved to hand movements. Laser photocoagulation was performed in the ST quadrant. Intravitreal injection of bevacizumab 1.25 mg/0.05 ml and photodynamic therapy were performed without any significant changes, progression of ST serous detachment of the neuroepithelium, and finally progression to macular fibrosis. Discussion Coats’ disease is usually diagnosed in childhood, but rare cases may occur in adults. Those cases usually have a more indolent course which was not observed in our patient. When there is macular involvement, prognosis is more guarded, despite treatment. PMID:22548045

  13. Similarity of HLA-DQ profiles in adult-onset type 1 insulin-dependent diabetic patients with and without extra-pancreatic auto-immune disease.

    PubMed

    Gu, X F; Larger, E; Clauser, E; Assan, R

    1992-01-01

    Some insulin-dependent diabetic patients present with auto-immune diseases involving extra pancreatic tissues (type 1b diabetes mellitus). The genetic specificity of this syndrome, as opposed to insulin dependent diabetes mellitus (IDDM) free of such associations (Type 1a IDDM) is not clearly established. We have analyzed the HLA-DQB1 and DQA1, loci, after PCR amplification of genomic DNA, in 44 Type 1b IDDM patients, 78 Type 1a IDDM patients and 105 control subjects. No essential difference in HLA-DQ profiles appeared between Type 1b and Type 1a IDDM patients. Both diabetic groups displayed a significant enrichment in DQB1 alleles negative for aspartate at position 57 (Type 1b: 83%; Type 1a: 89%; controls 48%; p < 0.001 vs both patient groups) and in DQB1 Asp 57 negative homozygosity: 71% of Type 1b; 80% of Type 1a; 25% of controls (p < 0.01). This enrichment in DQB1 Asp 57 negative alleles was accounted for by DQB1* 0201 in the Type 1b group, and by DQB1 % 0201 and 0302 in the Type 1a patients. Conversely, alleles DQB1* 0602 and 0301 (DQB1 Asp 57 positive) were protective. Both diabetic groups also displayed a significant enrichment in DQA1 alleles positives for arginine at position 52 (65% of Type 1b; 76% of Type 1a; 50% of control subjects; p < 0.01 and 0.001, respectively, vs controls), and in DQA1 Arg 52 positive homozygotes (48% of Type 1b, 58% of Type 1a, 22% of control subjects; p < 0.01). All differences between diabetic groups and the control group were more pronounced in the case of Type 1a than of Type 1b patients. The HLA-DQ genes shared by Type 1a and Type 1b patients must therefore be closely associated with islet autoimmunity. Genetic differences between Type 1a and Type 1b syndromes, if any, must be investigated in other MHC and non-MHC regions of the genome.

  14. Update on differences between childhood-onset and adult-onset systemic lupus erythematosus

    PubMed Central

    2013-01-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disease and occurs worldwide in both children and adults. The estimated annual incidence among children is 2.22/100,000 and among adults is 23.2/100,000 in the United States. There is increasing understanding about differences in disease manifestations, medication use, and disease severity between those with childhood-onset SLE as compared with adult-onset SLE. Children have a more fulminant disease onset and course than adults with SLE, resulting in two to three times higher mortality. In future years, we anticipate more insight into the genetics between childhood-onset SLE and adult-onset SLE to help delineate the best therapies for both subsets of patients. PMID:23998441

  15. Childhood Onset Schizophrenia: Cortical Brain Abnormalities as Young Adults

    ERIC Educational Resources Information Center

    Greenstein, Deanna; Lerch, Jason; Shaw, Philip; Clasen, Liv; Giedd, Jay; Gochman, Peter; Rapoport, Judith; Gogtay, Nitin

    2006-01-01

    Background: Childhood onset schizophrenia (COS) is a rare but severe form of the adult onset disorder. While structural brain imaging studies show robust, widespread, and progressive gray matter loss in COS during adolescence, there have been no longitudinal studies of sufficient duration to examine comparability with the more common adult onset…

  16. Comparison of Age of Onset and Frequency of Diabetic Complications in the Very Elderly Patients with Type 2 Diabetes

    PubMed Central

    2016-01-01

    Background The prevalence of type 2 diabetes in elderly people has increased dramatically in the last few decades. This study was designed to clarify the clinical characteristics of type 2 diabetes in patients aged ≥80 years according to age of onset. Methods We reviewed the medical records of 289 patients aged ≥80 years with type 2 diabetes at the outpatient diabetes clinics of Kangwon National University Hospital from September 2010 to June 2014. We divided the patients into middle-age-onset diabetes (onset before 65 years of age) and elderly-onset diabetes (onset at 65+ years of age). Results There were 141 male and 148 female patients. The patients had a mean age of 83.2±2.9 years and the mean duration of diabetes was 14.3±10.4 years. One hundred and ninety-nine patients had elderly-onset diabetes. The patients with elderly-onset diabetes had a significantly lower frequency of diabetic retinopathy and nephropathy, lower serum creatinine levels, lower glycated hemoglobin (HbA1c) levels, and similar coronary revascularization and cerebral infarction rates compared to those with middle-age-onset diabetes. There was no frequency difference in coronary revascularization and cerebral infarction and HbA1c levels between three subgroups (<5, 5 to 15, and ≥15 years) of diabetes duration in elderly onset diabetes. However, both in the elderly onset diabetes and middle-age-onset diabetes, the cumulative incidence of retinopathy was increasing rapidly according to the duration of diabetes. Conclusion We report that individuals with elderly-onset diabetes have a lower frequency of diabetic retinopathy and nephropathy and similar cardiovascular complications compared to those with middle-age-onset diabetes. PMID:27586451

  17. Is Adolescent-Onset First-Episode Psychosis Different from Adult Onset?

    ERIC Educational Resources Information Center

    Ballageer, Trevor; Malla, Ashok; Manchanda, Rahul; Takhar, Jatinder; Haricharan, Raj

    2005-01-01

    Objective: To examine whether first-episode psychosis patients with onset during adolescence (ages 15-18) differ significantly from those with young-adult onset (ages 19-30). Method: Consecutive patients presenting with first-episode psychosis (N = 242) were assessed for demographic and illness characteristics such as duration of untreated…

  18. Clinical Characteristics of Pediatric-Onset and Adult-Onset Multiple Sclerosis in Hispanic Americans.

    PubMed

    Langille, Megan M; Islam, Talat; Burnett, Margaret; Amezcua, Lilyana

    2016-07-01

    Multiple sclerosis can affect pediatric patients. Our aim was to compare characteristics between pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanic Americans. This was a cross-sectional analysis of 363 Hispanic American multiple scleroses cases; demographic and clinical characteristics were analyzed. A total of 110 Hispanic patients presented with multiple sclerosis before age 18 and 253 as adult multiple sclerosis. The most common presenting symptoms for both was optic neuritis. Polyfocal symptoms, seizures, and cognitive symptoms at presentation were more prevalent in pediatric-onset multiple sclerosis (P ≤ .001). Transverse myelitis was more frequent in adult-onset multiple sclerosis (P ≤ .001). Using multivariable analysis, pediatric-onset multiple sclerosis (adjusted odds ratio, 0.3OR 95% confidence interval 0.16-0.71, P = .004) and being US born (adjusted odds ratio, 0.553, 95% confidence interval 0.3-1.03, P = .006) were less likely to have severe ambulatory disability. Results suggest that pediatric-onset multiple sclerosis and adult-onset multiple sclerosis in Hispanics have differences that could be important for treatment and prognosis.

  19. Youth-onset type 2 diabetes mellitus: lessons learned from the TODAY study.

    PubMed

    Narasimhan, Sumana; Weinstock, Ruth S

    2014-06-01

    Type 2 diabetes mellitus is increasingly diagnosed in obese children and adolescents. Evidence suggests that this disease commonly progresses more rapidly in youth compared with adults and is associated with high rates of early microalbuminuria, hypertension, and dyslipidemia. The Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study was the first multiethnic, multicenter randomized trial in the United States to compare 3 treatment approaches in obese youth with new-onset type 2 diabetes (n=699; ages 10-17 years): monotherapy with metformin, metformin with rosiglitazone, and metformin with an intensive lifestyle intervention. The primary outcome was glycemic control. Diabetes-related complications and cardiovascular risk factors were also examined. Approximately half of the participants could not maintain glycemic control by using metformin alone. Combination therapy with metformin and rosiglitazone resulted in better durability of glycemic control, and metformin plus intensive lifestyle intervention was intermediate but not superior to metformin alone. Deterioration in glycemic control was associated with rapid loss of beta cell function, not worsened insulin sensitivity, and could not be explained by differences in adherence or body mass index. After 3.9 years, 236 (33.8%) of participants had hypertension and 116 participants (16.6%) had microalbuminuria. Only 55.9% of participants had a low-density lipoprotein cholesterol level less than 100 mg/dL (to convert to mmol/L, multiply by 0.0259) after 3 years, and 71 of 517 participants (13.7%) had retinopathy. The significance of the findings from this important trial for the management of youth and young adults with youth-onset type 2 diabetes and its complications is discussed. An aggressive multifaceted approach is needed to prevent or forestall premature microvascular and macrovascular complications in youth-onset type 2 diabetes.

  20. Dimethyl sulfoxide modulation of diabetes onset in NOD mice.

    PubMed

    Klandorf, H; Chirra, A R; DeGruccio, A; Girman, D J

    1989-02-01

    Dimethyl sulfoxide (DMSO), a hydroxyl radical scavenger, is known as an immunosuppressive agent and can reduce autoantibody levels in experimental autoimmune diseases. Because classic diabetogens damage the DNA and membrane of the beta-cell by the generation of free radicals, the purpose of these investigations was to determine whether the intake of DMSO or its derivatives methylsulfonylmethane (MSM) and dimethylsulfide (DMS) could prevent the expression of autoimmune diabetes in the spontaneously diabetic NOD mouse. DMSO (2.5%), MSM (2.5%), and DMS (0.25%) were added to the drinking water of female NOD mice immediately after weaning. Control animals were maintained on regular drinking water. The presence of overt diabetes was monitored from the age of 2 mo by weekly urinary glucose testing until the animals either became overtly glucosuric or were greater than 240 days of age. In contrast to what we expected, DMSO (2.5%) markedly increased the rate at which the animals expressed overt diabetes (P less than .0004, log-rank test). MSM had no effect, whereas DMS reduced the incidence and rate of diabetes onset. When DMSO (2.5%) was administered to male NOD mice and control strains of mice (BALB/c and ICR), the control group did not develop glucosuria or insipidus, whereas DMSO increased the incidence of diabetes in the male NOD mice from 21 to 79%. In contrast, when DMSO was fed to female NOD mice on a purified AIN-76 diet, diabetes onset was reduced to 36%. We conclude that DMSO accelerates the uptake of dietary diabetogens into the beta-cell of genetically susceptible animals (NOD mice). The protective effect of the purified diet in such animals may be due to a lack of putative diabetogens in purified diet, or alternatively, the diet itself contains factor(s) that protect the beta-cell from autoimmune attack and/or destruction.

  1. Monogenic Forms of Diabetes: Neonatal Diabetes Mellitus and Maturity-Onset Diabetes of the Young

    MedlinePlus

    ... Diabetes Monogenic Forms of Diabetes Monogenic Forms of Diabetes The most common forms of diabetes, type 1 ... is inherited from each parent. Monogenic Forms of Diabetes Some rare forms of diabetes result from mutations ...

  2. Glucose Intolerance and Hyperlipidemia Prior to Diabetes Onset in Female Spontaneously Diabetic Torii (SDT) Rats

    PubMed Central

    Oikawa, Toshihiro; Sato, Kahei; Kanazawa, Yasunori

    2004-01-01

    The Spontaneously Diabetic Torii (SDT) rat, a newly established animal model for diabetes mellitus, presents nonobese type 2 diabetes with ocular complications. In the present study, oral glucose tolerance tests and biochemical and histopathological examinations were performed in female SDT rats at 16 and/or 25 weeks of age, before the onset of diabetes. At 25 weeks of age, glucose tolerance was significantly impaired, and plasma immunoreactive insulin levels at 120 min after glucose loading were significantly higher (P < 0.05). Body weight and fasting levels of plasma triglycerides and nonesterified fatty acids were significantly higher than those in control animals. Histopathologically, inflammatory cell infiltration and fibrosis were observed in and around the pancreatic islets. These results strongly suggest that female SDT rats are useful as a model to investigate impairment of glucose tolerance and hyperlipidemia prior to the onset of diabetes. PMID:15763939

  3. Adult-onset idiopathic chondrolysis of the hip.

    PubMed

    Yapp, Liam Z; McClymont, Liusaidh; Beggs, Ian; Gaston, Paul; Salter, Donald M

    2017-05-01

    We report the case of a 23-year-old man diagnosed with adult-onset idiopathic chondrolysis of the hip. Chondrolysis of the hip is a disorder most frequently seen in children who have suffered with slipped capital femoral epiphyses. Idiopathic chondrolysis of the hip is extremely rare and to our knowledge, its onset has never been documented in adults aged over 20. With reference to the available medical literature, we summarise the current clinical management of this unusual but important cause of young adult hip pain.

  4. Adult Onset Still's Disease and Rocky Mountain Spotted Fever.

    PubMed

    Persad, Paul; Patel, Rajendrakumar; Patel, Niki

    2010-01-01

    Adult Still's Disease was first described in 1971 by Bywaters in fourteen adult female patients who presented with symptoms indistinguishable from that of classic childhood Still's Disease (Bywaters, 1971). George Still in 1896 first recognized this triad of quotidian (daily) fevers, evanescent rash, and arthritis in children with what later became known as juvenile inflammatory arthritis (Still, 1990). Adult Onset Still's Disease (AOSD) is an inflammatory condition of unknown etiology characterized by an evanescent rash, quotidian fevers, and arthralgias. Numerous infectious agents have been associated with its presentation. This case is to our knowledge the first presentation of AOSD in the setting of Rocky Mountain Spotted Fever. Although numerous infectious agents have been suggested, the etiology of this disorder remains elusive. Nevertheless, infection may in fact play a role in triggering the onset of symptoms in those with this disorder. Our case presentation is, to our knowledge, the first case of Adult Onset Still's Disease associated with Rocky Mountain spotted fever (RMSF).

  5. Sarcopenia, Frailty, and Diabetes in Older Adults

    PubMed Central

    2016-01-01

    Populations are aging and the prevalence of diabetes mellitus is increasing tremendously. The number of older people with diabetes is increasing unexpectedly. Aging and diabetes are both risk factors for functional disability. Thus, increasing numbers of frail or disabled older patients with diabetes will increase both direct and indirect health-related costs. Diabetes has been reported as an important risk factor of developing physical disability in older adults. Older people with diabetes have lower muscle mass and weaker muscle strength. In addition, muscle quality is poorer in diabetic patients. Sarcopenia and frailty have a common soil and may share a similar pathway for multiple pathologic processes in older people. Sarcopenia is thought to be an intermediate step in the development of frailty in patients with diabetes. Thus, early detection of sarcopenia and frailty in older adults with diabetes should be routine clinical practice to prevent frailty or to intervene earlier in frail patients. PMID:27098509

  6. Adult-onset acute rheumatic fever.

    PubMed

    Nakashima, Dainari; Ueda, Kohei; Tsukuda, Kyozo; Utsu, Noriaki; Kohki, Shimazu; Fushimi, Hiroaki; Miyakoshi, Kazuho

    2012-01-01

    A 62-year-old man was hospitalized for acute rheumatic fever. He had previously suffered from rheumatic fever at 15 years of age. The rheumatic fever was complicated by carditis, which caused valve disease that required surgical treatment. The incidence of rheumatic fever has decreased in most developed countries with improvements in sanitary conditions. The low incidence of this disease makes a timely and accurate diagnosis difficult. Due to the fact that both the first occurrence and recurrence of acute rheumatic fever can occur in the elderly and adults, this potential disease should not be overlooked when making a differential diagnosis.

  7. Adult-onset amenorrhea: a study of 262 patients.

    PubMed

    Reindollar, R H; Novak, M; Tho, S P; McDonough, P G

    1986-09-01

    A series of 262 patients with amenorrhea of adult onset are reported. Hypothalamic suppression followed by inappropriate positive feedback, and then hyperprolactinemia and ovarian failure are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. Amenorrhea after use of oral contraceptives, or postpill amenorrhea, occurred in 77 (29%) of all patients. The average age of presentation, prior menstrual history, associated morbidity, and subsequent reproductive potential of each diagnostic group are reported. Adult-onset amenorrhea has a less significant impact on future wellbeing than was reported for a similar-sized group of patients whose amenorrhea developed as a result of pubertal aberrancy.

  8. Verbal and Academic Skills in Children with Early-Onset Type 1 Diabetes

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Eklund, Kenneth; Tolvanen, Asko; Riikonen, Raili; Ahonen, Timo

    2010-01-01

    Aim: Basic verbal and academic skills can be adversely affected by early-onset diabetes, although these skills have been studied less than other cognitive functions. This study aimed to explore the mechanism of learning deficits in children with diabetes by assessing basic verbal and academic skills in children with early-onset diabetes and in…

  9. Etiopathogenesis and Therapeutic Approach to Adult Onset Acne

    PubMed Central

    Kaur, Sarabjit; Verma, Poonam; Sangwan, Ankita; Dayal, Surabhi; Jain, Vijay Kumar

    2016-01-01

    Acne vulgaris is usually considered as a skin disorder that primarily affects adolescents reaching a peak at the age of 14–17 years in females and 16–19 years in males. However, recent epidemiologic studies have shown that a significant number of female patients aged >25 years experience acne. As it is regarded as a disease of teenagers, adults are more apprehensive and experience social anxiety. Hence, adult onset acne has become a matter of concern. PMID:27512185

  10. [SERUM LEVEL OF ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE-II IN CHILDHOOD-ONSET TYPE 1 DIABETIC PATIENTS AND OBESE ADOLESCENTS].

    PubMed

    Mogylnytska, L A

    2015-01-01

    The atherosclerotic process begins in adolescence, and its progression is determined by the same risk factors as in adults. Endothelial monocyte activating polypeptide-II (EMAP-II) is a multifunctional cytokine with proinflammatory and antiangiogenetic activity that may play a pathogenic role in the development of endothelial dysfunction and atherosclerosis. The aim of our study was to determine the serum level of EMAP-II in childhood-onset type 1 diabetic patients and obese adolescents. We found increased of serum level of EMAP-II in childhood-onset type 1 diabetic patients and in patients with obesity that do not suffer from diabetes. Also, the level of EMAP-II correlated with the serum level of glycosylated hemoglobin and blood glucose, and key markers of lipid metabolism, body mass index. Increased serum level of EMAP-II may be one of the pathway of endothelial dysfunction in type 1 diabetes.

  11. [Diabetes education in adult diabetic patients].

    PubMed

    Weitgasser, Raimund; Clodi, Martin; Cvach, Sarah; Grafinger, Peter; Lechleitner, Monika; Howorka, Kinga; Ludvik, Bernhard

    2016-04-01

    Diabetes education and self management has gained a critical role in diabetes care. Patient empowerment aims to actively influence the course of the disease by self-monitoring and treatment modification, as well as integration of diabetes in patients' daily life to achieve changes in lifestyle accordingly.Diabetes education has to be made accessible for all patients with the disease. To be able to provide a structured and validated education program adequate personal as well as space, organizational and financial background are required. Besides an increase in knowledge about the disease it has been shown that structured diabetes education is able to improve diabetes outcome measured by parameters like blood glucose, HbA1c, blood pressure and body weight in follow-up evaluations. Modern education programs emphasize the ability of patients to integrate diabetes in everyday life and stress physical activity besides healthy eating as a main component of lifestyle therapy and use interactive methods in order to increase the acceptance of personal responsibility.

  12. Clinical profile of patients with adult-onset eosinophilic asthma

    PubMed Central

    Storm, Huib; Amelink, Marijke; de Nijs, Selma B.; Eichhorn, Edwin; Reitsma, Bennie H.; Bel, Elisabeth H.D.; ten Brinke, Anneke

    2016-01-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×109 L−1) were compared with 361 adult-onset asthma patients with low (<0.3×109 L−1) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7–8.1), 3.0 (95% CI 1.1–8.1) and 2.4 (95% CI 1.3–4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice. PMID:27730197

  13. Clinical profile of patients with adult-onset eosinophilic asthma.

    PubMed

    de Groot, Jantina C; Storm, Huib; Amelink, Marijke; de Nijs, Selma B; Eichhorn, Edwin; Reitsma, Bennie H; Bel, Elisabeth H D; Ten Brinke, Anneke

    2016-04-01

    Adult-onset eosinophilic asthma is increasingly recognised as a severe and difficult-to-treat subtype of asthma. In clinical practice, early recognition of patients with this asthma subtype is important because it may have treatment implications. Therefore, physicians need to know the distinct characteristics of this asthma phenotype. The objective of the present study was to determine the characteristic profile of patients with adult-onset eosinophilic asthma. 130 patients with adult-onset (>18 years of age) asthma and high blood eosinophil counts (≥0.3×10(9) L(-1)) were compared with 361 adult-onset asthma patients with low (<0.3×10(9) L(-1)) blood eosinophils. Measurements included a series of clinical, functional and imaging parameters. Patients with high blood eosinophils were more often male, had less well controlled asthma and higher exacerbation rates, despite the use of higher doses of inhaled corticosteroids. They had higher levels of total IgE without more sensitisation to common inhaled allergens. In addition, these patients had worse lung function, and more often showed fixed airflow limitation, air trapping, nasal polyposis and abnormalities on sinus computed tomography scanning. Chronic rhinosinusitis, air trapping and male sex were three independent factors associated with blood eosinophilia (adjusted OR 3.8 (95% CI 1.7-8.1), 3.0 (95% CI 1.1-8.1) and 2.4 (95% CI 1.3-4.4), respectively). Patients with adult-onset asthma with elevated blood eosinophils exhibit a distinct profile, which can readily be recognised in clinical practice.

  14. Clinicopathological features of adult-onset neuronal intranuclear inclusion disease

    PubMed Central

    Sone, Jun; Mori, Keiko; Inagaki, Tomonori; Katsumata, Ryu; Takagi, Shinnosuke; Yokoi, Satoshi; Araki, Kunihiko; Kato, Toshiyasu; Nakamura, Tomohiko; Koike, Haruki; Takashima, Hiroshi; Hashiguchi, Akihiro; Kohno, Yutaka; Kurashige, Takashi; Kuriyama, Masaru; Takiyama, Yoshihisa; Tsuchiya, Mai; Kitagawa, Naoyuki; Kawamoto, Michi; Yoshimura, Hajime; Suto, Yutaka; Nakayasu, Hiroyuki; Uehara, Naoko; Sugiyama, Hiroshi; Takahashi, Makoto; Kokubun, Norito; Konno, Takuya; Katsuno, Masahisa; Tanaka, Fumiaki; Iwasaki, Yasushi; Yoshida, Mari

    2016-01-01

    Neuronal intranuclear inclusion disease (NIID) is a slowly progressive neurodegenerative disease characterized by eosinophilic hyaline intranuclear inclusions in the central and peripheral nervous system, and also in the visceral organs. NIID has been considered to be a heterogeneous disease because of the highly variable clinical manifestations, and ante-mortem diagnosis has been difficult. However, since we reported the usefulness of skin biopsy for the diagnosis of NIID, the number of NIID diagnoses has increased, in particular adult-onset NIID. In this study, we studied 57 cases of adult-onset NIID and described their clinical and pathological features. We analysed both NIID cases diagnosed by post-mortem dissection and by ante-mortem skin biopsy based on the presence of characteristic eosinophilic, hyaline and ubiquitin-positive intanuclear inclusion: 38 sporadic cases and 19 familial cases, from six families. In the sporadic NIID cases with onset age from 51 to 76, dementia was the most prominent initial symptom (94.7%) as designated ‘dementia dominant group’, followed by miosis, ataxia and unconsciousness. Muscle weakness and sensory disturbance were also observed. It was observed that, in familial NIID cases with onset age less than 40 years, muscle weakness was seen most frequently (100%), as designated ‘limb weakness group’, followed by sensory disturbance, miosis, bladder dysfunction, and dementia. In familial cases with more than 40 years of onset age, dementia was most prominent (100%). Elevated cerebrospinal fluid protein and abnormal nerve conduction were frequently observed in both sporadic and familial NIID cases. Head magnetic resonance imaging showed high intensity signal in corticomedullary junction in diffusion-weighted image in both sporadic and familial NIID cases, a strong clue to the diagnosis. All of the dementia dominant cases presented with this type of leukoencephalopathy on head magnetic resonance imaging. Both sporadic and

  15. Adult onset pigmentary orthochromatic leukodystrophy with ovarian dysgenesis.

    PubMed

    Verghese, J; Weidenheim, K; Malik, S; Rapin, I

    2002-11-01

    Pigmentary type of orthochromatic leukodystrophy (POLD) is an adult-onset leukodystrophy, characterized pathologically by the presence of glial and microglial cytoplasmic pigment inclusions. The complete phenotype, genotype and pathogenetic mechanisms in POLD have not been elucidated. We followed for 18 years a woman with autopsy-proven POLD, who presented with 'frontal' dementia and spasticity. Her further course was marked by progressive mutism, apraxia and seizures. Her sister had died of the same disease after a much more rapidly progressing course. These sisters had primary infertility with pathologic evidence of streak ovaries. Diagnosis was confirmed in both cases by post-mortem examination. POLD is a rare cause of adult-onset leukodystrophy presenting with dementia. Ovarian dysgenesis is extremely rare in the absence of demonstrable chromosomal abnormalities and extends the clinical spectrum of POLD.

  16. Season of Birth and Risk for Adult Onset Glioma

    PubMed Central

    Efird, Jimmy T.

    2010-01-01

    Adult onset glioma is a rare cancer which occurs more frequently in Caucasians than African Americans, and in men than women. The etiology of this disease is largely unknown. Exposure to ionizing radiation is the only well established environmental risk factor, and this factor explains only a small percentage of cases. Several recent studies have reported an association between season of birth and glioma risk. This paper reviews the plausibility of evidence focusing on the seasonal interrelation of farming, allergies, viruses, vitamin D, diet, birth weight, and handedness. To date, a convincing explanation for the occurrence of adult gliomas decades after a seasonal exposure at birth remains elusive. PMID:20623001

  17. New onset diabetes mellitus induced by statins: current evidence.

    PubMed

    Chrysant, Steven G

    2017-02-24

    The hydroxyl-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase inhibitors of statin action are very effective and safe drugs, and they are widely used for the treatment of hyperlipidemia and the prevention of primary and secondary cardiovascular diseases (CVDs). However, recent meta-analyses of previous studies done with statins have shown that these drugs could induce new onset diabetes mellitus (NODM), especially in subjects prone to diabetes: obese, females, older age, Asian descent, and those with pre-diabetes or the metabolic syndrome. Several meta-analyses of randomized, controlled trials with statins and population-based studies of subjects taking statins have shown different incidence of NODM ranging from 28% in the JUPITER study to 43% in the UK clinical practice cohort. The exact cause of statin-induced NODM is not clearly known and several pathophysiologic mechanisms have been proposed, which include modification of the lipoprotein particle size, inhibition of HMG-CoA reductase, decreased expression of GLUT 4, and decreased adiponectin and ubiquinone levels, including others, which all lead to either increase in insulin resistance or decrease in insulin secretion. Based on the current evidence, the use of statins should not be withheld from subjects at high cardiovascular risk, even if they are prone to NODM, because their benefits outweigh their risks. However, in persons prone to the development of NODM, vigilance is required and periodic measurements of plasma glucose or HbA1c should be performed. If NODM develops, statin treatment should not be stopped, but a switch to administration of a more favorable statin, administration of statin on alternate days, or reduction of the dose should be considered, or antidiabetic therapy added.

  18. Characterization of peripheral regulatory CD4+ T cells that prevent diabetes onset in nonobese diabetic mice.

    PubMed

    Lepault, F; Gagnerault, M C

    2000-01-01

    The period that precedes onset of insulin-dependent diabetes mellitus corresponds to an active dynamic state in which pathogenic autoreactive T cells are kept from destroying beta cells by regulatory T cells. In prediabetic nonobese diabetic (NOD) mice, CD4+ splenocytes were shown to prevent diabetes transfer in immunodeficient NOD recipients. We now demonstrate that regulatory splenocytes belong to the CD4+ CD62Lhigh T cell subset that comprises a vast majority of naive cells producing low levels of IL-2 and IFN-gamma and no IL-4 and IL-10 upon in vitro stimulation. Consistently, the inhibition of diabetes transfer was not mediated by IL-4 and IL-10. Regulatory cells homed to the pancreas and modified the migration of diabetogenic to the islets, which resulted in a decreased insulitis severity. The efficiency of CD62L+ T cells was dose dependent, independent of sex and disease prevalence. Protection mechanisms did not involve the CD62L molecule, an observation that may relate to the fact that CD4+ CD62Lhigh lymph node cells were less potent than their splenic counterparts. Regulatory T cells were detectable after weaning and persist until disease onset, sustaining the notion that diabetes is a late and abrupt event. Thus, the CD62L molecule appears as a unique marker that can discriminate diabetogenic (previously shown to be CD62L-) from regulatory T cells. The phenotypic and functional characteristics of protective CD4+ CD62L+ cells suggest they are different from Th2-, Tr1-, and NK T-type cells, reported to be implicated in the control of diabetes in NOD mice, and may represent a new immunoregulatory population.

  19. New onset of idiopathic bilateral ear tics in an adult.

    PubMed

    Agrawal, Amit; Shrestha, Rabin

    2009-04-01

    Tic disorders are commonly considered to be childhood syndromes. Newly presenting tic disorders during adulthood are uncommon and mostly described in relation to an acquired brain lesion or as incidental tics, particularly in context with other neurological or psychiatric diseases. Tic disorder involving the ears is extremely uncommon with only few studies in English literature. In the present case, we describe an adult patient with new-onset idiopathic tics disorder involving both ears, causing social embarrassment. In addition, our patient had recent onset of the tics without any childhood or family history of tic disorders. The single most important component of management is an accurate diagnosis. At the same time, tics should be differentiated from other movement disorders such as chorea, stereotypy, and dystonias.

  20. Diabetes Resources for Older Adults

    MedlinePlus

    ... Story Sandra’s Story Promotional Tools for Managing Diabetes Contact Us Health Information Center Phone: 1-800-860- ... encourages people to share this content freely. [ Top ] Contact Us Health Information Center Phone: 1-800-860- ...

  1. Hepatitis A infection mimicking adult onset Still's disease.

    PubMed

    Sridharan, S; Mossad, S; Hoffman, G

    2000-07-01

    Fever, rash, and arthritis may be components of the prodrome of viral hepatitis. In the absence of jaundice and abnormal liver function tests, this form of polyarthritis is easily confused with primary autoimmune diseases. Whereas the association of systemic illness with musculoskeletal symptoms and numerous viral infections is well known, such an association with hepatitis A has only been rarely reported. We describe a case of hepatitis A infection mimicking adult onset Still's disease, and review the pathogenesis and differential diagnosis of Still's disease and the extraarticular manifestations of hepatitis.

  2. Type II diabetes of early onset: a distinct clinical and genetic syndrome?

    PubMed Central

    O'Rahilly, S; Spivey, R S; Holman, R R; Nugent, Z; Clark, A; Turner, R C

    1987-01-01

    The inheritance of non-insulin-dependent (type II) diabetes was studied by a continuous infusion of glucose test in all available first degree relatives of 48 diabetic probands of various ages and with differing severity of disease. In an initial study of 38 type II diabetic subjects and their first degree relatives six islet cell antibody negative patients with early onset disease (aged 25-40 at diagnosis) were found to have a particularly high familial prevalence of diabetes or glucose intolerance. Nine of 10 parents available for study either had type II diabetes or were glucose intolerant. A high prevalence of diabetes or glucose intolerance was also found in their siblings (11/16;69%). In a second study of the families of a further 10 young diabetic probands (presenting age 25-40) whose islet cell antibody state was unknown a similar high prevalence of diabetes or glucose intolerance was found among parents of the five islet cell antibody negative probands (8/9; 89%) but not among parents of the five islet cell antibody positive probands (3/8;38%). Islet cell antibody negative diabetics with early onset type II disease may have inherited a diabetogenic gene or genes from both parents. They commonly need insulin to maintain adequate glycaemic control and may develop severe diabetic complications. Early onset type II diabetes may represent a syndrome in which characteristic pedigrees, clinical severity, and absence of islet autoimmunity make it distinct from either type I diabetes, maturity onset diabetes of the young, or late onset type II diabetes. PMID:3107658

  3. Predicting abscesses in adults with community-onset monomicrobial Enterobacteriaceae bacteremia: microorganisms matters.

    PubMed

    Lee, Chung-Hsun; Lee, Ching-Chi; Hsieh, Chih-Chia; Hong, Ming-Yuan; Chi, Chih-Hsien

    2016-01-01

    Enterobacteriaceae is a leading pathogen of community-onset bacteremia. This study aims to establish a predictive scoring algorithm to identify adults with community-onset Enterobacteriaceae bacteremia who are at risk for abscesses. Of the total 1262 adults, 152 (12.0%) with abscess occurrence were noted. The 6 risk factors significantly associated with abscess occurrence-liver cirrhosis, diabetes mellitus, thrombocytopenia and high C-reactive protein (>100 mg/L) at bacteremic onset, delayed defervescence, and bacteremia-causing Klebsiella pneumoniae-were each assigned +1 point to form the scoring algorithm. In contrast, the elderly, fatal comorbidity (McCabe classification), and bacteremia-causing Escherichia coli were each assigned -1 point, owing to their negative associations with abscess occurrence. Using the proposed scoring algorithm, a cut-off value of +1 yielded a high sensitivity (85.5%) and an acceptable specificity (60.4%). Although the proposed predictive model needs further validation, this simple scoring algorithm may be useful for the early identification of abscesses by clinicians.

  4. Relationship between Inpatient Hyperglycemia and Insulin Treatment after Kidney Transplantation and Future New Onset Diabetes Mellitus

    PubMed Central

    Knowler, William C.; Devarapalli, Yugandhara; Weil, E. Jennifer; Heilman, Raymond L.; Dueck, Amylou; Mulligan, David C.; Reddy, Kunam S.; Moss, Adyr A.; Mekeel, Kristin L.; Mazur, Marek J.; Hamawi, Khaled; Castro, Janna C.; Cook, Curtiss B.

    2010-01-01

    Background and objectives: Approximately two-thirds of kidney transplant recipients with no previous history of diabetes experience inpatient hyperglycemia immediately after kidney transplant surgery; whether inpatient hyperglycemia predicts future new onset diabetes after transplant (NODAT) is not established. Design, setting, participants, & measurements: A retrospective study was conducted to determine the risk conferred by inpatient hyperglycemia on development of NODAT within 1 year posttransplant. All adult nondiabetic kidney transplant recipients between June 1999 and January 2008 were included. Posttransplant inpatient hyperglycemia was defined as any bedside capillary blood glucose ≥ 200 mg/dl or insulin therapy during hospitalization. NODAT was defined as HbA1C ≥ 6.5%, fasting venous serum glucose ≥ 126 mg/dl, or prescribed diet or medical therapy for diabetes mellitus. Results: The study cohort included 377 patients. NODAT developed in 1 (4%) of the 28 patients without inpatient hyperglycemia, 4 (18%) of the 22 patients with inpatient hyperglycemia but not treated with insulin, and in 98 (30%) of the 327 of the patients who were diagnosed with inpatient hyperglycemia and were treated with insulin. In adjusted analyses, requirement of insulin therapy during hospitalization posttransplant was associated with a 4-fold increase in NODAT (relative risk 4.01; confidence interval, 1.49 to 10.7; P = 0.006). Conclusion: Development of inpatient hyperglycemia after kidney transplantation in nondiabetic patients significantly increased the risk of NODAT. Additionally, we observed a significantly increased risk of cardiovascular events in patients who developed NODAT. PMID:20558559

  5. Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy

    PubMed Central

    Yu, Hsu-Sheng; Tu, Hung-Pin; Hong, Chien-Hui; Lee, Chih-Hung

    2016-01-01

    Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD. PMID:28035995

  6. Diabetes Onset at 31–45 Years of Age is Associated with an Increased Risk of Diabetic Retinopathy in Type 2 Diabetes

    PubMed Central

    Zou, Wenjun; Ni, Lisha; Lu, Qianyi; Zou, Chen; Zhao, Minjie; Xu, Xun; Chen, Haibing; Zheng, Zhi

    2016-01-01

    This hospital-based, cross-sectional study investigated the effect of age of diabetes onset on the development of diabetic retinopathy (DR) among Chinese type 2 diabetes mellitus (DM) patients. A total of 5,214 patients with type 2 DM who were referred to the Department of Ophthalmology at the Shanghai First People’s Hospital from 2009 to 2013 was eligible for inclusion. Diabetic retinopathy status was classified using the grading system of the Early Treatment Diabetic Retinopathy Study (ETDRS). Logistic and hierarchical regression analyses were used to identify independent variables affecting the development of DR. Upon multiple logistic regression analysis, patient age at the time of diabetes onset was significantly associated with development of DR. Further, when the risk of retinopathy was stratified by patient age at the onset of diabetes, the risk was highest in patients in whom diabetes developed at an age of 31–45 years (odds ratio [OR] 1.815 [1.139–2.892]; p = 0.012). Furthermore, when patients were divided into four groups based on the duration of diabetes, DR development was maximal at a diabetes onset age of 31–45 years within each group. A diabetes onset age of 31–45 years is an independent risk factor for DR development in Chinese type 2 DM patients. PMID:27897261

  7. Influenza immunization in adults with diabetes mellitus.

    PubMed

    Feery, B J; Hartman, L J; Hampson, A W; Proietto, J

    1983-01-01

    The antibody responses to influenza vaccination of a group of adult diabetic patients were compared with responses in a healthy group of regular volunteer vaccinees. The initial and final geometric mean hemagglutination-inhibiting antibody titers were lower in the patient group, but the relative increase in titers was greater for each of the vaccine components. The percentage of fourfold rises in individual titers was greater in the diabetic group than in the control group. It was concluded that patients with diabetes mellitus responded normally to influenza vaccination. This was confirmed in an additional study. There was no significant difference in the antibody responses of patients treated with insulin or oral antidiabetic agents. There was no impairment of diabetic control as a result of influenza vaccination when this was evaluated by measuring the concentration of glycosylated hemoglobin, or by random blood glucose estimations. There was no significant change in the serum insulin level after immunization in patients on oral diabetic agents. It was concluded that influenza vaccination was safe and effective in adult diabetic patients.

  8. Type 2 Diabetes

    MedlinePlus

    Type 2 diabetes Overview By Mayo Clinic Staff Type 2 diabetes, once known as adult-onset or noninsulin-dependent ... your body's important source of fuel. With type 2 diabetes, your body either resists the effects of ...

  9. Academic Skills in Children with Early-Onset Type 1 Diabetes: The Effects of Diabetes-Related Risk Factors

    ERIC Educational Resources Information Center

    Hannonen, Riitta; Komulainen, Jorma; Riikonen, Raili; Ahonen, Timo; Eklund, Kenneth; Tolvanen, Asko; Keskinen, Paivi; Nuuja, Anja

    2012-01-01

    Aim: The study aimed to assess the effects of diabetes-related risk factors, especially severe hypoglycaemia, on the academic skills of children with early-onset type 1 diabetes mellitus (T1DM). Method: The study comprised 63 children with T1DM (31 females, 32 males; mean age 9y 11mo, SD 4mo) and 92 comparison children without diabetes (40…

  10. Diabetes and Adult Day Health Services

    ERIC Educational Resources Information Center

    Dabelko, Holly I.; DeCoster, Vaughn A.

    2007-01-01

    The purpose of this study is to provide a profile of individuals with diabetes who receive services in adult day centers. This exploratory study uses an administrative data set (N = 280) from five programs in central Ohio to examine four areas: demographics, health and mental health, financial and social resources, and disenrollment status. Older…

  11. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening

    PubMed Central

    Lazzeri, L.; Cammi, A.; Dragoni, F.

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients. PMID:27747240

  12. Adult Onset Vitiligo: Multivariate Analysis Suggests the Need for a Thyroid Screening.

    PubMed

    Lazzeri, L; Colucci, R; Cammi, A; Dragoni, F; Moretti, S

    2016-01-01

    Background. There are limited epidemiological studies evaluating the effect of age at onset on disease features in vitiligo. Objectives. To identify factors associated with adult onset vitiligo in comparison with childhood onset vitiligo. Patients and Methods. We retrospectively collected medical records of 191 patients. Such records included clinical examination, personal and familial medical history, laboratory evaluations, concomitant vitiligo treatment and drug assumption. Results. 123 patients with a disease onset after the age of 40 (adult onset vitiligo) were compared with 68 patients who developed vitiligo before the age of 12 (childhood onset vitiligo). Multivariate analysis revealed that personal history of thyroid diseases (P = 0.04; OR 0.4), stress at onset (P = 0.002; OR = 0.34), personal history of autoimmune thyroid disease (ATD) (P = 0.003; OR = 0.23), and thyroid nodules (P = 0.001; OR 0.90) were independently associated with adult onset vitiligo, whereas family history of dermatological diseases (P = 0.003; OR = 2.87) and Koebner phenomenon (P < 0.001; OR = 4.73) with childhood onset vitiligo. Moreover, in the adult onset group, concomitant thyroid disease preceded vitiligo in a statistically significant number of patients (P = 0.014). Conclusions. Childhood onset and adult onset vitiligo have different clinical features. In particular, ATD and thyroid nodules were significantly associated with adult onset vitiligo, suggesting that a thyroid screening should be recommended in this group of patients.

  13. Acute Versus Progressive Onset of Diabetes in NOD Mice: Potential Implications for Therapeutic Interventions in Type 1 Diabetes.

    PubMed

    Mathews, Clayton E; Xue, Song; Posgai, Amanda; Lightfoot, Yaima L; Li, Xia; Lin, Andrea; Wasserfall, Clive; Haller, Michael J; Schatz, Desmond; Atkinson, Mark A

    2015-11-01

    Most natural history models for type 1 diabetes (T1D) propose that overt hyperglycemia results after a progressive loss of insulin-secreting β-cell mass and/or function. To experimentally address this concept, we prospectively determined morning blood glucose measurements every other day in multiple cohorts (total n = 660) of female NOD/ShiLtJ mice starting at 8 weeks of age until diabetes onset or 26 weeks of age. Consistent with this notion, a majority of mice that developed diabetes (354 of 489 [72%]) displayed a progressive increase in blood glucose with transient excursions >200 mg/dL, followed by acute and persistent hyperglycemia at diabetes onset. However, 135 of the 489 (28%) diabetic animals demonstrated normal glucose values followed by acute (i.e., sudden) hyperglycemia. Interestingly, diabetes onset occurred earlier in mice with acute versus progressive disease onset (15.37 ± 0.3207 vs. 17.44 ± 0.2073 weeks of age, P < 0.0001). Moreover, the pattern of onset (i.e., progressive vs. acute) dramatically influenced the ability to achieve reversal of T1D by immunotherapeutic intervention, with increased effectiveness observed in situations of a progressive deterioration in euglycemia. These studies highlight a novel natural history aspect in this animal model, one that may provide important guidance for the selection of subjects participating in human trials seeking disease reversal.

  14. Reversal of new-onset type 1 diabetes in mice by syngeneic bone marrow transplantation.

    PubMed

    Wen, Yanting; Ouyang, Jian; Yang, Rong; Chen, Junhao; Liu, Yong; Zhou, Xiaojun; Burt, Richard K

    2008-09-19

    Autologous hematopoietic stem cell transplantation (HSCT) has recently been performed as a novel strategy to treat patients with new-onset type 1 diabetes (T1D). However, the mechanism of autologous HSCT-induced remission of diabetes remains unknown. In order to help clarify the mechanism of remission-induction following autologous HSCT in patients with T1D, mice treated with multiple low doses of streptozotocin to induce diabetes were used as both donors (n=20) and recipients (n=20). Compared to streptozocin-treated mice not receiving transplantation, syngeneic bone marrow transplantation (syn-BMT) from a streptozocin-treated diabetic donor, if applied during new-onset T1D (day 10 after diabetes onset), can reverse hyperglycemia without relapse (P<0.001), maintain normal blood insulin levels (P<0.001), and preserve islet cell mass. Compared to diabetic mice not undergoing HSCT, syn-BMT, results in restoration of Tregs in spleens (P<0.01), increased Foxp3 mRNA expression (P<0.01) and increased Foxp3 protein expression (P<0.05). This diabetic-remission-inducing effect occurred in mice receiving bone marrow from either streptozocin-treated diabetic or non-diabetic normal donors. We conclude that autologous HSCT remission of diabetes is more than transient immune suppression, and is capable of prolonged remission-induction via regeneration of CD4+CD25+FoxP3+ Tregs.

  15. Autoimmune diabetes not requiring insulin at diagnosis (latent autoimmune diabetes of the adult): definition, characterization, and potential prevention.

    PubMed

    Pozzilli, P; Di Mario, U

    2001-08-01

    Type 1 diabetes is caused by the immune-mediated destruction of islet insulin-secreting beta-cells. This chronic destructive process is associated with both cellular and humoral immune changes in the peripheral blood that can be detected months or even years before the onset of clinical diabetes. Throughout this prediabetic period, metabolic changes, including altered glucose tolerance and reduced insulin secretion, deteriorate at variable rates and eventually result in clinical diabetes. A fraction of individuals with humoral immunological changes have clinical diabetes that initially is not insulin-requiring. The onset of diabetes in these patients is usually in adult life, and because their diabetes is at least initially not insulin-requiring, they appear clinically to be affected by type 2 diabetes. Such patients probably have the same disease process as patients with type 1 diabetes in that they have similar HLA genetic susceptibility as well as autoantibodies to islet antigens, low insulin secretion, and a higher rate of progression to insulin dependency. These patients are defined as being affected by an autoimmune type of diabetes not requiring insulin at diagnosis, which is also named latent autoimmune diabetes of the adult (LADA). Special attention should be paid to diagnose such patients because therapy may influence the speed of progression toward insulin dependency, and in this respect, efforts should be made to protect residual C-peptide secretion. LADA can serve as a model for designing new strategies for prevention of type 1 diabetes but also as a target group for prevention in its own right.

  16. Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus.

    PubMed

    Williams, Kristen M; Fazzio, Pamela; Oberfield, Sharon E; Gallagher, Mary P; Aranoff, Gaya S

    2017-02-01

    There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age ( P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 µg/dL, with a range of 7.8 to 119 µg/dL. Cortisol levels were found to be inversely associated with serum pH ( P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 µg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA.

  17. Maturity-Onset Diabetes of the Young: What Do Clinicians Need to Know?

    PubMed Central

    2015-01-01

    Maturity-onset diabetes of the young (MODY) is a monogenic form of diabetes that is characterized by an early onset, autosomal dominant mode of inheritance and a primary defect in pancreatic β-cell function. MODY represents less than 2% of all diabetes cases and is commonly misdiagnosed as type 1 or type 2 diabetes mellitus. At least 13 MODY subtypes with distinct genetic etiologies have been identified to date. A correct genetic diagnosis is important as it often leads to personalized treatment for those with diabetes and enables predictive genetic testing for their asymptomatic relatives. Next-generation sequencing may provide an efficient method for screening mutations in this form of diabetes as well as identifying new MODY genes. In this review, I discuss a current update on MODY in the literatures and cover the studies that have been performed in Korea. PMID:26706916

  18. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease

    PubMed Central

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María.L.; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A.; Hernández, María V.; Sifuentes-Giraldo, Walter A.; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R.; Moreno, Mireia; Fiter, Jordi; Riscos, Marina de los; Carreira, Patricia; Rodriguez-Valls, María J.; González-Vela, M. Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A.

    2015-01-01

    Abstract Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2–6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3–47.5] mg/day at ANK onset to 5 [0–10] at 12 months. After a median [IQR] follow-up of 16 [5–50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations. PMID:26426623

  19. Refractory Genital HPV Infection and Adult-Onset Still Disease

    PubMed Central

    Yu, Xin; Zheng, Heyi

    2016-01-01

    Abstract Adult-onset Still disease (AOSD) is a systemic autoimmune disease (AIID) that can develop after exposure to infectious agents. Genital human papillomavirus (HPV) infection has been reported to induce or exacerbate AIIDs, such as systemic lupus erythematosus (SLE). No guidelines are available for the management of genital warts in AOSD. Case report and literature review. We report a patient who was diagnosed AOSD in the setting of refractory and recurrent genital HPV infection, demonstrating a possible link between HPV infection and AOSD. In addition, we also discuss the management of genital warts in patients with AOSD. To the best of our knowledge, no previous cases of AOSD with genital HPV infection have been reported in literature. We then conclude that the patient AOSD may be triggered by primary HPV infection. Larger number of patient samples is needed to confirm whether HPV could trigger AOSD. PMID:27082556

  20. Statins and risk for new-onset diabetes mellitus

    PubMed Central

    Yoon, Dukyong; Sheen, Seung Soo; Lee, Sukhyang; Choi, Yong Jun; Park, Rae Woong; Lim, Hong-Seok

    2016-01-01

    Abstract Although concern regarding the increased risk for new-onset diabetes mellitus (NODM) after statin treatment has been raised, there has been a lack of evidence in real-world clinical practice, particularly in East Asians. We investigated whether statin use is associated with risk for NODM in Koreans. We conducted a retrospective cohort study using the clinical research database from electronic health records. The study cohort consisted of 8265 statin-exposed and 33,060 matched nonexposed patients between January 1996 and August 2013. Matching at a 1:4 ratio was performed using a propensity score based on age, gender, baseline glucose levels (mg/dL), and hypertension. The comparative risks for NODM with various statins (atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) were estimated by both statin exposure versus matched nonexposed and within-class comparisons. The incidence of NODM among the statin-exposed group (6.000 per 1000 patient-years [PY]) was higher than that of the nonexposed group (3.244 per 1000 PY). The hazard ratio (HR) of NODM after statin exposure was 1.872 (95% confidence interval [CI], 1.432–2.445). Male gender (HR, 1.944; 95% CI, 1.497–2.523), baseline glucose per mg/dL (HR, 1.014; 95% CI, 1.013–1.016), hypertension (HR, 2.232; 95% CI, 1.515–3.288), and thiazide use (HR, 1.337; 95% CI, 1.081–1.655) showed an increased risk for NODM, while angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker showed a decreased risk (HR, 0.774; 95% CI, 0.668–0.897). Atorvastatin-exposed patients showed a higher risk for NODM than their matched nonexposed counterparts (HR, 1.939; 95% CI, 1.278–2.943). However, the risk for NODM was not significantly different among statins in within-class comparisons. In conclusion, an increased risk for NODM was observed among statin users in a practical healthcare setting in Korea. PMID:27861386

  1. Diabetes in Utah among adults: interaction between diabetes and other risk factors for microvascular and macrovascular complications.

    PubMed Central

    Schumacher, M C; Smith, K R

    1988-01-01

    From a telephone survey of the health status of a random sample of the general population of Utah, we identified 255 people with adult onset diabetes. We compared them to 622 non-diabetic controls, matched for age, sex, and urban/rural country of residence. We examined diabetes as a risk factor for heart diseases, stroke, and blindness and its interaction with other known risk factors. Diabetes interacted with smoking history so as to increase the risk of stroke, heart disease, and blindness. Diabetes also interacted with hypertension in their effect on the prevalence of blindness and, to a small extent, heart disease. Among the diabetics, duration of diabetes was associated with macrovascular and microvascular complications developing after the diagnosis of diabetes. Those with longer duration of disease showed an increase in risk for microvascular (kidney disease, blindness) and macrovascular (heart disease, stroke, amputations) complications. Although the estimates were imprecise, the effect of duration on macrovascular complications was greater among diabetics with a history of hypertension; the effect on microvascular complications was greater among smokers. The findings are compared to previous studies and the utility of diabetes prevalence data is discussed. PMID:3407819

  2. Acute-Onset Type 1 Diabetes that Developed During the Administration of Olanzapine

    PubMed Central

    Iwaku, Kenji; Otuka, Fumiko; Taniyama, Matsuo

    2017-01-01

    The patient was 32-year-old man, who received olanzapine for schizophrenia and developed polyuria and thirst without drinking soft-drinks after 4 months. Five months after the initiation of treatment, he developed diabetic ketoacidosis (blood glucose: 490 mg/dL, HbA1c: 15.5%). He was diagnosed with type 1 diabetes (glutamic acid decarboxylase (GAD)-Ab: 5.6 U/mL, IA-2 Ab: 5.9 U/mL, fasting C-peptide: 0.12 ng/mL) and was put on intensive insulin therapy. At four months after the onset of 1A diabetes, he experienced a honeymoon phase that was sustained until the 40th month of treatment. We hypothesize that the administration of olanzapine to a patient with pre-type 1A diabetes induced marked hyperglycemia and accelerated the onset of type 1A diabetes. PMID:28154279

  3. Childhood adversities and adult-onset asthma: a cohort study

    PubMed Central

    Korkeila, Jyrki; Lietzen, Raija; Sillanmäki, Lauri H; Rautava, Päivi; Korkeila, Katariina; Kivimäki, Mika; Koskenvuo, Markku; Vahtera, Jussi

    2012-01-01

    Objectives Childhood adversities may be important determinants of later illnesses and poor health behaviour. However, large-scale prospective studies on the associations between childhood adversities and the onset of asthma in adulthood are lacking. Design Prospective cohort study with 7-year follow-up. Setting Nationally representative study. Data were collected from the Health and Social Support (HeSSup) survey and national registers. Participants The participants represent the Finnish population from the following age groups: 20–24, 30–34, 40–44, and 50–54 years at baseline in 1998 (24 057 survey participants formed the final cohort of this study). The occurrence of childhood adversities was assessed at baseline with a six-item survey scale. The analyses were adjusted for sociodemographic characteristics, behavioural health risks and common mental disorders. Primary and secondary outcomes The survey data were linked to data from national health registers on incident asthma during a 7-year follow-up to define new-onset asthma cases with verified diagnoses. Results A total of 12 126 (59%) participants reported that they encountered a childhood adversity. Of them 3677 (18% of all) endured three to six adversities. During a follow-up of 7 years, 593 (2.9%) participants were diagnosed with incident asthma. Those who reported three or more childhood adversities had a 1.6-fold (95% CI 1.31 to 2.01) greater risk of asthma compared to those without childhood adversities. This hazard attenuated but remained statistically significant after adjustment for conventional risk factors (HR 1.33; 95% CI 1.06 to 1.67). Conclusions Adults who report having encountered adversities in childhood may have an increased risk of developing asthma. PMID:23069774

  4. Parenchymal lung involvement in adult-onset Still disease

    PubMed Central

    Gerfaud-Valentin, Mathieu; Cottin, Vincent; Jamilloux, Yvan; Hot, Arnaud; Gaillard-Coadon, Agathe; Durieu, Isabelle; Broussolle, Christiane; Iwaz, Jean; Sève, Pascal

    2016-01-01

    Abstract Parenchymal lung involvement (PLI) in adult-onset Still's disease (AOSD) has seldom, if ever, been studied. We examine here retrospective cohort AOSD cases and present a review of the literature (1971–2014) on AOSD-related PLI cases. Patients with PLI were identified in 57 AOSD cases. For inclusion, the patients had to fulfill Yamaguchi or Fautrel classification criteria, show respiratory symptoms, and have imaging evidence of pulmonary involvement, and data allowing exclusion of infectious, cardiogenic, toxic, or iatrogenic cause of PLI should be available. This AOSD + PLI group was compared with a control group (non–PLI-complicated AOSD cases from the same cohort). AOSD + PLI was found in 3 out of the 57 patients with AOSD (5.3%) and the literature mentioned 27 patients. Among these 30 AOSD + PLI cases, 12 presented an acute respiratory distress syndrome (ARDS) and the remaining 18 another PLI. In the latter, a nonspecific interstitial pneumonia computed tomography pattern prevailed in the lower lobes, pulmonary function tests showed a restrictive lung function, the alveolar differential cell count was neutrophilic in half of the cases, and the histological findings were consistent with bronchiolitis and nonspecific interstitial pneumonia. Corticosteroids were fully efficient in all but 3 patients. Ten out of 12 ARDS cases occurred during the first year of the disease course. All ARDS-complicated AOSD cases received corticosteroids with favorable outcomes in 10 (2 deceased). Most PLIs occurred during the systemic onset of AOSD. PLI may occur in 5% of AOSDs, of which ARDS is the most severe. Very often, corticosteroids are efficient in controlling this complication. PMID:27472698

  5. Delayed onset diabetic striatopathy: Hemichorea-hemiballism one month after a hyperglycemic episode.

    PubMed

    Lin, Chiu-Jung; Huang, Poyin

    2017-02-05

    Diabetic striatopathy is an uncommon and life threatening manifestation of diabetes mellitus. It has a tendency to occur in the elderly, female and people of Asian descent. Patients usually present with hemichorea-hemiballism caused by non-ketotic hyperglycemia. However, patients could develop diabetic striatopathy weeks after the hyperglycemic event, even when blood sugar has been well controlled. Herein, we report a case of delayed onset diabetic striatopathy and discuss the importance of detailed history and brain magnetic resonance imaging for making prompt and accurate diagnosis.

  6. Prophylactic fenbendazole therapy does not affect the incidence and onset of type 1 diabetes in non-obese diabetic mice.

    PubMed

    Franke, Deanna D H; Shirwan, Haval

    2006-03-01

    Fenbendazole (FBZ) is a common, highly efficacious broad-spectrum anthelmintic drug used to treat and limit rodent pinworm infections. However, the effect of its prophylactic use on the immune response of rodents is largely undefined. The non-obese diabetic (NOD) mouse is a model commonly used to study type 1 diabetes (T1D). Parasitic infections will inhibit diabetes development in NOD mice; thus, in the presence of contamination, prophylactic treatment with anthelmintics must be considered to maintain experimental research. Herein, we investigated the prophylactic use of FBZ in NOD mice to determine its effect on the incidence and onset of diabetes, lymphocyte sub-populations and T cell proliferative responses. NOD mice were separated into control and treatment groups. The treatment group received a diet containing FBZ. Animals were monitored for the incidence and onset of T1D. At matched time points, diabetic and non-diabetic mice were killed and splenic lymphocytes analyzed for various cell sub-populations and mitogen-induced proliferative responses using flow cytometry. Treated and control mice were monitored >23 weeks with no detectable effects on the incidence or onset of diabetes. Moreover, no significant differences were detected in lymphocyte sub-populations and mitogen-induced CD4(+) and CD8(+) proliferative responses between control and treatment groups. These results suggest that prophylactic FBZ treatment does not significantly alter the incidence or onset of diabetes in NOD mice. The prophylactic use of FBZ, therefore, presents a viable approach for the prevention of pinworm infection in precious experimental animals with substantial scientific and economic benefits.

  7. New-Onset Diabetes After Acute and Critical Illness: A Systematic Review.

    PubMed

    Jivanji, Chirag J; Asrani, Varsha M; Windsor, John A; Petrov, Maxim S

    2017-03-13

    Hyperglycemia is commonly observed during acute and critical illness. Recent studies have investigated the risk of developing diabetes after acute and critical illness, but the relationship between degree of in-hospital hyperglycemia and new-onset diabetes has not been investigated. This study examines the evidence for the relationship between in-hospital hyperglycemia and prevalence of new-onset diabetes after acute and critical illness. A literature search was performed of the MEDLINE, EMBASE, and Scopus databases for relevant studies published from January 1, 2000, through August 4, 2016. Patients with no history of diabetes before hospital discharge were included in the systematic review. In-hospital glucose concentration was classified as normoglycemia, mild hyperglycemia, or severe hyperglycemia for the meta-analysis. Twenty-three studies were included in the systematic review, and 18 of these (111,078 patients) met the eligibility criteria for the meta-analysis. The prevalence of new-onset diabetes was significantly related to in-hospital glucose concentration and was 4% (95% CI, 2%-7%), 12% (95% CI, 9%-15%), and 28% (95% CI, 18%-39%) for patients with normoglycemia, mild hyperglycemia, and severe hyperglycemia, respectively. The prevalence of new-onset diabetes was not influenced by disease setting, follow-up duration, or study design. In summary, this study found stepwise growth in the prevalence of new-onset diabetes with increasing in-hospital glucose concentration. Patients with severe hyperglycemia are at the highest risk, with 28% developing diabetes after hospital discharge.

  8. Young-onset parkinsonism in a Hong Kong Chinese man with adult-onset Hallervorden-Spatz syndrome.

    PubMed

    Mak, Chloe Miu; Sheng, Bun; Lee, Hencher Han-chih; Lau, Kwok-kwong; Chan, Wing-tak; Lam, Ching-wan; Chan, Yan-wo

    2011-04-01

    Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders varied in genetic etiologies, clinical presentations, and radiological features. NBIA is an iron homeostasis disorder with progressive iron accumulation in the central nervous systems and is clinically characterized by extrapyramidal movement abnormalities, retinal pigmentary changes, and cognitive impairment. Panthothenate kinase-associated neurodegeneration (Hallervorden-Spatz disease) is the commonest disorder of NBIA with a prevalence of one-three per million. Clinically, it is classified into early-onset childhood, atypical late-onset, and adult-onset type. Adult-onset type is rarer. We report the first case of adult-onset panthothenate kinase-associated neurodegeneration in Hong Kong in a 28-year-old Chinese man who presented with pure young-onset parkinsonism. Magnetic resonance imaging (MRI) of the brain showed the presence of eye-of-the-tiger sign. Two compound heterozygous mutations PANK2 NM_153638.2: c.445G > T; NP_705902.2: p.E149X and PANK2 NM_153638.2: c.1133A > G; NP_705902.2: p.D378G were detected. Parkinsonism per se is a very heterogeneous phenotypic group. In view of the readily available genetic analysis of PANK2, panthothenate kinase-associated neurodegeneration should be considered in adult patients with young-onset parkinsonism with or without the eye-of-the-tiger sign. The exact diagnosis offers a different management approach and genetic counseling. NBIA is likely under- or misdiagnosed in Hong Kong Chinese.

  9. Warming up Improves Speech Production in Patients with Adult Onset Myotonic Dystrophy

    ERIC Educational Resources Information Center

    de Swart, B.J.M.; van Engelen, B.G.M.; Maassen, B.A.M.

    2007-01-01

    This investigation was conducted to study whether warming up decreases myotonia (muscle stiffness) during speech production or causes adverse effects due to fatigue or exhaustion caused by intensive speech activity in patients with adult onset myotonic dystrophy. Thirty patients with adult onset myotonic dystrophy (MD) and ten healthy controls…

  10. Periocular xanthogranulomas associated with severe adult-onset asthma.

    PubMed Central

    Jakobiec, F A; Mills, M D; Hidayat, A A; Dallow, R L; Townsend, D J; Brinker, E A; Charles, N C

    1993-01-01

    This article describes six patients who presented, usually bilaterally, with yellow-orange, elevated, indurated, and nonulcerated xanthomatous eyelid lesions, typically extending into the anterior orbital fat, and sometimes involving the extraocular muscles and the lacrimal gland. Because the eyelids remained intact and because the process did not reach the deep orbital and perioptic connective tissues, visual acuity was well preserved. There is cosmetic morbidity and occasionally motility restriction with advancing involvement of the extraocular muscles. All patients had variably severe adult-onset asthma that required treatment with systemic prednisone and inhalants. No evidence of Erdheim-Chester disease was found in any patient, but the appearance in one patient, after 25 years of follow-up, of a separate subcutaneous necrobiotic xanthogranulomatous lesion in the mandibular region with an associated paraproteinemia, suggests that at least some of our cases might be a mild form of necrobiotic xanthogranuloma. For this reason, we would suggest repeated periodic serum protein immunoelectrophoretic studies as well as evaluation for lymphoma. Therapy probably should consist of low doses of periorbital radiotherapy coupled with high doses of corticosteroids. Should this not be successful, then systemic administration of corticosteroids with chemotherapeutic agents might be efficacious, as in necrobiotic xanthogranuloma. Images FIGURE 1 FIGURE 2 FIGURE 3 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 FIGURE 9 FIGURE 10 FIGURE 11 FIGURE 12 FIGURE 13 FIGURE 14 FIGURE 15 FIGURE 16 FIGURE 17 FIGURE 18 FIGURE 19 PMID:8140711

  11. Adult onset Still’s disease with dermatopathic lymphadenopathy

    PubMed Central

    Qureshi, Ahmad Z.; AlSheef, Mohammad; Qureshi, Waqas T.; Amjad, Waseem

    2016-01-01

    Adult onset Still’s disease (AOSD) is a chronic inflammatory disorder involving multiple systems. The symptoms mimic those of lymphomas, therefore, the diagnosis of lymphoma needs to be excluded prior to establishing the diagnosis of AOSD. Another similar condition is dermatopathic lymphadenopathy (DL). In DL, the histopathological appearance of lymph node biopsy may also mimic AOSD. The DL is associated with several systemic pathologies, such as malignant lymphomas, and rarely AOSD. We present a case of a 43-year-old male presented with 3 months history of fatigue, fever, and lymphadenopathy. Initial work-up satisfactorily met the criteria for diagnosis of AOSD. But considering the well-known association of DL with hematological malignancies, detailed pathological studies were considered, including tumor markers to rule out the possibility of malignancy. The patient was started on steroids and showed remarkable recovery within 2 weeks. Evaluation of malignant lymphomas in a patient with DL is important, in order to diagnose AOSD and rule out hematological malignancy. PMID:27761568

  12. Adult-onset hypophosphatemic osteomalacia associated with Sjogren syndrome

    PubMed Central

    Shen, Guohua; Zhang, Yuwei; Hu, Shuang; Liu, Bin; Kuang, Anren

    2017-01-01

    Abstract Rationale: Hypophosphatemic osteomalacia (HO) is a metabolic bone disease, exhibiting different etiologies such as genetic mutation, tumor induction, dysimmunity, or renal disease. Sjogren's syndrome (SS) is a connective tissue disorder commonly involving exocrine glands; however kidney involvement is also encountered, leading to abnormal phosphorus metabolism, even HO. Patient concerns: A 47-year-old female patient presented progressively worsening pain in the chest wall, back and bilateral lower extremities as well as muscle weakness was referred to our department. Diagnoses, interventions and outcomes: Due to the laboratory test results, radiographic findings and pathologic results, she was diagnosed with adult-onset HO associated with SS. She was then treated with alkalinization, steroids, neutral phosphate, calcium supplements together with activated vitamin D. So far, she recovered uneventfully with relieved pain and increased serum phosphorus level. Lessons: HO may be secondary to renal tubular acidosis of SS patients, and it might be a diagnostic challenge when the kidney involvement in SS is latent and precede the typical sicca symptoms. PMID:28353596

  13. Latent Autoimmune Diabetes in Adults: a case report.

    PubMed

    Bermúdez, Valmore; Aparicio, Daniel; Colmenares, Carlos; Peñaranda, Lianny; Luti, Yettana; Gotera, Daniela; Rojas, Joselyn; Cabrera, Mayela; Reyna, Nadia; Velasco, Manuel; Israili, Zafar H

    2010-01-01

    Latent Autoimmune Diabetes in Adults (LADA) is an autoimmune endocrine disorder in which despite the presence of antipancreatic islets antibodies in the moment of diagnostics, the progression to beta-cell secretory insufficiency is slow. It is often confused with others types of diabetes and therefore the management is frequently inadequate. We report a clinical case of a 23-year-old man with diagnosis of type 2 diabetes since 6 months ago, poorly controlled with a sulfonylurea, who initially presented 2 months ago from polyuria, polydipsia, and asthenia and 6 kg weight loss. History of past illness was negative, however, his mother relates exclusive breastfeeding during the first 15 days of life and later (until the 6 months) he was fed with infant formula (S-26). Family history revealed a first-degree relative (father) with diabetes mellitus secondary to steroid administration due to diagnosis of bone marrow hypoplasia. Also presents second-degree family history (uncle and grandfather) of type 2 diabetes mellitus. There were no pathologic findings at the physical examination. Anthropometry and laboratory tests were as follows: body mass index (BMI) = 19.66 kg/m, basal and postprandial glycemia = 108, and 276 mg/dL respectively, glycated haemoglobin = 8.9%, basal and postprandial C-peptide (2 hours) = 1.9, and 3.2 ng/mL, homeostasis model assessment of beta cell function: 87.5%, homeostasis model assessment of insulin resistance: 1.6. LADA presumptive diagnosis was confirmed with presence of autoantibodies anti-tyrosin-phosphatase and GAD65. At the time of diagnosis, individuals with LADA present an onset age <50, BMI <25 kg/m2, low magnitude postprandial and basal hyperglycemia, normal or close to normal C-peptide values, and thus not occur with acute hyperglycemic crises. Insulin therapy preserves pancreatic b-cell function, at the point that eventually prescribed insulin doses need to be reduced.

  14. The IL-1β Receptor Antagonist SER140 Postpones the Onset of Diabetes in Female Nonobese Diabetic Mice

    PubMed Central

    Cucak, Helena; Hansen, Gitte; Vrang, Niels; Skarsfeldt, Torben; Steiness, Eva; Jelsing, Jacob

    2016-01-01

    The cytokine interleukin-1β (IL-1β) is known to stimulate proinflammatory immune responses and impair β-cell function and viability, all critical events in the pathogenesis of type 1 diabetes (T1D). Here we evaluate the effect of SER140, a small peptide IL-1β receptor antagonist, on diabetes progression and cellular pancreatic changes in female nonobese diabetic (NOD) mice. Eight weeks of treatment with SER140 reduced the incidence of diabetes by more than 50% compared with vehicle, decreased blood glucose, and increased plasma insulin. Additionally, SER140 changed the endocrine and immune cells dynamics in the NOD mouse pancreas. Together, the data suggest that SER140 treatment postpones the onset of diabetes in female NOD mice by interfering with IL-1β activated pathways. PMID:26953152

  15. Pediatric-Onset and Adult-Onset Separation Anxiety Disorder Across Countries in the World Mental Health Survey

    PubMed Central

    Silove, Derrick; Alonso, Jordi; Bromet, Evelyn; Gruber, Mike; Sampson, Nancy; Scott, Kate; Andrade, Laura; Benjet, Corina; de Almeida, Jose Miguel Caldas; De Girolamo, Giovanni; de Jonge, Peter; Demyttenaere, Koen; Fiestas, Fabian; Florescu, Silvia; Gureje, Oye; He, Yanling; Karam, Elie; Lepine, Jean-Pierre; Murphy, Sam; Villa-Posada, Jose; Zarkov, Zahari; Kessler, Ronald C.

    2016-01-01

    Objective The age-at-onset criterion for separation anxiety disorder was removed in DSM-5, making it timely to examine the epidemiology of separation anxiety disorder as a disorder with onsets spanning the life course, using cross-country data. Method The sample included 38,993 adults in 18 countries in the World Health Organization (WHO) World Mental Health Surveys. The WHO Composite International Diagnostic Interview was used to assess a range of DSM-IV disorders that included an expanded definition of separation anxiety disorder allowing onsets in adulthood. Analyses focused on prevalence, age at onset, comorbidity, predictors of onset and persistence, and separation anxiety-related role impairment. Results Lifetime separation anxiety disorder prevalence averaged 4.8% across countries (interquartile range [25th–75th percentiles]=1.4%–6.4%), with 43.1% of lifetime onsets occurring after age 18. Significant time-lagged associations were found between earlier separation anxiety disorder and subsequent onset of internalizing and externalizing DSM-IV disorders and conversely between these disorders and subsequent onset of separation anxiety disorder. Other consistently significant predictors of lifetime separation anxiety disorder included female gender, retrospectively reported childhood adversities, and lifetime traumatic events. These predictors were largely comparable for separation anxiety disorder onsets in childhood, adolescence, and adulthood and across country income groups. Twelve-month separation anxiety disorder prevalence was considerably lower than lifetime prevalence (1.0% of the total sample; interquartile range=0.2%–1.2%). Severe separation anxiety-related 12-month role impairment was significantly more common in the presence (42.4%) than absence (18.3%) of 12-month comorbidity. Conclusions Separation anxiety disorder is a common and highly comorbid disorder that can have onset across the lifespan. Childhood adversity and lifetime trauma are

  16. The effect of genetic counseling for adult offspring of patients with type 2 diabetes on attitudes toward diabetes and its heredity: a randomized controlled trial.

    PubMed

    Nishigaki, M; Tokunaga-Nakawatase, Y; Nishida, J; Kazuma, K

    2014-10-01

    The aim of this study is to investigate the effect of diabetes genetic counseling on attitudes toward diabetes and its heredity in relatives of type 2 diabetes patients. This study was an unmasked, randomized controlled trial at a medical check-up center in Japan. Subjects in this study are healthy adults between 30 and 60 years of age who have a family history of type 2 diabetes in their first degree relatives. Participants in the intervention group received a brief genetic counseling session for approximately 10 min. Genetic counseling was structured based on the Health Belief Model. Both intervention and control groups received a booklet for general diabetes prevention. Risk perception and recognition of diabetes, and attitude towards its prevention were measured at baseline, 1 week and 1 year after genetic counseling. Participants who received genetic counseling showed significantly higher recognition about their sense of control over diabetes onset than control group both at 1 week and 1 year after the session. On the other hand, anxiety about diabetes did not change significantly. The findings show that genetic counseling for diabetes at a medical check center helped adults with diabetes family history understand they are able to exert control over the onset of their disease through lifestyle modification.

  17. The relationships among health functioning indicators and depression in older adults with diabetes.

    PubMed

    Hu, Jie; Amoako, Emelia P; Gruber, Kenneth J; Rossen, Eileen K

    2007-02-01

    A common health problem among the elderly with diabetes is the onset of depressive symptoms that can adversely affect self-care and control of diabetes. The study examined the relationships of gender, race, comorbid conditions, symptom distress, and functional status with depression in a sample (N = 55) of older adults with diabetes. Most participants were female and black; mean age was 73 years. Gender and symptom distress were the strongest predictors of depression, accounting for 53% of the variance in depression. Although the sample was reasonably high functioning with only moderate levels of symptom distress, these findings serve as an important reminder for nurses that even moderate levels of symptom distress may be an indicator of depressive symptomatology among older diabetic adults.

  18. Interleukin 6 SNP rs1800797 associates with the risk of adult-onset asthma.

    PubMed

    Lajunen, T K; Jaakkola, J J K; Jaakkola, M S

    2016-04-01

    Interleukin 6 (IL6) is an inflammatory cytokine that has been suggested to have an important role in the pathogenesis of asthma. IL6 single-nucleotide polymorphisms (SNPs) have been associated with levels of IL6, and with childhood and prevalent adult asthma. A recent study also suggested that IL6 SNPs associate especially with atopic asthma. However, association of IL6 SNPs with adult-onset asthma has not been studied. In a population-based study of 467 incident adult-onset asthma cases and 613 disease-free controls from South Finland, we analyzed association of 6 tagging SNPs of the IL6 locus with the risk of adult-onset asthma and with atopy. Asthma was clinically diagnosed, and atopy was defined based on Phadiatop test. IL6 SNP rs1800797 associated with the risk of adult-onset asthma in a log additive model, with adjusted odds ratio (aOR) 1.31 (95% confidence interval 1.09-1.57), and especially with the risk of atopic adult-onset asthma when compared with non-atopic controls, aOR 1.46 (95% CI 1.12-1.90). This is the first study to show an association of IL6 with adult-onset asthma, and especially with atopic adult-onset asthma.

  19. The Adult Diabetic Patient: An Education Challenge

    DTIC Science & Technology

    1993-05-01

    finding that he/she, too, must care for sicker patients. To better prepare these patients for life after discharge, patient education must be initiated as...admitted, patient education often begins at the physicians’ office. This paper explores diabetes mellitus in relation to concepts of self-care and adult...betting foj.L eduuation and iio.w, wore ofteni, patient education and follow-up sercvices- a:leL beiny p~rovided on ani outpatient bcdtsis" (p. 36) . Thet

  20. Adult-onset Still's disease with atypical cutaneous manifestations

    PubMed Central

    Narváez Garcia, Francisco Javier; Pascual, María; López de Recalde, Mercè; Juarez, Pablo; Morales-Ivorra, Isabel; Notario, Jaime; Jucglà, Anna; Nolla, Joan M.

    2017-01-01

    Abstract The diagnosis of adult-onset Still's disease (AOSD) can be very difficult. There are no specific tests available, and diagnosis is usually based on a symptom complex and the well-described typical evanescent rash seen in the majority of patients. However, in recent years, other atypical cutaneous manifestations of AOSD have been reported. These atypical skin eruptions often present in addition to the typical evanescent rash but may also be the only skin manifestation, resulting in delayed diagnosis because of under-recognition. In this study, we present 3 new cases of AOSD with atypical cutaneous manifestations diagnosed during a 30-year period in our department and review 78 additional cases previously reported (PubMed 1990–2016). These 81 patients form the basis of the present analysis. The overall prevalence of atypical cutaneous manifestations in our AOSD population was 14%. These manifestations may appear at any time over the course of the disease, and usually occur in patients who have persistent and severe disease, with a considerable frequency of clinical complications (23%), including serositis, myopericarditis, lung involvement, abdominal pain, neurologic involvement, and reactive hemophagocytic syndrome. The most representative and frequent lesion among the nonclassical skin rashes is the development of persistent pruritic papules and/or plaques. Interestingly, these lesions show a distinctive histological pattern. Other, less frequently observed lesions include urticaria and urticaria-like eruptions, generalized or widespread non-pruritic persistent erythema, vesiculopustular eruptions, a widespread peau d’orange appearance of the skin, and edema of the eyelids mimicking dermatomyositis without any accompanying skin lesion. The great majority of these patients required medium or high doses of glucocorticoids (including intravenous methylprednisolone pulse therapy in some cases) and, in nearly 40%, a more potent or maintenance immunotherapy

  1. Long-Term Blood Pressure Variability, New-Onset Diabetes Mellitus, and New-Onset Chronic Kidney Disease in the Japanese General Population.

    PubMed

    Yano, Yuichiro; Fujimoto, Shouichi; Kramer, Holly; Sato, Yuji; Konta, Tsuneo; Iseki, Kunitoshi; Iseki, Chiho; Moriyama, Toshiki; Yamagata, Kunihiro; Tsuruya, Kazuhiko; Narita, Ichiei; Kondo, Masahide; Kimura, Kenjiro; Asahi, Koichi; Kurahashi, Issei; Ohashi, Yasuo; Watanabe, Tsuyoshi

    2015-07-01

    Whether long-term blood pressure (BP) variability among individuals without diabetes mellitus is associated with new-onset chronic kidney disease (CKD) risk, independently of other BP parameters (eg, mean BP, cumulative exposure to BP) and metabolic profile changes during follow-up, remains uncertain. We used data from a nationwide study of 48 587 Japanese adults aged 40 to 74 years (mean age, 61.7 years; 39% men) without diabetes mellitus or CKD (estimated glomerular filtration rate <60 mL/min per 1.73 m2 or proteinuria by dipstick). BP was measured at baseline and during 3 annual follow-up visits (4 visits). BP variability was defined as standard deviation (SD) and average real variability during the 4 visits. At the year 3 follow-up visit, 6.3% of the population had developed CKD. In multivariable-adjusted logistic regression models, 1 SD increases in SDSBP (per 5 mmHg), SDDBP (per 3 mmHg), average real variabilitySBP (per 6 mmHg), and average real variabilityDBP (per 4 mmHg) were associated with new-onset CKD (odds ratios [ORs] and 95% confidence intervals, 1.15 [1.11-1.20], 1.08 [1.04-1.12], 1.13 [1.09-1.17], 1.06 [1.02-1.10], respectively; all P<0.01) after adjustment for clinical characteristics, and with mean BP from year 0 to year 3. The associations of SDBP and average real variabilityBP with CKD remained significant after additional adjustments for metabolic parameter changes during follow-up (ORs, 1.06-1.15; all P<0.01). Sensitivity analyses by sex, antihypertensive medication use, and the presence of hypertension showed similar conclusions. Among those in the middle-aged and elderly general population without diabetes mellitus, long-term BP variability during 3 years was associated with new-onset CKD risk, independently of mean or cumulative exposure to BP and metabolic profile changes during follow-up.

  2. The Keap1-Nrf2 system prevents onset of diabetes mellitus.

    PubMed

    Uruno, Akira; Furusawa, Yuki; Yagishita, Yoko; Fukutomi, Toshiaki; Muramatsu, Hiroyuki; Negishi, Takaaki; Sugawara, Akira; Kensler, Thomas W; Yamamoto, Masayuki

    2013-08-01

    Transcription factor Nrf2 (NF-E2-related factor 2) regulates a broad cytoprotective response to environmental stresses. Keap1 (Kelch-like ECH-associated protein 1) is an adaptor protein for cullin3-based ubiquitin E3 ligase and negatively regulates Nrf2. Whereas the Keap1-Nrf2 system plays important roles in oxidative stress response and metabolism, the roles Nrf2 plays in the prevention of diabetes mellitus remain elusive. Here we show that genetic activation of Nrf2 signaling by Keap1 gene hypomorphic knockdown (Keap1flox/-) markedly suppresses the onset of diabetes. When Keap1flox/- mice were crossed with diabetic db/db mice, blood glucose levels became lower through improvement of both insulin secretion and insulin resistance. Keap1flox/- also prevented high-calorie-diet-induced diabetes. Oral administration of the Nrf2 inducer CDDO-Im {oleanolic acid 1-[2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl] imidazole} also attenuated diabetes in db/db mice. Nrf2 induction altered antioxidant-, energy consumption-, and gluconeogenesis-related gene expression in metabolic tissues. Thus, the Keap1-Nrf2 system is a critical target for preventing the onset of diabetes mellitus.

  3. Genetics Home Reference: adult-onset leukoencephalopathy with axonal spheroids and pigmented glia

    MedlinePlus

    ... it causes a severe decline in thinking and reasoning abilities (dementia). Over time, motor skills are affected, ... Schmahmann JD. Adult onset leukodystrophy with neuroaxonal spheroids: clinical, neuroimaging and neuropathologic observations. Brain Pathol. 2009 Jan; ...

  4. Pediatric diabetes consortium type 1 diabetes new onset (NeOn) study: Factors associated with HbA1c levels one year after diagnosis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To identify determinants of hemoglobin A1c (HbA1c) levels 1 yr after the diagnosis of type 1 diabetes (T1D) in participants in the Pediatric Diabetes Consortium (PDC) T1D New Onset (NeOn) Study. Diabetes-specific as well as socioeconomic factors during the first year following diagnosis were analyze...

  5. [Kimura's disease: an unrecognized cause of adult-onset nephrotic syndrome with minimal change disease].

    PubMed

    Shehwaro, N; Langlois, A-L; Gueutin, V; Debchi, L; Charlotte, F; Rouvier, P; Rottembourg, J; Izzedine, H

    2014-02-01

    Kimura's disease (KD) is an angiolymphoid proliferative disorder of soft tissue with eosinophilia, with a predilection for head and neck regions in young Oriental men. Kidney disease is thought to be rare in KD. About a case of adult-onset nephrotic syndrome with minimal change disease, we comment Kimura's disease and its associated kidney damage. Kimura disease should be suspected and included in the diagnosis of adult-onset nephrotic syndrome with minimal change disease.

  6. Commissioning specialist diabetes services for adults with diabetes: summary of a Diabetes UK Task and Finish group report.

    PubMed

    Goenka, N; Turner, B; Vora, J

    2011-12-01

    The increasing prevalence of diabetes, the drive to develop community services for diabetes and the Quality and Outcomes Framework for diabetes have led to improvements in the management of diabetes in primary care settings, with services traditionally provided only in specialist care now provided for many patients with diabetes by non-specialists. Consequently, there is a need to redefine roles, responsibilities and components of a specialist diabetes service to provide for the needs of patients in the National Health Service (NHS) today. The delivery of diabetes care is complex and touches on almost every aspect of the health service. It is the responsibility of those working within commissioning and specialist provider roles to work together with people with diabetes to develop, organize and deliver a full range of integrated diabetes care services. The local delivery model agreed within the local diabetes network, comprising specialist teams, primary care teams, commissioners and people with diabetes, should determine how the diabetes specialist services are organizsed. It should identify the roles and responsibilities of provider organizations to ensure that the right person provides the right care, at the right time, and in the right place. We summarize a report entitled 'Commissioning Diabetes Specialist Services for Adults with Diabetes', which has been produced, as a 'Task and Finish' group activity within Diabetes UK, to assist managers, commissioners and healthcare professionals to provide advice on the structure, roles and components of specialist diabetes services for adults.

  7. New-onset diabetic ketoacidosis in a 13-months old african toddler: a case report

    PubMed Central

    Katte, Jean-Claude; Djoumessi, Romance; Njindam, Gisele; Fetse, Gerard Tama; Dehayem, Mesmin; Kengne, Andre-Pascal

    2015-01-01

    Type 1 diabetes mellitus is very rare in infants and toddlers and is usually associated with high mortality when complicated with diabetic ketoacidosis (DKA). Toddlers in DKA are often missed in our typical African setting where there is low index of suspicion. Usually, the classical symptoms are not usually at the forefront and many infants and toddlers who develop DKA are mistreated for infections. The case of a 13-months old toddler with new-onset type 1 diabetes mellitus, complicated with DKA at diagnosis is reported in view of its rarity and elevated mortality even when diagnosed in our African setting. She was subsequently treated with intravenous insulin and was passed over to subcutaneous insulin after the eradication of ketones in urine. She continues follow-up at the out-patient children diabetes clinic at the Bafoussam Regional Hospital. PMID:26966489

  8. A clinical path for adult diabetes.

    PubMed

    Courtney, L; Gordon, M; Romer, L

    1997-01-01

    The use of clinical paths for patient care management was explored by this development team as a mechanism to provide consistent, high-quality care to hospitalized patients in high-volume, high-risk diagnostic categories. Reviewing the historical aspects and importance of clinical paths helped expand the team's perspective to incorporate pre- and posthospitalization phases of patient care into the clinical path being developed. A multidisciplinary team of physicians, nurses, health educators, and dietitians from both inpatient and outpatient departments of Kaiser-Santa Teresa Medical Center in San Jose, California, devised and implemented an Adult Diabetes Mellitus care path. Staff education preceded the implementation of the care paths. Measurements of quality indicators showed improvements in patient satisfaction, patient education, patient knowledge, and nutrition assessments.

  9. Raloxifene prevents skeletal fragility in adult female Zucker Diabetic Sprague-Dawley rats.

    PubMed

    Hill Gallant, Kathleen M; Gallant, Maxime A; Brown, Drew M; Sato, Amy Y; Williams, Justin N; Burr, David B

    2014-01-01

    Fracture risk in type 2 diabetes is increased despite normal or high bone mineral density, implicating poor bone quality as a risk factor. Raloxifene improves bone material and mechanical properties independent of bone mineral density. This study aimed to determine if raloxifene prevents the negative effects of diabetes on skeletal fragility in diabetes-prone rats. Adult Zucker Diabetic Sprague-Dawley (ZDSD) female rats (20-week-old, n = 24) were fed a diabetogenic high-fat diet and were randomized to receive daily subcutaneous injections of raloxifene or vehicle for 12 weeks. Blood glucose was measured weekly and glycated hemoglobin was measured at baseline and 12 weeks. At sacrifice, femora and lumbar vertebrae were harvested for imaging and mechanical testing. Raloxifene-treated rats had a lower incidence of type 2 diabetes compared with vehicle-treated rats. In addition, raloxifene-treated rats had blood glucose levels significantly lower than both diabetic vehicle-treated rats as well as vehicle-treated rats that did not become diabetic. Femoral toughness was greater in raloxifene-treated rats compared with both diabetic and non-diabetic vehicle-treated ZDSD rats, due to greater energy absorption in the post-yield region of the stress-strain curve. Similar differences between groups were observed for the structural (extrinsic) mechanical properties of energy-to-failure, post-yield energy-to-failure, and post-yield displacement. These results show that raloxifene is beneficial in preventing the onset of diabetes and improving bone material properties in the diabetes-prone ZDSD rat. This presents unique therapeutic potential for raloxifene in preserving bone quality in diabetes as well as in diabetes prevention, if these results can be supported by future experimental and clinical studies.

  10. Management of hyperosmolar hyperglycaemic state in adults with diabetes.

    PubMed

    Scott, A R

    2015-06-01

    Hyperglycaemic hyperosmolar state (HHS) is a medical emergency, which differs from diabetic ketoacidosis (DKA) and requires a different approach. The present article summarizes the recent guidance on HHS that has been produced by the Joint British Diabetes Societies for Inpatient Care, available in full at http://www.diabetologists-abcd.org.uk/JBDS/JBDS_IP_HHS_Adults.pdf. HHS has a higher mortality rate than DKA and may be complicated by myocardial infarction, stroke, seizures, cerebral oedema and central pontine myelinolysis and there is some evidence that rapid changes in osmolality during treatment may be the precipitant of central pontine myelinolysis. Whilst DKA presents within hours of onset, HHS comes on over many days, and the dehydration and metabolic disturbances are more extreme. The key points in these HHS guidelines include: (1) monitoring of the response to treatment: (i) measure or calculate the serum osmolality regularly to monitor the response to treatment and (ii) aim to reduce osmolality by 3-8 mOsm/kg/h; (2) fluid and insulin administration: (i) use i.v. 0.9% sodium chloride solution as the principal fluid to restore circulating volume and reverse dehydration, (ii) fluid replacement alone will cause a fall in blood glucose (BG) level, (iii) withhold insulin until the BG level is no longer falling with i.v. fluids alone (unless ketonaemic), (iv) an initial rise in sodium level is expected and is not itself an indication for hypotonic fluids and (v) early use of insulin (before fluids) may be detrimental; and (3) delivery of care: (i) The diabetes specialist team should be involved as soon as possible and (ii) patients should be nursed in areas where staff are experienced in the management of HHS.

  11. Peripheral blood monocyte gene expression profile clinically stratifies patients with recent-onset type 1 diabetes.

    PubMed

    Irvine, Katharine M; Gallego, Patricia; An, Xiaoyu; Best, Shannon E; Thomas, Gethin; Wells, Christine; Harris, Mark; Cotterill, Andrew; Thomas, Ranjeny

    2012-05-01

    Novel biomarkers of disease progression after type 1 diabetes onset are needed. We profiled peripheral blood (PB) monocyte gene expression in six healthy subjects and 16 children with type 1 diabetes diagnosed ∼3 months previously and analyzed clinical features from diagnosis to 1 year. Monocyte expression profiles clustered into two distinct subgroups, representing mild and severe deviation from healthy control subjects, along the same continuum. Patients with strongly divergent monocyte gene expression had significantly higher insulin dose-adjusted HbA(1c) levels during the first year, compared with patients with mild deviation. The diabetes-associated expression signature identified multiple perturbations in pathways controlling cellular metabolism and survival, including endoplasmic reticulum and oxidative stress (e.g., induction of HIF1A, DDIT3, DDIT4, and GRP78). Quantitative PCR (qPCR) of a 9-gene panel correlated with glycemic control in 12 additional recent-onset patients. The qPCR signature was also detected in PB from healthy first-degree relatives. A PB gene expression signature correlates with glycemic control in the first year after diabetes diagnosis and is present in at-risk subjects. These findings implicate monocyte phenotype as a candidate biomarker for disease progression pre- and postonset and systemic stresses as contributors to innate immune function in type 1 diabetes.

  12. Searching for Maturity-Onset Diabetes of the Young (MODY): When and What for?

    PubMed

    Timsit, José; Saint-Martin, Cécile; Dubois-Laforgue, Danièle; Bellanné-Chantelot, Christine

    2016-10-01

    Maturity-onset diabetes of the young (MODY) is a group of monogenic diseases that results in primary defects in insulin secretion and dominantly inherited forms of nonautoimmune diabetes. Although many genes may be associated with monogenic diabetes, heterozygous mutations in 6 of them are responsible for the majority of cases of MODY. Glucokinase (GCK)-MODY is due to mutations in the glucokinase gene, 3 MODY subtypes are associated with mutations in the hepatocyte nuclear factor (HNF) transcription factors, and 2 others with mutations in ABCC8 and KCNJ11, which encode the subunits of the ATP-dependent potassium channel in pancreatic beta cells. GCK-MODY and HNF1A-MODY are the most common subtypes. The clinical presentation of MODY subtypes has been reported to differ according to the gene involved, and the diagnosis of MODY may be considered in various clinical circumstances. However, except in patients with GCK-MODY whose phenotype is very homogeneous, in most cases the penetrance and expressivity of a given molecular abnormality vary greatly among patients and, conversely, alterations in various genes may lead to similar phenotypes. Moreover, differential diagnosis among more common forms of diabetes may be difficult, particularly with type 2 diabetes. Thus, careful assessment of the personal and family histories of patients with diabetes is mandatory to select those in whom genetic screening is worthwhile. The diagnosis of monogenic diabetes has many consequences in terms of prognosis, therapeutics and family screening.

  13. Predisposition to essential hypertension and renal hemodynamics in recent-onset insulin-dependent diabetic patients.

    PubMed

    Hannedouche, T P; Marques, L P; Guicheney, P; Lacour, B; Boitard, C; Grünfeld, J P

    1992-10-01

    The offspring of essential hypertensive parents have been found to exhibit abnormalities in renal hemodynamics and sodium handling before the eventual occurrence of hypertension. The reported abnormalities represent a wide spectrum of changes including increased GFR, normal or decreased RPF, slight increase in blood pressure (although within the normal range), and an exaggerated natriuresis response to a sodium load. The heterogeneity of these abnormalities may reflect the specific conditions of the studies, the lability of the changes, or different subgroups of subjects with genetic predisposition to essential hypertension. Several lines of evidence have suggested a relationship between hypertension and the development of diabetic nephropathy in insulin-dependent diabetics. This laboratory has found that recent-onset insulin-dependent diabetics can exhibit renal hemodynamics abnormalities very early in the course of diabetes according to a positive or negative family history of essential hypertension. These changes include increased GFR and mean arterial pressure, but no differences in renal sodium and lithium handling in diabetics with a genetic predisposition to essential hypertension. In addition, diabetics with a positive family history of essential hypertension exhibited a more-marked vasodilative response to an acute interruption of the renin-angiotensin system, further suggesting inadequate angiotensin modulation of renal vascular tone. The significance of these abnormalities in relation to the development of diabetic nephropathy requires further investigation.

  14. Mediterranean style diet is associated with low risk of new-onset diabetes after renal transplantation

    PubMed Central

    Osté, Maryse C J; Corpeleijn, Eva; Navis, Gerjan J; Keyzer, Charlotte A; Soedamah-Muthu, Sabita S; van den Berg, Else; Postmus, Douwe; de Borst, Martin H; Kromhout, Daan; Bakker, Stephan J L

    2017-01-01

    Objective The incidence of new-onset diabetes after transplantation (NODAT) and premature mortality is high in renal transplant recipients (RTR). We hypothesized that a Mediterranean Style diet protects against NODAT and premature mortality in RTR. Research design and methods A prospective cohort study of adult RTR with a functioning graft for >1 year. Dietary intake was assessed with a 177-item validated food frequency questionnaire. Patients were divided based on a 9-point Mediterranean Style Diet Score (MDS): low MDS (0–4 points) versus high MDS (5–9 points). A total of 468 RTR were eligible for analyses. Logistic multivariable regression analyses were used to study the association of MDS with NODAT and Cox multivariable regression models for the association with all-cause mortality. Results Mean±SD age was 51.3±13.2 years and 56.6% were men. About 50% of the patients had a high MDS. During median follow-up of 4.0 (IQR, 0.4–5.4) years, 22 (5%) RTR developed NODAT and 50 (11%) died. High MDS was significantly associated with both a lower risk of NODAT (HR=0.23; 95% CI 0.09 to 0.64; p=0.004) and all-cause mortality (HR=0.51; 95% CI 0.29 to 0.89, p=0.02) compared to low MDS, independent of age and sex. Adjustment for other potential confounders, including total energy intake, physical activity and smoking status, did not materially change the results of the analyses. Conclusions Dietary habits leading to high MDS were associated with lower risk of NODAT. These results suggest that healthy dietary habits are of paramount importance for RTR. PMID:28123752

  15. Adult onset Hallervorden-Spatz disease with psychotic symptoms.

    PubMed

    del Valle-López, Pilar; Pérez-García, Rosa; Sanguino-Andrés, Rosa; González-Pablos, Emilio

    2011-01-01

    Hallervorden-Spatz disease is a rare neurological disorder characterized by pyramidal and extrapyramidal manifestations, dysarthria and dementia. Its onset is usually in childhood and most patients have a fatal outcome in few years. A high percentage of cases are hereditary with a recessive autosomal pattern. In the majority of the patients reported, a mutation of the gene that encodes the pantothenate kinase (PANK2) located in the 20p13-p12.3 chromosome that causes iron storage in the basal ganglia of the brain has been found. Its diagnosis is based on clinical symptoms as well as specific MRI imaging findings. The most common psychiatric features are cognitive impairment as well as depressive symptoms. There are few documented cases with psychotic disorders. We present the case of a patient with late onset Hallervorden-Spatz disease and psychotic symptoms that preceded the development of neurological manifestations. The pathophysiology and the treatment of psychotic symptomatology are presented and discussed. Key words: Psicosis, Hallervorden-Spatz, late onset, Basal ganglia.

  16. Incidence of diabetes mellitus type 2 complications among Saudi adult patients at primary health care center

    PubMed Central

    Alsenany, Samira; Al Saif, Amer

    2015-01-01

    [Purpose] This study analyzed type 2 diabetes and its role in complications among adult Saudi patients. [Subjects] Patients attending four primary health care centers in Jeddah were enrolled. [Methods] A cross-sectional design study among Saudi patients attending Ministry of Health primary health care centers in Jeddah was selected for use by the Primary Health Care administration. Patients were interviewed with structured questionnaires to determine the presence of diabetes and risk factors using questions about the history of any disease. [Results] Diabetes mellitus was present in 234 subjects during the data collection period (March–June 2014). Mean patient age was 58 years; diabetes prevalence was 42% in males and 58% in females. The mean age for diabetes onset in males and females was 34 and 39 years, respectively. There was a higher incidence of obesity (75%) associated with a sedentary lifestyle (body mass index ≥25) in females (N= 96; 40%) compared with males (N= 87; 36%). In this study, >44% of individuals aged 55 or older had severe to uncontrolled diabetes with long-term complications. The age-adjusted incidence of hypertension and coronary heart disease was 38% and 24%, respectively, showing a clear incidence of diabetes associated with cardiovascular disease in Saudi Arabia. [Conclusion] This study found that a multifactorial approach to managing diabetes complication risks is needed. PMID:26180307

  17. Sandhoff disease mimicking adult-onset bulbospinal neuronopathy.

    PubMed Central

    Thomas, P K; Young, E; King, R H

    1989-01-01

    A 32 year old male is described with an onset of upper limb postural tremor in adolescence followed by muscle cramps. Progressive proximal amyotrophy and weakness in the limbs developed late in the third decade. Examination disclosed, in addition, bilateral facial weakness and mild dysarthria. Enzyme studies revealed hexosaminidase A and B deficiency, indicating a diagnosis of Sandhoff disease. Intra-axonal membranocytoplasmic bodies were present in a rectal biopsy. The presentation, which resembled that of X-linked bulbospinal neuronopathy, widens the clinical spectrum for disorders related to G(M2) gangliosidosis. Images PMID:2795083

  18. Niemann-Pick type C: focus on the adolescent/adult onset form.

    PubMed

    Di Lazzaro, Vincenzo; Marano, Massimo; Florio, Lucia; De Santis, Stefano

    2016-11-01

    Niemann-Pick disease type C (NP-C) is an inherited sphingolipidosis characterized by progressive neurological deterioration and early mortality. The symptomatology and disease progression of NP-C are markedly affected by the age at onset of neurological manifestations, and categorization into early-infantile, late-infantile, juvenile, adolescent/adult neurological onset forms can aid evaluation of disease course and responses to therapy. Here, we review current information on the detection, diagnosis, monitoring and treatment of NP-C, with a focus on the adolescent/adult-onset form. A recent analysis indicated that the combined incidence of NP-C related to NPC1 gene mutations (NPC1) and NP-C related to NPC2 gene mutations (NPC2) is approximately 1 case in every 89 000 live births. In particular, late-onset phenotypes might well provide a greater contribution to the overall incidence than has previously been reported. Some neuropathological features in NP-C are held in common with other advanced age-onset diseases such as Alzheimer's disease. Visceral symptoms such as splenomegaly are frequently asymptomatic in patients with adolescent/adult-onset NP-C, and are only occasionally detected during routine ultrasound assessments. In contrast, most patients with adolescent/adult-onset exhibit some degree of slowly progressive, non-disease-specific movement disorders (e.g. cerebellar ataxia), and/or more pathognomonic neurological signs such as vertical supranuclear gaze palsy. An increasing number of adolescent/adult-onset cases have been reported following initial recognition of cognitive impairment and/or psychiatric signs. The recent development and implementation of new clinical screening tools (e.g. the NP-C suspicion index) and biomarkers (e.g. plasma oxysterols) should help identify patients who warrant further investigation and possible treatment.

  19. Incretin hormones and maturity onset diabetes of the young--pathophysiological implications and anti-diabetic treatment potential.

    PubMed

    Østoft, Signe Harring

    2015-09-01

    Maturity onset diabetes of the young (MODY) designates monogenic forms of non-autoimmune diabetes characterised by autosomal dominant inheritance, non-insulin dependent diabetes at onset and diagnosis often before 25 years of age. MODY constitutes genetically and clinically heterogeneous forms of diabetes. More than 8 different genes are known to cause MODY, among which hepatocyte nuclear factor 1 alpha (HNF1A) (MODY3) and glucokinase (GCK) (MODY2) mutations are the most common. Both forms of MODY are characterised by specific beta cell dysfunction, with patients with HNF1A-diabetes having a reduced insulin secretory capacity, while patients with GCK-diabetes have a glucose-sensing defect, but preserved insulin secretory capacity. Patients with MODY are effectively treated with sulphonylurea (SU) due to very high sensitivity to these drugs, but they are also prone to develop hypoglycaemia. The objectives of this thesis were to study the pathophysiology of GCK-diabetes and HNF1A-diabetes by investigating the incretin effect, the physiological response to food ingestion and to estimate the treatment potential of a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with HNF1A-diabetes. In Study I we investigated the incretin effect and the responses of islet hormones and incretin hormones to oral glucose tolerance test (OGTT) and isoglycaemic IV glucose infusion (IIGI) in patients with GCK-diabetes, in patients with HNF1A-diabetes, and in BMI and age matched healthy individuals (CTRLs). In Study II we investigated responses of islet hormones and incretin hormones to a more physiological stimulus consisting of a standardised meal test in patients with GCK-diabetes, in patients with HNF1A--diabetes, and in BMI and age matched CTRLs. In Study III we conducted a randomised, double-blind, crossover trial investigating the glucose lowering effect and risk of hypoglycaemia during 6 weeks of treatment with the GLP-1RA, liraglutide compared to the SU, glimepiride

  20. [Identifying different susceptibility loci associated with early onset diabetes and cardiovascular disease in Mexican families].

    PubMed

    Canizales-Quinteros, Samuel; Huertas-Vázquez, Adriana; Riba-Ramírez, Laura; Monroy-Guzmán, Adriana; Domínguez-López, Aarón; Romero-Hidalgo, Sandra; Aguilar-Salinas, Carlos; Rodríguez-Torres, Maribel; Ramírez-Jiménez, Salvador; Tusié-Luna, María Teresa

    2005-01-01

    Coronary artery disease and diabetes mellitus are among the primary mortality and morbidity causes in Mexico. Genetic factors play a fundamental role in the development of these entities. In the past few years due to the recognition and study of families with monogenic forms of diabetes and dislipidemias associated with development of atherosclerosis, several genes and loci have been associated with these conditions through genetic linkage studies. These studies have provided evidence of the genetic heterogeneity that exists and the type of genes involved in different ethnic groups. The study of Mexican families with early-onset diabetes and combined familial hyperlipidemia showed the participation of different genetic loci associated with these conditions in the Mexican population. These findings show the value of gene mapping strategies in the identification of the genetic component in these entities in our population.

  1. Differential effects of low-dose fenofibrate treatment in diabetic rats with early onset nephropathy and established nephropathy.

    PubMed

    Kadian, Supriya; Mahadevan, Nanjaian; Balakumar, Pitchai

    2013-01-05

    We have previously shown that low-dose fenofibrate treatment has an ability to prevent diabetes-induced nephropathy in rats. We investigated here the comparative pre- and post-treatment effects of low-dose fenofibrate (30 mg/kg/day p.o.) in diabetes-induced onset of nephropathy. Rats were made diabetics by single administration of streptozotocin (STZ, 55 mg/kg i.p.). The development of diabetic nephropathy was assessed biochemically and histologically. Moreover, lipid profile and renal oxidative stress were assessed. Diabetic rats after 8 weeks of STZ-administration developed apparent nephropathy by elevating serum creatinine, blood urea nitrogen and microproteinuria, and inducing glomerular-capsular wall distortion, mesangial expansion and tubular damage and renal oxidative stress. Fenofibrate (30 mg/kg/day p.o., 4 weeks) pretreatment (4 weeks after STZ-administration) markedly prevented diabetes-induced onset of diabetic nephropathy, while the fenofibrate (30 mg/kg/day p.o., 4 weeks) post-treatment (8 weeks after STZ-administration) was less-effective. However, both pre-and post fenofibrate treatments were effective in preventing diabetes-induced renal oxidative stress and lipid alteration in diabetic rats though the pretreatment was slightly more effective. Conversely, both pre-and post fenofibrate treatments did not alter elevated glucose levels in diabetic rats. It may be concluded that diabetes-induced oxidative stress and lipid alteration, in addition to a marked glucose elevation, play a detrimental role in the onset of nephropathy in diabetic rats. The pretreatment with low-dose fenofibrate might be a potential therapeutic approach in preventing the onset of nephropathy in diabetic subjects under the risk of renal disease induction. However, low-dose fenofibrate treatment might not be effective in treating the established nephropathy in diabetic subjects.

  2. Marital Adjustment to Adult Diabetes: Interpersonal Congruence and Spouse Satisfaction.

    ERIC Educational Resources Information Center

    Peyrot, Mark; And Others

    1988-01-01

    Investigated adjustment to insulin-treated diabetes among 20 adult patients and spouses. Found illness-related perceptions of patients and spouses were positively correlated and discrepancies decreased with increasing duration of marriage after diagnosis. Marital satisfaction of spouses was negatively related to knowledge about diabetes,…

  3. A Microsphere-Based Vaccine Prevents and Reverses New-Onset Autoimmune Diabetes

    PubMed Central

    Phillips, Brett; Nylander, Karen; Harnaha, Jo; Machen, Jennifer; Lakomy, Robert; Styche, Alexis; Gillis, Kimberly; Brown, Larry; Gallo, Michael; Knox, Janet; Hogeland, Kenneth; Trucco, Massimo; Giannoukakis, Nick

    2009-01-01

    OBJECTIVE This study was aimed at ascertaining the efficacy of antisense oligonucleotide-formulated microspheres to prevent type 1 diabetes and to reverse new-onset disease. RESEARCH DESIGN AND METHODS Microspheres carrying antisense oligonucleotides to CD40, CD80, and CD86 were delivered into NOD mice. Glycemia was monitored to determine disease prevention and reversal. In recipients that remained and/or became diabetes free, spleen and lymph node T-cells were enriched to determine the prevalence of Foxp3+ putative regulatory T-cells (Treg cells). Splenocytes from diabetes-free microsphere-treated recipients were adoptively cotransferred with splenocytes from diabetic NOD mice into NOD-scid recipients. Live animal in vivo imaging measured the microsphere accumulation pattern. To rule out nonspecific systemic immunosuppression, splenocytes from successfully treated recipients were pulsed with β-cell antigen or ovalbumin or cocultured with allogeneic splenocytes. RESULTS The microspheres prevented type 1 diabetes and, most importantly, exhibited a capacity to reverse clinical hyperglycemia, suggesting reversal of new-onset disease. The microspheres augmented Foxp3+ Treg cells and induced hyporesponsiveness to NOD-derived pancreatic β-cell antigen, without compromising global immune responses to alloantigens and nominal antigens. T-cells from successfully treated mice suppressed adoptive transfer of disease by diabetogenic splenocytes into secondary immunodeficient recipients. Finally, microspheres accumulated within the pancreas and the spleen after either intraperitoneal or subcutaneous injection. Dendritic cells from spleen of the microsphere-treated mice exhibit decreased cell surface CD40, CD80, and CD86. CONCLUSIONS This novel microsphere formulation represents the first diabetes-suppressive and reversing nucleic acid vaccine that confers an immunoregulatory phenotype to endogenous dendritic cells. PMID:18316361

  4. Precipitation of new onset diabetes by H1N1 infection.

    PubMed

    Krishna, S V S; Sunil, K; Prasad, R Devi; Modi, K D

    2012-12-01

    Infectious diseases in type 2 diabetes can complicate diabetic ketoacidosis, derange hyperglycemia, or precipitate new onset diabetes. Pulmonary tuberculosis being the most common. High index of clinical suspicion is required for co-existing H1N1 virus, which if present has high mortality if not treated. A 63-year-old female, with no known chronic illness, was hospitalized in month of Aug 2010 with influenza-like symptoms and diabetes. Quick evaluation revealed tachycardia, tachypnea, p02 90% at room air, and normotensive. Clinical chest examination was normal. Further evaluation revealed NHO in both lung fields on chest X-ray, hyperglycemia 325 mg/dl, detected for first time. Her signs and symptoms were out of proportion to clinical findings and chest X-ray findings. Patient was managed with insulin infusion and empirical broad-spectrum antibiotic coverage in ICU. As her condition worsened over next 12 hrs, infection with H1N1 was suspected and empirically started on oseltamavir after taking throat swab for H1N1 test and later, the sample was tested positive for H1N1 influenza by RT-PCR. Clinical course in the hospital was complicated by oxygen dependence requiring 10-12 ltr/hr by nasal mask. She made an uneventful recovery. In a known diabetic, infection with H1N1 quadruples ICU hospitalization, and only few cases of new onset diabetes with H1N1 were reported. Two reported from Iran had fatal outcome. This case emphasis on clinical acumen in recognition, and prompt institution of therapy will reduce associated mortality.

  5. Audiovisual Integration Delayed by Stimulus Onset Asynchrony Between Auditory and Visual Stimuli in Older Adults.

    PubMed

    Ren, Yanna; Yang, Weiping; Nakahashi, Kohei; Takahashi, Satoshi; Wu, Jinglong

    2017-02-01

    Although neuronal studies have shown that audiovisual integration is regulated by temporal factors, there is still little knowledge about the impact of temporal factors on audiovisual integration in older adults. To clarify how stimulus onset asynchrony (SOA) between auditory and visual stimuli modulates age-related audiovisual integration, 20 younger adults (21-24 years) and 20 older adults (61-80 years) were instructed to perform an auditory or visual stimuli discrimination experiment. The results showed that in younger adults, audiovisual integration was altered from an enhancement (AV, A ± 50 V) to a depression (A ± 150 V). In older adults, the alterative pattern was similar to that for younger adults with the expansion of SOA; however, older adults showed significantly delayed onset for the time-window-of-integration and peak latency in all conditions, which further demonstrated that audiovisual integration was delayed more severely with the expansion of SOA, especially in the peak latency for V-preceded-A conditions in older adults. Our study suggested that audiovisual facilitative integration occurs only within a certain SOA range (e.g., -50 to 50 ms) in both younger and older adults. Moreover, our results confirm that the response for older adults was slowed and provided empirical evidence that integration ability is much more sensitive to the temporal alignment of audiovisual stimuli in older adults.

  6. Adult-Onset Esophageal Crohn’s Disease

    PubMed Central

    Kasarala, George; Durrett, Sam

    2016-01-01

    Crohn’s disease (CD) is an idiopathic inflammatory bowel disease that can involve any part of the gastrointestinal tract. Esophageal involvement is rarely seen in adults, especially at the initial diagnosis of CD. Esophageal symptoms as primary manifestations of the disease are extremely rare. We report a case of a CD with esophageal involvement at the time of her initial diagnosis of CD. PMID:27761477

  7. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q.

    PubMed Central

    Wirtz, M K; Samples, J R; Kramer, P L; Rust, K; Topinka, J R; Yount, J; Koler, R D; Acott, T S

    1997-01-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-onset primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. PMID:9012402

  8. Maturity-Onset Diabetes of the Young (MODY): Making the Right Diagnosis to Optimize Treatment.

    PubMed

    Amed, Shazhan; Oram, Richard

    2016-10-01

    Maturity onset diabetes of the young (MODY) is a rare but increasingly recognized cause of diabetes in young people. It is a monogenic disorder that typically presents at <25 years of age, is non-insulin dependent and is familial, with an autosomal dominant pattern of inheritance. The most common forms of MODY are caused by mutations in glucokinase and hepatic nuclear factor 1 alpha or 4 alpha genes and account for almost 80% of cases of MODY. MODY is commonly misdiagnosed as type 1 or type 2 diabetes and, as a result, patients are often inappropriately managed with insulin when they can be more effectively managed with oral sulfonylureas. Therefore, making the right diagnosis is critical for effective treatment as well as for genetic counselling and, more important, for patients' quality of life. In this review, we aim to raise awareness about MODY among diabetes clinicians by describing key clinical and laboratory features of the most common forms of MODY, outlining features that might help to differentiate MODY from type 1 and type 2 diabetes and providing information about clinical tests and tools that might assist in identifying patients who are most likely to benefit from molecular genetic testing.

  9. Sulfur amino acid metabolism in juvenile-onset nonketotic and ketotic diabetic patients.

    PubMed

    Mårtensson, J; Hermansson, G

    1984-05-01

    Sulfur amino acid metabolism was studied in non-fasting nonketotic and ketotic juvenile-onset diabetic children and the results were compared to age-matched healthy children on an ordinary diet. An increased excretion of total sulfur and inorganic sulfate was found in diabetic children, probably a result of a decreased protein-serum synthesis and/or increased endogenous protein catabolism, although as a result of hyperglycemia a decreased tubular reabsorption may also have contributed. All diabetics showed a normal excretion of methionine. For cyst(e)ine and taurine an increased excretion was seen in ketotic diabetics, probably also a consequence of an increased endogenous protein degradation. As a sign of the latter, an increased output of 3-methylhistidine was also observed, a confirmation of earlier reports. The increased output of mercaptolactate and mercaptoacetate found in ketotic patients, was probably also a result of enhanced endogenous protein degradation. An increased urinary excretion of N-acetylcysteine was seen in diabetic children, which may reflect an enhanced availability to acetyl coenzyme A.

  10. Adult-onset Still's disease and cardiac tamponade: a rare association.

    PubMed

    Carrilho-Ferreira, Pedro; Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-06-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity.

  11. Adult-Onset Still's Disease and Cardiac Tamponade: A Rare Association

    PubMed Central

    Silva, Doroteia; de Jesus Silva, Maria; André, Rui; Varela, Manuel Gato; Diogo, António Nunes

    2015-01-01

    Adult-onset Still's disease is a rare disorder with potentially severe clinical features, including cardiac involvement. This systemic inflammatory disease of unknown origin should be considered in the differential diagnosis of pericarditis, with or without pericardial effusion. Cardiac tamponade is a very rare sequela that requires an invasive approach, such as percutaneous or surgical pericardial drainage, in addition to the usual conservative therapy. The authors describe a case of adult-onset Still's disease rendered more difficult by pericarditis and cardiac tamponade, and they briefly review the literature on this entity. PMID:26175648

  12. [Adult onset Still's disease as a diagnostics challenge in case of fever of unknown origin].

    PubMed

    Debski, Marcin; Stepniewski, Piotr; Wróbel, Michał

    2013-01-01

    Fever of unknown origin is often a diagnostic challenge. Here we present a case of 55-year-old woman with a history of a few months fever, progressing weakness and salmon-coloured, macular skin rash. The differential diagnosis included neoplasmatic conditions, infections and connective tissue disorders. Finally adult onset Still's disease was suspected. Glucocorticosteroid treatment was induced. During the therapy a central nervous system infection occurred, which was fatal for the patient. The presented clinical case shows that among many causes of fever of unknown origin, adult onset Still's disease should be taken into account.

  13. Diabetes Self-Care and the Older Adult

    PubMed Central

    Weinger, Katie; Beverly, Elizabeth A.; Smaldone, Arlene

    2014-01-01

    The prevalence of diabetes is highest in older adults, a population that is increasing. Diabetes self-care is complex with important recommendations for nutrition, physical activity, checking glucose levels, and taking medication. Older adults with diabetes have unique issues which impact self-care. As people age, their health status, support systems, physical and mental abilities, and nutritional requirements change. Furthermore, comorbidities, complications, and polypharmacy complicate diabetes self-care. Depression is also more common among the elderly and may lead to deterioration in self-care behaviors. Because of concerns about cognitive deficits and multiple comorbidities, adults older than 65 years are often excluded from research trials. Thus, little clinical evidence is available and the most appropriate treatment approaches and how to best support older patients’ self-care efforts are unclear. This review summarizes the current literature, research findings, and expert and consensus recommendations with their rationales. PMID:24510969

  14. New-Onset Diabetes Mellitus After Transplantation in a Cynomolgus Macaque (Macaca fasicularis).

    PubMed

    Matthews, Kristin A; Tonsho, Makoto; Madsen, Joren C

    2015-08-01

    A 5.5-y-old intact male cynomolgus macaque (Macaca fasicularis) presented with inappetence and weight loss 57 d after heterotopic heart and thymus transplantation while receiving an immunosuppressant regimen consisting of tacrolimus, mycophenolate mofetil, and methylprednisolone to prevent graft rejection. A serum chemistry panel, a glycated hemoglobin test, and urinalysis performed at presentation revealed elevated blood glucose and glycated hemoglobin (HbA1c) levels (727 mg/dL and 10.1%, respectively), glucosuria, and ketonuria. Diabetes mellitus was diagnosed, and insulin therapy was initiated immediately. The macaque was weaned off the immunosuppressive therapy as his clinical condition improved and stabilized. Approximately 74 d after discontinuation of the immunosuppressants, the blood glucose normalized, and the insulin therapy was stopped. The animal's blood glucose and HbA1c values have remained within normal limits since this time. We suspect that our macaque experienced new-onset diabetes mellitus after transplantation, a condition that is commonly observed in human transplant patients but not well described in NHP. To our knowledge, this report represents the first documented case of new-onset diabetes mellitus after transplantation in a cynomolgus macaque.

  15. The distinction between juvenile and adult-onset primary open-angle glaucoma

    SciTech Connect

    Wiggs, J.L.; Haines, J.L.; Damji, K.F.

    1996-01-01

    Because of the significant differences between the juvenile and adult forms of open-angle glaucoma, especially with regard to inheritance, prevalence, severity, and age of onset, we read with interest the recent publication by Morissette et al., describing a pedigree with a phenotype that overlaps the distinctive features of juvenile-onset open-angle glaucoma (JOAG) and adult-onset primary open-angle glaucoma (usually abbreviated as POAG or COAG). These authors conclude that a gene mapped to human chromosome 1q21-q31 (GLC1A) can be responsible for both juvenile and adult forms of open-angle glaucoma. The implications of such a result could be extremely important, in light of the high prevalence of the adult form of the disease. However, while the data presented in this report suggest that variable expressivity of the GLC1A gene may lead to a broader range of onset for this form of juvenile glaucoma, these data do not identify the GLC1A gene as an important cause of POAG. To prevent misleading interpretations of this and similar studies, we wish to clarify the distinction between the juvenile and adult forms of open-angle glaucoma. 8 refs.

  16. Adult Onset of Xanthelasmoid Mastocytosis: Report of a Rare Entity

    PubMed Central

    Nabavi, Nafiseh Sadat; Nejad, Masumeh Hosseini; Feli, Shahab; Bakhshoodeh, Behnoosh; Layegh, Pouran

    2016-01-01

    Xanthelasmoid or pseudoxanthomatous mastocytosis is an extremely rare variant of diffuse cutaneous mastocytosis. Herein, we describe an adult male with cutaneous mastocytosis showing multiple widespread yellowish ovoid papules like eruptive xanthoma. A 60-year-old male visited our outpatient clinic with a 1-year history of generalized yellowish, ovoid, and skin color papular eruption located on the trunk, groin, extremities, with the modest pruritus. Vital signs were stable, and Darier's sign was negative. No other subjective and objective signs were detected during the examination. No abnormality was detected in his diagnostic laboratory tests. Skin biopsy was taken, and histopathologic examination revealed proliferation of mast cells with ovoid and spindle nuclei with distinct cytoplasm borders around the capillaries, which was compatible with mastocytosis. Antihistamine was prescribed for pruritus control which was successful, but eruptions were persistent, and even 1-year phototherapy was not useful. PMID:27512209

  17. Childhood obesity affects adult metabolic syndrome and diabetes.

    PubMed

    Liang, Yajun; Hou, Dongqing; Zhao, Xiaoyuan; Wang, Liang; Hu, Yuehua; Liu, Junting; Cheng, Hong; Yang, Ping; Shan, Xinying; Yan, Yinkun; Cruickshank, J Kennedy; Mi, Jie

    2015-09-01

    We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥ 28 kg/m(2). MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥ 90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥ 11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6-4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

  18. Management of adults with paediatric-onset chronic liver disease: strategic issues for transition care.

    PubMed

    Vajro, Pietro; Ferrante, Lorenza; Lenta, Selvaggia; Mandato, Claudia; Persico, Marcello

    2014-04-01

    Advances in the management of children with chronic liver disease have enabled many to survive into adulthood with or without their native livers, so that the most common of these conditions are becoming increasingly common in adult hepatology practice. Because the aetiologies of chronic liver disease in children may vary significantly from those in adulthood, adults with paediatric-onset chronic liver disease may often present with clinical manifestations unfamiliar to their adulthood physician. Transition of medical care to adult practice requires that the adulthood medical staff (primary physicians and subspecialists) have a comprehensive knowledge of childhood liver disease and their implications, and of the differences in caring for these patients. Pending still unavailable Scientific Society guidelines, this article examines causes, presentation modes, evaluation, management, and complications of the main paediatric-onset chronic liver diseases, and discusses key issues to aid in planning a program of transition from paediatric to adult patients.

  19. Obesity and diabetes as accelerators of functional decline: can lifestyle interventions maintain functional status in high risk older adults?

    PubMed

    Anton, Stephen D; Karabetian, Christy; Naugle, Kelly; Buford, Thomas W

    2013-09-01

    Obesity and diabetes are known risk factors for the development of physical disability among older adults. With the number of seniors with these conditions rising worldwide, the prevention and treatment of physical disability in these persons have become a major public health challenge. Sarcopenia, the progressive loss of muscle mass and strength, has been identified as a common pathway associated with the initial onset and progression of physical disability among older adults. A growing body of evidence suggests that metabolic dysregulation associated with obesity and diabetes accelerates the progression of sarcopenia, and subsequently functional decline in older adults. The focus of this brief review is on the contributions of obesity and diabetes in accelerating sarcopenia and functional decline among older adults. We also briefly discuss the underexplored interaction between obesity and diabetes that may further accelerate sarcopenia and place obese older adults with diabetes at particularly high risk of disability. Finally, we review findings from studies that have specifically tested the efficacy of lifestyle-based interventions in maintaining the functional status of older persons with obesity and/or diabetes.

  20. Metabolic syndrome in hemodialysis patients as a risk factor for new-onset diabetes mellitus after renal transplant: a prospective observational study

    PubMed Central

    Bonet, Josep; Martinez-Castelao, Albert; Bayés, Beatriz

    2013-01-01

    Purpose Metabolic syndrome is a cluster of biochemical abnormalities including cardiovascular and diabetes risk factors. The development of diabetes mellitus after renal transplant represents a major posttransplant complication that may adversely affect graft/patient survival. The aim of this study was to assess the role of metabolic syndrome in patients on hemodialysis as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant. Patients and methods This was a prospective observational epidemiologic study carried out in adult nondiabetic patients undergoing chronic hemodialysis and on the renal transplant waiting list between November 2008 and April 2009. Patients were followed up from Visit 1 (baseline) to 6 months after the renal transplant. The analysis of the role of metabolic syndrome in hemodialysis patients as a risk factor for the incidence of new-onset diabetes mellitus after renal transplant included the estimation of relative risk and its 95% confidence interval (CI). Results A total of 383 evaluable patients were entered into the study (mean age, 52.7 years; male, 57.7%; Caucasian, 90.1%). The prevalence of metabolic syndrome on hemodialysis was 30.4% (95% CI, 25.8%–35.4%). Hypertension was the most prevalent criterion for metabolic syndrome (65.0%), followed by low levels of high-density lipoprotein cholesterol (52.7%), abdominal obesity (36.2%), hypertriglyceridemia (32.4%), and impaired glucose (8.9%). After the renal transplant, the prevalence of metabolic syndrome was still 25.8%. During the posttransplant period, the incidence of new-onset diabetes mellitus reached 13.0% (95% CI, 7.8%–20.6%) and patients with pretransplant metabolic syndrome were 2.6 times (95% CI, 1.043–6.608) more likely to develop new-onset diabetes mellitus after the renal transplant than those without metabolic syndrome. Conclusion The presence of metabolic syndrome in patients undergoing hemodialysis represents an independent risk factor

  1. Comprehensive Maturity Onset Diabetes of the Young (MODY) Gene Screening in Pregnant Women with Diabetes in India

    PubMed Central

    Hesarghatta Shyamasunder, Asha; Varghese, Deny; Varshney, Manika; Paul, Johan; Inbakumari, Mercy; Christina, Flory; Varghese, Ron Thomas; Kuruvilla, Kurien Anil; V. Paul, Thomas; Jose, Ruby; Regi, Annie; Lionel, Jessie; Jeyaseelan, L.; Mathew, Jiji; Thomas, Nihal

    2017-01-01

    Pregnant women with diabetes may have underlying beta cell dysfunction due to mutations/rare variants in genes associated with Maturity Onset Diabetes of the Young (MODY). MODY gene screening would reveal those women genetically predisposed and previously unrecognized with a monogenic form of diabetes for further clinical management, family screening and genetic counselling. However, there are minimal data available on MODY gene variants in pregnant women with diabetes from India. In this study, utilizing the Next generation sequencing (NGS) based protocol fifty subjects were screened for variants in a panel of thirteen MODY genes. Of these subjects 18% (9/50) were positive for definite or likely pathogenic or uncertain MODY variants. The majority of these variants was identified in subjects with autosomal dominant family history, of whom five were in women with pre-GDM and four with overt-GDM. The identified variants included one patient with HNF1A Ser3Cys, two PDX1 Glu224Lys, His94Gln, two NEUROD1 Glu59Gln, Phe318Ser, one INS Gly44Arg, one GCK, one ABCC8 Arg620Cys and one BLK Val418Met variants. In addition, three of the seven offspring screened were positive for the identified variant. These identified variants were further confirmed by Sanger sequencing. In conclusion, these findings in pregnant women with diabetes, imply that a proportion of GDM patients with autosomal dominant family history may have MODY. Further NGS based comprehensive studies with larger samples are required to confirm these finding PMID:28095440

  2. A novel ALMS1 splice mutation in a non-obese juvenile-onset insulin-dependent syndromic diabetic patient.

    PubMed

    Sanyoura, May; Woudstra, Cédric; Halaby, George; Baz, Patrick; Senée, Valérie; Guillausseau, Pierre-Jean; Zalloua, Pierre; Julier, Cécile

    2014-01-01

    Insulin-dependent juvenile-onset diabetes may occur in the context of rare syndromic presentations suggesting monogenic inheritance rather than common multifactorial autoimmune type 1 diabetes. Here, we report the case of a Lebanese patient diagnosed with juvenile-onset insulin-dependent diabetes presenting ketoacidosis, early-onset retinopathy with optic atrophy, hearing loss, diabetes insipidus, epilepsy, and normal weight and stature, who later developed insulin resistance. Despite similarities with Wolfram syndrome, we excluded the WFS1 gene as responsible for this disease. Using combined linkage and candidate gene study, we selected ALMS1, responsible for Alström syndrome, as a candidate gene. We identified a novel splice mutation in intron 18 located 3 bp before the intron-exon junction (IVS18-3T>G), resulting in exon 19 skipping and consequent frameshift generating a truncated protein (V3958fs3964X). The clinical presentation of the patient significantly differed from typical Alström syndrome by the absence of truncal obesity and short stature, and by the presence of ketoacidotic insulin-dependent diabetes, optic atrophy and diabetes insipidus. Our observation broadens the clinical spectrum of Alström syndrome and suggests that ALMS1 mutations may be considered in patients who initially present with an acute onset of insulin-dependent diabetes.

  3. Role of dipeptidyl peptidase-4 inhibitors in new-onset diabetes after transplantation

    PubMed Central

    Lim, Sun Woo; Jin, Ji Zhe; Jin, Long; Jin, Jian; Li, Can

    2015-01-01

    Despite strict pre- and post-transplantation screening, the incidence of new-onset diabetes after transplantation (NODAT) remains as high as 60%. This complication affects the risk of cardiovascular events and patient and graft survival rates. Thus, reducing the impact of NODAT could improve overall transplant success. The pathogenesis of NODAT is multifactorial, and both modifiable and nonmodifiable risk factors have been implicated. Monitoring and controlling the blood glucose profile, implementing multidisciplinary care, performing lifestyle modifications, using a modified immunosuppressive regimen, administering anti-metabolite agents, and taking a conventional antidiabetic approach may diminish the incidence of NODAT. In addition to these preventive strategies, inhibition of dipeptidyl peptidase-4 (DPP4) by the gliptin family of drugs has recently gained considerable interest as therapy for type 2 diabetes mellitus and NODAT. This review focuses on the role of DPP4 inhibitors and discusses recent literature regarding management of NODAT. PMID:26552451

  4. Prevention and management of new-onset diabetes mellitus in kidney transplantation.

    PubMed

    Juan Khong, M; Ping Chong, Ch

    2014-04-01

    New-onset diabetes mellitus after transplantation (NODAT) is one of the complications that is increasingly occurring among kidney transplanted patients. It is associated with the risk of cardiovascular disease, graft failure and mortality. The risk of NODAT development increases with time from transplantation. Therefore, early detection and prompt action are essential in reducing the risk of NODAT and its complications. This paper aims to review the screening parameters, prevention and management strategies for NODAT in both pre- and post-transplantation conditions. The pre-transplant patient should be screened for diabetes and cardiometabolic risk factors. Blood glucose evaluation for the pre-transplantation period is important for early detection of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), which are highly associated with the incidence of NODAT. Post-kidney transplant patients should have periodical blood glucose monitoring with more frequent assessment in the initial phase. As early hyperglycaemia development is a strong predictor for NODAT, prompt intervention is needed. When NODAT develops, monitoring and control of blood glucose profile, lipid profile, microalbuminuria, diabetic complications and comorbid conditions is recommended. Immunosuppressive regimen modification may be considered as suggested by the Kidney Disease: Improving Global Outcomes (KDIGO) guideline to reverse or to improve the diabetes after weighing the risk of rejection and other potential adverse effects. Strategies for modifying immunosuppressive agents include dose reduction, discontinuation, and selection of calcineurin inhibitor (CNI), anti-metabolite agents, mammalian target of rapamycin inhibitors (mTORi), belatacept and corticosteroids. Lifestyle modification and a conventional anti-diabetic approach, as in the type 2 diabetes mellitus guidelines, are also recommended in NODAT management.

  5. A Deeper Look into Type 1 Diabetes – Imaging Immune Responses during Onset of Disease

    PubMed Central

    Christoffersson, Gustaf; von Herrath, Matthias G.

    2016-01-01

    Cytotoxic T lymphocytes execute the killing of insulin-producing beta cells during onset of type 1 diabetes mellitus (T1D). The research community has come far in dissecting the major events in the development of this disease, but still the trigger and high-resolved information of the immunological events leading up to beta cell loss are missing. During the past decades, intravital imaging of immune responses has led to significant scientific breakthroughs in diverse models of disease, including T1D. Dynamic imaging of immune cells at the pancreatic islets during T1D onset has been made possible through the development of both advanced microscopes, and animal models that allow long-term immobilization of the pancreas. The use of these modalities has revealed a milling microenvironment at the pancreatic islets during disease onset with a plethora of active players. Clues to answering the remaining questions in this disease may lie in intravital imaging, including how key immune cells traffic to and from the pancreas, and how cells interact at this target tissue. This review highlights and discusses recent studies, models, and techniques focused to understand the immune responses during T1D onset through intravital imaging. PMID:27574523

  6. Administration of pioglitazone alone or with alogliptin delays diabetes onset in UCD-T2DM rats.

    PubMed

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber; Haj, Fawaz G; Havel, Peter J

    2014-04-01

    There is a need to identify strategies for type 2 diabetes prevention. Therefore, we investigated the efficacy of pioglitazone and alogliptin alone and in combination to prevent type 2 diabetes onset in UCD-T2DM rats, a model of polygenic obese type 2 diabetes. At 2 months of age, rats were divided into four groups: control, alogliptin (20 mg/kg per day), pioglitazone (2.5 mg/kg per day), and alogliptin+pioglitazone. Non-fasting blood glucose was measured weekly to determine diabetes onset. Pioglitazone alone and in combination with alogliptin lead to a 5-month delay in diabetes onset despite promoting increased food intake and body weight (BW). Alogliptin alone did not delay diabetes onset or affect food intake or BW relative to controls. Fasting plasma glucose, insulin, and lipid concentrations were lower and adiponectin concentrations were threefold higher in groups treated with pioglitazone. All treatment groups demonstrated improvements in glucose tolerance and insulin secretion during an oral glucose tolerance test with an additive improvement observed with alogliptin+pioglitazone. Islet histology revealed an improvement of islet morphology in all treatment groups compared with control. Pioglitazone treatment also resulted in increased expression of markers of mitochondrial biogenesis in brown adipose tissue and white adipose tissue, with mild elevations observed in animals treated with alogliptin alone. Pioglitazone markedly delays the onset of type 2 diabetes in UCD-T2DM rats through improvements of glucose tolerance, insulin sensitivity, islet function, and markers of adipose mitochondrial biogenesis; however, addition of alogliptin at a dose of 20 mg/kg per day to pioglitazone treatment does not enhance the prevention/delay of diabetes onset.

  7. Exploring the role of BCHE in the onset of Diabetes, Obesity and Neurological Disorders.

    PubMed

    Rao, Allam Appa; Jyothsna, Gundlapally; Shalini, Pulipati; Kumar, Amit; Bhattacharya, Anupam; Kashyap, Amita

    2012-01-01

    Diabetes, Obesity and Neurological disturbances, most often show co-occurrence. There has been an extensive research in this domain, but the exact mechanism underlying the co-occurrence of the three conditions is still an enigma. The current paper is an approach to establish the role of Butyryl cholinesterase (BCHE) in Diabetes, Obesity and Neurological disorders by performing a comparative analysis with Neuroligin (NLGN2) a protein belonging to the same family. BCHE has its role in glucose regulation, Lipid metabolism and nerve signaling. Emphasis is laid on BCHE's diverse functions whose impediment affects the above mentioned metabolic pathways. Insilco techniques were employed to analyze the sequence, structural and functional similarities of the two proteins. A point mutation is focused which is common to both BCHE and Neuroligin. The mutation occurs at the homologous position in both the proteins making them deficient. This affects the three metabolic pathways leading to the respective disorders. The work describes the pathway that describes the role of BCHE in the onset of obesity mediated diabetes. The pathway further explains the association between Diabetes, Obesity and neurological disturbances.

  8. Early-Onset Psychoses: Comparison of Clinical Features and Adult Outcome in 3 Diagnostic Groups

    ERIC Educational Resources Information Center

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-01-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a…

  9. Physical Therapists' Perceptions of Providing Services to Adults with Childhood-Onset Neuromotor Disabilities

    ERIC Educational Resources Information Center

    Compton-Griffith, Kelsi N.; Cicirello, Nancy A.; Turner, Anne

    2011-01-01

    Adults with childhood-onset neuromotor disabilities face problems accessing health care services. There are often challenges finding primary care providers or specialized providers, such as physical therapists, who are knowledgeable about neuromotor disabilities. The purpose of this study was to determine the perceptions of physical therapists…

  10. Epidemiology and outcome of articular complications in adult onset Still's disease.

    PubMed

    Mahfoudhi, Madiha; Shimi, Rafik; Turki, Sami; Kheder, Adel

    2015-01-01

    The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

  11. Genetic architecture differences between pediatric and adult-onset inflammatory bowel diseases in the Polish population

    PubMed Central

    Ostrowski, Jerzy; Paziewska, Agnieszka; Lazowska, Izabella; Ambrozkiewicz, Filip; Goryca, Krzysztof; Kulecka, Maria; Rawa, Tomasz; Karczmarski, Jakub; Dabrowska, Michalina; Zeber-Lubecka, Natalia; Tomecki, Roman; Kluska, Anna; Balabas, Aneta; Piatkowska, Magdalena; Paczkowska, Katarzyna; Kierkus, Jaroslaw; Socha, Piotr; Lodyga, Michal; Rydzewska, Grazyna; Klopocka, Maria; Mierzwa, Grazyna; Iwanczak, Barbara; Krzesiek, Elzbieta; Bak-Drabik, Katarzyna; Walkowiak, Jaroslaw; Klincewicz, Beata; Radwan, Piotr; Grzybowska-Chlebowczyk, Urszula; Landowski, Piotr; Jankowska, Agnieszka; Korczowski, Bartosz; Starzynska, Teresa; Albrecht, Piotr; Mikula, Michal

    2016-01-01

    Most inflammatory bowel diseases (IBDs) are classic complex disorders represented by common alleles. Here we aimed to define the genetic architecture of pediatric and adult-onset IBDs for the Polish population. A total of 1495 patients were recruited, including 761 patients with Crohn’s disease (CD; 424 pediatric), 734 patients with ulcerative colitis (UC; 390 pediatric), and 934 healthy controls. Allelotyping employed a pooled-DNA genome-wide association study (GWAS) and was validated by individual genotyping. Whole exome sequencing (WES) was performed on 44 IBD patients diagnosed before 6 years of age, 45 patients diagnosed after 40 years of age, and 18 healthy controls. Altogether, out of 88 selected SNPs, 31 SNPs were replicated for association with IBD. A novel BRD2 (rs1049526) association reached significance of P = 5.2 × 10−11 and odds ratio (OR) = 2.43. Twenty SNPs were shared between pediatric and adult patients; 1 and 7 were unique to adult-onset and pediatric-onset IBD, respectively. WES identified numerous rare and potentially deleterious variants in IBD-associated or innate immunity-associated genes. Deleterious alleles in both groups were over-represented among rare variants in affected children. Our GWAS revealed differences in the polygenic architecture of pediatric- and adult-onset IBD. A significant accumulation of rare and deleterious variants in affected children suggests a contribution by yet unexplained genetic components. PMID:28008999

  12. Adult-Onset Antisocial Behavior Trajectories: Associations with Adolescent Family Processes and Emerging Adulthood Functioning

    ERIC Educational Resources Information Center

    Mata, Andrea D.; van Dulmen, Manfred H. M.

    2012-01-01

    Guided by conceptual and empirical work on emerging adulthood, this study investigated the role of closeness to mother and father and behavioral autonomy during adolescence on the development of adult-onset antisocial behavior. Using data from the National Longitudinal Study of Adolescent Health (Add Health), we identified four aggressive…

  13. Lost opportunities to prevent early onset type 2 diabetes mellitus after a pregnancy complicated by gestational diabetes

    PubMed Central

    Bernstein, Judith A; McCloskey, Lois; Gebel, Christina M; Iverson, Ronald E; Lee-Parritz, Aviva

    2016-01-01

    Objectives Gestational diabetes mellitus (GDM) greatly increases the risk of developing diabetes in the decade after delivery, but few women receive appropriately timed postpartum glucose testing (PPGT) or a referral to primary care (PC) for continued monitoring. This qualitative study was designed to identify barriers and facilitators to testing and referral from patient and providers' perspectives. Methods We interviewed patients and clinicians in depth about knowledge, values, priorities, challenges, and recommendations for increasing PPGT rates and PC linkage. Interviews were coded with NVIVO data analysis software, and analyzed using an implementation science framework. Results Women reported motivation to address GDM for the health of the fetus. Most women did not anticipate future diabetes for themselves, and focused on delivery outcomes rather than future health risks. Patients sought and received reassurance from clinicians, and were unlikely to discuss early onset following GDM or preventive measures. PPGT barriers described by patients included provider not mentioning the test or setting it up, transportation difficulties, work responsibilities, fatigue, concerns about fasting while breastfeeding, and timing of the test after discharge from obstetrics, and no referral to PC for follow-up. Practitioners described limited communication among multiple care providers during pregnancy and delivery, systems issues, and separation of obstetrics from PC. Conclusions Patients' barriers to PPGT included low motivation for self-care, structural obstacles, and competing priorities. Providers reported the need to balance risk with reassurance, and identified systems failures related to test timing, limitations of electronic medical record systems (EMR), lack of referrals to PC, and inadequate communication between specialties. Prevention of early onset has great potential for medical cost savings and improvements in quality of life. PMID:27347422

  14. Childhood-Onset Disease Predicts Mortality in an Adult Cohort of Patients with Systemic Lupus Erythematosus

    PubMed Central

    Hersh, Aimee O.; Trupin, Laura; Yazdany, Jinoos; Panopalis, Peter; Julian, Laura; Katz, Patricia; Criswell, Lindsey A.; Yelin, Edward

    2013-01-01

    Objective To examine childhood-onset disease as a predictor of mortality in a cohort of adult patients with systemic lupus erythematosus (SLE). Methods Data were derived from the University of California Lupus Outcomes Study, a longitudinal cohort of 957 adult subjects with SLE that includes 98 subjects with childhood-onset SLE. Baseline and follow-up data were obtained via telephone interviews conducted between 2002-2007. The number of deaths during 5 years of follow-up was determined and standardized mortality ratios (SMRs) for the cohort, and across age groups, were calculated. Kaplan-Meier life table analysis was used to compare mortality rates between childhood (defined as SLE diagnosis <18 years) and adult-onset SLE. Multivariate Cox proportional hazard models were used to determine predictors of mortality. Results During the median follow-up period of 48 months, 72 deaths (7.5% of subjects) occurred, including 9 (12.5%) among those with childhood-onset SLE. The overall SMR was 2.5 (CI 2.0-3.2). In Kaplan-Meier survival analysis, after adjusting for age, childhood-onset subjects were at increased risk for mortality throughout the follow-up period (p<0.0001). In a multivariate model adjusting for age, disease duration and other covariates, childhood-onset SLE was independently associated with an increased mortality risk (hazard ratio [HR]: 3.1; 95% confidence interval [CI]: 1.3-7.3), as was low socioeconomic status measured by education (HR: 1.9; 95% CI 1.1-3.2) and end stage renal disease (HR: 2.1; 95% CI 1.1-4.0). Conclusion Childhood-onset SLE was a strong predictor of mortality in this cohort. Interventions are needed to prevent early mortality in this population. PMID:20235215

  15. Cortisol Levels in Children With Diabetic Ketoacidosis Associated With New-Onset Type 1 Diabetes Mellitus: A Retrospective Review

    PubMed Central

    Williams, Kristen M.; Fazzio, Pamela; Oberfield, Sharon E.; Gallagher, Mary P.; Aranoff, Gaya S.

    2017-01-01

    There is little data documenting cortisol levels in children with diabetic ketoacidosis (DKA), despite the fact that untreated adrenal insufficiency (AI) could worsen the outcome of DKA. In this cross-sectional study, we assessed serum cortisol levels in 28 children with DKA and new onset type 1 diabetes mellitus evaluated at our center over a 5-year period. Average duration of diabetes-related symptoms was positively associated with age (P = .002), and significantly lower hemoglobin A1c levels were observed in the youngest children. The mean cortisol level was 40.9 mg/dL, with a range of 7.8 to 119 mg/dL. Cortisol levels were found to be inversely associated with serum pH (P = .007). There was no difference in the clinical outcome of the 4 patients who had cortisol levels less than 18 mg/dL. Overall, we did not find clinical or laboratory evidence of diminished cortisol reserve; however, the possibility of AI must be kept in mind when treating children with DKA. PMID:28145127

  16. Risk of New-Onset Diabetes After Long-Term Treatment With Clozapine in Comparison to Other Antipsychotics in Patients With Schizophrenia.

    PubMed

    Schulte, Peter F J; Bocxe, Johanna T H; Doodeman, Hieronymus J; van Haelst, Ingrid M M; Cohen, Dan

    2016-04-01

    It has been suggested that clozapine has one of the largest diabetic effects of all atypical antipsychotics. To confirm these findings, we examined retrospectively the risk of new-onset diabetes in long-term clozapine treatment compared to treatment with other antipsychotics in a matched control population with schizophrenia or schizoaffective disorder. Ninety-four adult patients with schizophrenia or schizoaffective disorder who had been treated with clozapine for 5 years or longer were matched on age, diagnosis, and sex to 94 patients without any use of clozapine. The groups were followed up for as long as 20 years. The cumulative incidence of new detection of diabetes in the clozapine group was 22.3% (mean follow-up, 12.3 years; absolute risk difference, 6.3%; 95% confidence interval, -4.9% to 17.5%). An additional rigorous analysis of the 83 matched pairs with normal glucose measurement before end point showed a significant risk difference between the 2 groups (21.7% compared with 8.4%) but may have been biased against clozapine. We conclude that definitive evidence showing a clinically significant larger risk for new-onset diabetes after long-term treatment with clozapine in comparison to other antipsychotics is lacking.

  17. Single nucleotide polymorphisms in type 2 diabetes among Hispanic adults.

    PubMed

    Watson, Amanda L; Hu, Jie; Chiu, Norman H L

    2015-05-01

    In this pilot study, we explore the genetic variation that may relate to type 2 diabetes (T2D) among Hispanic adults. The genotypes of 36 Hispanic adults were analyzed by using the Cardio-Metabochip. The goal is to identify single nucleotide polymorphisms (SNPs) associated to T2D among Hispanic adults. A total of 26 SNPs were identified to be associated with T2D among Hispanic adults. None of these SNPs have been reported for T2D. By using the principle components analysis to analyze the genotype of 26 SNPs in 36 samples, the samples obtained from diabetic patients could be distinguished from the control samples. The findings support genetic involvement in T2D among Hispanic adults.

  18. Mapping a gene for adult-onset primary open-angle glaucoma to chromosome 3q

    SciTech Connect

    Wirtz, M.K.; Samples, J.R.; Kramer, P.L.

    1997-02-01

    Glaucoma is the third-leading cause of blindness in the world, affecting >13.5 million people. Adult-on-set primary open-angle glaucoma (POAG) is the most common form of glaucoma in the United States. We present a family in which adult-onset POAG is inherited as an autosomal dominant trait. Twelve affected family members were identified from 44 at-risk individuals. The disease-causing gene was mapped to chromosome 3q21-24, with analysis of recombinant haplotypes suggesting a total inclusion region of 11.1 cM between markers D3S3637 and D3S1744. This is the first report of mapping of an adult-onset POAG gene to chromosome 3q, gene symbol GLC1C. 57 refs., 3 figs., 3 tabs.

  19. Thyroid gland diseases in adult patients with diabetes mellitus.

    PubMed

    Vondra, K; Vrbikova, J; Dvorakova, K

    2005-12-01

    This review concerns the relation between most frequent thyroid gland diseases and diabetes mellitus in adult patients. Special attention is paid to autoimmune thyroiditis, Graves' disease, thyroid autoimmunity in pregnant diabetic women, and iodine metabolism. We focused on mechanisms leading to coexistence of both endocrine disorders, and on distinctions in the prevalence, diagnosis, clinical course and treatment of thyroid diseases in diabetic patients. The prevalence of thyroid diseases in diabetic patients is 2-3 times higher than in nondiabetic subjects; it raises with age, and is strongly influenced by female gender and autoimmune diabetes. Clinical relevance of thyroid diseases, especially in diabetic patients, significantly increases if it is associated with deteriorated function, which always cause a number problems with metabolic compensation of diabetes. Most serious consequences are increased frequency of hypoglycaemia in hypothyroidism and development of potentially life-threatening ketoacidosis in thyrotoxicosis. In spite of that, little attention is paid to the diagnosis of thyroid diseases in diabetics, as they are diagnosed in only about half of the patients. At the end, we provide recommendations for the thyroid disease screening and diagnosis in patients with diabetes mellitus based on our experience.

  20. Urinary tract infections in adults with diabetes.

    PubMed

    Ronald, A; Ludwig, E

    2001-04-01

    Urinary tract (UTI) is a major disease burden for many patients with diabetes. Asymptomatic bacteriuria is several-fold more common among women and acute plyelonephritis is five to ten times more common in both sexes. The complications of pyelonephritis are also more common in patients with diabetes. These complications include acute papillary necrosis, emphysematous pyelonephritis, and bacteremia with metastatic localization to other sites. The management of urinary infection in patients with diabetes is essentially the same as patients without diabetes. Most infections should be managed as uncomplicated except when they occur in a milieu with obstruction or other factors that merit a diagnosis of complicated UTI. Strategies to prevent these infections and reduce morbidity should be a priority for research.

  1. Epidemiology of adult-onset hydrocephalus: institutional experience with 2001 patients.

    PubMed

    Bir, Shyamal C; Patra, Devi Prasad; Maiti, Tanmoy K; Sun, Hai; Guthikonda, Bharat; Notarianni, Christina; Nanda, Anil

    2016-09-01

    OBJECTIVE Adult-onset hydrocephalus is not commonly discussed in the literature, especially regarding its demographic distribution. In contrast to pediatric hydrocephalus, which is related to a primary CSF pathway defect, its development in adults is often secondary to other pathologies. In this study, the authors investigated the epidemiology of adult-onset hydrocephalus as it pertains to different etiologies and in reference to age, sex, and race distributions. METHODS The authors retrospectively reviewed the clinical notes of 2001 patients with adult-onset hydrocephalus who presented to Louisiana State University Health Sciences Center within a 25-year span. Significant differences between the groups were analyzed by a chi-square test; p < 0.05 was considered significant. RESULTS The overall mean (± SEM) incidence of adult hydrocephalus in this population was 77 ± 30 per year, with a significant increase in incidence in the past decade (55 ± 3 [1990-2003] vs 102 ± 6 [2004-2015]; p < 0.0001). Hydrocephalus in a majority of the patients had a vascular etiology (45.5%) or was a result of a tumor (30.2%). The incidence of hydrocephalus in different age groups varied according to various pathologies. The incidence was significantly higher in males with normal-pressure hydrocephalus (p = 0.03) or head injury (p = 0.01) and higher in females with pseudotumor cerebri (p < 0.0001). In addition, the overall incidence of hydrocephalus was significantly higher in Caucasian patients (p = 0.0002) than in those of any other race. CONCLUSIONS Knowledge of the demographic variations in adult-onset hydrocephalus is helpful in achieving better risk stratification and better managing the disease in patients. For general applicability, these results should be validated in a large-scale meta-analysis based on a national population database.

  2. Nephrin mutations cause childhood- and adult-onset focal segmental glomerulosclerosis.

    PubMed

    Santín, Sheila; García-Maset, Rafael; Ruíz, Patricia; Giménez, Isabel; Zamora, Isabel; Peña, Antonia; Madrid, Alvaro; Camacho, Juan A; Fraga, Gloria; Sánchez-Moreno, Ana; Cobo, Maria Angeles; Bernis, Carmen; Ortiz, Alberto; de Pablos, Augusto Luque; Pintos, Guillem; Justa, Maria Luisa; Hidalgo-Barquero, Emilia; Fernández-Llama, Patricia; Ballarín, José; Ars, Elisabet; Torra, Roser

    2009-12-01

    Mutations in the NPHS1 gene cause congenital nephrotic syndrome of the Finnish type presenting before the first 3 months of life. Recently, NPHS1 mutations have also been identified in childhood-onset steroid-resistant nephrotic syndrome and milder courses of disease, but their role in adults with focal segmental glomerulosclerosis remains unknown. Here we developed an in silico scoring matrix to evaluate the pathogenicity of amino-acid substitutions using the biophysical and biochemical difference between wild-type and mutant amino acid, the evolutionary conservation of the amino-acid residue in orthologs, and defined domains, with the addition of contextual information. Mutation analysis was performed in 97 patients from 89 unrelated families, of which 52 presented with steroid-resistant nephrotic syndrome after 18 years of age. Compound heterozygous or homozygous NPHS1 mutations were identified in five familial and seven sporadic cases, including one patient 27 years old at onset of the disease. Substitutions were classified as 'severe' or 'mild' using this in silico approach. Our results suggest an earlier onset of the disease in patients with two 'severe' mutations compared to patients with at least one 'mild' mutation. The finding of mutations in a patient with adult-onset focal segmental glomerulosclerosis indicates that NPHS1 analysis could be considered in patients with later onset of the disease.

  3. Niacin therapy and the risk of new-onset diabetes: a meta-analysis of randomised controlled trials

    PubMed Central

    Goldie, Christina; Taylor, Allen J; Nguyen, Peter; McCoy, Cody; Zhao, Xue-Qiao; Preiss, David

    2016-01-01

    Objective Previous studies have suggested that niacin treatment raises glucose levels in patients with diabetes and may increase the risk of developing diabetes. We undertook a meta-analysis of published and unpublished data from randomised trials to confirm whether an association exists between niacin and new-onset diabetes. Methods We searched Medline, EMBASE and the Cochrane Central Register of Controlled Trials, from 1975 to 2014, for randomised controlled trials of niacin primarily designed to assess its effects on cardiovascular endpoints and cardiovascular surrogate markers. We included trials with ≥50 non-diabetic participants and average follow-up of ≥24 weeks. Published data were tabulated and unpublished data sought from investigators. We calculated risk ratios (RR) for new-onset diabetes with random-effects meta-analysis. Heterogeneity between trials was assessed using the I2 statistic. Results In 11 trials with 26 340 non-diabetic participants, 1371 (725/13 121 assigned niacin; 646/13 219 assigned control) were diagnosed with diabetes during a weighted mean follow-up of 3.6 years. Niacin therapy was associated with a RR of 1.34 (95% CIs 1.21 to 1.49) for new-onset diabetes, with limited heterogeneity between trials (I2=0.0%, p=0.87). This equates to one additional case of diabetes per 43 (95% CI 30 to 70) initially non-diabetic individuals who are treated with niacin for 5 years. Results were consistent regardless of whether participants received background statin therapy (p for interaction=0.88) or combined therapy with laropiprant (p for interaction=0.52). Conclusions Niacin therapy is associated with a moderately increased risk of developing diabetes regardless of background statin or combination laropiprant therapy. PMID:26370223

  4. A self-assessment tool for screening young adults at risk of type 2 diabetes using Strong Heart Family Study data

    PubMed Central

    Yan, Fengxia; Cha, EunSeok; Lee, Elisa T.; Mayberry, Robert M.; Wang, Wenyu; Umpierrez, Guillermo

    2016-01-01

    Purpose The purpose of this study is to characterize risk factors associated with type 2 diabetes in young adults ages 18–29 in order to develop a non-invasive risk assessment tool for use with younger American populations. Methods The self-assessment tool was developed using the Strong Heart Family Study data. A total of 590 young American Indian adults aged 18–29 (males=242) with normoglycemia and not receiving diabetes treatment were included. Risk factors recommended by the American Diabetes Association were used to assess diabetes risk in these young adults. A logistic regression model was developed to calculate the predicted probability. The area under receiver operating characteristic curve (AUROC) was used to evaluate the model. Results The final model showed that parental history of diabetes, obesity level, alcohol consumption, and high fasting glucose even within normal range were significantly associated with onset of prediabetes or diabetes in 5 years. The AUROC value was 0.68 with original and validated data, indicating the risk assessment tool had reasonably good discrimination ability. Conclusions This new non-invasive screening tool, based on data from American Indian young adults, has potential to screen young adults’ early-onset diabetes risk. Future studies are warranted to test this risk assessment tool in other racial/ethnic young adults. PMID:27480523

  5. Profiling of circulating microRNAs in children with recent onset of type 1 diabetes

    PubMed Central

    Erener, Suheda; Marwaha, Ashish; Tan, Rusung; Kieffer, Timothy J.

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune disease that is clinically silent until the majority of β cells are destroyed. There is an unmet need for reliable and cost-effective biomarkers to predict and diagnose diabetes at an early stage. A number of stable microRNAs (miRNAs) have been reported in serum and plasma and are now being investigated as biomarkers of different diseases. We measured the levels of 745 miRNAs in sera of children with recent-onset T1D and age-matched controls using locked nucleic acid–enhanced (LNA-enhanced) quantitative PCR profiling. Thirty-five miRNAs were significantly different between the groups, and 27 miRNAs were elevated in T1D. Good discriminating power was obtained for 6 miRNAs (miR-454-3p, miR-222-3p, miR-144-5p, miR-345-5p, miR-24-3p, and miR-140-5p), which were not elevated at later stages of diabetes. In silico pathway analysis, based on inferred miRNA target genes, associated glycosaminoglycan biosynthesis as well as PI3K/Akt, MAPK, and Wnt signaling pathways with early stages of T1D. Among the 27 upregulated miRNAs in T1D, 2 miRNAs significantly correlated with hemoglobin A1c (HbA1c), as did 5 of 8 downregulated miRNAs. A total of 134 miRNAs significantly correlated with HbA1c when stratifying hyperglycemia-induced miRNAs from T1D-specific miRNAs. In conclusion, we have identified a serum miRNA pattern of recent-onset T1D and signaling pathways that may be involved in its pathogenesis. PMID:28239651

  6. Rapid Deterioration of Insulin Secretion in Obese Adolescents Preceding the Onset of Type 2 Diabetes

    PubMed Central

    Elder, Deborah A.; Hornung, Lindsey N.; Herbers, Patricia M.; Prigeon, Ron; Woo, Jessica G.; D'Alessio, David A.

    2014-01-01

    Objective To identify pathophysiologic changes that lead to the onset of type 2 diabetes (T2DM) in adolescents. Study design Obese adolescents with NGT (n=41) were studied longitudinally over 4 years with serial measure of the acute insulin response to IV glucose (AIRg) as well as proinsulin (PI) concentrations. Insulin resistance was estimated with HOMA modeling, the disposition index (DI) computed as AIRg × 1/HOMA-IR, and IV glucose tolerance estimated as the glucose disappearance constant (kg). Results Four adolescents developed diabetes during the study (DM), and the rest of the cohort remained non-diabetic (NDM). Baseline PI exceeded the interquartile range of the NDM group in 3 of 4 subjects with DM and all had > 85% reduction from baseline AIRg, and DI, within 6 months of diagnosis. All the subjects with DM gained weight over the course of the study but these changes paralleled those for the NDM group. HOMA-IR increased substantially in 1 of the subjects with DM at the time of diagnosis, but was comparable with baseline in the other 3. The DI and kg of the subjects with DM was below the 10th percentile of the NDM group before and after diagnosis. Conclusion Conversion from NGT to T2DM in adolescents can occur rapidly, and T2DM onset is heralded by a substantial decline in AIRg and DI, as well as increased release of PI. These results support loss of beta-cell function as the proximate step in the development of T2DM in this age group. PMID:25557969

  7. Familial Adult-onset Alexander Disease: Clinical and Neuroradiological Findings of Three Cases

    PubMed Central

    ELMALI, Ayşe Deniz; ÇETİNÇELİK, Ümran; IŞLAK, Civan; UZUN ADATEPE, Nurten; KARAALİ SAVRUN, Feray; YALÇINKAYA, Cengiz

    2016-01-01

    The adult-onset Alexander disease (AOAD) dramatically differs from the early onset AD with respect to clinical and neuroradiological findings. Herein we report the detailed clinical and neuroradiological findings of a Turkish family with AOAD. In all three cases, magnetic resonance imaging revealed marked atrophy of the mesencephalon, bulbus, and cervical spinal cord accompanied with signal abnormalities in the same regions along with supratentorial white matter. Basal ganglia were affected in two cases. Molecular genetic analysis revealed heterozygous mutation in the 8th exon of the glial fibrillary acidic protein gene M451I (c.1245G>A), leading to the diagnosis of AOAD in all cases. PMID:28360791

  8. [Adult-onset Still's disease with liver failure requiring liver transplantation].

    PubMed

    Terán, Alvaro; Casafont, Fernando; Fábrega, Emilio; Martínez-Taboada, Víctor Manuel; Rodríguez-Valverde, Vicente; Pons-Romero, Fernando

    2009-12-01

    We present the case of a 23-year-old man with fever of unknown origin, who developed acute liver failure 2 months after symptom onset, requiring an urgent liver transplantation. The diagnosis of adult-onset Still's disease was established after the reappearance of symptoms after transplantation, and high doses of corticosteroids were used to control disease activity. Subsequently, given the impossibility of tapering the steroid dose, interleukin-1 receptor blocking treatment was started with satisfactory outcome. We also review the published literature.

  9. A novel mouse model that recapitulates adult-onset glycogenosis type 4

    PubMed Central

    Orhan Akman, H.; Emmanuele, Valentina; Kurt, Yasemin Gülcan; Kurt, Bülent; Sheiko, Tatiana; DiMauro, Salvatore; Craigen, William J.

    2015-01-01

    Glycogen storage disease type IV (GSD IV) is a rare autosomal recessive disorder caused by deficiency of the glycogen-branching enzyme (GBE). The diagnostic hallmark of the disease is the accumulation of a poorly branched form of glycogen known as polyglucosan (PG). The disease is clinically heterogeneous, with variable tissue involvement and age at onset. Complete loss of enzyme activity is lethal in utero or in infancy and affects primarily the muscle and the liver. However, residual enzyme activity as low as 5–20% leads to juvenile or adult onset of a disorder that primarily affects the central and peripheral nervous system and muscles and in the latter is termed adult polyglucosan body disease (APBD). Here, we describe a mouse model of GSD IV that reflects this spectrum of disease. Homologous recombination was used to knock in the most common GBE1 mutation p.Y329S c.986A > C found in APBD patients of Ashkenazi Jewish decent. Mice homozygous for this allele (Gbe1ys/ys) exhibit a phenotype similar to APBD, with widespread accumulation of PG. Adult mice exhibit progressive neuromuscular dysfunction and die prematurely. While the onset of symptoms is limited to adult mice, PG accumulates in tissues of newborn mice but is initially absent from the cerebral cortex and heart muscle. Thus, PG is well tolerated in most tissues, but the eventual accumulation in neurons and their axons causes neuropathy that leads to hind limb spasticity and premature death. This mouse model mimics the pathology and pathophysiologic features of human adult-onset branching enzyme deficiency. PMID:26385640

  10. Effect of Pioglitazone on the Course of New-Onset Type 1 Diabetes Mellitus

    PubMed Central

    Tafuri, Kimberly Sue; Godil, Mushtaq Ahmed; Lane, Andrew Harry; Wilson, Thomas Allen

    2013-01-01

    Objective: Type 1 diabetes mellitus (T1DM) is caused by insulin deficiency resulting from progressive destruction of β cells. The histological hallmark of the diabetic islet is mononuclear cell infiltration. Thiazolidinediones (TZDs) activate PPARg and enhance the actions of insulin. Studies in non-obese diabetic and streptocotozin-treated mouse models demonstrated that pretreatment with TZDs prevented the development of T1DM. The purpose of this study was to examine whether pioglitazone, given with insulin, preserved β cell function in patients with new-onset T1DM. Methods: This was a randomized, double-blind, placebo-controlled 24-week study. Subjects received pioglitazone or placebo. Blood sugar, glycated hemoglobin (HbA1c), C-peptide, and liver enzymes were measured at baseline. Boost© stimulated C-peptide responses were measured at baseline and at 24 weeks. Blood sugar, insulin dose, height, weight, and liver enzymes were monitored at each visit. HbA1c was performed every 12 weeks. Results: Of the 15 patients, 8 received pioglitazone, and 7 - placebo. There was no clinical improvement in HbA1c between or within groups at the completion of the study. Mean peak C-peptide values were similar between groups at baseline. Mean peak C-peptide level was slightly higher at 24 weeks in the pioglitazone group compared to the placebo (1.8 vs. 1.5 ng/mL) which was considered as clinically insignificant. The interaction of HbA1c and insulin dose (HbA1c* insulin/kg/day), which combines degree of diabetic control and dose of insulin required to achieve this control, showed transient improvement in the pioglitazone group at 12 weeks but was not sustained at 24 weeks. Conclusion: In this pilot study, pioglitazone did not preserve β cell function when compared to placebo. Conflict of interest:None declared. PMID:24379032

  11. Effects of Age, Gender, Bolus Volume, Bolus Viscosity, and Gustation on Swallowing Apnea Onset Relative to Lingual Bolus Propulsion Onset in Normal Adults

    ERIC Educational Resources Information Center

    Hiss, Susan G.; Strauss, Monica; Treole, Kathleen; Stuart, Andrew; Boutilier, Susan

    2004-01-01

    The purpose of this study was to ascertain the normal relation of swallowing apnea (SA) onset relative to lingual bolus propulsion along with factors that may alter this relation. Forty adults, composed of 10 men and 10 women in each of 2 age groups (i.e., 20-30 and 63-79 years) participated. SA onset was assessed during 5- and 20-ml bolus volumes…

  12. [Pathophysiology, subtypes, and treatments of adult-onset Still's disease: An update].

    PubMed

    Gerfaud-Valentin, M; Sève, P; Hot, A; Broussolle, C; Jamilloux, Y

    2015-05-01

    Adult-onset Still's disease is a rare and difficult to diagnose multisystemic disorder considered as a multigenic autoinflammatory syndrome. Its immunopathogenesis seems to be at the crossroads between inflammasomopathies and hemophagocytic lymphohistiocytosis, the most severe manifestation of the disease. According to recent insights in the pathophysiology and thanks to cohort studies and therapeutic trials, two phenotypes of adult-onset Still's disease may be distinguished: a systemic pattern, initially highly symptomatic and with a higher risk to exhibit life-threatening complications such as reactive hemophagocytic lymphohistiocytosis, where interleukin-1 blockade seems to be very effective, a chronic articular pattern, more indolent with arthritis in the foreground and less severe systemic manifestations, which would threat functional outcome and where interleukin-6 blockade seems to be more effective. This review focuses on these data.

  13. Adult-onset Still's disease as a mask of Hodgkin lymphoma

    PubMed Central

    Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied. PMID:27407236

  14. Adult-onset Still's disease as a mask of Hodgkin lymphoma.

    PubMed

    Dudziec, Ewa; Pawlak-Buś, Katarzyna; Leszczyński, Piotr

    2015-01-01

    Adult-onset Still's disease is a rare disorder, which creates difficulties in making a proper diagnosis. Ambiguous symptoms and results of auxiliary tests, lack of unequivocal diagnostic tests and the need to exclude other causes of the disease are major problems in clinical practice. A case of a 22-year-old woman with dominated recurrent fever, significantly elevated inflammation markers and arthritis is presented. Based on clinical signs after exclusion of infection, hematological and other reasons, the patient was diagnosed with adult-onset Still's disease. Standard treatment, with high doses of glucocorticoids and a disease-modifying drug, was applied, without the anticipated effects. The diagnostic tests were conducted again due to the lack of clinical improvement, increase of inflammatory markers and unusual response to treatment. A new symptom of significance, i.e. mediastinal lymphadenopathy, was found. After the histopathological examination of lymph nodes, Hodgkin's disease was diagnosed and targeted therapy for hematological malignancy was applied.

  15. Epigenetic transgenerational inheritance of vinclozolin induced mouse adult onset disease and associated sperm epigenome biomarkers.

    PubMed

    Guerrero-Bosagna, Carlos; Covert, Trevor R; Haque, Md M; Settles, Matthew; Nilsson, Eric E; Anway, Matthew D; Skinner, Michael K

    2012-12-01

    The endocrine disruptor vinclozolin has previously been shown to promote epigenetic transgenerational inheritance of adult onset disease in the rat. The current study was designed to investigate the transgenerational actions of vinclozolin on the mouse. Transient exposure of the F0 generation gestating female during gonadal sex determination promoted transgenerational adult onset disease in F3 generation male and female mice, including spermatogenic cell defects, testicular abnormalities, prostate abnormalities, kidney abnormalities and polycystic ovarian disease. Pathology analysis demonstrated 75% of the vinclozolin lineage animals developed disease with 34% having two or more different disease states. Interestingly, the vinclozolin induced transgenerational disease was observed in the outbred CD-1 strain, but not the inbred 129 mouse strain. Analysis of the F3 generation sperm epigenome identified differential DNA methylation regions that can potentially be utilized as epigenetic biomarkers for transgenerational exposure and disease.

  16. A positive family history of hypertension might be associated with an accelerated onset of type 2 diabetes: Results from the National Center Diabetes Database (NCDD-02).

    PubMed

    Yamamoto-Honda, Ritsuko; Takahashi, Yoshihiko; Mori, Yasumichi; Yamashita, Shigeo; Yoshida, Yoko; Kawazu, Shoji; Iwamoto, Yasuhiko; Kajio, Hiroshi; Yanai, Hidekatsu; Mishima, Shuichi; Handa, Nobuhiro; Shimokawa, Kotaro; Yoshida, Akiko; Watanabe, Hiroki; Ohe, Kazuhiko; Shimbo, Takuro; Noda, Mitsuhiko

    2017-03-18

    Type 2 diabetes, which is characterized by a combination of decreased insulin secretion and decreased insulin sensitivity, can be delayed or prevented by healthy lifestyle behaviors. Therefore, it is important that the population in general understands their personal risk at an early age to reduce their chances of ever developing the disease. A family history of hypertension is known to be associated with insulin resistance, but the effect of a family history of hypertension on the onset of type 2 diabetes has not well been examined. We performed a retrospective study examining patient age at the time of the diagnosis of type 2 diabetes by analyzing a dataset of 1,299 patients (1,021 men and 278 women) who had been diagnosed as having type 2 diabetes during a health checkup. The mean ± standard deviation of the patient age at the time of the diagnosis of diabetes was 49.1 ± 10.4 years for patients with a family history of hypertension and 51.8 ± 11.4 years for patients without a family history of hypertension (p < 0.001). A multivariate linear regression analysis showed a significant association between a family history of hypertension and a younger age at the time of the diagnosis of type 2 diabetes, independent of a family history of diabetes mellitus and a male sex, suggesting that a positive family history of hypertension might be associated with the accelerated onset of type 2 diabetes.

  17. How does dementia onset in parents influence unmarried adult children's wealth.

    PubMed

    Arora, Kanika

    2016-03-01

    There is a growing concern that long-term care (LTC) needs of older adults lead to negative financial consequences for their family members. This paper examines whether the onset of dementia in parents influences wealth change among unmarried adult children regardless of their status as informal caregivers. Longitudinal data from seven waves (1998-2010) of the Health and Retirement Study (1540 person-wave observations) are used to analyze this question. Unconditional quantile regressions demonstrate that as a result of parental dementia diagnosis, unmarried adult children have lower wealth accumulation above the median of the wealth change distribution. These effects are more pronounced for unmarried adult children without siblings. Further, this response is observed to persist in the subsequent period as well. Both losses in labor income and nursing home expenditures may play a role in leading to wealth declines.

  18. Diabetes Risk May Be Higher for HIV-Positive Adults

    MedlinePlus

    ... Español You Are Here: Home → Latest Health News → Article URL of this page: https://medlineplus.gov/news/fullstory_163344.html Diabetes Risk May Be Higher for HIV-Positive Adults Longer survival with the virus might ...

  19. Non-motor symptoms in patients with adult-onset focal dystonia: Sensory and psychiatric disturbances.

    PubMed

    Conte, Antonella; Berardelli, Isabella; Ferrazzano, Gina; Pasquini, Massimo; Berardelli, Alfredo; Fabbrini, Giovanni

    2016-01-01

    Dystonia is characterized by the presence of involuntary muscle contractions that cause abnormal movements and posture. Adult onset focal dystonia include cervical dystonia, blepharospasm, arm dystonia and laryngeal dystonia. Besides motor manifestations, patients with focal dystonia frequently also display non-motor signs and symptoms. In this paper, we review the evidence of sensory and psychiatric disturbances in adult patients with focal dystonia. Clinical studies and neurophysiological investigations consistently show that the sensory system is involved in dystonia. Several studies have also demonstrated that neuropsychiatric disorders, particularly depression and anxiety, are more frequent in patients with focal dystonia, whereas data on obsessive compulsive disorders are more contrasting.

  20. Adult-onset Still's disease revealed by perimyocarditis and a concomitant reactivation of an EBV infection

    PubMed Central

    Meckenstock, Roderich; Therby, Audrey; Gibault-Genty, Geraldine; Khau, David; Monnier, Sebastien; Greder-Belan, Alix

    2012-01-01

    We describe a 17-year-old patient presenting perimyocarditis as the initial manifestation of the adult-onset Still's disease. Corticotherapy was rapidly successful but induced major acute hepatitis in relation with Epstein-Barr virus reactivation. After 1 year, even if the global outcome is favourable, a slightly lowered ejection fraction still persists. Former case reports and differential diagnosis with reactive haemophagocytic syndrome would be discussed. PMID:23166163

  1. Guinea worm cause of adult onset asthmatic attack, a radiological diagnosis.

    PubMed

    Marchie, T T

    1999-01-01

    A case report of a fifty years old Hausa male from Sokoto town, Nigeria an endemic region of guinea worm infestation, who presented with sudden adult onset of asthmatic attack and was evaluated radiologically and the diagnosis of acute obstructive airway disease was confirmed. It was noted, that there were associated calcified chain of guinea worms in the lung parenchyma. A rare association of acute asthmatic attack. Patient responded there-after to an anti-asthmatic regime of management.

  2. Dioxin (TCDD) induces epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

    PubMed

    Manikkam, Mohan; Tracey, Rebecca; Guerrero-Bosagna, Carlos; Skinner, Michael K

    2012-01-01

    Environmental compounds can promote epigenetic transgenerational inheritance of adult-onset disease in subsequent generations following ancestral exposure during fetal gonadal sex determination. The current study examined the ability of dioxin (2,3,7,8-tetrachlorodibenzo[p]dioxin, TCDD) to promote epigenetic transgenerational inheritance of disease and DNA methylation epimutations in sperm. Gestating F0 generation females were exposed to dioxin during fetal day 8 to 14 and adult-onset disease was evaluated in F1 and F3 generation rats. The incidences of total disease and multiple disease increased in F1 and F3 generations. Prostate disease, ovarian primordial follicle loss and polycystic ovary disease were increased in F1 generation dioxin lineage. Kidney disease in males, pubertal abnormalities in females, ovarian primordial follicle loss and polycystic ovary disease were increased in F3 generation dioxin lineage animals. Analysis of the F3 generation sperm epigenome identified 50 differentially DNA methylated regions (DMR) in gene promoters. These DMR provide potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures. Observations demonstrate dioxin exposure of a gestating female promotes epigenetic transgenerational inheritance of adult onset disease and sperm epimutations.

  3. Breakout character of islet amyloid polypeptide hydrophobic mutations at the onset of type-2 diabetes

    NASA Astrophysics Data System (ADS)

    Frigori, Rafael B.

    2014-11-01

    Toxic fibrillar aggregates of islet amyloid polypeptide (IAPP) appear as the physical outcome of a peptidic phase transition signaling the onset of type-2 diabetes mellitus in different mammalian species. In particular, experimentally verified mutations on the amyloidogenic segment 20-29 in humans, cats, and rats are highly correlated with the molecular aggregation propensities. Through a microcanonical analysis of the aggregation of IAPP20 -29 isoforms, we show that a minimalist one-bead hydrophobic-polar continuum model for protein interactions properly quantifies those propensities from free-energy barriers. Our results highlight the central role of sequence-dependent hydrophobic mutations on hot spots for stabilization, and thus for the engineering, of such biological peptides.

  4. Self–reported diabetes education among Chinese middle–aged and older adults with diabetes

    PubMed Central

    Xu, Hanzhang; Luo, Jianfeng; Wu, Bei

    2016-01-01

    Background To compare self–reported diabetes education among Chinese middle–aged and older adults with diabetes in three population groups: urban residents, migrants in urban settings, and rural residents. Methods We used data from the 2011 China Health and Retirement Longitudinal Study. The sample included 993 participants age 45 and older who reported having diabetes diagnosed from a health professional. We performed multilevel regressions performed to examine the associations between characteristics and different aspects of diabetes education received. Findings Our study shows that 20.24% of the participants received no diabetes education at all. Among those who received information, 46.82% of respondents with diabetes received weight control advice from a health care provider, 90.97% received advice on exercise, 60.37% received diet advice, 35.12% were spoken to smoking control, and only 17.89% of persons were informed of foot care. After controlling socioeconomic factors, life style, number of comorbidities and community factors, we found that compared with migrant population and rural residents, urban residents were more likely to receive diabetes education on diet. Urban residents were also more likely to obtain diabetes education and more aspects of diabetes education comparison with migrants and rural residents. Conclusions Our study suggests diabetes education is a serious concern in China, and a significant proportion of the participants did not receive advice on smoking control and foot care. Rural residents and migrants from rural areas received much less diabetes education compared with urban residents. Efforts to improve diabetes educations are urgently needed in China. PMID:27698998

  5. Prediabetes, undiagnosed diabetes, and diabetes among Mexican adults: findings from the Mexican Health and Aging Study

    PubMed Central

    Kumar, Amit; Wong, Rebeca; Ottenbacher, Kenneth J.; Al Snih, Soham

    2016-01-01

    Purpose The purpose of the study was to examine the prevalence and determinants of prediabetes, undiagnosed diabetes, and diabetes among Mexican adults from a subsample of the Mexican Health and Aging Study. Methods We examined 2012 participants from a subsample of the Mexican Health and Aging Study. Measures included sociodemographic characteristics, body mass index, central obesity, medical conditions, cholesterol, high-density lipoprotein cholesterol, hemoglobin A1c, and vitamin D. Logistic regression was performed to identify factors associated with prediabetes, undiagnosed diabetes, and self-reported diabetes. Results Prevalence of prediabetes, undiagnosed, and self-reported diabetes in this cohort was 44.2%, 18.0%, and 21.4%, respectively. Participants with high waist-hip ratio (1.61, 95% confidence interval [CI] = 1.05–2.45) and high cholesterol (1.85, 95% CI = 1.36–2.51) had higher odds of prediabetes. Overweight (1.68, 95% CI = 1.07–2.64), obesity (2.38, 95% CI = 1.41–4.02), and high waist circumference (1.60, 95% CI = 1.06–2.40) were significantly associated with higher odds of having undiagnosed diabetes. Those residing in a Mexican state with high U.S. migration had lower odds of prediabetes (0.61, 95% CI = 0.45–0.82) and undiagnosed diabetes (0.53, 95% CI = 0.41–0.70). Those engaged in regular physical activity had lower odds of undiagnosed diabetes (0.74, 95% CI = 0.57–0.97). Conclusions There is a high prevalence of prediabetes and undiagnosed diabetes among Mexican adults in this subsample. Findings suggest the need for resources to prevent, identify, and treat persons with prediabetes and undiagnosed diabetes. PMID:26872919

  6. The PTPN22 C1858T gene variant is associated with proinsulin in new-onset type 1 diabetes

    PubMed Central

    2011-01-01

    Background The protein tyrosine phosphatase nonreceptor type 2 (PTPN22) has been established as a type 1 diabetes susceptibility gene. A recent study found the C1858T variant of this gene to be associated with lower residual fasting C-peptide levels and poorer glycemic control in patients with type 1 diabetes. We investigated the association of the C1858T variant with residual beta-cell function (as assessed by stimulated C-peptide, proinsulin and insulin dose-adjusted HbA1c), glycemic control, daily insulin requirements, diabetic ketoacidosis (DKA) and diabetes-related autoantibodies (IA-2A, GADA, ICA, ZnT8Ab) in children during the first year after diagnosis of type 1 diabetes. Methods The C1858T variant was genotyped in an international cohort of children (n = 257 patients) with newly diagnosed type 1 diabetes during 12 months after onset. We investigated the association of this variant with liquid-meal stimulated beta-cell function (proinsulin and C-peptide) and antibody status 1, 6 and 12 months after onset. In addition HbA1c and daily insulin requirements were determined 1, 3, 6, 9 and 12 months after diagnosis. DKA was defined at disease onset. Results A repeated measurement model of all time points showed the stimulated proinsulin level is significantly higher (22%, p = 0.03) for the T allele carriers the first year after onset. We also found a significant positive association between proinsulin and IA levels (est.: 1.12, p = 0.002), which did not influence the association between PTPN22 and proinsulin (est.: 1.28, p = 0.03). Conclusions The T allele of the C1858T variant is positively associated with proinsulin levels during the first 12 months in newly diagnosed type 1 diabetes children. PMID:21429197

  7. Vertical sleeve gastrectomy improves glucose and lipid metabolism and delays diabetes onset in UCD-T2DM rats.

    PubMed

    Cummings, Bethany P; Bettaieb, Ahmed; Graham, James L; Stanhope, Kimber L; Kowala, Mark; Haj, Fawaz G; Chouinard, Michael L; Havel, Peter J

    2012-08-01

    Vertical sleeve gastrectomy (VSG) has gained interest as a low morbidity bariatric surgery, which is effective in producing weight loss and causing type 2 diabetes resolution. However, the efficacy of VSG to prevent the onset of type 2 diabetes has not been previously investigated. VSG or sham surgery was performed on 2-month-old prediabetic male University of California Davis-type 2 diabetes mellitus rats. Sham-operated animals were either sham-operated ad libitum fed (S-AL) or were weight-matched to VSG-operated animals (S-WM). Diabetes onset was determined by weekly nonfasting blood glucose measurements. Animals underwent oral glucose tolerance tests at 1 and 4 months after surgery and indirect calorimetry at 1.5 months after surgery. VSG surgery significantly delayed diabetes onset compared with both S-AL and S-WM animals. VSG-operated animals ate 23% less and weighed 20% less than S-AL. Energy expenditure did not differ between VSG-operated animals and controls. Results from the oral glucose tolerance tests demonstrate improved glucose tolerance and islet function in VSG-operated animals compared with S-AL and S-WM. Nutrient-stimulated glucagon-like peptide (GLP)-1, GLP-2, and peptide YY excursions were greater in VSG-operated animals. VSG surgery resulted in decreased fasting plasma insulin, ghrelin and lipid concentrations, and markedly higher fasting plasma adiponectin and bile acid concentrations, independent of body weight. Increases of circulating bile acid concentrations were due to selective increases of taurine-conjugated bile acids. Thus, VSG delays type 2 diabetes onset in the University of California Davis-type 2 diabetes mellitus rat, independent of body weight. This is potentially mediated by increases of circulating bile acids, adiponectin, and nutrient-stimulated GLP-1 secretion and decreased circulating ghrelin concentrations.

  8. Comparison between New-Onset and Old-Diagnosed Type 2 Diabetes with Ketosis in Rural Regions of China.

    PubMed

    Du, Shichun; Yang, Xia; Shi, Degang; Su, Qing

    2016-01-01

    Objectives. Type 2 diabetes (T2D) with ketosis was common because of late diagnosis and lacking adequate treatment in rural regions of China. This study aimed to provide the data of T2D with ketosis among inpatients in a south-west border city of China. Methods. Data of 371 patients of T2D with ketosis who were hospitalized between January 2011 and July 2015 in Baoshan People's Hospital, Yunnan, China, were analyzed. New-onset and old-diagnosed T2D patients presenting with ketosis were compared according to clinical characteristics, laboratory results, and chronic diabetic complications. Results. Overall, the blood glucose control was poor in our study subjects. Male predominated in both groups (male prevalence was 68% in new-onset and 64% in old-diagnosed groups). Overweight and obesity accounted for 50% in new-onset and 46% in old-diagnosed cases. Inducements of ketosis were 13.8% in new-onset and 38.7% in old-diagnosed patients. Infections were the first inducements in both groups. The prevalence of chronic complications of diabetes was common in both groups. Conclusions. More medical supports were needed for the early detection and adequate treatment of diabetes in rural areas of China.

  9. Chinese new immigrant mothers' perception about adult-onset non-communicable diseases prevention during childhood.

    PubMed

    Wang, Linda Dong Ling; Lam, Wendy Wing Tak; Wu, Joseph Tsz Kei; Fielding, Richard

    2015-12-01

    Many non-communicable diseases (NCDs) are largely preventable via behaviour change and healthy lifestyle, which may be best established during childhood. This study sought insights into Chinese new immigrant mothers' perceptions about adult-onset NCDs prevention during childhood. Twenty-three semi-structured interviews were carried out with new immigrant mothers from mainland China who had at least one child aged 14 years or younger living in Hong Kong. Interviews were audio taped, transcribed and analysed using a Grounded Theory approach. The present study identified three major themes: perceived causes of adult NCDs, beliefs about NCDs prevention and everyday health information practices. Unhealthy lifestyle, contaminated food and environment pollution were perceived as the primary causes of adult NCDs. Less than half of the participants recognized that parents had responsibility for helping children establish healthy behaviours from an early age to prevent diseases in later life. Most participants expressed helplessness about chronic diseases prevention due to lack of knowledge of prevention, being perceived as beyond individual control. Many participants experienced barriers to seeking health information, the most common sources of health information being interpersonal conversation and television. Participants' everyday information practice was passive and generally lacked awareness regarding early prevention of adult-onset NCDs. Updated understanding of this issue has notable implications for future health promotion interventions.

  10. Body mass index trajectory patterns and changes in visceral fat and glucose metabolism before the onset of type 2 diabetes

    PubMed Central

    Kuwahara, Keisuke; Honda, Toru; Nakagawa, Tohru; Yamamoto, Shuichiro; Hayashi, Takeshi; Mizoue, Tetsuya

    2017-01-01

    We investigated BMI trajectory patterns before diabetes diagnosis and examined associated changes in visceral adiposity and glucose metabolism. 23,978 non-diabetic Japanese participants (2,789 women) aged 30–64 years were assessed with a mean follow-up of 7.6 years. Diabetes was diagnosed via fasting glucose, HbA1c, and self-report. Latent-class trajectory analyses were performed to identify BMI trajectories. Longitudinal changes in BMI, visceral adiposity, and glucose metabolism were estimated using mixed models. 1,892 individuals developed diabetes. Three distinct BMI trajectories were identified in adults developing and not developing diabetes, respectively. Among adults developing diabetes, 47.3% were classified as “medium BMI” (n = 895), and had increased mean BMI within the obesity category before diagnosis. The “low BMI” group (38.4%, n = 726) had an initial mean BMI of 21.9 kg/m2, and demonstrated small weight gain. The “high BMI” group (n = 271) were severely obese and showed greater increase in BMI until diagnosis. All groups which developed diabetes showed absolute and/or relative increase in visceral fat and impaired β-cell compensation for insulin resistance. All groups not developing diabetes showed measured variables were relatively stable during observation. These data suggest that visceral fat gain may induce β-cell failure in compensation for insulin resistance, resulting in diabetes regardless of obesity level. PMID:28266592

  11. Distinguishing adult-onset asthma from COPD: a review and a new approach

    PubMed Central

    Abramson, Michael J; Perret, Jennifer L; Dharmage, Shyamali C; McDonald, Vanessa M; McDonald, Christine F

    2014-01-01

    Adult-onset asthma and chronic obstructive pulmonary disease (COPD) are major public health burdens. This review presents a comprehensive synopsis of their epidemiology, pathophysiology, and clinical presentations; describes how they can be distinguished; and considers both established and proposed new approaches to their management. Both adult-onset asthma and COPD are complex diseases arising from gene–environment interactions. Early life exposures such as childhood infections, smoke, obesity, and allergy influence adult-onset asthma. While the established environmental risk factors for COPD are adult tobacco and biomass smoke, there is emerging evidence that some childhood exposures such as maternal smoking and infections may cause COPD. Asthma has been characterized predominantly by Type 2 helper T cell (Th2) cytokine-mediated eosinophilic airway inflammation associated with airway hyperresponsiveness. In established COPD, the inflammatory cell infiltrate in small airways comprises predominantly neutrophils and cytotoxic T cells (CD8 positive lymphocytes). Parenchymal destruction (emphysema) in COPD is associated with loss of lung tissue elasticity, and small airways collapse during exhalation. The precise definition of chronic airflow limitation is affected by age; a fixed cut-off of forced expiratory volume in 1 second/forced vital capacity leads to overdiagnosis of COPD in the elderly. Traditional approaches to distinguishing between asthma and COPD have highlighted age of onset, variability of symptoms, reversibility of airflow limitation, and atopy. Each of these is associated with error due to overlap and convergence of clinical characteristics. The management of chronic stable asthma and COPD is similarly convergent. New approaches to the management of obstructive airway diseases in adults have been proposed based on inflammometry and also multidimensional assessment, which focuses on the four domains of the airways, comorbidity, self-management, and

  12. Pesticide methoxychlor promotes the epigenetic transgenerational inheritance of adult-onset disease through the female germline.

    PubMed

    Manikkam, Mohan; Haque, M Muksitul; Guerrero-Bosagna, Carlos; Nilsson, Eric E; Skinner, Michael K

    2014-01-01

    Environmental compounds including fungicides, plastics, pesticides, dioxin and hydrocarbons can promote the epigenetic transgenerational inheritance of adult-onset disease in future generation progeny following ancestral exposure during the critical period of fetal gonadal sex determination. This study examined the actions of the pesticide methoxychlor to promote the epigenetic transgenerational inheritance of adult-onset disease and associated differential DNA methylation regions (i.e. epimutations) in sperm. Gestating F0 generation female rats were transiently exposed to methoxychlor during fetal gonadal development (gestation days 8 to 14) and then adult-onset disease was evaluated in adult F1 and F3 (great-grand offspring) generation progeny for control (vehicle exposed) and methoxychlor lineage offspring. There were increases in the incidence of kidney disease, ovary disease, and obesity in the methoxychlor lineage animals. In females and males the incidence of disease increased in both the F1 and the F3 generations and the incidence of multiple disease increased in the F3 generation. There was increased disease incidence in F4 generation reverse outcross (female) offspring indicating disease transmission was primarily transmitted through the female germline. Analysis of the F3 generation sperm epigenome of the methoxychlor lineage males identified differentially DNA methylated regions (DMR) termed epimutations in a genome-wide gene promoters analysis. These epimutations were found to be methoxychlor exposure specific in comparison with other exposure specific sperm epimutation signatures. Observations indicate that the pesticide methoxychlor has the potential to promote the epigenetic transgenerational inheritance of disease and the sperm epimutations appear to provide exposure specific epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.

  13. The Onset of Depression During the Great Recession: Foreclosure and Older Adult Mental Health

    PubMed Central

    Cagney, Kathleen A.; Browning, Christopher R.; Iveniuk, James; English, Ned

    2014-01-01

    Objectives. We examined neighborhood-level foreclosure rates and their association with onset of depressive symptoms in older adults. Methods. We linked data from the National Social Life, Health, and Aging Project (2005–2006 and 2010–2011 waves), a longitudinal, nationally representative survey, to data on zip code–level foreclosure rates, and predicted the onset of depressive symptoms using logit-linked regression. Results. Multiple stages of the foreclosure process predicted the onset of depressive symptoms, with adjustment for demographic characteristics and changes in household assets, neighborhood poverty, and visible neighborhood disorder. A large increase in the number of notices of default (odds ratio [OR] = 1.75; 95% confidence interval [CI] = 1.14, 2.67) and properties returning to ownership by the bank (OR = 1.62; 95% CI = 1.06, 2.47) were associated with depressive symptoms. A large increase in properties going to auction was suggestive of such an association (OR = 1.45; 95% CI = 0.96, 2.19). Age, fewer years of education, and functional limitations also were predictive. Conclusions. Increases in neighborhood-level foreclosure represent an important risk factor for depression in older adults. These results accord with previous studies suggesting that the effects of economic crises are typically first experienced through deficits in emotional well-being. PMID:24446830

  14. Frequency of Fish Intake and Diabetes among Adult Indians

    PubMed Central

    Agrawal, Sutapa; Millett, Christopher; Subramanian, S. V.; Ebrahim, Shah

    2014-01-01

    Objectives: Recent studies have shown that the choice of foods plays a role in diabetes prevention. However, little empirical evidence on this association exists in developing countries. We aimed to examine the association between frequency of fish intake and self-reported diabetes status among adult men and women in India. Methods: Analysis of cross-sectional data from participants in India's third National Family Health Survey conducted during 2005–2006 was performed. Associations between fish intake, determined by frequency of consumption (daily, weekly, occasionally, and never), and self-reported diabetes were estimated using multivariable-adjusted models in 99,574 women, 56,742 men, and 39,257 couples aged 20–49 years after adjusting for frequency of consumption of other food items, body mass index (BMI) status, tobacco smoking, alcohol drinking, watching television, age, education, living standard of the household, and place of residence. Results: After adjustment for other dietary, lifestyle, and socioeconomic and demographic characteristics, odds of diabetes were 2 times higher (odds ratio [OR]: 2.02; 95% confidence interval [CI], 1.59–2.57; p < 0.0001) among those who reported consuming fish daily compared to those who never consumed fish. Weekly fish intake was also associated with a higher odds of having diabetes (OR: 1.55; 95% CI, 1.25–1.93; p < 0.0001). The adjusted effect of daily fish intake on diabetes was greater among men (OR: 2.46; 95% CI, 1.66–3.65) than among women (OR: 1.72; 95% CI, 1.26–2.33). In cross-spousal sensitivity analysis, the odds of a husband having diabetes was also associated with wife's daily/weekly consumption of fish (OR: 1.36; 95% CI, 0.92–2.01) and the odds of a wife having diabetes was also associated with husband's daily/weekly consumption of fish (OR: 1.21; 95% CI, 0.87–1.68). Conclusions: In a large nationally representative sample of adult men and women in India, daily or weekly fish intake was

  15. Juvenile versus adult-onset ankylosing spondylitis -- clinical, radiographic, and social outcomes. a systematic review.

    PubMed

    Jadon, Deepak R; Ramanan, Athimalaipet V; Sengupta, Raj

    2013-11-01

    Ankylosing spondylitis (AS) has 2 main modes of onset: juvenile-onset AS (JoAS) and adult-onset AS (AoAS). It is not known whether JoAS is a subtype of AS, or AS modulated by early age of onset and longer disease duration. We performed a systematic review of the literature, identifying 12 articles and 1 abstract directly comparing JoAS and AoAS cohorts, with observational study design. Patients with JoAS appear to have more peripheral joint involvement both clinically and radiographically (especially knees and ankles) and more root joint involvement (hips and shoulders); they are more likely to proceed to hip arthroplasty and often initially present with peripheral rather than axial symptoms. Patients with AoAS appear to have more axial symptoms and radiographic disease, particularly in the lumbar spine, and worse axial metrology. In terms of other characteristics, more evidence is needed to confidently state whether JoAS and AoAS are different.

  16. Empowered Diabetes Management: Life Coaching and Pharmacist Counseling for Employed Adults with Diabetes

    ERIC Educational Resources Information Center

    Nishita, Christy; Cardazone, Gina; Uehara, Denise Lea; Tom, Tammy

    2013-01-01

    The Hawai'i Demonstration to Maintain Independence and Employment was a randomized controlled trial examining the effect of a participant-driven, multicomponent intervention on 190 employed adults with diabetes, 36% of whom were Asian and 35% of whom were Native Hawaiian or Pacific Islander. A no treatment concurrent control group was used, and…

  17. Gut microbial markers are associated with diabetes onset, regulatory imbalance, and IFN-γ level in NOD mice.

    PubMed

    Krych, Ł; Nielsen, D S; Hansen, A K; Hansen, C H F

    2015-01-01

    Gut microbiota regulated imbalances in the host's immune profile seem to be an important factor in the etiology of type 1 diabetes (T1D), and identifying bacterial markers for T1D may therefore be useful in diagnosis and prevention of T1D. The aim of the present study was to investigate the link between the early gut microbiota and immune parameters of non-obese diabetic (NOD) mice in order to select alleged bacterial markers of T1D. Gut microbial composition in feces was analyzed with 454/FLX Titanium (Roche) pyro-sequencing and correlated with diabetes onset age and immune cell populations measured in diabetic and non-diabetic mice at 30 weeks of age. The early gut microbiota composition was found to be different between NOD mice that later in life were classified as diabetic or non-diabetic. Those differences were further associated with changes in FoxP3(+) regulatory T cells, CD11b(+) dendritic cells, and IFN-γ production. The model proposed in this work suggests that operational taxonomic units classified to S24-7, Prevotella, and an unknown Bacteriodales (all Bacteroidetes) act in favor of diabetes protection whereas members of Lachnospiraceae, Ruminococcus, and Oscillospira (all Firmicutes) promote pathogenesis.

  18. Linkage of type 2 diabetes mellitus and of age at onset to a genetic location on chromosome 10q in Mexican Americans.

    PubMed Central

    Duggirala, R; Blangero, J; Almasy, L; Dyer, T D; Williams, K L; Leach, R J; O'Connell, P; Stern, M P

    1999-01-01

    Since little is known about chromosomal locations harboring type 2 diabetes-susceptibility genes, we conducted a genomewide scan for such genes in a Mexican American population. We used data from 27 low-income extended Mexican American pedigrees consisting of 440 individuals for whom genotypic data are available for 379 markers. We used a variance-components technique to conduct multipoint linkage analyses for two phenotypes: type 2 diabetes (a discrete trait) and age at onset of diabetes (a truncated quantitative trait). For the multipoint analyses, a subset of 295 markers was selected on the basis of optimal spacing and informativeness. We found significant evidence that a susceptibility locus near the marker D10S587 on chromosome 10q influences age at onset of diabetes (LOD score 3.75) and is also linked with type 2 diabetes itself (LOD score 2.88). This susceptibility locus explains 63.8%+/-9.9% (P=. 000016) of the total phenotypic variation in age at onset of diabetes and 65.7%+/-10.9% (P=.000135) of the total variation in liability to type 2 diabetes. Weaker evidence was found for linkage of diabetes and of age at onset to regions on chromosomes 3p, 4q, and 9p. In conclusion, our strongest evidence for linkage to both age at onset of diabetes and type 2 diabetes itself in the Mexican American population was for a region on chromosome 10q. PMID:10090898

  19. The DPP4 inhibitor linagliptin delays the onset of diabetes and preserves β-cell mass in non-obese diabetic mice.

    PubMed

    Jelsing, Jacob; Vrang, Niels; van Witteloostuijn, Søren B; Mark, Michael; Klein, Thomas

    2012-09-01

    Recent data indicate that dipeptidyl peptidase 4 (DPP4) inhibitors have anti-inflammatory and β-cell-sparing effects in animal models of type 1 diabetes. To evaluate the effects of the DPP4 inhibitor linagliptin on β-cell mass and insulinitis, we examined the progression of diabetes (blood glucose >11  mmol/l) in non-obese diabetic (NOD) mice with terminal stereological assessment of cellular pancreatic changes. Female NOD mice were fed a normal chow diet or a diet containing linagliptin 0.083  g/kg chow for 60 days. At study end, the incidence of diabetes in linagliptin-treated mice was reduced by almost 50% compared with vehicle (10 of 31 mice vs 18 of 30 mice, P=0.021). The total islet mass and total β-cell mass, identified by insulin immunoreactivity, were greater in non-diabetic linagliptin-treated mice compared with non-diabetic vehicle-treated mice (P<0.01 for both) but were greatly reduced in diabetic mice irrespective of treatment. No changes were seen in the α, δ and γ endocrine cell pool. Moreover, the total mass of lymphocyte insulinitis was significantly reduced in linagliptin-treated mice compared with vehicle. The data indicate that linagliptin treatment delays the onset of diabetes in NOD mice by protecting β-cell mass.

  20. Stress increases the risk of type 2 diabetes onset in women: A 12-year longitudinal study using causal modelling

    PubMed Central

    Oldmeadow, Christopher; Hure, Alexis; Luu, Judy; Loxton, Deborah

    2017-01-01

    Background Type 2 diabetes is associated with significant morbidity and mortality. Modifiable risk factors have been found to contribute up to 60% of type 2 diabetes risk. However, type 2 diabetes continues to rise despite implementation of interventions based on traditional risk factors. There is a clear need to identify additional risk factors for chronic disease prevention. The aim of this study was to examine the relationship between perceived stress and type 2 diabetes onset, and partition the estimates into direct and indirect effects. Methods and findings Women born in 1946–1951 (n = 12,844) completed surveys for the Australian Longitudinal Study on Women’s Health in 1998, 2001, 2004, 2007 and 2010. The total causal effect was estimated using logistic regression and marginal structural modelling. Controlled direct effects were estimated through conditioning in the regression model. A graded association was found between perceived stress and all mediators in the multivariate time lag analyses. A significant association was found between hypertension, as well as physical activity and body mass index, and diabetes, but not smoking or diet quality. Moderate/high stress levels were associated with a 2.3-fold increase in the odds of diabetes three years later, for the total estimated effect. Results were only slightly attenuated when the direct and indirect effects of perceived stress on diabetes were partitioned, with the mediators only explaining 10–20% of the excess variation in diabetes. Conclusions Perceived stress is a strong risk factor for type 2 diabetes. The majority of the effect estimate of stress on diabetes risk is not mediated by the traditional risk factors of hypertension, physical activity, smoking, diet quality, and body mass index. This gives a new pathway for diabetes prevention trials and clinical practice. PMID:28222165

  1. [Proportion of low insulin responders to glucose among the offspring of maturity-onset diabetics (author's transl)].

    PubMed

    Vague, P; Ramahandridona, G; Vague, J

    1975-03-01

    The insensitivity of B cells to glucose, a characteristic of mild essential glucose intolerance may be estimated in a given individual by the comparison of the immediate plasma insulin response to glucose (0 to 10' plasma insulin area or iG) with that to Tolbutamide (iT). It was shown that iG/iT clearly differentiates between nondiabetics and diabetics, whatever their body weight. All the diabetics had an iT/iT lower than 0,65. A high proportion of the offspring of diabetics had an iG/iT ratio in the diabetic range, whether or not they were diabetic. Among these subjects aged from 10 to 49 and weighing between 90 and 144% of their ideal body weight, the iG/iT ratio was not correlated with age nor with relative body weight while the K value was negatively correlated with age. We were thus able to look for the frequency of a "diabetic" iG/iT ratio in the offspring of diabetics, For this in sibships in which all the sibs had been tested, one subject was selected by randomisation. A "diabetic" iG/iT ratio was observed in 7 of 41 subjects with no family history of diabetes, in 27 of 50 with one parent having clinical, maturity-onset diabetes melitus, and in 15 of 19 subjects with two diabetic parents. These results are not compatible with the hypothesis of recessive transmission of the "low insulin response to glucose" characteristic.

  2. Management of Type 1 Diabetes in Older Adults

    PubMed Central

    Dhaliwal, Ruban; Weinstock, Ruth S.

    2014-01-01

    In Brief Older adults with type 1 diabetes are at high risk for severe hypoglycemia and may have serious comorbid conditions. Problems with cognition, mobility, dexterity, vision, hearing, depression, and chronic pain interfere with the ability to follow complex insulin regimens. With the development of geriatric syndromes, unpredictable eating, and frailty, treatment regimens must be modified with the goal of minimizing hypoglycemia and severe hyperglycemia and maximizing quality of life. PMID:26246751

  3. Adult Onset Still's Disease: A Review on Diagnostic Workup and Treatment Options

    PubMed Central

    Gopalarathinam, Rajesh; Orlowsky, Eric; Kesavalu, Ramesh; Yelaminchili, Sreeteja

    2016-01-01

    Adult onset Still's disease (AOSD) is a rare systemic inflammatory disease of unknown etiology and pathogenesis that presents in 5 to 10% of patients as fever of unknown origin (FUO) accompanied by systemic manifestations. We report an interesting case of a 33-year-old African-American male who presented with one-month duration of FUO along with skin rash, sore throat, and arthralgia. After extensive workup, potential differential diagnoses were ruled out and the patient was diagnosed with AOSD based on the Yamaguchi criteria. The case history, incidence, pathogenesis, clinical manifestations, differential diagnoses, diagnostic workup, treatment modalities, and prognosis of AOSD are discussed in this case report. PMID:27042373

  4. Piriform sinus carcinoma with a paraneoplastic syndrome misdiagnosed as adult onset Still's disease: a case report.

    PubMed

    Yang, Liu; Li, Wen; Du, Jintao

    2015-01-01

    Paraneoplastic syndromes (PS) occur less commonly in association with otolaryngologic neoplasms than other carcinomas such as those of lung or breast. Piriform sinus carcinoma with PS is extremely rare. We here report a case of piriform sinus carcinoma accompanied by PS that was initially misdiagnosed as adult onset Still's disease and describe our diagnosis and treatment. One lesson we have drawn from the experience of this misdiagnosis is that PS symptoms may manifest before the primary tumor is evident and complicate the diagnostic process.

  5. Adult onset primary focal dystonia of the foot: an orthopaedic intervention.

    PubMed

    Logan, Loretta; Resseque, Barbara; Dontamsetti, Monica Sakshi

    2016-03-30

    A 54-year-old woman presented to a foot centre with a chief symptom of cramping in her toes, which, she believed, was of a secondary cause originating from a bunion. She was treated conservatively; however, she returned a month later as the symptoms had progressed to painful cramping of toes, toe-curling and instability while walking, due to involuntary movement of her toes. It was believed that the patient presented with a rare case of primary adult onset focal foot dystonia. This case report explains dystonia further in detail and delves into the different treatment and management options available today, including the unique orthopaedic intervention provided for this patient.

  6. Adult-onset opsoclonus-myoclonus syndrome due to West Nile Virus treated with intravenous immunoglobulin.

    PubMed

    Hébert, Julien; Armstrong, David; Daneman, Nick; Jain, Jennifer Deborah; Perry, James

    2017-02-01

    A 63-year-old female with no significant past medical history was presented with a 5-day history of progressive opsoclonus-myoclonus, headaches, and fevers. Her workup was significant only for positive West-Nile Virus serum serologies. She received a 2-day course of intravenous immunoglobulin (IvIG). At an 8-week follow up, she had a complete neurological remission. Adult-onset opsoclonus-myoclonus syndrome is a rare condition for which paraneoplastic and infectious causes have been attributed. To our knowledge, this is the first case reported of opsoclonus-myoclonus secondary to West-Nile Virus treated with intravenous immunoglobulin monotherapy.

  7. Herpes Zoster Meningitis Complicating Combined Tocilizumab and Cyclosporine Therapy for Adult-Onset Still's Disease

    PubMed Central

    Tsurukawa, Shinichiro; Iwanaga, Nozomi; Izumi, Yasumori; Shirakawa, Atsunori; Kawahara, Chieko; Shukuwa, Tetsuo; Inamoto, Miwako; Kawakami, Atsushi; Migita, Kiyoshi

    2016-01-01

    A 56-year-old female with refractory adult-onset Still's disease presented with ocular herpes zoster infection during TCZ treatment. After three days of acyclovir treatment (5 mg/kg), she developed a severe headache and high fever. Viral DNA isolation and cerebral spinal fluid abnormalities led to a herpes zoster meningitis diagnosis. Her meningitis was cured by high doses of intravenous acyclovir (10 mg/kg for 14 days). To our knowledge, this is the first report of meningeal herpes zoster infection in rheumatic diseases under TCZ treatment. PMID:27092286

  8. Adult-onset Still disease with peculiar persistent plaques and papules.

    PubMed

    Yoshifuku, A; Kawai, K; Kanekura, T

    2014-06-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder characterized clinically by high spiking fever, polyarthralgia/arthritis, a salmon-pink evanescent rash, predominantly neutrophilic leucocytosis, lymphadenopathy, liver dysfunction, and splenomegaly. Recently, a nonclassic, nonevanescent skin rash has been reported. We report a 27-year-old woman with AOSD showing persistent pruritic papular lesions. Histologically, dyskeratotic keratinocytes were seen in the upper epidermis. We describe this case in detail and review the previous literature. Nonclassic pruritic eruptions with characteristic dyskeratotic keratinocytes might provide an important clue for the diagnosis of AOSD.

  9. Mutations in KCNJ11 are associated with the development of autosomal dominant, early-onset type 2 diabetes

    PubMed Central

    Nagashima, Kazuaki; Yasuda, Takao; Liu, Yanjun; Hu, Hai-rong; He, Guang; Feng, Bo; Zhao, Mingming; Zhuang, Langen; Zheng, Taishan; Friedman, Theodore C.; Xiang, Kunsan

    2017-01-01

    Aims/hypothesis More than 90% of Chinese familial early-onset type 2 diabetes mellitus is genetically unexplained. To investigate the molecular aetiology, we identified and characterised whether mutations in the KCNJ11 gene are responsible for these families. Methods KCNJ11 mutations were screened for 96 familial early-onset type 2 diabetic probands and their families. Functional significance of the identified mutations was confirmed by physiological analysis, molecular modelling and population survey. Results Three novel KCNJ11 mutations, R27H, R192H and S116F117del, were identified in three families with early-onset type 2 diabetes mellitus. Mutated KCNJ11 with R27H or R192H markedly reduced ATP sensitivity (E23K>R27H>C42R>R192H>R201H), but no ATP-sensitive potassium channel currents were detected in the loss-of-function S116F117del channel in vitro. Molecular modelling indicated that R192H had a larger effect on the channel ATP-binding pocket than R27H, which may qualitatively explain why the ATP sensitivity of the R192H mutation is seven times less than R27H. The shape of the S116F117del channel may be compressed, which may explain why the mutated channel had no currents. Discontinuation of insulin and implementation of sulfonylureas for R27H or R192H carriers and continuation/switch to insulin therapy for S116F117del carriers resulted in good glycaemic control. Conclusions/interpretation Our results suggest that genetic diagnosis for the KCNJ11 mutations in familial early-onset type 2 diabetes mellitus may help in understanding the molecular aetiology and in providing more personalised treatment for these specific forms of diabetes in Chinese and other Asian patients. PMID:24018988

  10. Rapid onset of syndrome of inappropriate antidiuretic hormone secretion induced by duloxetine in an elderly type 2 diabetic patient with painful diabetic neuropathy.

    PubMed

    Kamei, Shinji; Kaneto, Hideaki; Tanabe, Akihito; Irie, Shintaro; Hirata, Yurie; Shimoda, Masashi; Kohara, Kenji; Mune, Tomoatsu; Kaku, Kohei

    2015-05-01

    Diabetic neuropathy is the most common diabetic complication. Duloxetine, a serotonin noradrenaline reuptake inhibitor (SNRI), is widely used for the treatment of diabetic painful neuropathy (DPN) because of the efficacy and safety profile. Syndrome of inappropriate antidiuretic hormone secretion, which is strongly associated duloxetine, is a rare but occasionally life-threatening adverse effect. Here, we report a case of syndrome of inappropriate antidiuretic hormone secretion that rapidly developed after starting duloxetine in an elderly Japanese female type 2 diabetes mellitus patient. Furthermore, we discuss the possible relationship between the onset of syndrome of inappropriate antidiuretic hormone secretion and the gene polymorphism of cytochrome P450 isoform 1A2 and 2D6, both of which are responsible for duloxetine metabolism.

  11. Adult-onset Still's disease and chronic recurrent multifocal osteomyelitis: a hitherto undescribed manifestation of autoinflammation.

    PubMed

    Rech, J; Manger, B; Lang, B; Schett, G; Wilhelm, M; Birkmann, J

    2012-06-01

    Still's disease and chronic recurrent multifocal osteomyelitis (CRMO) are febrile rheumatic diseases of unknown etiology, which predominantly affect children but can also have their initial manifestation in adults. Both can present as intermittent, relapsing episodes and are considered potential candidates within the expanding spectrum of autoinflammatory disorders, although no genetic abnormalities have been described for either of them. Here, we describe a man with an initial manifestation of abacterial multifocal osteitis at the age of 41. During a relapsing-remitting course of his illness, he increasingly developed symptoms of adult-onset Still's disease (AOSD), and the diagnosis was established according to the Yamaguchi criteria. When treated with anakinra, not only the acute symptoms disappeared promptly, but also the osteitis went into complete remission. This is to our knowledge the first description of a simultaneous occurrence of these two manifestations of autoinflammation in adulthood.

  12. Geometric phase transition in the cellular network of the pancreatic islets may underlie the onset of type 1diabetes

    NASA Astrophysics Data System (ADS)

    Wang, Xujing

    Living systems are characterized by complexity in structure and emergent dynamic orders. In many aspects the onset of a chronic disease resembles phase transition in a dynamic system: quantitative changes accumulate largely unnoticed until a critical threshold is reached, which causes abrupt qualitative changes of the system. In this study we investigate this idea in a real example, the insulin-producing pancreatic islet β-cells and the onset of type 1 diabetes. Within each islet, the β-cells are electrically coupled to each other, and function as a network with synchronized actions. Using percolation theory we show how normal islet function is intrinsically linked to network connectivity, and the critical point where the islet cellular network loses site percolation, is consistent with laboratory and clinical observations of the threshold β-cell loss that causes islet functional failure. Numerical simulations confirm that the islet cellular network needs to be percolated for β-cells to synchronize. Furthermore, the interplay between site percolation and bond strength predicts the existence of a transient phase of islet functional recovery after disease onset and introduction of treatment, potentially explaining a long time mystery in the clinical study of type 1 diabetes: the honeymoon phenomenon. Based on these results, we hypothesized that the onset of T1D may be the result of a phase transition of the islet β-cell network. We further discuss the potential applications in identifying disease-driving factors, and the critical parameters that are predictive of disease onset.

  13. Culture-independent identification of gut bacteria correlated with the onset of diabetes in a rat model.

    PubMed

    Roesch, Luiz F W; Lorca, Graciela L; Casella, George; Giongo, Adriana; Naranjo, Andres; Pionzio, Arianna M; Li, Nan; Mai, Volker; Wasserfall, Clive H; Schatz, Desmond; Atkinson, Mark A; Neu, Josef; Triplett, Eric W

    2009-05-01

    Bacteria associated with the onset of type 1 diabetes in a rat model system were identified. In two experiments, stool samples were collected at three time points after birth from bio-breeding diabetes-prone (BB-DP) and bio-breeding diabetes-resistant (BB-DR) rats. DNA was isolated from these samples and the 16S rRNA gene was amplified using universal primer sets. In the first experiment, bands specific to BB-DP and BB-DR genotypes were identified by automated ribosomal intergenic spacer analysis at the time of diabetes onset in BB-DP. Lactobacillus and Bacteroides strains were identified in the BB-DR- and BB-DP-specific bands, respectively. Sanger sequencing showed that the BB-DP and BB-DR bacterial communities differed significantly but too few reads were available to identify significant differences at the genus or species levels. A second experiment confirmed these results using higher throughput pyrosequencing and quantitative PCR of 16S rRNA with more rats per genotype. An average of 4541 and 3381 16S rRNA bacterial reads were obtained from each of the 10 BB-DR and 10 BB-DP samples collected at time of diabetes onset. Nine genera were more abundant in BB-DP whereas another nine genera were more abundant in BB-DR. Thirteen and eleven species were more abundant in BB-DP and BB-DR, respectively. An average of 23% and 10% of all reads could be classified at the genus and species levels, respectively. Quantitative PCR verified the higher abundance of Lactobacillus and Bifidobacterium in the BB-DR samples. Whether these changes are caused by diabetes or are involved in the development of the disease is unknown.

  14. The ocular motor features of adult-onset alexander disease: a case and review of the literature.

    PubMed

    Pfeffer, Gerald; Abegg, Mathias; Vertinsky, A Talia; Ceccherini, Isabella; Caroli, Francesco; Barton, Jason J S

    2011-06-01

    A 51-year-old Chinese man presented with gaze-evoked nystagmus, impaired smooth pursuit and vestibular ocular reflex cancellation, and saccadic dysmetria, along with a family history suggestive of late-onset autosomal dominant parkinsonism. MRI revealed abnormalities of the medulla and cervical spinal cord typical of adult-onset Alexander disease, and genetic testing showed homozygosity for the p.D295N polymorphic allele in the gene encoding the glial fibrillary acidic protein. A review of the literature shows that ocular signs are frequent in adult-onset Alexander disease, most commonly gaze-evoked nystagmus, pendular nystagmus, and/or oculopalatal myoclonus, and less commonly ptosis, miosis, and saccadic dysmetria. These signs are consistent with the propensity of adult-onset Alexander disease to cause medullary abnormalities on neuroimaging.

  15. Possible Role of Interleukin-1β in Type 2 Diabetes Onset and Implications for Anti-inflammatory Therapy Strategies

    PubMed Central

    Zhao, Gang; Dharmadhikari, Gitanjali; Maedler, Kathrin; Meyer-Hermann, Michael

    2014-01-01

    Increasing evidence of a role of chronic inflammation in type 2 diabetes progression has led to the development of therapies targeting the immune system. We develop a model of interleukin-1β dynamics in order to explain principles of disease onset. The parameters in the model are derived from in vitro experiments and patient data. In the framework of this model, an IL-1β switch is sufficient and necessary to account for type 2 diabetes onset. The model suggests that treatments targeting glucose bear the potential of stopping progression from pre-diabetes to overt type 2 diabetes. However, once in overt type 2 diabetes, these treatments have to be complemented by adjuvant anti-inflammatory therapies in order to stop or decelerate disease progression. Moreover, the model suggests that while glucose-lowering therapy needs to be continued all the way, dose and duration of the anti-inflammatory therapy needs to be specifically controlled. The model proposes a framework for the discussion of clinical trial outcomes. PMID:25167060

  16. Immunoproteomic Profiling of Antiviral Antibodies in New-Onset Type 1 Diabetes Using Protein Arrays

    PubMed Central

    Bian, Xiaofang; Wallstrom, Garrick; Davis, Amy; Wang, Jie; Park, Jin; Throop, Andrea; Steel, Jason; Yu, Xiaobo; Wasserfall, Clive; Schatz, Desmond; Atkinson, Mark

    2016-01-01

    The rapid rise in the incidence of type 1 diabetes (T1D) suggests the involvement of environmental factors including viral infections. We evaluated the association between viral infections and T1D by profiling antiviral antibodies using a high-throughput immunoproteomics approach in patients with new-onset T1D. We constructed a viral protein array comprising the complete proteomes of seven viruses associated with T1D and open reading frames from other common viruses. Antibody responses to 646 viral antigens were assessed in 42 patients with T1D and 42 age- and sex-matched healthy control subjects (mean age 12.7 years, 50% males). Prevalence of antiviral antibodies agreed with known infection rates for the corresponding virus based on epidemiological studies. Antibody responses to Epstein-Barr virus (EBV) were significantly higher in case than control subjects (odds ratio 6.6; 95% CI 2.0–25.7), whereas the other viruses showed no differences. The EBV and T1D association was significant in both sex and age subgroups (≤12 and >12 years), and there was a trend toward early EBV infections among the case subjects. These results suggest a potential role for EBV in T1D development. We believe our innovative immunoproteomics platform is useful for understanding the role of viral infections in T1D and other disorders where associations between viral infection and disease are unclear. PMID:26450993

  17. Reversal of new-onset diabetes through modulating inflammation and stimulating beta-cell replication in nonobese diabetic mice by a dipeptidyl peptidase IV inhibitor.

    PubMed

    Tian, Lei; Gao, Jie; Hao, Jianqiang; Zhang, Yu; Yi, Huimin; O'Brien, Timothy D; Sorenson, Robert; Luo, Jian; Guo, Zhiguang

    2010-07-01

    Inhibition of dipeptidyl peptidase IV (DPP-IV) activity by NVP-DPP728, a DPP-IV inhibitor, improves the therapeutic efficacy of glucagon-like peptide-1 (GLP-1). CD26 is a membrane-associated glycoprotein with DPP-IV activity and is expressed on lymphocytes. We investigated the effect of NVP-DPP728 on reversing new-onset diabetes in nonobese diabetic (NOD) mice and modulating the inflammatory response and stimulating beta-cell regeneration. New-onset diabetic NOD mice were treated with NVP-DPP728 for 2, 4, and 6 wk. Blood glucose level was monitored. Regulatory T cells in thymus and secondary lymph nodes, TGF-beta1 and GLP-1 in plasma, and the insulin content in the pancreas were measured. Immunostaining for insulin and bromodeoxyuridine (BrdU) were performed. The correlation of beta-cell replication with inflammation was determined. In NVP-DPP728-treated NOD mice, diabetes could be reversed in 57, 74, and 73% of mice after 2, 4, and 6 wk treatment, respectively. Insulitis was reduced and the percentage of CD4(+)CD25(+)FoxP3(+) regulatory T cells was increased in treated NOD mice with remission. Plasma TGF-beta1 and GLP-1, the insulin content, and both insulin(+) and BrdU(+) beta-cells in pancreas were also significantly increased. No significant correlations were found between numbers of both insulin(+) and BrdU(+) beta-cells in islets and beta-cell area or islets with different insulitis score in NOD mice with remission of diabetes. In conclusion, NVP-DPP728 treatment can reverse new-onset diabetes in NOD mice by reducing insulitis, increasing CD4(+)CD25(+)FoxP3(+) regulatory T cells, and stimulating beta-cell replication. beta-Cell replication is not associated with the degree of inflammation in NVP-DPP728-treated NOD mice.

  18. Adult onset leukodystrophy with neuroaxonal spheroids and demyelinating plaque-like lesions.

    PubMed

    Martinez-Saez, Elena; Shah, Sachit; Costa, Carme; Fleminger, Simon; Connor, Stephen; Bodi, Istvan

    2012-06-01

    Adult onset leukodystrophy with neuroaxonal spheroids is an uncommon cause of dementia. Both hereditary (autosomal dominant) and sporadic cases have been described. A 41-year-old African woman presented with inappropriate behavior and personality change consistent with frontal lobe dysfunction. MRI demonstrated diffuse frontoparietal white matter signal abnormality and volume loss, as well as focal enhancing white matter lesions, while CT scan showed white matter calcifications. She had been gradually deteriorating over the last 5 years, diagnosed as having progressive demyelinating illness. She died of recurrent chest infections. There was no familial history. The brain showed prominent symmetrical white matter changes with greyish discolorization mainly affecting the frontal and parietal lobes, with less involvement of the temporal lobe and only mildly affecting the occipital white matter. Histology revealed deep white matter atrophy with many neuroaxonal spheroids labelled by neurofilament and β-amyloid precursor protein. In addition, scattered inactive demyelinating plaque-like lesions were found in the periventricular areas, brainstem and the cervical spinal cord. This case had typical features of an adult onset leukodystrophy with neuroaxonal spheroids. However, we also demonstrated demyelinating plaque-like lesions, which has not been previously described. The possibility of a demyelinating origin contributing to the changes may be considered in the pathogenesis of this condition.

  19. Compound heterozygote mutations in SPG7 in a family with adult-onset primary lateral sclerosis

    PubMed Central

    Yang, Yi; Lynch, David R.; Lukas, Thomas; Ahmeti, Kreshnik; Sleiman, Patrick M.A.; Ryan, Eanna; Schadt, Kimberly A.; Newman, Jordan H.; Deng, Han-Xiang; Siddique, Nailah

    2016-01-01

    Objective: To identify the genetic defect for adult-onset primary lateral sclerosis (PLS) in a family with 5 patients. Methods: Whole-exome sequencing was performed to identify the shared genetic variants in 3 affected members in a PLS family with 5 affected individuals. Sanger sequencing was used for validation of the variants and for cosegregation analysis. Mitochondrial activity for both patients and unaffected siblings was measured using a SeaHorse metabolic analyzer. Results: Whole-exome sequencing and subsequent cosegregation analysis demonstrated that compound heterozygous missense variants L695P and I743T in SPG7 were the only mutations cosegregating with the disease in an autosomal recessive fashion in this family. The parents and siblings are genetically heterozygous and clinically unaffected. Functional studies suggested that the PLS-associated SPG7 mutants affect mitochondrial function when glucose is reduced. Conclusions: Compound heterozygote mutations in SPG7 are associated with adult-onset PLS, extending the spectrum of SPG7-linked neurologic diseases. Patients with the PLS phenotype should have genetic testing for paraplegin, especially when the condition is familial. PMID:27123479

  20. The role of childhood social position in adult type 2 diabetes: evidence from the English Longitudinal Study of Ageing

    PubMed Central

    2014-01-01

    Background Socioeconomic circumstances in childhood and early adulthood may influence the later onset of chronic disease, although such research is limited for type 2 diabetes and its risk factors at the different stages of life. The main aim of the present study is to examine the role of childhood social position and later inflammatory markers and health behaviours in developing type 2 diabetes at older ages using a pathway analytic approach. Methods Data on childhood and adult life circumstances of 2,994 men and 4,021 women from English Longitudinal Study of Ageing (ELSA) were used to evaluate their association with diabetes at age 50 years and more. The cases of diabetes were based on having increased blood levels of glycated haemoglobin and/or self-reported medication for diabetes and/or being diagnosed with type 2 diabetes. Father’s job when ELSA participants were aged 14 years was used as the measure of childhood social position. Current social characteristics, health behaviours and inflammatory biomarkers were used as potential mediators in the statistical analysis to assess direct and indirect effects of childhood circumstances on diabetes in later life. Results 12.6 per cent of participants were classified as having diabetes. A disadvantaged social position in childhood, as measured by father’s manual occupation, was associated at conventional levels of statistical significance with an increased risk of type 2 diabetes in adulthood, both directly and indirectly through inflammation, adulthood social position and a risk score constructed from adult health behaviours including tobacco smoking and limited physical activity. The direct effect of childhood social position was reduced by mediation analysis (standardised coefficient decreased from 0.089 to 0.043) but remained statistically significant (p = 0.035). All three indirect pathways made a statistically significantly contribution to the overall effect of childhood social position on adulthood

  1. Effect of Socioeconomic Factors and Family History on the Incidence of Diabetes in an Adult Diabetic Population from Algeria

    PubMed Central

    FERDI, Nour El Houda; ABLA, Khalida; CHENCHOUNI, Haroun

    2016-01-01

    Background: Diabetes mellitus is a serious public health problem worldwide and particularly in developing countries. In Algeria, this metabolic disorder occurs with a wide variety or atypical forms that linked to multiple risk factors including local habits and traditions. This study aimed to determine the impact of risk factors (metabolic syndrome, social, cultural, physical activity, family history and the treatment used) on the incidence of diabetes. Methods: This cross-sectional study was conducted in 2013 on a random sample from a resident population in Tebessa, Northeast Algeria, which underwent a significant expanding of diabetes prevalence conditioned by profound socioeconomic changes. The survey included 200 subjects, randomly selected; with 100 controls and 100 diabetic patients, (26 diabetic subjects with type 1 diabetes mellitus ‘T1DM’ and 74 subjects with type two diabetes mellitus ‘T2DM’). Results: Diabetic subjects were significantly affected by all these risk factors, including metabolic syndrome that was higher in women. The most common treatment among surveyed T1DM subjects was insulin, whereas T2DM patients used metformin. In addition, the duration from T1DM onset in the surveyed subjects is older than T2DM onset. The incidence of diabetes is significantly in close relationship between the majorities of these factors of risk. Conclusion: Subjects with a high socioeconomic status can afford a healthier way of life to avoid the risk of developing diabetes compared to subjects with lower social level. PMID:28053930

  2. Sensorimotor Oscillations Prior to Speech Onset Reflect Altered Motor Networks in Adults Who Stutter

    PubMed Central

    Mersov, Anna-Maria; Jobst, Cecilia; Cheyne, Douglas O.; De Nil, Luc

    2016-01-01

    Adults who stutter (AWS) have demonstrated atypical coordination of motor and sensory regions during speech production. Yet little is known of the speech-motor network in AWS in the brief time window preceding audible speech onset. The purpose of the current study was to characterize neural oscillations in the speech-motor network during preparation for and execution of overt speech production in AWS using magnetoencephalography (MEG). Twelve AWS and 12 age-matched controls were presented with 220 words, each word embedded in a carrier phrase. Controls were presented with the same word list as their matched AWS participant. Neural oscillatory activity was localized using minimum-variance beamforming during two time periods of interest: speech preparation (prior to speech onset) and speech execution (following speech onset). Compared to controls, AWS showed stronger beta (15–25 Hz) suppression in the speech preparation stage, followed by stronger beta synchronization in the bilateral mouth motor cortex. AWS also recruited the right mouth motor cortex significantly earlier in the speech preparation stage compared to controls. Exaggerated motor preparation is discussed in the context of reduced coordination in the speech-motor network of AWS. It is further proposed that exaggerated beta synchronization may reflect a more strongly inhibited motor system that requires a stronger beta suppression to disengage prior to speech initiation. These novel findings highlight critical differences in the speech-motor network of AWS that occur prior to speech onset and emphasize the need to investigate further the speech-motor assembly in the stuttering population. PMID:27642279

  3. Mutated CTSF in adult-onset neuronal ceroid lipofuscinosis and FTD

    PubMed Central

    van der Zee, Julie; Mariën, Peter; Crols, Roeland; Van Mossevelde, Sara; Dillen, Lubina; Perrone, Federica; Engelborghs, Sebastiaan; Verhoeven, Jo; D'aes, Tine; Ceuterick-De Groote, Chantal; Sieben, Anne; Versijpt, Jan; Cras, Patrick; Martin, Jean-Jacques

    2016-01-01

    Objective: To investigate the molecular basis of a Belgian family with autosomal recessive adult-onset neuronal ceroid lipofuscinosis (ANCL or Kufs disease [KD]) with pronounced frontal lobe involvement and to expand the findings to a cohort of unrelated Belgian patients with frontotemporal dementia (FTD). Methods: Genetic screening in the ANCL family and FTD cohort (n = 461) was performed using exome sequencing and targeted massive parallel resequencing. Results: We identified a homozygous mutation (p.Ile404Thr) in the Cathepsin F (CTSF) gene cosegregating in the ANCL family. No other mutations were found that could explain the disease in this family. All 4 affected sibs developed motor symptoms and early-onset dementia with prominent frontal features. Two of them evolved to akinetic mutism. Disease presentation showed marked phenotypic variation with the onset ranging from 26 to 50 years. Myoclonic epilepsy in one of the sibs was suggestive for KD type A, while epilepsy was not present in the other sibs who presented with clinical features of KD type B. In a Belgian cohort of unrelated patients with FTD, the same heterozygous p.Arg245His mutation was identified in 2 patients who shared a common haplotype. Conclusions: A homozygous CTSF mutation was identified in a recessive ANCL pedigree. In contrast to the previous associations of CTSF with KD type B, our findings suggest that CTSF genetic testing should also be considered in patients with KD type A as well as in early-onset dementia with prominent frontal lobe and motor symptoms. PMID:27668283

  4. Patient perspectives on peer support for adults with type 1 diabetes: a need for diabetes-specific social capital

    PubMed Central

    Joensen, Lene E; Filges, Tine; Willaing, Ingrid

    2016-01-01

    Aim To explore the function of peer support from the perspective of adults with type 1 diabetes in Denmark. Methods The study population consisted of 20 adults with type 1 diabetes. The sample was diverse in relation to educational background, age, sex, and cohabitation status. Inspired by action research, several methods and perspectives on peer support were explored and tested. Workshops and group and individual interviews were performed. Systematic text condensation was used to analyze data, supplemented with theory-based interpretive analysis. Results Adults with type 1 diabetes found peer support highly relevant to reduce a burdensome feeling of diabetes-specific loneliness. Peer support showed potential to create diabetes-specific social capital not only by creating reciprocal social support between peers but also, more importantly, by creating space for genuine trust and a feeling of communality. There was a widespread feeling of the pervasive impact of diabetes on daily life and thus the relevance of discussing all aspects of life. However, participants perceived peer support as particularly relevant in relation to big changes in life, for example, in family life, at work, or through treatment events such as getting an insulin pump. Conclusion Peer support programs focusing on creating and establishing diabetes-specific social capital using participatory approaches seem highly relevant among adults with type 1 diabetes. Content, methods, and effects of peer support need further exploration in collaboration with adults with type 1 diabetes. PMID:27536076

  5. Distinct clinical and laboratory characteristics of latent autoimmune diabetes in adults in relation to type 1 and type 2 diabetes mellitus.

    PubMed

    Pipi, Elena; Marketou, Marietta; Tsirogianni, Alexandra

    2014-08-15

    Ever since its first appearance among the multiple forms of diabetes, latent autoimmune diabetes in adults (LADA), has been the focus of endless discussions concerning mainly its existence as a special type of diabetes. In this mini-review, through browsing important peer-reviewed publications, (original articles and reviews), we will attempt to refresh our knowledge regarding LADA hoping to enhance our understanding of this controversial diabetes entity. A unique combination of immunological, clinical and metabolic characteristics has been identified in this group of patients, namely persistent islet cell antibodies, high frequency of thyroid and gastric autoimmunity, DR3 and DR4 human leukocyte antigen haplotypes, progressive loss of beta cells, adult disease onset, normal weight, defective glycaemic control, and without tendency to ketoacidosis. Although anthropomorphic measurements are useful as a first line screening, the detection of C-peptide levels and the presence of glutamic acid decarboxylase (GAD) autoantibodies is undoubtedly the sine qua non condition for a confirmatory LADA diagnosis. In point of fact, GAD autoantibodies are far from being solely a biomarker and the specific role of these autoantibodies in disease pathogenesis is still to be thoroughly studied. Nevertheless, the lack of diagnostic criteria and guidelines still puzzle the physicians, who struggle between early diagnosis and correct timing for insulin treatment.

  6. Novel case of Trevor’s disease: Adult onset and later recurrence

    PubMed Central

    Khalsa, Amrit S; Kumar, Neil S; Chin, Matthew A; Lackman, Richard D

    2017-01-01

    Dysplasia epiphysealis hemimelica (DEH), or Trevor’s disease, is an osteocartilaginous epiphyseal overgrowth typically occurring in children. The literature reports 6 adult cases and none describe recurrence requiring additional procedures. We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision. A 39-year-old female presented with a history of right knee pain, swelling, and instability. Physical examination revealed a firm proximal tibial mass. Computed tomography (CT) imaging showed an exophytic, lobulated, sclerotic mass involving the anterolateral margin of the lateral tibial plateau. Magnetic resonance imaging was suggestive of an osteochondroma. The patient underwent curettage of the lesion due to its periarticular location. Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma. Two and a half years later, the patient presented with a firm, palpable mass larger than the initial lesion. CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intra-articular DEH. A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis. DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old. DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance. Adult-onset cases comprise less than 1% of reported cases. Recurrence rate after surgical intervention is unknown. Only 1 such case, occurring in a child, has been described. Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision. A follow-up period of several years may be warranted to identify recurrent lesions. PMID:28144583

  7. Occupational exposures and uncontrolled adult-onset asthma in the European Community Respiratory Health Survey II.

    PubMed

    Le Moual, Nicole; Carsin, Anne-Elie; Siroux, Valérie; Radon, Katja; Norback, Dan; Torén, Kjell; Olivieri, Mario; Urrutia, Isabel; Cazzoletti, Lucia; Jacquemin, Bénédicte; Benke, Geza; Kromhout, Hans; Mirabelli, Maria C; Mehta, Amar J; Schlünssen, Vivi; Sigsgaard, Torben; Blanc, Paul D; Kogevinas, Manolis; Antó, Josep M; Zock, Jan-Paul

    2014-02-01

    Occupational exposure is a well-recognised modifiable risk factor for asthma, but the relationship between occupational exposure and asthma control has not been studied. We aimed to study this association among working-age adults from the European Community Respiratory Health Survey (ECRHS). Data were available for 7077 participants (mean age 43 years, 45% never-smokers, 5867 without asthma and 1210 with current asthma). Associations between occupational exposure to specific asthmagens and asthma control status (33% with uncontrolled asthma, based on the Global Initiative for Asthma guidelines) were evaluated using logistic and multinomial regressions, adjusted for age, sex and smoking status, with study areas included as a random effect. Statistically significant positive associations were observed between uncontrolled adult-onset asthma and both past 12-month and 10-year exposure to any occupational asthmagens (OR (95% CI) 1.6 (1.0-2.40) and 1.7 (1.2-2.5), respectively); high (1.7 (1.0-2.8) and 1.9 (1.3-2.9), respectively) and low (1.6 (1.0-2.7) and 1.8 (1.2-2.7), respectively) molecular weight agents; and cleaning agents (2.0 (1.1-3.6) and 2.3 (1.4-3.6), respectively), with stronger associations for long-term exposures. These associations were mainly explained by the exacerbation domain of asthma control and no associations were observed between asthmagens and partly controlled asthma. These findings suggest that occupational exposure to asthmagens is associated with uncontrolled adult-onset asthma. Occupational risk factors should be quickly identified to prevent uncontrolled asthma.

  8. Diabetes autoantibodies do not predict progression to diabetes in adults: the Diabetes Prevention Program

    PubMed Central

    Dabelea, D.; Ma, Y.; Knowler, W. C.; Marcovina, S.; Saudek, C. D.; Arakaki, R.; White, N. H.; Kahn, S. E.; Orchard, T. J.; Goldberg, R.; Palmer, J.; Hamman, R. F.

    2014-01-01

    Aims To determine if the presence of diabetes autoantibodies predicts the development of diabetes among participants in the Diabetes Prevention Program. Methods A total of 3050 participants were randomized into three treatment groups: intensive lifestyle intervention, metformin and placebo. Glutamic acid decarboxylase (GAD) 65 autoantibodies and insulinoma-associated-2 autoantibodies were measured at baseline and participants were followed for 3.2 years for the development of diabetes. Results The overall prevalence of GAD autoantibodies was 4.0%, and it varied across racial/ethnic groups from 2.4% among Asian-Pacific Islanders to 7.0% among non-Hispanic black people. There were no significant differences in BMI or metabolic variables (glucose, insulin, HbA1c, estimated insulin resistance, corrected insulin response) stratified by baseline GAD antibody status. GAD autoantibody positivity did not predict diabetes overall (adjusted hazard ratio 0.98; 95% CI 0.56–1.73) or in any of the three treatment groups. Insulinoma-associated-2 autoantibodies were positive in only one participant (0.033%). Conclusions These data suggest that ‘diabetes autoimmunity’, as reflected by GAD antibodies and insulinoma-associated-2 autoantibodies, in middle-aged individuals at risk for diabetes is not a clinically relevant risk factor for progression to diabetes. PMID:24646311

  9. No Protective Effect of Calcitriol on β-Cell Function in Recent-Onset Type 1 Diabetes

    PubMed Central

    Bizzarri, Carla; Pitocco, Dario; Napoli, Nicola; Di Stasio, Enrico; Maggi, Daria; Manfrini, Silvia; Suraci, Concetta; Cavallo, Maria Gisella; Cappa, Marco; Ghirlanda, Giovanni; Pozzilli, Paolo

    2010-01-01

    OBJECTIVE We investigated whether supplementation of the active form of vitamin D (calcitriol) in recent-onset type 1 diabetes can protect β-cell function evaluated by C-peptide and improve glycemic control assessed by A1C and insulin requirement. RESEARCH DESIGN AND METHODS Thirty-four subjects (aged 11–35 years, median 18 years) with recent-onset type 1 diabetes and high basal C-peptide >0.25 nmol/l were randomized in a double-blind trial to 0.25 μg/day calcitriol or placebo and followed-up for 2 years. RESULTS At 6, 12, and 24 months follow-up, A1C and insulin requirement in the calcitriol group did not differ from the placebo group. C-peptide dropped significantly (P < 0.001) but similarly in both groups, with no significant differences at each time point. CONCLUSIONS At the doses used, calcitriol is ineffective in protecting β-cell function in subjects (including children) with recent-onset type 1 diabetes and high C-peptide at diagnosis. PMID:20805274

  10. Diabetic Ketoacidosis with Ebstein's Anomaly in an Adult.

    PubMed

    Patra, Soumya; Beeresha P, Nagamani A C; B, Ramesh; C N, Manjunath

    2016-03-01

    Ebstein's anomaly is a rare form of congenital malformation of the heart, characterized by apical displacement of the septal and posterior tricuspid valve leaflets, leading to atrialisation of the right ventricle with a variable degree of malformation and displacement of the anterior leaflet. It may not be detected until late in adolescence or adulthood. The clinical manifestations of Ebstein's anomaly vary greatly. We are reporting a case of 35-year male who presented with generalized fatigue, palpitation and effort intolerance. Laboratory investigations confirmed the diagnosis of diabetes ketosis. Transthoracic echocardiography showed severe Ebstein's anomaly with severe tricuspid regurgitation, no residual atrial septal defect, but with severe right ventricular dysfunction. Though only few studies showed the high prevalence of abnormal glucose metabolism in young adult patients with complex congenital heart disease, but Epstein's anomaly with diabetes ketosis was nowhere mentioned.

  11. Serum Parathyroid Hormone Levels Predict Falls in Older Diabetic Adults

    PubMed Central

    Houston, Denise K.; Schwartz, Ann V.; Cauley, Jane A.; Tylavsky, Frances A.; Simonsick, Eleanor M.; Harris, Tamara B.; de Rekeneire, Nathalie; Schwartz, Gary G.; Kritchevsky, Stephen B.

    2008-01-01

    Objectives To examine the association between serum parathyroid hormone (PTH) levels and incident falls in older diabetic adults. Design Longitudinal analysis of incident falls over 1 year in a sub-study of diabetic participants in the Health, Aging and Body Composition study. Setting Pittsburgh, PA, and Memphis, TN. Participants Well-functioning, community-dwelling black and white adults aged 70-79 with diabetes (n = 472). Measurements Measured baseline serum PTH. Self-report of falls over the subsequent 12 months. Baseline physical performance and self-reported demographic, behavioral, and health status measures including kidney function, chronic conditions and medication use. Results 30.3% of participants reported falling over one year of follow-up. The mean ± SD baseline serum PTH was 53.5 ± 30.0 pg/mL in non-fallers and 62.6 ± 46.2 pg/mL in fallers (p = 0.01). For every 1 SD (36 pg/mL) increment in baseline serum PTH, there was approximately a 30% increased likelihood of reporting a fall in the subsequent year after adjusting for age, gender, race, field center, alcohol consumption, BMI, physical activity, and winter/spring season (adjusted odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.06-1.59). Further adjustment for kidney function, chronic conditions, medication and supplement use, and physical performance attenuated the association slightly (OR (95% CI): 1.26 (1.01-1.58)). A trend remained after additional adjustment for reported falls in the previous year. Conclusion Higher serum PTH was associated with incident falls among older, well-functioning diabetic men and women. Further investigation aimed at understanding the underlying mechanism for the association between serum PTH and falls is needed. PMID:19016936

  12. Adult-onset Alexander disease: a series of eleven unrelated cases with review of the literature.

    PubMed

    Pareyson, Davide; Fancellu, Roberto; Mariotti, Caterina; Romano, Silvia; Salmaggi, Andrea; Carella, Francesco; Girotti, Floriano; Gattellaro, Grazietta; Carriero, Maria Rita; Farina, Laura; Ceccherini, Isabella; Savoiardo, Mario

    2008-09-01

    Alexander disease (AD) in its typical form is an infantile lethal leucodystrophy, characterized pathologically by Rosenthal fibre accumulation. Following the identification of glial fibrillary acidic protein (GFAP) gene as the causative gene, cases of adult-onset AD (AOAD) are being described with increasing frequency. AOAD has a different clinical and neuroradiological presentation with respect to early-onset AD, as abnormalities are mainly concentrated in the brainstem-spinal cord junction. We report detailed clinical and genetic data of 11 cases of AOAD, observed over a 4-year period, and a review of the previously reported 25 cases of genetically confirmed AOAD. In our series, onset occurred as late as age 62, and up to 71 in an affected deceased relative. Most cases appeared sporadic, but family history may be misleading. The most frequent symptoms were related to bulbar dysfunction-with dysarthria, dysphagia, dysphonia (seven patients)-, pyramidal involvement (seven patients) and cerebellar ataxia (seven patients). Four patients had palatal myoclonus. Sleep disorders were also observed (four cases). Bulbar symptoms, however, were infrequent at onset and two symptomatic patients had an almost pure pyramidal involvement. Two subjects were asymptomatic. Misdiagnosis at presentation was frequent and MRI was instrumental in suggesting the correct diagnosis by showing, in all cases, mild to severe atrophy of the medulla oblongata extending caudally to the cervical spinal cord. In ten patients, molecular studies revealed six novel missense mutations and three previously reported changes in GFAP. The last typical patient carried no definitely pathogenic mutation, but a missense variant (p.D157N), supposedly a rare polymorphism. Revision of the literature and the present series indicate that the clinical picture is not specific, but AOAD must be considered in patients of any age with lower brainstem signs. When present, palatal myoclonus is strongly suggestive

  13. Gene for non-insulin-dependent diabetes mellitus (maturity-onset diabetes of the young subtype) is linked to DNA polymorphism on human chromosome 20q

    SciTech Connect

    Bell, G.I.; Xiang, Kunsan; Newman, M.V.; Wu, Songhua; Cox, N.J. ); Wright, L.G.; Spielman, R.S. ); Fajans, S.S. )

    1991-02-15

    Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterized by an early age of onset, usually before 25 years of age, and an autosomal dominant mode of inheritance. The largest and best-studies MODY pedigree is the TW family. The majority of the diabetic subjects in this pedigree has a reduced and delayed insulin-secretory response to glucose, and it has been proposed that this abnormal response is the manifestation of the basic genetic defect that leads to diabetes. Using DNA from members of the TW family, the authors tested more than 75 DNA markers for linkage with MODY. A DNA polymorphism in the adenosine deaminase gene (ADA) on the long arm of chromosome 20 was found to cosegregate with MODY. The maximum logarithm of adds (lod score) for linkage between MODY and ADA was 5.25 at a recombination fraction of 0.00. These results indicate that the odds are {gt}178,000:1 that the gene responsible for MODY is this family is tightly linked to the ADA gene on chromosome 20q.

  14. Hypomagnesemia and the Risk of New-Onset Diabetes Mellitus after Kidney Transplantation.

    PubMed

    Huang, Johnny W; Famure, Olusegun; Li, Yanhong; Kim, S Joseph

    2016-06-01

    Several studies suggest a link between post-transplant hypomagnesemia and new-onset diabetes after transplantation (NODAT), but this relationship remains controversial. We conducted a retrospective cohort study of 948 nondiabetic kidney transplant recipients from January 1, 2000, to December 31, 2011, to examine the association between serum magnesium level and NODAT. Multivariable Cox proportional hazards models were fitted to evaluate the risk of NODAT as a function of baseline (at 1 month), time-varying (every 3 months), and rolling-average (i.e., mean for 3 months moving at 3-month intervals) serum magnesium levels while adjusting for potential confounders. A total of 182 NODAT events were observed over 2951.2 person-years of follow-up. Multivariable models showed an inverse relationship between baseline serum magnesium level and NODAT (hazard ratio [HR], 1.24 per 0.1 mmol/L decrease; 95% confidence interval [95% CI], 1.05 to 1.46; P=0.01). The association with the risk of NODAT persisted in conventional time-varying (HR, 1.32; 95% CI, 1.14 to 1.52; P<0.001) and rolling-average models (HR, 1.34; 95% CI, 1.13 to 1.57; P=0.001). Hypomagnesemia (serum magnesium <0.74 mmol/L) also significantly associated with increased risk of NODAT in baseline (HR, 1.58; 95% CI, 1.07 to 2.34; P=0.02), time-varying (HR, 1.78; 95% CI, 1.29 to 2.45; P<0.001), and rolling-average models (HR, 1.83; 95% CI, 1.30 to 2.57; P=0.001). Our results suggest that lower post-transplant serum magnesium level is an independent risk factor for NODAT in kidney transplant recipients. Interventions targeting serum magnesium to reduce the risk of NODAT should be evaluated.

  15. Hypercalcemia induces targeted autophagic degradation of aquaporin-2 at the onset of nephrogenic diabetes insipidus.

    PubMed

    Khositseth, Sookkasem; Charngkaew, Komgrid; Boonkrai, Chatikorn; Somparn, Poorichaya; Uawithya, Panapat; Chomanee, Nusara; Payne, D Michael; Fenton, Robert A; Pisitkun, Trairak

    2017-01-27

    Hypercalcemia can cause renal dysfunction such as nephrogenic diabetes insipidus (NDI), but the mechanisms underlying hypercalcemia-induced NDI are not well understood. To elucidate the early molecular changes responsible for this disorder, we employed mass spectrometry-based proteomic analysis of inner medullary collecting ducts (IMCD) isolated from parathyroid hormone-treated rats at onset of hypercalcemia-induced NDI. Forty-one proteins, including the water channel aquaporin-2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the downregulated proteins were associated with cytoskeletal protein binding, regulation of actin filament polymerization, and cell-cell junctions. Targeted LC-MS/MS and immunoblot studies confirmed the downregulation of 16 proteins identified in the initial proteomic analysis and in additional experiments using a vitamin D treatment model of hypercalcemia-induced NDI. Evaluation of transcript levels and estimated half-life of the downregulated proteins suggested enhanced protein degradation as the possible regulatory mechanism. Electron microscopy showed defective intercellular junctions and autophagy in the IMCD cells from both vitamin D- and parathyroid hormone-treated rats. A significant increase in the number of autophagosomes was confirmed by immunofluorescence labeling of LC3. Colocalization of LC3 and Lamp1 with aquaporin-2 and other downregulated proteins was found in both models. Immunogold electron microscopy revealed aquaporin-2 in autophagosomes in IMCD cells from both hypercalcemia models. Finally, parathyroid hormone withdrawal reversed the NDI phenotype, accompanied by termination of aquaporin-2 autophagic degradation and normalization of both nonphoshorylated and S256-phosphorylated aquaporin-2 levels. Thus, enhanced autophagic degradation of proteins plays an important role in the initial mechanism of hypercalcemic-induced NDI.

  16. Severe Hypertriglyceridemia Causing Pancreatitis in a Child with New-onset Type-I Diabetes Mellitus Presenting with Diabetic Ketoacidosis

    PubMed Central

    Sharma, Pradeep Kumar; Kumar, Maneesh; Yadav, Dinesh Kumar

    2017-01-01

    The triad of pancreatitis, hypertriglyceridemia, and diabetic ketoacidosis and its treatment has not been extensively discussed in the pediatric literature. We report a 4-year-old child with severe hypertriglyceridemia, pancreatitis, and diabetic ketoacidosis. Hypertriglyceridemia and pancreatitis with diabetic ketoacidosis can be successfully managed with insulin and hydration therapy in children. Early recognition of this triad is important as insulin requirements, recovery duration, and prognosis can be altered.

  17. Group B streptococcal necrotizing pneumonia in a diabetic adult patient.

    PubMed

    Pacha, Andrea; Luna Cian, Ramiro; Bonofiglio, Laura; Solari, Melisa; Strada, Virginia; Suárez, Mariana; Vigliarolo, Laura; Tersigni, Carina; Mollerach, Marta; Lopardo, Horacio

    2017-03-18

    The aim of this report is to describe a rare case of necrotizing pneumonia due to group B Streptococcus serotype III in a relatively young male adult (48 years old) suffering from diabetes. The organism was isolated from his pleural fluid and was only resistant to tetracycline. The patient first received ceftazidime (2g/8h i.v.)+clindamycin (300mg/8h) for 18 days and then he was discharged home and orally treated with amoxicillin clavulanic acid (1g/12h) for 23 days with an uneventful evolution. As in the cases of invasive infection by Streptococcus pyogenes, clindamycin could prevent streptococcal toxic shock syndrome.

  18. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still’s disease

    PubMed Central

    Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23rd day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still’s disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision. PMID:27826176

  19. Limited diagnostic value of procalcitonin in early diagnosis of adult onset Still's disease.

    PubMed

    Gowin, Ewelina; Wysocki, Jacek

    2016-01-01

    A 17-year-old female patient was referred to the Infectious Diseases Ward because of fever lasting for 14 days. On admission to the hospital the patient was in a generally good state, without any abnormalities on physical examination. Laboratory investigation revealed elevated inflammatory markers. Diagnostic imaging comprising chest X-ray, abdominal ultrasonography, and echocardiography showed no abnormalities. During the hospitalization, there occurred episodes of fever with skin rash and musculoskeletal pain of the lower limbs. Procalcitonin concentrations continued to increase. C-reactive protein concentrations decreased during therapy, starting from 191 mg/l. On the 23(rd) day of the disease, edema of the feet, ankles, and knees appeared. On the basis of the clinical picture and after excluding other possible causes of fever, the patient was diagnosed with adult onset Still's disease. The procalcitonin concentration was normalized after 5 days of steroid therapy. The patient was discharged under ambulatory rheumatologic supervision.

  20. [A case of adult-onset type II citrullinemia in an elderly patient].

    PubMed

    Kitaoka, Mayuko; Sakaeda, Hiroshi; Suzuki, Mika; Miki, Toshifumi; Saito, Junko; Chikamori, Masayasu; Tomita, Hideharu; Ichikawa, Hiromoto; Yoshimoto, Kaori; Takamatsu, Masahiro; Okada, Mitsuo; Aono, Rei; Enzan, Hideaki; Miyamoto, Takako

    2013-03-01

    A 72-year-old man presented with consciousness disturbance. The results of brain magnetic resonance imaging and cerebrospinal fluid examination were normal, but triphasic waves were noted on electroencephalography. His plasma ammonia level was elevated due to which encephalopathy secondary to hyperammonemia was suspected. However, his liver function was normal, and no evidence of cirrhosis or portal-systemic shunt was noted. The patient's medical history revealed that he had a tendency to excessively consume pulse products since childhood, and an amino acid analysis showed elevation of citrulline and arginine levels. Thus, we diagnosed the patient with an extremely rare case of adult-onset type II citrullinemia, which was triggered by cessation of the intake of pulse foods (soybeans and peanuts) due to dental problems.

  1. Adult-onset nemaline myopathy in a dog presenting with persistent atrial standstill and primary hypothyroidism.

    PubMed

    Nakamura, R K; Russell, N J; Shelton, G D

    2012-06-01

    A nine-year-old neutered female mixed breed dog presented for evaluation following a five-day history of lethargy, inappetence, weakness, abdominal distension and generalised muscle atrophy. Persistent vatrial standstill with a junctional rhythm was identified on electrocardiogram. Echocardiogram identified moderate dilation of all cardiac chambers and mild thickening of the mitral and tricuspid valves. Serology was negative for Neospora caninum and Toxoplasma gondii. Permanent pacemaker implantation was performed in addition to endomyocardial and skeletal muscle biopsies. Cryosections from the biceps femoris muscle showed numerous nemaline rod bodies while endomyocardial biopsies were possibly consistent with end-stage myocarditis. Rod bodies have rarely been reported in the veterinary literature. To the authors' knowledge, this is the first report of adult-onset nemaline rod myopathy and hypothyroidism with concurrent cardiac disease in a dog.

  2. Adult-onset Still’s disease: current challenges and future prospects

    PubMed Central

    Siddiqui, Mariam; Putman, Michael S; Dua, Anisha B

    2016-01-01

    Adult-onset Still’s disease (AOSD) – a multi-systemic inflammatory condition characterized by high fevers, polyarthritis, an evanescent rash, and pharyngitis – has been a challenging condition to diagnose expediently and treat effectively. Questions remain regarding the underlying pathophysiology and etiology of AOSD. Pathognomonic diagnostic tests and reliable biomarkers remain undiscovered. Over the past decade, important progress has been made. Diagnostic criteria employing glycosylated ferritin have improved specificity. More important, novel biologic therapies have offered important clues to AOSD’s underlying pathophysiology. Cytokine-specific biologic therapies have been instrumental in providing more effective treatment for disease refractory to conventional treatment. While IL-1 therapy has demonstrated efficacy in refractory disease, novel therapies targeting IL-6 and IL-18 show great promise and are currently under investigation. PMID:27843366

  3. Adult-onset intradural spinal teratoma in the lumbar spine: A case report.

    PubMed

    Arai, Yasuhisa; Takahashi, Masaki; Takeda, Koutarou; Shitoto, Katsuo

    2000-12-01

    Intradural spinal teratoma is a very rare tumour that can be associated with dysraphic defects. We report a case of adult-onset intradural spinal teratoma in the lumbar spine. The patient was a 54-year-old female who had chief complaints of a gait disturbance. X-rays showed an enlargement of the interpedicular distance at L3/L4 and spina bifida distal to L4. MRI showed a spindle-shaped tumour between L2 and L5. We performed laminotomy using an ultrasonic surgical knife. Pathological diagnosis of the resected tumour was matured teratoma. The diagnosis of matured teratoma was made because the tumour had no epithelium and a layered structure including prostate tissue, matured fat, cartilage and sweat gland.

  4. Acute-onset unilateral psychogenic hearing loss in adults: report of six cases and diagnostic pitfalls.

    PubMed

    Oishi, Naoki; Kanzaki, Sho; Kataoka, Chinatsu; Tazoe, Mami; Takei, Yasuhiko; Nagai, Keiichi; Kohno, Naoyuki; Ogawa, Kaoru

    2009-01-01

    We encountered 6 rare cases of acute-onset unilateral psychogenic hearing loss in adults. All were women in their 20s and 30s. Three cases had severe hearing impairment characterized by hearing loss at every frequency; 2 cases had profound hearing impairment, and 1 case had low-frequency hearing impairment. Of the 6 cases, 3 had a history of hearing loss, and 1 had a history of psychogenic visual disturbance. All 6 cases were initially diagnosed as having idiopathic sudden sensorineural hearing loss; all subsequently received steroid therapy. Three cases were not diagnosed as being psychogenic in origin until otoacoustic emissions and auditory brain responses were performed. Although the presence of distinctive clinical features (age, gender, and past history) is important for suspecting psychogenic hearing loss, objective audiological tests such as otoacoustic emissions are essential for diagnosing some cases. Compared to the existing reports of similar cases, our cases had a poorer prognosis (only 2 cases were cured).

  5. Hidden in plain sight: macrophage activation syndrome complicating Adult Onset Still's Disease.

    PubMed

    Benitez, Lourdes; Vila, Salvador; Mellado, Robert Hunter

    2010-01-01

    Hemophagocytic Lymphystiocytosis is a rare and fatal complication of rheumatic diseases, particularly Adult Onset Still's Disease (AOSD). It may be precipitated with immunosuppressive drugs and with viral and bacterial infections. A diagnosis depends on a high index of suspicion associated to certain clinical manifestations (fever, rash, Splemomegaly, any cytology blood dyscrasia, hipertrigliceridemia, hiperfibrinogenemia, and others), as well as pathologic evidence of hemophagocitosis from bone marrow biopsy or tissue samples of affected organs. Therapy consists of high dose corticosteroids and immunosuppressive drugs. We present a 42 year old woman with AOSD in remission who developed HLH in spite of receiving therapy with high dose steroids and immunosuppressive drugs. She had 2 negative bone marrow aspirates. Evidence of Hemophagocytosis was detected in both bone marrow biopsies. Timely evaluation and recognition of the signs and symptoms of HLH is crucial for the prompt management and a decrease in the mortality associated with this disease.

  6. Predictive Medicine: Recombinant DNA Technology and Adult-Onset Genetic Disorders

    PubMed Central

    Hayden, Michael

    1988-01-01

    Genetic factors are of great importance in common adult-onset disorders such as atherosclerosis, cancer, and neuro-degenerative diseases. Advances in DNA technology now allow identification of persons at high-risk of developing some of these diseases. This advance is leading to predictive medicine. In some genetic disorders, such as those leading to atherosclerosis and cancer, identification of high-risk individuals allows intervention which alters the natural history of the disorder. In other diseases, for which there is no treatment, such as Huntington's disease, the application of this technology provides information that relieves uncertainty and may affect quality of life, but does not alter the course of the illness. General implementation of predictive testing programs awaits the results of pilot projects, which will demonstrate the needs, appropriate levels of support, and guidelines for delivery of such testing. PMID:21253100

  7. Case report: An adult-onset type II citrin deficiency patient in the emergency department

    PubMed Central

    TANG, LUJIA; CHEN, LIANG; WANG, HAIRONG; DAI, LIHUA; PAN, SHUMING

    2016-01-01

    Mutations in the solute carrier family 25 (SLC25A13) gene may result in neonatal intrahepatic cholestasis caused by citrin deficiency and/or adult-onset type II citrullinemia. These conditions are inherited in an autosomal recessive manner. The current case report describes a 43-year-old man who presented with sudden delirium and upper limb weakness. Upon admission, the patient was fully conscious and alert but later lost consciousness subsequent to a sudden convulsive seizure. Hyperammonemia was detected and analysis of the SLC25A13 gene identified an 851del4 mutation. Thus, the possibility of genetic disease should be considered as a potential cause of the symptoms of patients with altered states of consciousness, such as delirium and loss of consciousness, in cases where the cause of the disturbance is unknown. PMID:27347070

  8. Frontal Gray Matter Atrophy in Middle Aged Adults with Type 1 Diabetes is Independent of Cardiovascular Risk Factors and Diabetes Complications

    PubMed Central

    Hughes, Timothy M.; Ryan, Christopher M.; Aizenstein, Howard J.; Nunley, Karen; Gianaros, Peter J.; Miller, Rachel; Costacou, Tina; Strotmeyer, Elsa S.; Orchard, Trevor J.; Rosano, Caterina

    2013-01-01

    Aims To determine if regional gray matter volume (GMV) differences in middle-aged adults with and without type-1 diabetes (T1D) are localized in areas most vulnerable to aging, e.g. fronto-subcortical networks; and if these differences are explained by cardiovascular risk factors and diabetes complications. Methods Regional GMV was computed using 3 Tesla MRI of 104 adults with a childhood onset of T1D (mean age: 49+7 and duration: 41±6 years) and 151 adults without diabetes (mean age: 40+6). A Bonferroni threshold (n=45, p≤0.001) was applied to account for multiple between-group comparisons and analyses were repeated in an age- and gender-matched subset of participants with T1D and controls (n=44 in each group, mean age [SD] and range: 44.0, [4.3], 17.4 and 44.6 [4.3], 17.0, respectively). Results Compared to controls, T1D patients had smaller GMV in the frontal lobe (6 to 19% smaller) and adjacent supramarginal and postcentral gyri (8 to 13% smaller). Between-group differences were independent of age, waist circumference, systolic blood pressure, fasting total cholesterol and smoking status and were similar in sensitivity analyses restricted to age- and gender-matched participants. Associations between GMV and diabetes complications were not significant. Conclusions These findings extend the notion of accelerated brain aging in T1D to middle-aged adults. The pathophysiology of frontal gray matter atrophy and its impact on future development of disability and dementia need further study, especially as middle-aged T1D patients progress to older age. PMID:23994432

  9. Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease

    PubMed Central

    Lococo, Filippo; Bajocchi, Gianluigi; Caruso, Andrea; Valli, Riccardo; Ricchetti, Tommaso; Sgarbi, Giorgio; Salvarani, Carlo

    2016-01-01

    Abstract Background: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. Methods: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). Results: The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. Conclusion: Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history. PMID:27603335

  10. Macrophage Activation Syndrome Associated with Adult-Onset Still's Disease Successfully Treated with Anakinra

    PubMed Central

    Kato, Hiroshi

    2016-01-01

    Macrophage activation syndrome (MAS) is a potentially fatal complication of Adult-Onset Still's disease (Still's disease). Whereas an increasing body of evidence supports interleukin-1 (IL-1) blockade as a promising treatment for Still's disease, whether it is therapeutic for MAS associated with Still's disease remains unclear. We report a 34-year-old Caucasian man with one-decade history of TNF-blockade-responsive seronegative arthritis who presented with abrupt onset of fever, serositis, bicytopenia, splenomegaly, hepatitis, and disseminated intravascular coagulation. Striking hyperferritinemia was noted without evidence of infection, malignancy, or hemophagocytosis on bone marrow biopsy. NK cells were undetectable in the peripheral blood, whereas soluble IL-2 receptor was elevated. His multiorgan disease resolved in association with methylprednisolone pulse therapy, Anakinra, and a tapering course of prednisone. This case reinforces the notion that Still's disease is inherently poised to manifest MAS as one of the clinical phenotypes by shedding light on the role of IL-1 underlying both Still's disease and related MAS. PMID:27818826

  11. Childhood attachment, childhood sexual abuse, and onset of masturbation among adult sexual offenders.

    PubMed

    Smallbone, Stephen W; McCabe, Billee-Anne

    2003-01-01

    Written autobiographies of 48 incarcerated adult male sexual offenders (22 rapists, 13 intrafamilial child molesters, and 13 extrafamilial child molesters) were used to generate retrospective self-report measures of their childhood maternal and paternal attachment, childhood sexual abuse experiences, and onset of masturbation. Contrary to expectation, the offenders as a combined group more often reported secure than they did insecure childhood maternal and paternal attachment. There were no differences between the three offender subgroups with respect to maternal attachment; however the rapists and the intrafamilial child molesters were more likely to report insecure paternal attachment than were the extrafamilial child molesters. There were no differences between these offender subgroups in the frequency with which childhood sexual abuse was reported. However, offenders with insecure paternal attachment were more likely to report having been sexually abused than were those with secure paternal attachment. Sexually abused offenders in turn reported earlier onset of masturbation than did those who were not sexually abused. These results are consistent with contemporary attachment models linking insecure childhood attachment to childhood sexual abuse, and with traditional conditioning models linking childhood sexual abuse, early masturbation, and sexual offending.

  12. Delayed Onset Muscle Soreness After Inspiratory Threshold Loading in Healthy Adults

    PubMed Central

    Mathur, Sunita; Sheel, A. William; Road, Jeremy D.; Reid, W. Darlene

    2010-01-01

    Purpose: Skeletal muscle damage occurs following high-intensity or unaccustomed exercise; however, it is difficult to monitor damage to the respiratory muscles, particularly in humans. The aim of this study was to use clinical measures to investigate the presence of skeletal muscle damage in the inspiratory muscles. Methods: Ten healthy subjects underwent 60 minutes of voluntary inspiratory threshold loading (ITL) at 70% of maximal inspiratory pressure. Maximal inspiratory and expiratory mouth pressures, delayed onset muscle soreness on a visual analogue scale and plasma creatine kinase were measured prior to ITL, and at repeated time points after ITL (4, 24 and 48 hours post-ITL). Results: Delayed onset muscle soreness was present in all subjects 24 hours following ITL (intensity = 22 ± 6 mm; significantly higher than baseline p = 0.02). Muscle soreness was reported primarily in the anterior neck region, and was correlated to the amount of work done by the inspiratory muscles during ITL (r = 0.72, p = 0.02). However, no significant change was observed in maximal inspiratory or expiratory pressures or creatine kinase. Conclusions: These findings suggest that an intense bout of ITL results in muscle soreness primarily in the accessory muscles of inspiration, however, may be insufficient to cause significant muscle damage in healthy adults. PMID:20467514

  13. Adult-onset NREM parasomnia with hypnopompic hallucinatory pain: a case report.

    PubMed

    Mantoan, Laura; Eriksson, Sofia H; Nisbet, Angus P; Walker, Matthew C

    2013-02-01

    We report the case of a 43-year-old woman presenting with nocturnal episodes of pain and screaming during sleep starting at age 30. There was no childhood or family history of parasomnia. The events had gradually become more frequent over the years, occurring in the first half of the night within 2 h of sleep onset. There were no triggers, and she had partial amnesia for the events. A diagnosis of adult-onset sleep terrors was made on clinical grounds and supported polysomnographically. Seizures and periodic limb movements were excluded as triggering factors. There was some mild sleep disordered breathing (predominantly non-desaturating hypopnea with a propensity for REM sleep of debatable significance). Imaging of the brain and spine and neurophysiological investigations ruled out lesions, entrapments, or neuropathies as possible causes of pain. Treatment (clonazepam, paroxetine, or gabapentin) was poorly tolerated and made no difference to the nocturnal episodes, while trazodone worsened them. This is the first report of hypnopompic psychic pain in association with a NREM parasomnia. We hypothesize that the pain may represent a sensory hallucination analogous to the more commonly recognized visual NREM parasomnia-associated hypnopompic visual hallucinations and that, as such, it may arise during arousal of the sensory neocortex as confabulatory response.

  14. B-cell populations discriminate between pediatric- and adult-onset multiple sclerosis

    PubMed Central

    Schwarz, Alexander; Balint, Bettina; Korporal-Kuhnke, Mirjam; Jarius, Sven; von Engelhardt, Kathrin; Fürwentsches, Alexandra; Bussmann, Cornelia; Ebinger, Friedrich; Haas, Jürgen

    2016-01-01

    Objective: To comparatively assess the B-cell composition in blood and CSF of patients with pediatric-onset multiple sclerosis (pedMS) and adult-onset multiple sclerosis (adMS). Methods: In this cross-sectional study, we obtained blood and CSF samples from 25 patients with pedMS (8–18 years) and 40 patients with adMS (23–65 years) and blood specimens from 66 controls (1–55 years). By using multicolor flow cytometry, we identified naive, transitional, isotype class-switched memory, nonswitched memory, and double-negative memory B-cell subsets as well as plasmablasts (PB) and terminally differentiated plasma cells (PC). Flow cytometric data were compared to concentrations of B-cell-specific cytokines in serum and CSF as determined by ELISA. Results: Frequencies of circulating naive B-cells decreased with higher age in controls but not in patients with multiple sclerosis (MS). B-cell patterns in CSF differed between pedMS and adMS with an acute relapse: in pedMS-derived CSF samples, high frequencies of nonswitched memory B cells and PB were present, whereas class-switched memory B cells and PC dominated in the CSF of patients with adMS. In pedMS, PB were also elevated in the periphery. Accumulation of PB in the CSF correlated with high intrathecal CXCL-13 levels and augmented intrathecal synthesis of immunoglobulin G and immunoglobulin M. Conclusions: We demonstrate distinct changes in intrathecal B-cell homeostasis in patients with pedMS during active disease, which differ from those in adults by an expansion of plasmablasts in blood and CSF and similarly occur in prototypic autoantibody-driven autoimmune disorders. This emphasizes the particular importance of activated B-lymphocyte subsets for disease progression in the earliest clinical stages of MS. PMID:28053999

  15. Early-onset psychoses: comparison of clinical features and adult outcome in 3 diagnostic groups.

    PubMed

    Ledda, Maria Giuseppina; Fratta, Anna Lisa; Pintor, Manuela; Zuddas, Alessandro; Cianchetti, Carlo

    2009-09-01

    A comparison of clinical features and adult outcome in adolescents with three types of psychotic disorders: schizophrenic (SPh), schizoaffective (SA) and bipolar with psychotic features (BPP). Subjects (n = 41) were finally diagnosed (DSM-IV criteria) with SPh (n = 17), SA (n = 11) or BPP (n = 13). Clinical evaluation took place at onset and at a 3-year follow-up in all 41, and at least after 5 years in 36 patients. Symptoms were rated on the basis of the Positive and Negative Syndrome Scale (PANSS), integrating items from the Brief Psychiatric Rating Scale (BPRS) and the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL). The Children Global Assessment Scale (C-GAS) and the Global Assessment Scale (GAF) were used to evaluate global functioning. Significant differences in clinical features were found in the three diagnostic groups as regards several parameters, some present on one and not on other rating scales, underscoring the insufficiency of a single scale for accurate analysis of the features of a psychotic disorder. At onset, a comparison using the simple presence/absence of symptoms showed scant differences among groups, while differences emerged if symptom severity was included in the comparison. Functioning at 3- and 5-year follow-ups showed a significantly better outcome in the BPP group and more substantial deterioration, with similar evolution, in the SPh and SA groups. The integration of several rating scales differentiated between diagnostic groups more effectively. The similar adult functioning outcome in the SPh and SA groups showed how difficult it is to clearly separate these two disorders.

  16. Increased Insomnia Symptoms Predict the Onset of Back Pain among Employed Adults

    PubMed Central

    2014-01-01

    Background Back pain is among the most prevalent pain disorders causing chronic disability among adults, and insomnia is a common co-morbidity. However, whether insomnia precedes back pain or vice versa remains unclear. The current study tested the temporal association between insomnia and back pain. Methods A longitudinal design was used to investigate whether changes in insomnia over time predict the onset of back pain and vice versa. The study was conducted on a cohort of active healthy working adults (N = 2,131, 34% women) at three time points (T1, T2, and T3) over a period of 3.7 years (range = 2.2–5.12) years. Logistic regression analysis was used to test whether increased insomnia symptoms from T1 to T2 predicted the onset of new back pain. Ordinary least squares regression was used to test whether the existence of back pain at T2 predicted an increase in insomnia from T2 to T3. Results The results indicated that after controlling for socioeconomic variables, self-reported health, lifestyle behaviors, and anthropometrics, a T1–T2 increase in insomnia symptoms was associated with a 1.40-fold increased risk of back pain at T3 (OR = 1.40; 95% CI = 1.10–1.71). No support was found for reverse causation; i.e., that back pain predicts subsequent increase in insomnia. Conclusions Insomnia appears to be a risk factor in the development of back pain in healthy individuals. However, no evidence of reverse causation was found. PMID:25084165

  17. Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium

    PubMed Central

    Postma, D. S.; Moffatt, M. F.; Jarvis, D.; Ramasamy, A.; Wjst, M.; Omenaas, E. R.; Bouzigon, E.; Demenais, F.; Nadif, R.; Siroux, V.; Polonikov, A. V.; Solodilova, M.; Ivanov, V. P.; Curjuric, I.; Imboden, M.; Kumar, A.; Probst-Hensch, N.; Ogorodova, L. M.; Puzyrev, V. P.; Bragina, E. Yu; Freidin, M. B.; Nolte, I. M.; Farrall, A. M.; Cookson, W. O. C. M.; Strachan, D. P.; Koppelman, G. H.; Boezen, H. M.

    2017-01-01

    Background Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. Methods We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. Results First approach: 50 SNPs were selected based on an overall interaction effect at p<10−4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10−5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10−4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10−4; replication: ORint = 1.40, p = 0.03). Conclusions Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma. PMID:28253294

  18. Contribution of known and unknown susceptibility genes to early-onset diabetes in scandinavia: evidence for heterogeneity.

    PubMed

    Lindgren, Cecilia M; Widén, Elisabeth; Tuomi, Tiinamaija; Li, Haiyan; Almgren, Peter; Kanninen, Timo; Melander, Olle; Weng, Jianping; Lehto, Markku; Groop, Leif C

    2002-05-01

    In an attempt to identify novel susceptibility genes predisposing to early-onset diabetes (EOD), we performed a genome-wide scan using 433 markers in 222 individuals (119 with diabetes) from 29 Scandinavian families with > or =2 members with onset of diabetes < or =45 years. The highest nonparametric linkage (NPL) score, 2.7 (P < 0.01), was observed on chromosome 1p (D1S473/D1S438). Six other regions on chromosomes 3p, 7q, 11q, 18q, 20q, and 21q showed a nominal P value <0.05. Of the EOD subjects in these 29 families, 20% were GAD antibody positive and 68% displayed type 1 diabetes HLA risk alleles (DQB*02 or 0302). Mutations in maturity-onset diabetes of the young (MODY) 1-5 genes and the A3243G mitochondrial DNA mutation were detected by single-strand conformation polymorphism and direct sequencing. To increase homogeneity, we analyzed a subsample of five families with autosomal dominant inheritance of EOD (greater than or equal to two members with age at diagnosis < or =35 years). The highest NPL scores were found on chromosome 1p (D1S438-D1S1665; NPL 3.0; P < 0.01) and 16q (D16S419; NPL 2.9; P < 0.01). After exclusion of three families with MODY1, MODY3, and mitochondrial mutations, the highest NPL scores were observed on chromosomes 1p (D1S438; NPL 2.6; P < 0.01), 3p (D3S1620; NPL 2.2; P < 0.03), 5q (D5S1465; NPL 2.1; P < 0.03), 7q (D7S820; NPL 2.0; P < 0.03), 18q (D18S535; NPL 1.9; P < 0.04), 20q (D20S195; NPL 2.5; P < 0.02), and 21q (D21S1446; NPL 2.2; P < 0.03). We conclude that considerable heterogeneity exists in Scandinavian subjects with EOD; 24% had MODY or maternally inherited diabetes and deafness, and approximately 60% were GAD antibody positive or had type 1 diabetes-associated HLA genotypes. Our data also point at putative chromosomal regions, which could harbor novel genes that contribute to EOD.

  19. Oxidative stress and susceptibility to mitochondrial permeability transition precedes the onset of diabetes in autoimmune non-obese diabetic mice.

    PubMed

    Malaguti, C; La Guardia, P G; Leite, A C R; Oliveira, D N; de Lima Zollner, R L; Catharino, R R; Vercesi, A E; Oliveira, H C F

    2014-12-01

    Beta cell destruction in type 1 diabetes (TID) is associated with cellular oxidative stress and mitochondrial pathway of cell death. The aim of this study was to determine whether oxidative stress and mitochondrial dysfunction are present in T1D model (non-obese diabetic mouse, NOD) and if they are related to the stages of disease development. NOD mice were studied at three stages: non-diabetic, pre-diabetic, and diabetic and compared with age-matched Balb/c mice. Mitochondria respiration rates measured at phosphorylating and resting states in liver and soleus biopsies and in isolated liver mitochondria were similar in NOD and Balb/c mice at the three disease stages. However, NOD liver mitochondria were more susceptible to calcium-induced mitochondrial permeability transition as determined by cyclosporine-A-sensitive swelling and by decreased calcium retention capacity in all three stages of diabetes development. Mitochondria H2O2 production rate was higher in non-diabetic, but unaltered in pre-diabetic and diabetic NOD mice. The global cell reactive oxygen species (ROS), but not specific mitochondria ROS production, was significantly increased in NOD lymphomononuclear and stem cells in all disease stages. In addition, marked elevated rates of 2',7'-dichlorodihydrofluorescein (H2DCF) oxidation were observed in pancreatic islets from non-diabetic NOD mice. Using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) and lipidomic approach, we identified oxidized lipid markers in NOD liver mitochondria for each disease stage, most of them being derivatives of diacylglycerols and phospholipids. These results suggest that the cellular oxidative stress precedes the establishment of diabetes and may be the cause of mitochondrial dysfunction that is involved in beta cell death.

  20. Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a 4-decade longitudinal cohort study

    PubMed Central

    Moffitt, Terrie E.; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, Honalee; Hogan, Sean; Meier, Madeline; Polanczyk, Guilherme V.; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom

    2015-01-01

    Objective Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective-longitudinal study has described the childhoods of the adult-ADHD population. We report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort. Method Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand in 1972-73 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, GWAS-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological testing, and administrative records. Adult ADHD diagnoses used DSM5 criteria, apart from onset-age and cross-setting corroboration, which were study outcomes. Results As expected, the childhood-ADHD group showed 6% prevalence, male excess, childhood comorbid disorders, neurocognitive deficits, polygenic risk, and, despite having outgrown their ADHD diagnosis, residual adult life impairment. As expected, the adult-ADHD group showed 3% prevalence, gender balance, adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood-ADHD and adult-ADHD groups comprised virtually non-overlapping sets; 90% of adult-ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult-ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD. Conclusion Findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder's place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD. PMID:25998281

  1. Primary and Specialty Medical Care Among Ethnically Diverse, Older Rural Adults With Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  2. Primary and Specialty Medical Care among Ethnically Diverse, Older Rural Adults with Type 2 Diabetes: The ELDER Diabetes Study

    ERIC Educational Resources Information Center

    Bell, Ronny A.; Quandt, Sara A.; Arcury, Thomas A.; Snively, Beverly M.; Stafford, Jeanette M.; Smith, Shannon L.; Skelly, Anne H.

    2005-01-01

    Purpose: Residents in rural communities in the United States, especially ethnic minority group members, have limited access to primary and specialty health care that is critical for diabetes management. This study examines primary and specialty medical care utilization among a rural, ethnically diverse, older adult population with diabetes.…

  3. Obesity and non-insulin-dependent diabetes mellitus in Swiss-Webster mice associated with late-onset hepatocellular carcinoma.

    PubMed

    Lemke, Laura B; Rogers, Arlin B; Nambiar, Prashant R; Fox, James G

    2008-10-01

    Genetic mutations resulting in obesity and type 2 diabetes mellitus (T2D) are described for both inbred and outbred mice. However, no known mouse model completely recapitulates human T2D and its comorbidities. We identified a cohort of obese, male, outbred Swiss-Webster (SW) mice as polyuric, polydipsic, glucosuric, and hyperglycemic. Prevalence of glucosuria in the SW colony reached 60% (n=70) in males 8 weeks to 6 months of age. Despite severe obesity in some females, no females were diabetic. Pathologic findings in affected males included cachexia, dilated gastrointestinal tracts with poor muscular tone, pancreatic islet degeneration and atrophy with compensatory metaplasia and/or neogenesis, bacterial pyelonephritis, membranous glomerulopathy, and late-onset hepatic tumors with macrosteatosis, microsteatosis, and hydropic change in aged males. Serum insulin correlated with blood glucose in a nonlinear pattern, suggestive of islet exhaustion. Circulating leptin levels showed a weak inverse correlation with glucose. Diabetic males were bred with obese colony females to produce 20 male and 20 female offspring. Prevalence of diabetes in male offspring was 80% (16/20) with a median age of onset of 18 weeks. By contrast, no diabetic females were identified, despite being significantly more obese than males. Male predominance is likewise a feature of T2D in humans. To our knowledge, this is the first documentation of hepatocellular carcinoma and islet metaplasia and/or neogenesis in a spontaneous outbred mouse model of T2D. The SW availability and histopathologic features represent a promising new model for the study of T2D.

  4. Glucagon-like peptide-2 reduces intestinal permeability but does not modify the onset of type 1 diabetes in the nonobese diabetic mouse.

    PubMed

    Hadjiyanni, Irene; Li, Kunmin Karen; Drucker, Daniel J

    2009-02-01

    The development of type 1 diabetes (T1D) has been linked to environmental factors and dietary components. Increasing evidence indicates that the integrity of the gut mucosa plays a role in the development of autoimmune diseases, and evidence from both preclinical and clinical studies demonstrates that increased leakiness of the intestinal epithelium precedes the development of type 1 diabetes. However, there is limited information on modulation of gut barrier function and its relationship to diabetes development. Here we show that the nonobese diabetic (NOD) mouse, a model of T1D, exhibits enhanced intestinal transcellular permeability before the development of autoimmune diabetes. Treatment of NOD mice with a glucagon-like peptide 2 (GLP-2) analog, synthetic human [Gly(2)] glucagon-like peptide-2 (h[Gly(2)]GLP-2, increased the length and weight of the small bowel and significantly improved jejunal transepithelial resistance. However, chronic administration of once daily h[Gly(2)]GLP-2 failed to delay or reverse the onset of T1D when treatment was initiated in young, normoglycemic female NOD mice. Furthermore, h[Gly(2)]GLP-2 administration had no significant effect on lymphocyte subpopulations in NOD mice. These findings demonstrate that h[Gly(2)]GLP-2-mediated enhancement of gut barrier function in normoglycemic NOD mice disease is not sufficient to prevent or delay the development of experimental T1D.

  5. UNDERSTANDING THE SOURCES OF DIABETES DISTRESS IN ADULTS WITH TYPE 1 DIABETES

    PubMed Central

    Fisher, Lawrence; Polonsky, William H.; Hessler, Danielle M.; Masharani, Umesh; Blumer, Ian; Peters, Anne L.; Strycker, Lisa A.; Bowyer, Vicky

    2015-01-01

    Aims To identify the unique sources of diabetes distress (DD) for adults with type 1 diabetes (T1D). Methods Sources of DD were developed from qualitative interviews with 25 T1D adults and 10 diabetes health care providers. Survey items were then developed and analyzed using both exploratory (EFA) and confirmatory CFA) analyses on two patient samples. Construct validity was assessed by correlations with depressive symptoms (PHQ8), complications, HbA1C, BMI, and hypoglycemia worry scale (HWS). Scale cut-points were created using multiple regression. Results An EFA with 305 U.S. participants yielded 7 coherent, reliable sources of distress that were replicated by a CFA with 109 Canadian participants: Powerlessness, Negative Social Perceptions, Physician Distress, Friend/Family Distress, Hypoglycemia Distress, Management Distress, Eating Distress. Prevalence of DD was high with 41.6% reporting at least moderate DD. Higher DD was reported for women, those with complications, poor glycemic control, younger age, without a partner, and non-White patients. Conclusions We identified a profile of seven major sources of DD among T1D using a newly developed assessment instrument. The prevalence of DD is high and is related to glycemic control and several patient demographic and disease-related patient characteristics, arguing for a need to address DD in clinical care. PMID:25765489

  6. Prediabetes in California: Nearly Half of California Adults on Path to Diabetes.

    PubMed

    Babey, Susan H; Wolstein, Joelle; Diamant, Allison L; Goldstein, Harold

    2016-03-01

    In California, more than 13 million adults (46 percent of all adults in the state) are estimated to have prediabetes or undiagnosed diabetes. An additional 2.5 million adults have diagnosed diabetes. Altogether, 15.5 million adults (55 percent of all California adults) have prediabetes or diabetes. Although rates of prediabetes increase with age, rates are also high among young adults, with one-third of those ages 18-39 having prediabetes. In addition, rates of prediabetes are disproportionately high among young adults of color, with more than one-third of Latino, Pacific Islander, American Indian, African-American, and multiracial Californians ages 18-39 estimated to have prediabetes. Policy efforts should focus on reducing the burden of prediabetes and diabetes through support for prevention and treatment.

  7. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability

    PubMed Central

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-01-01

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability. PMID:26251896

  8. Effects of Aging and Adult-Onset Hearing Loss on Cortical Auditory Regions

    PubMed Central

    Cardin, Velia

    2016-01-01

    Hearing loss is a common feature in human aging. It has been argued that dysfunctions in central processing are important contributing factors to hearing loss during older age. Aging also has well documented consequences for neural structure and function, but it is not clear how these effects interact with those that arise as a consequence of hearing loss. This paper reviews the effects of aging and adult-onset hearing loss in the structure and function of cortical auditory regions. The evidence reviewed suggests that aging and hearing loss result in atrophy of cortical auditory regions and stronger engagement of networks involved in the detection of salient events, adaptive control and re-allocation of attention. These cortical mechanisms are engaged during listening in effortful conditions in normal hearing individuals. Therefore, as a consequence of aging and hearing loss, all listening becomes effortful and cognitive load is constantly high, reducing the amount of available cognitive resources. This constant effortful listening and reduced cognitive spare capacity could be what accelerates cognitive decline in older adults with hearing loss. PMID:27242405

  9. Genes and Pathways Involved in Adult Onset Disorders Featuring Muscle Mitochondrial DNA Instability.

    PubMed

    Ahmed, Naghia; Ronchi, Dario; Comi, Giacomo Pietro

    2015-08-05

    Replication and maintenance of mtDNA entirely relies on a set of proteins encoded by the nuclear genome, which include members of the core replicative machinery, proteins involved in the homeostasis of mitochondrial dNTPs pools or deputed to the control of mitochondrial dynamics and morphology. Mutations in their coding genes have been observed in familial and sporadic forms of pediatric and adult-onset clinical phenotypes featuring mtDNA instability. The list of defects involved in these disorders has recently expanded, including mutations in the exo-/endo-nuclease flap-processing proteins MGME1 and DNA2, supporting the notion that an enzymatic DNA repair system actively takes place in mitochondria. The results obtained in the last few years acknowledge the contribution of next-generation sequencing methods in the identification of new disease loci in small groups of patients and even single probands. Although heterogeneous, these genes can be conveniently classified according to the pathway to which they belong. The definition of the molecular and biochemical features of these pathways might be helpful for fundamental knowledge of these disorders, to accelerate genetic diagnosis of patients and the development of rational therapies. In this review, we discuss the molecular findings disclosed in adult patients with muscle pathology hallmarked by mtDNA instability.

  10. Signal Detection Analysis of Factors Associated with Diabetes among Semirural Mexican American Adults

    ERIC Educational Resources Information Center

    Hanni, K. D.; Ahn, D. A.; Winkleby, M. A.

    2013-01-01

    Signal detection analysis was used to evaluate a combination of sociodemographic, acculturation, mental health, health care, and chronic disease risk factors potentially associated with diabetes in a sample of 4,505 semirural Mexican American adults. Overall, 8.9% of adults had been diagnosed with diabetes. The analysis resulted in 12 mutually…

  11. Development of early-onset type 2 diabetes in the young: implications for child bearing.

    PubMed

    Homko, Carol J; Reece, E Albert

    2003-08-01

    The prevalence of type 2 diabetes mellitus is increasing in children and adolescents worldwide, particularly among minority youth. This has led to an increase in the number of pregnancies complicated by type 2 diabetes, which has now exceeded pregnancies complicated by type 1 diabetes. Although the data are somewhat limited, those studies that are available seem to indicate that the rate of adverse maternal and fetal outcomes is at least as great, if not greater, for type 2 as for type 1 diabetes. It has been postulated that some of the excess risk is due to the fact that women with type 2 diabetes are older, heavier, less likely to seek early prenatal care, and are generally in less satisfactory glycemic control. This article reviews the existing data on pregnancies complicated by type 2 diabetes and the implications for management and prevention.

  12. Acute Myocardial Infarction Is a Risk Factor for New Onset Diabetes in Patients with Coronary Artery Disease

    PubMed Central

    Park, Chul Soo; Chung, Woo Baek; Choi, Yun Seok; Kim, Pum Joon; Lee, Jong Min; Baek, Ki-Hyun; Kim, Hee Yeol; Yoo, Ki Dong; Song, Ki-Ho; Chung, Wook Sung; Seung, Ki Bae; Lee, Man Young; Kwon, Hyuk-Sang

    2015-01-01

    Objective To test the hypothesis that acute myocardial infarction (AMI) might accelerate development of new onset diabetes in patients with coronary artery disease independent of known risk factors. Methods We conducted a retrospective cohort study within COACT (CathOlic medical center percutAneous Coronary inTervention) registry. From a total of 9,127 subjects, 2,036 subjects were diabetes naïve and followed up for at least one year with both index and follow-up laboratory data about diabetes. Cox proportional hazard model was used to derive hazard ratios (HRs) and 95% confidence interval (CI) for new onset diabetes associated with AMI in univariate and multivariate analysis after adjusting several covariates. Results The overall hazard for diabetes was higher in AMI compared to non-AMI patients (p by log rank <0.01) with HR of 1.78 and 95% CI of 1.37–2.32 in univariate analysis. This association remained significant after adjusting covariates (HR, 1.54; 95% CI, 1.14–2.07; p<0.01). AMI was an independent predictor for higher quartile of WBC count in multivariate ordinal logistic regression analysis (OR, 6.75; 95% CI, 5.53–8.22, p<0.01). In subgroup analysis, the diabetogenic effect of AMI was more prominent in the subgroup without MetS compared to MetS patients (p for interaction<0.05). Compared to the reference group of non-AMI+nonMetS, the group of AMI+non-MetS (HR, 2.44; 95% CI, 1.58–3.76), non-AMI+MetS (HR, 3.42; 95% CI, 2.34–4.98) and AMI+MetS (HR, 4.12; 95% CI, 2.67–6.36) showed higher HR after adjusting covariates. However, the hazard was not different between the non-AMI+MetS and AMI+non-MetS groups. Conclusions AMI patients have a greater risk of new-onset diabetes when compared to non AMI patients, especially those with mild metabolic abnormalities. PMID:26295946

  13. Sexuality Among Middle-Aged and Older Adults With Diagnosed and Undiagnosed Diabetes

    PubMed Central

    Lindau, Stacy Tessler; Tang, Hui; Gomero, Ada; Vable, Anusha; Huang, Elbert S.; Drum, Melinda L.; Qato, Dima M.; Chin, Marshall H.

    2010-01-01

    OBJECTIVE To describe sexual activity, behavior, and problems among middle-age and older adults by diabetes status. RESEARCH DESIGN AND METHODS This was a substudy of 1,993 community-residing adults, aged 57–85 years, from a cross-sectional, nationally representative sample (N = 3,005). In-home interviews, observed medications, and A1C were used to stratify by diagnosed diabetes, undiagnosed diabetes, or no diabetes. Logistic regression was used to model associations between diabetes conditions and sexual characteristics, separately by gender. RESULTS The survey response rate was 75.5%. More than 60% of partnered individuals with diagnosed diabetes were sexually active. Women with diagnosed diabetes were less likely than men with diagnosed diabetes (adjusted odds ratio 0.28 [95% CI 0.16–0.49]) and other women (0.63 [0.45–0.87]) to be sexually active. Partnered sexual behaviors did not differ by gender or diabetes status. The prevalence of orgasm problems was similarly elevated among men with diagnosed and undiagnosed diabetes compared with that for other men, but erectile difficulties were elevated only among men with diagnosed diabetes (2.51 [1.53 to 4.14]). Women with undiagnosed diabetes were less likely to have discussed sex with a physician (11%) than women with diagnosed diabetes (19%) and men with undiagnosed (28%) or diagnosed (47%) diabetes. CONCLUSIONS Many middle-age and older adults with diabetes are sexually active and engage in sexual behaviors similarly to individuals without diabetes. Women with diabetes were more likely than men to cease all sexual activity. Older women with diabetes are as likely to have sexual problems but are significantly less likely than men to discuss them. PMID:20802158

  14. No Association Between Time of Onset of Hearing Loss (Childhood Versus Adulthood) and Self-Reported Hearing Handicap in Adults

    PubMed Central

    Tambs, Kristian; Engdahl, Bo

    2015-01-01

    Purpose This study examined the association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap in adults. Methods This is a population-based cohort study of 2,024 adults (mean = 48 years) with hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL) who completed a hearing handicap questionnaire. In childhood, the same persons (N = 2,024) underwent audiometry in a school investigation (at ages 7, 10, and 13 years), in which 129 were diagnosed with sensorineural hearing loss (binaural pure-tone average 0.5–4 kHz ≥ 20 dB HL), whereas 1,895 had normal hearing thresholds. Results Hearing handicap was measured in adulthood as the sum-score of various speech perception and social impairment items (15 items). The sum-score increased with adult hearing threshold level (p < .001). After adjustment for adult hearing threshold level, hearing aid use, adult age, sex, and socioeconomic status, there was no significant difference in hearing handicap sum-score between the group with childhood-onset hearing loss (n = 129) and the group with adult-onset hearing loss (n = 1,895; p = .882). Conclusion Self-reported hearing handicap in adults increased with hearing threshold level. After adjustment for adult hearing threshold level, this cohort study revealed no significant association between time of onset of hearing loss (childhood vs. adulthood) and self-reported hearing handicap. PMID:26649831

  15. INSULIN RESISTANCE IS ASSOCIATED WITH ALZHEIMER-LIKE REDUCTIONS IN REGIONAL CEREBRAL GLUCOSE METABOLISM FOR COGNITIVELY NORMAL ADULTS WITH PRE-DIABETES OR EARLY TYPE 2 DIABETES

    PubMed Central

    Baker, Laura D.; Cross, Donna; Minoshima, Satoshi; Belongia, Dana; Watson, G. Stennis; Craft, Suzanne

    2010-01-01

    Background Insulin resistance is a causal factor in pre-diabetes and type 2 diabetes (T2D), and also increases the risk of developing Alzheimer’s disease (AD). Reductions in cerebral glucose metabolic rate (CMRglu) as measured by fluorodeoxyglucose positron emission tomography (FDG PET) in parietotemporal, frontal, and cingulate cortex are also associated with increased AD risk, and can be observed years before dementia onset. Objectives We examined whether greater insulin resistance as indexed by the homeostasis model assessment (HOMA-IR) would be associated with reduced resting CMRglu in areas known to be vulnerable in AD in a sample of cognitively normal adults with newly diagnosed pre-diabetes or T2D (P-D/T2D). We also determined whether P-D/T2D adults have abnormal patterns of CMRglu during a memory encoding task. Design Randomized crossover design of resting and activation [F-18] FDG-PET. Setting University Imaging Center and VA Clinical Research Unit. Participants Participants included 23 older adults (mean age±SEM=74.4±1.4) with no prior diagnosis of or treatment for diabetes, but who met American Diabetes Association glycemic criteria for pre-diabetes (n=11) or diabetes (n=12) based on fasting or 2-h oral glucose tolerance test (OGTT) glucose values, and 6 adults (mean age±SEM=74.3±2.8) with normal fasting glucose and glucose tolerance. No participant met Petersen criteria for mild cognitive impairment (MCI). Intervention Fasting participants rested with eyes open in a dimly lit room and underwent resting and cognitive activation [F-18]FDG PET imaging on separate days, in randomized order, at 9 am. Following a 30-min transmission scan, subjects received an intravenous injection of 5 mCi [F-18]FDG, and the emission scan commenced 40 min post-injection. In the activation condition, a 35-min memory encoding task was initiated at the time of tracer injection. Subjects were instructed to remember a repeating list of 20 words that were randomly presented

  16. Impact of sustained virological response to chronic hepatitic C antiviral therapy on new onset diabetes mellitus type 2 after controlling for metabolic syndrome.

    PubMed

    Pandya, Prashant; Pant, Chaitanya; Taylor, Ryan; Oni, Olurinde

    2017-04-01

    The high cost associated with antiviral treatment for chronic hepatitis C virus (HCV) infection mandates further investigation in the context of preventing complications such as type 2 diabetes mellitus (DM2). We determined the cumulative incidence of DM2 in subjects with chronic HCV infection who received concomitant pegylated interferon (Peg-IFN) and ribavirin. We conducted a retrospective analysis of data obtained from Veterans Administrations Informatics and Computing Infrastructure (VINCI) to identify an adult cohort of patients without diabetes with chronic HCV infection who received Peg-IFN-based therapy between October 2001 and December 2011. Patients with history of HIV, hepatitis B infection, hepatocellular cancer (HCC), non-HCC cancers, and history of transplantation were excluded. Sustained virological response (SVR) was defined as negative HCV RNA 3 months after completion of therapy. Using Cox proportional hazards regression for multivariable analysis, we determined that patients who achieved SVR were at a significantly less risk of developing DM2. Adjusted survival rates showed that the responders' group was significantly less likely to develop DM2 over time (HR 0.60, CI 0.48 to 0.74, p<0.001). Peg-IFN-based therapy in chronic HCV patients that resulted in SVR significantly decreased the risk of developing DM2 and independently predicts the development of new onset disease after controlling for correlates of metabolic syndrome.

  17. Evolution of disease phenotype in adult and pediatric onset Crohn’s disease in a population-based cohort

    PubMed Central

    Lovasz, Barbara Dorottya; Lakatos, Laszlo; Horvath, Agnes; Szita, Istvan; Pandur, Tunde; Mandel, Michael; Vegh, Zsuzsanna; Golovics, Petra Anna; Mester, Gabor; Balogh, Mihaly; Molnar, Csaba; Komaromi, Erzsebet; Kiss, Lajos Sandor; Lakatos, Peter Laszlo

    2013-01-01

    AIM: To investigate the evolution of disease phenotype in adult and pediatric onset Crohn’s disease (CD) populations, diagnosed between 1977 and 2008. METHODS: Data of 506 incident CD patients were analyzed (age at diagnosis: 28.5 years, interquartile range: 22-38 years). Both in- and outpatient records were collected prospectively with a complete clinical follow-up and comprehensively reviewed in the population-based Veszprem province database, which included incident patients diagnosed between January 1, 1977 and December 31, 2008 in adult and pediatric onset CD populations. Disease phenotype according to the Montreal classification and long-term disease course was analysed according to the age at onset in time-dependent univariate and multivariate analysis. RESULTS: Among this population-based cohort, seventy-four (12.8%) pediatric-onset CD patients were identified (diagnosed ≤ 17 years of age). There was no significant difference in the distribution of disease behavior between pediatric (B1: 62%, B2: 15%, B3: 23%) and adult-onset CD patients (B1: 56%, B2: 21%, B3: 23%) at diagnosis, or during follow-up. Overall, the probability of developing complicated disease behaviour was 49.7% and 61.3% in the pediatric and 55.1% and 62.4% in the adult onset patients after 5- and 10-years of follow-up. Similarly, time to change in disease behaviour from non stricturing, non penetrating (B1) to complicated, stricturing or penetrating (B2/B3) disease was not significantly different between pediatric and adult onset CD in a Kaplan-Meier analysis. Calendar year of diagnosis (P = 0.04), ileal location (P < 0.001), perianal disease (P < 0.001), smoking (P = 0.038) and need for steroids (P < 0.001) were associated with presence of, or progression to, complicated disease behavior at diagnosis and during follow-up. A change in disease location was observed in 8.9% of patients and it was associated with smoking status (P = 0.01), but not with age at diagnosis. CONCLUSION: Long

  18. C-Peptide Response and HLA Genotypes in Subjects With Recent-Onset Type 1 Diabetes After Immunotherapy With DiaPep277

    PubMed Central

    Buzzetti, Raffaella; Cernea, Simona; Petrone, Antonio; Capizzi, Marco; Spoletini, Marialuisa; Zampetti, Simona; Guglielmi, Chiara; Venditti, Chiara; Pozzilli, Paolo

    2011-01-01

    OBJECTIVE To investigate whether lower risk HLA class II genotypes would influence the efficacy of DiaPep277 therapy in protecting β-cell function evaluated by C-peptide secretion in recent-onset type 1 diabetic subjects. RESEARCH DESIGN AND METHODS Data were collected from type 1 diabetic subjects enrolled in multicenter phase II studies with a randomized, double-blind, and placebo-controlled design in whom fasting and stimulated C-peptide levels were measured. HLA genotypes were classified in high, moderate, and low risk categories. RESULTS A total of 146 subjects (aged 4.3 to 58.5 years) were enrolled, including 76 children (<18 years old) and 70 adults. At baseline, there was a significant increase in fasting, maximal, and area under the curve (AUC) C-peptide from high to moderate and low risk HLA genotypes in adults (P for trend <0.04) but not in children. Children showed a decrease of the three parameters over time regardless of therapy and HLA genotype. DiaPep277-treated adults with low risk genotype had significantly higher maximal and AUC C-peptide versus placebo at 12 months (0.04 ± 0.07 vs. −0.28 ± 0.09 nmol/L, P < 0.01, and 0.53 ± 1.3 vs. −4.59 ± 1.5 nmol/L, P < 0.05, respectively). In the moderate risk genotype group, Δmaximal and AUC C-peptide values were significantly higher in DiaPep277-treated versus placebo-treated patients (P < 0.01 and P < 0.05, respectively). CONCLUSIONS This exploratory study demonstrates that type 1 diabetic adults with low and moderate risk HLA genotypes benefit the most from intervention with DiaPep277; the only subgroup with an increase of C-peptide at 12 months after diagnosis was the low risk DiaPep277-treated subgroup. PMID:21896927

  19. Differential Insulitic Profiles Determine the Extent of β-Cell Destruction and the Age at Onset of Type 1 Diabetes.

    PubMed

    Leete, Pia; Willcox, Abby; Krogvold, Lars; Dahl-Jørgensen, Knut; Foulis, Alan K; Richardson, Sarah J; Morgan, Noel G

    2016-05-01

    Type 1 diabetes (T1D) results from a T cell-mediated destruction of pancreatic β-cells following the infiltration of leukocytes (including CD8(+), CD4(+), and CD20(+) cells) into and around pancreatic islets (insulitis). Recently, we reported that two distinct patterns of insulitis occur in patients with recent-onset T1D from the U.K. and that these differ principally in the proportion of infiltrating CD20(+) B cells (designated CD20Hi and CD20Lo, respectively). We have now extended this analysis to include patients from the Network for Pancreatic Organ Donors with Diabetes (U.S.) and Diabetes Virus Detection (DiViD) study (Norway) cohorts and confirm that the two profiles of insulitis occur more widely. Moreover, we show that patients can be directly stratified according to their insulitic profile and that those receiving a diagnosis before the age of 7 years always display the CD20Hi profile. By contrast, individuals who received a diagnosis beyond the age of 13 years are uniformly defined as CD20Lo. This implies that the two forms of insulitis are differentially aggressive and that patients with a CD20Hi profile lose their β-cells at a more rapid rate. In support of this, we also find that the proportion of residual insulin-containing islets (ICIs) increases in parallel with age at the onset of T1D. Importantly, those receiving a diagnosis in, or beyond, their teenage years retain ∼40% ICIs at diagnosis, implying that a functional deficit rather than an absolute β-cell loss may be causal for disease onset in these patients. We conclude that appropriate patient stratification will be critical for correct interpretation of the outcomes of intervention therapies targeted to islet-infiltrating immune cells in T1D.

  20. Adult-onset Still's disease presenting as fever of unknown origin in a patient with HIV infection.

    PubMed

    DelVecchio, Sally; Skidmore, Peter

    2008-02-15

    A 43-year-old African American man with known human immunodeficiency virus (HIV) infection was found to have adult-onset Still's disease manifesting as fever of unknown origin. In the era of highly active antiretroviral therapy, HIV-infected patients are preserving their immune status and, thus, must be evaluated in a manner similar to that for the general population.

  1. Cerebral Cell Renewal in Adult Mice Controls the Onset of Obesity

    PubMed Central

    Gouazé, Alexandra; Brenachot, Xavier; Rigault, Caroline; Krezymon, Alice; Rauch, Camille; Nédélec, Emmanuelle; Lemoine, Aleth; Gascuel, Jean; Bauer, Sylvian; Pénicaud, Luc; Benani, Alexandre

    2013-01-01

    The hypothalamus plays a crucial role in the control of the energy balance and also retains neurogenic potential into adulthood. Recent studies have reported the severe alteration of the cell turn-over in the hypothalamus of obese animals and it has been proposed that a neurogenic deficiency in the hypothalamus could be involved in the development of obesity. To explore this possibility, we examined hypothalamic cell renewal during the homeostatic response to dietary fat in mice, i.e., at the onset of diet-induced obesity. We found that switching to high-fat diet (HFD) accelerated cell renewal in the hypothalamus through a local, rapid and transient increase in cell proliferation, peaking three days after introducing the HFD. Blocking HFD-induced cell proliferation by central delivery of an antimitotic drug prevented the food intake normalization observed after HFD introduction and accelerated the onset of obesity. This result showed that HFD-induced dividing brain cells supported an adaptive anorectic function. In addition, we found that the percentage of newly generated neurons adopting a POMC-phenotype in the arcuate nucleus was increased by HFD. This observation suggested that the maturation of neurons in feeding circuits was nutritionally regulated to adjust future energy intake. Taken together, these results showed that adult cerebral cell renewal was remarkably responsive to nutritional conditions. This constituted a physiological trait required to prevent severe weight gain under HFD. Hence this report highlighted the amazing plasticity of feeding circuits and brought new insights into our understanding of the nutritional regulation of the energy balance. PMID:23967273

  2. Factors associated with the age of the onset of diabetes in women aged 50 years or more: a population-based study

    PubMed Central

    Valadares, Ana L R; Machado, Vanessa S S; Costa-Paiva, Lúcia S; de Sousa, Maria H; Pinto-Neto, Aarão M

    2014-01-01

    Objective Investigate factors associated with the onset of diabetes in women aged more than 49 years. Design and methods Cross-sectional, population-based study using self-reports with 622 women. The dependent variable was the age of occurrence of diabetes using the life table method. Cox multiple regression models were adjusted to analyse the onset of diabetes according to predictor variables. Sociodemographic, clinical and behavioural factors were evaluated. Results Of the 622 women interviewed, 22.7% had diabetes. The mean age at onset was 56 years. The factors associated with the age of occurrence of diabetes were self-rated health (very good, good) (coefficient=−0.792; SE of the coefficient=0.215; p=0.0001), more than two individuals living in the household (coefficient=0.656, SE of the coefficient=0.223; p=0.003), and body mass index (BMI) (kg/m2) at 20–30 years of age (coefficient= 0.056, SE of the coefficient=0.023; p=0.014). Conclusions Self-rated health considered good or very good was associated with a higher rate of survival without diabetes. Sharing a home with two or more other people and a weight increase at 20–30 years of age was associated with the onset of type 2 diabetes. PMID:25428628

  3. Sedentary behavior and physical activity in youth with recent onset of type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    With the rise of type 2 diabetes in youth, it is critical to investigate factors such as physical activity (PA) and time spent sedentary that may be contributing to this public health problem. This article describes PA and sedentary time in a large cohort of youth with type 2 diabetes and compares t...

  4. Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome

    PubMed Central

    Santín, Sheila; Tazón-Vega, Bárbara; Silva, Irene; Cobo, María Ángeles; Giménez, Isabel; Ruíz, Patricia; García-Maset, Rafael; Ballarín, José

    2011-01-01

    Summary Background and objectives To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. Design, setting, participants, & measurements Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. Results Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio = 2.65; P = 0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. Conclusions NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant. PMID:20947785

  5. Prediction at First Year of Incident New-Onset Diabetes After Kidney Transplantation by Risk Prediction Models

    PubMed Central

    Rodrigo, Emilio; Santos, Lidia; Piñera, Celestino; Ruiz San Millán, Juan Carlos; Quintela, Maria Estrella; Toyos, Carmen; Allende, Natalia; Gómez-Alamillo, Carlos; Arias, Manuel

    2012-01-01

    OBJECTIVE Our aim was to analyze the performance of two scores developed for predicting diabetes in nontransplant populations for identifying kidney transplant recipients with a higher new-onset diabetes mellitus after transplantation (NODAT) risk beyond the first year after transplantation. RESEARCH DESIGN AND METHODS We analyzed 191 kidney transplants, which had at least 1-year follow-up posttransplant. First-year posttransplant variables were collected to estimate the San Antonio Diabetes Prediction Model (SADPM) and Framingham Offspring Study–Diabetes Mellitus (FOS-DM) algorithm. RESULTS Areas under the receiver operating characteristic curve of FOS-DM and SADPM scores to predict NODAT were 0.756 and 0.807 (P < 0.001), respectively. FOS-DM and SADPM scores over 75 percentile (hazard ratio 5.074 and 8.179, respectively, P < 0.001) were associated with NODAT. CONCLUSIONS Both scores can be used to identify kidney recipients at higher risk for NODAT beyond the first year. SADPM score detects some 25% of kidney transplant patients with an eightfold risk for NODAT. PMID:22279030

  6. Pilot Study: Association of Traditional and Genetic Risk Factors and New-Onset Diabetes Mellitus Following Kidney Transplantation

    PubMed Central

    Chakkera, H.A.; Hanson, R.L.; Raza, S.M.; DiStefano, J.K.; Millis, M.P.; Heilman, R.L.; Mulligan, D.C.; Reddy, K.S.; Mazur, M.J.; Hamawi, K.; Moss, A.A.; Mekeel, K.L.; Cerhan, J.R.

    2012-01-01

    Introduction New-onset diabetes mellitus, which occurs after kidney transplant and type 2 diabetes mellitus (T2DM), shares common risk factors and antecedents in impaired insulin secretion and action. Several genetic polymorphisms have been shown to be associated with T2DM. We hypothesized that transplant recipients who carry risk alleles for T2DM are “tipped over” to develop diabetes mellitus in the posttransplant milieu. Methods We investigated the association of genetic and traditional risk factors present before transplantation and the development of new-onset diabetes mellitus after kidney transplantation (NODAT). Markers in 8 known T2DM-linked genes were genotyped using either the iPLEX assay or allelic discrimination (AD)-PCR in the study cohort testing for association with NODAT. We used univariate and multivariate logistic regression models for the association of pretransplant nongenetic and genetic variables with the development of NODAT. Results The study cohort included 91 kidney transplant recipients with at least 1 year posttransplant follow-up, including 22 who developed NODAT. We observed that increased age, family history of T2DM, pretransplant obesity, and triglyceridemia were associated with NODAT development. In addition, we observed positive trends, although statistically not significant, for association between T2DM-associated genes and NODAT. Conclusions These findings demonstrated an increased NODAT risk among patient with a positive family history for T2DM, which, in conjunction with the observed positive predictive trends of known T2DM-associated genetic polymorphisms with NODAT, was suggestive of a genetic predisposition to NODAT. PMID:20005362

  7. Altered natural killer (NK) cell frequency and phenotype in latent autoimmune diabetes in adults (LADA) prior to insulin deficiency.

    PubMed

    Akesson, C; Uvebrant, K; Oderup, C; Lynch, K; Harris, R A; Lernmark, A; Agardh, C-D; Cilio, C M

    2010-07-01

    Approximately 10% of the patients diagnosed with type 2 diabetes (T2D) have detectable serum levels of glutamic acid decarboxylase 65 autoantibodies (GADA). These patients usually progress to insulin dependency within a few years, and are classified as being latent autoimmune diabetes in adults (LADA). A decrease in the frequency of peripheral blood natural killer (NK) cells has been reported recently in recent-onset T1D and in high-risk individuals prior to the clinical onset. As NK cells in LADA patients have been investigated scarcely, the aim of this study was to use multicolour flow cytometry to define possible deficiencies or abnormalities in the frequency or activation state of NK cells in LADA patients prior to insulin dependency. All patients were GADA-positive and metabolically compensated, but none were insulin-dependent at the time blood samples were taken. LADA patients exhibited a significant decrease in NK cell frequency in peripheral blood compared to healthy individuals (P=0.0018), as reported previously for recent-onset T1D patients. Interestingly, NKG2D expression was increased significantly (P<0.0001), whereas killer cell immunoglobulin-like receptor (KIR)3DL1 expression was decreased (P<0.0001) within the NK cell population. These observations highlight a defect in both frequency and activation status of NK cells in LADA patients and suggest that this immunological alteration may contribute to the development of autoimmune diabetes by affecting peripheral tolerance. Indeed, recent evidence has demonstrated a regulatory function for NK cells in autoimmunity. Moreover, the decrease in NK cell number concords with observations obtained in recent-onset T1D, implying that similar immunological dysfunctions may contribute to the progression of both LADA and T1D.

  8. A regular meal and insulin infusion regimen: its use in the treatment of acute-onset ketotic diabetes and in stabilization of poorly controlled established diabetic subjects.

    PubMed

    Davis, T M; Holman, R R; Eaton, P M; Turner, R C

    1982-01-01

    A simple regimen, consisting of a constant intravenous insulin infusion at either a basal, nocturnal rate or at a daytime rate matched by seven small, isocaloric meals taken every 2 h, has been applied to two clinical situations requiring optimal blood glucose control. In eight poorly controlled established diabetic subjects, quantitative estimates of daily insulin requirements were possible, with consequent improved control upon reinstitution of twice-daily subcutaneous insulin. In five acute-onset, ketotic diabetic subjects first treated by intravenous saline and low-dose intramuscular insulin, the regimen was used to achieve and maintain basal and postprandial normoglycemia. Ketonuria was abolished quickly in these patients, and falling insulin requirements and large doses of insulin were handled easily. In both clinical situations, subsequent subcutaneous insulin doses required little adjustment. The regimen is cheap, convenient to use, and widely applicable.

  9. Measuring insulin adherence among adults with type 2 diabetes.

    PubMed

    Osborn, Chandra Y; Gonzalez, Jeffery S

    2016-08-01

    Non-adherence to insulin is common and associated with suboptimal health. We adapted the Morisky Medication Adherence Scale to specify insulin adherence (MIAS) and compared it to the Adherence to Refills and Medication Scale for Diabetes (ARMS-D) and the Summary of Diabetes Self-Care Activities medications subscale (SDSCA-MS) and an insulin-specific (SDSCA-IS) version. A sample of 144 insulin-treated adults (58 % African American/Black, 34 % Caucasian/White, 8 % Other/Mixed race; 6.9 % Hispanic) completed these measures along with a HbA1C test. The internal consistency and factor structure of the MIAS were adequate; 59 % of participants forgot to take insulin and 46 % reported non-adherence. The MIAS was associated with the ARMS-D, SDSCA-MS, and SDSCA-IS (p < 0.001), and higher MIAS scores were marginally associated with better self-rated health (p = 0.057), but significantly associated with fewer emergency room visits (p = 0.001), and better HbA1C (p = 0.001). The MIAS is a valid and reliable insulin adherence assessment tool for practice and research applications.

  10. Diabetes-related quality of life and the demands and burdens of diabetes care among emerging adults with type 1 diabetes in the year after high school graduation.

    PubMed

    Hanna, Kathleen M; Weaver, Michael T; Slaven, James E; Fortenberry, J Dennis; DiMeglio, Linda A

    2014-10-01

    The roles of glycemic control, diabetes management, diabetes care responsibility, living independently of parents, and time since high school graduation in predicting diabetes-related quality of life (DQOL) were examined in 184 emerging adults with type 1 diabetes. Data were collected at graduation and 1 year later. Analyses controlling for selected covariates were completed using generalized linear mixed models. Better diabetes management was associated with more positive responses on all four dimensions of DQOL. Impact and worry of DQOL were greater in the presence of depressive symptoms, and life satisfaction was lower. DQOL life satisfaction was lower in those living independently of parents. Young women reported poorer diabetes-related health status than did young men. Time since graduation was not linked to DQOL. Further research is needed on ways to improve DQOL in conjunction with diabetes management and on ways that families can support DQOL when youth live independently.

  11. A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy

    PubMed Central

    Bee, Leonardo; Nasca, Alessia; Zanolini, Alice; Cendron, Filippo; d'Adamo, Pio; Costa, Rodolfo; Lamperti, Costanza; Celotti, Lucia; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients. PMID:25872942

  12. Adult-onset hypogonadism: evaluation and role of testosterone replacement therapy

    PubMed Central

    Davidiuk, Andrew J.

    2016-01-01

    Testosterone deficiency (TD) has become a growing concern in the field of men’s sexual health, with an increasing number of men presenting for evaluation of this condition. Given the increasing demand for testosterone replacement therapy (TRT), a panel of experts met in August of 2015 to discuss the treatment of men who present for evaluation in the setting of low or normal gonadotropin levels and the associated signs and symptoms of hypogonadism. This constellation of factors can be associated with elements of both primary and secondary hypogonadism. Because this syndrome commonly occurs in men who are middle-aged and older, it was termed adult-onset hypogonadism (AOH). AOH can be defined by the following elements: low levels of testosterone, associated signs and symptoms of hypogonadism, and low or normal gonadotropin levels. Although there are significant benefits of TRT for patients with AOH, candidates also need to understand the potential risks. Patients undergoing TRT will need to be monitored regularly because there are potential complications that can develop with long-term use. This review is aimed at providing a deeper understanding of AOH, discussing the benefits and risks of TRT, and outlining each modality of TRT in use for AOH. PMID:28078213

  13. Patient fibroblasts-derived induced neurons demonstrate autonomous neuronal defects in adult-onset Krabbe disease

    PubMed Central

    Choi, Won Jun; Oh, Ki-Wook; Nahm, Minyeop; Xue, Yuanchao; Choi, Jae Hyeok; Choi, Ji Young; Kim, Young-Eun; Chung, Ki Wha; Fu, Xiang-Dong; Ki, Chang-Seok; Kim, Seung Hyun

    2016-01-01

    Krabbe disease (KD) is an autosomal recessive neurodegenerative disorder caused by defective β-galactosylceramidase (GALC), a lysosomal enzyme responsible for cleavage of several key substrates including psychosine. Accumulation of psychosine to the cytotoxic levels in KD patients is thought to cause dysfunctions in myelinating glial cells based on a comprehensive study of demyelination in KD. However, recent evidence suggests myelin-independent neuronal death in the murine model of KD, thus indicating defective GALC in neurons as an autonomous mechanism for neuronal cell death in KD. These observations prompted us to generate induced neurons (iNeurons) from two adult-onset KD patients carrying compound heterozygous mutations (p.[K563*];[L634S]) and (p.[N228_S232delinsTP];[G286D]) to determine the direct contribution of autonomous neuronal toxicity to KD. Here we report that directly converted KD iNeurons showed not only diminished GALC activity and increased psychosine levels, as expected, but also neurite fragmentation and abnormal neuritic branching. The lysosomal-associated membrane proteins 1 (LAMP1) was expressed at higher levels than controls, LAMP1-positive vesicles were significantly enlarged and fragmented, and mitochondrial morphology and its function were altered in KD iNeurons. Strikingly, we demonstrated that psychosine was sufficient to induce neurite defects, mitochondrial fragmentation, and lysosomal alterations in iNeurons derived in healthy individuals, thus establishing the causal effect of the cytotoxic GALC substrate in KD and the autonomous neuronal toxicity in KD pathology. PMID:27780934

  14. Clinical and histopathological features of cutaneous manifestations of adult-onset Still disease.

    PubMed

    Santa, Erin; McFalls, Jeanne M; Sahu, Joya; Lee, Jason B

    2017-03-25

    Adult-onset Still disease (AOSD) is a rare autoinflammatory syndrome characterized by recurring fevers, arthralgia, and consistent laboratory abnormalities that include leukocytosis and hyperferritinemia. Skin findings accompany the disease in nearly 90% of the cases. Early reports described evanescent, pruritic, salmon-pink or urticarial lesions, referred to as the typical eruption of AOSD. Histopathologic findings consist of superficial perivascular dermatitis with varying number of interstitial neutrophils. Later reports described a more persistent rash that tended to be photodistributed, hyperpigmented, often in a linear configuration, sometimes in a rippled pattern, referred to as the atypical eruption of AOSD. The presence of individual necrotic keratinocytes in the upper spinous layer has been the consistent histopathologic finding. The persistent rash may not represent an atypical presentation of AOSD as recent reports indicate a high prevalence of the rash. Emerging data also suggest that patients with persistent eruption have a worse prognosis. The recognition of the clinical and histopathological findings of skin eruptions of AOSD may facilitate an earlier diagnosis, potentially improving disease outcome. Herein, clinical and histopathological features of cutaneous manifestation of AOSD in two Asian women are highlighted accompanied by relevant review of the disease.

  15. Updates in adult-onset Still disease: Atypical cutaneous manifestations and associations with delayed malignancy.

    PubMed

    Sun, Natalie Z; Brezinski, Elizabeth A; Berliner, Jacqueline; Haemel, Anna; Connolly, M Kari; Gensler, Lianne; McCalmont, Timothy H; Shinkai, Kanade

    2015-08-01

    Adult-onset Still disease (AOSD) is a systemic inflammatory disorder that is clinically characterized by a heterogeneous constellation of symptoms and signs. Though an evanescent eruption is the classic cutaneous finding, recent literature has highlighted atypical rashes associated with Still disease. A second emerging concept in presentations of AOSD is its association with malignancy. This review focuses on these concepts: the clinical spectrum of atypical skin manifestations and AOSD as a paraneoplastic phenomenon. PubMed-MEDLINE was screened for peer-reviewed articles describing atypical presentations of AOSD and cases associated with malignancy. Erythematous, brown or violaceous, persistent papules and plaques were the most common cutaneous finding (28/30 [93%]). Linear configurations were also rarely described. Of these patients, 81% concurrently had the typical evanescent skin eruption. There were 31 patients with associated malignancies, most commonly breast cancer and lymphoma. The diagnosis of malignancy did not precede or immediately follow a clinical presentation otherwise consistent with AOSD in a considerable subset of patients (42%). Understanding the cutaneous spectrum of AOSD and heightened awareness for its delayed association with malignancy may lead to improved recognition of cutaneous variants and reinforce the need for diagnostic evaluation and long-term follow-up for malignancy in patients with this clinical presentation.

  16. A search for the primary abnormality in adult-onset type II citrullinemia

    SciTech Connect

    Kobayashi, Keiko; Shaheen, Nazma; Saheki, Takeyori ); Kumashiro, Ryukichi; Tanikawa, Kyuichi ); O'Brien, W.E.; Beaudet, A.L. )

    1993-11-01

    Deficiency of argininosuccinate synthetase (ASS) causes citrullinemia in human beings. Type II citrullinemia is found in most patients with adult-onset citrullinemia in Japan, and ASS deficiency is found specifically in the liver. Previous studies have shown that the decrease of hepatic ASS activity is caused by a decrease in enzyme protein with normal kinetic properties and that there were no apparent abnormalities in the amount, translational activity, and gross structure of hepatic ASS mRNA. In the present work, the authors show by sequencing analysis that there was no mutation in the ASS mRNA from two patients with type II citrullinemia. The authors also report RFLP analysis of a consanguineous family with type II citrullinemia, by using three DNA polymorphisms located within the ASS gene locus. In spite of having consanguineous parents, the patient was not a homozygous haplotype for the ASS gene. The RFLP analysis of 16 affected patients from consanguineous parents showed that 5 of 16 patients had the heterozygous pattern for one of the three DNA probes and that the frequency of the heterozygous haplotype was not different from the control frequency. These results suggest that the primary defect of type II citrullinemia is not within the ASS gene locus. 29 refs., 1 fig., 3 tabs.

  17. Unique histopathologic findings in a patient with adult-onset Still disease.

    PubMed

    Wolgamot, Greg; Yoo, Jane; Hurst, Stan; Gardner, Greg; Olerud, John; Argenyi, Zsolt

    2007-04-01

    Adult-onset Still disease (AOSD) is an uncommon disorder characterized by fever, polyarthralgia, elevated white blood cell count, and a maculopapular rash, the histologic features of which have not been well-known. A 55-year-old Asian woman presented initially with a "burning" and severely pruritic eruption on her face, hands, and arms, thought clinically to be urticaria. Within 1 month, she began spiking high fevers, developed diffuse joint pain, and had marked elevations of ferritin, C-reactive protein, and erythrocyte sedimentation rate, characteristic of AOSD. The cutaneous eruption became more widespread, involving the trunk, scalp, and remainder of the extremities, with diffuse thickening of the skin with papular and linear hyperpigmentation and accentuation. Biopsies from several locations showed focal hyperkeratosis associated with dyskeratotic keratinocytes with a peculiar, distinctive distribution in the upper epidermis and cornified layers. In addition, increased dermal mucin was present, with minimal fibroblast proliferation and inflammation. This unusual combination of diffuse dermal mucinosis and a unique pattern of dyskeratosis can present a challenge in generating an accurate differential diagnosis, and may represent an unusual response to chronic scratching or be a distinctive histologic manifestation of AOSD.

  18. Stroke as the presenting feature of new onset diabetes in a young man.

    PubMed

    Jones, Ruth; McMurray, Emily; Robinson, Oliver

    2014-06-25

    A 34-year-old man presented to a hospital with a 7-day history of nausea, vertigo, ataxia and frontal headache. Examination revealed ipsilateral cerebellar signs. CT of the brain demonstrated left cerebellar hypodensity suggestive of ischaemic stroke or space occupying lesion. Full blood count showed a markedly raised haemoglobin (219 g/L) and haematocrit (0.56). Admission urinalysis was performed but the results not reviewed. Owing to patient deterioration, an arterial blood gas was performed. This showed profound metabolic acidosis. Repeat urinalysis was positive for glucose and ketones. MRI of the brain confirmed ischaemic stroke. The underlying cause of this was hyperviscosity secondary to relative polycythaemia, resulting from undiagnosed diabetic ketoacidosis as a first presentation of diabetes. This case report highlights ischaemic stroke as an unusual presenting feature of diabetic ketoacidosis. Notably, the underlying diagnosis of diabetic ketoacidosis was initially missed, thereby emphasising the importance of performing an admission urinalysis and acting on the results.

  19. When aging-onset diabetes is coming across with Alzheimer disease: comparable pathogenesis and therapy.

    PubMed

    Tang, Jun; Pei, Yijin; Zhou, Guangji

    2013-08-01

    Diabetes mellitus is a metabolic disorder that is characterized by high blood glucose because of the insulin-resistance and insulin-deficiency in Type 2, while the insulin deficiency due to destruction of islet cells in the pancreas in Type 1. The development of Type 2 diabetes is caused by a combination of lifestyle and genetic factors. Aging patients with diabetes are at increased risk of developing cognitive and memory dysfunctions, which is one of the significant symptoms of Alzheimer disease (AD). Also, over 2/3 of AD patients were clinically indentified with impairment of glucose. Cognitive dysfunction would be associated with poor self-care ability in diabetes patients. This review will briefly summarize the current knowledge of the pathogenesis of these two diseases and highlight similarities in their pathophysiologies. Furthermore, we will shortly discuss recent progress in the insulin-targeted strategy, aiming to explore the inner linkage between these two diseases in aging populations.

  20. Decreased cord-blood phospholipids in young age-at-onset type 1 diabetes.

    PubMed

    La Torre, Daria; Seppänen-Laakso, Tuulikki; Larsson, Helena E; Hyötyläinen, Tuulia; Ivarsson, Sten A; Lernmark, Ake; Oresic, Matej

    2013-11-01

    Children developing type 1 diabetes may have risk markers already in their umbilical cord blood. It is hypothesized that the risk for type 1 diabetes at an early age may be increased by a pathogenic pregnancy and be reflected in altered cord-blood composition. This study used metabolomics to test if the cord-blood lipidome was affected in children diagnosed with type 1 diabetes before 8 years of age. The present case-control study of 76 index children diagnosed with type 1 diabetes before 8 years of age and 76 healthy control subjects matched for HLA risk, sex, and date of birth, as well as the mother's age and gestational age, revealed that cord-blood phosphatidylcholines and phosphatidylethanolamines were significantly decreased in children diagnosed with type 1 diabetes before 4 years of age. Reduced levels of triglycerides correlated to gestational age in index and control children and to age at diagnosis only in the index children. Finally, gestational infection during the first trimester was associated with lower cord-blood total lysophosphatidylcholines in index and control children. In conclusion, metabolomics of umbilical cord blood may identify children at increased risk for type 1 diabetes. Low phospholipid levels at birth may represent key mediators of the immune system and contribute to early induction of islet autoimmunity.

  1. Reversal of New-Onset Type 1 Diabetes With an Agonistic TLR4/MD-2 Monoclonal Antibody.

    PubMed

    Bednar, Kyle J; Tsukamoto, Hiroki; Kachapati, Kritika; Ohta, Shoichiro; Wu, Yuehong; Katz, Jonathan D; Ascherman, Dana P; Ridgway, William M

    2015-10-01

    Type 1 diabetes (T1D) is currently an incurable disease, characterized by a silent prodromal phase followed by an acute clinical phase, reflecting progressive autoimmune destruction of insulin-producing pancreatic β-cells. Autoreactive T cells play a major role in β-cell destruction, but innate immune cell cytokines and costimulatory molecules critically affect T-cell functional status. We show that an agonistic monoclonal antibody to TLR4/MD-2 (TLR4-Ab) reverses new-onset diabetes in a high percentage of NOD mice. TLR4-Ab induces antigen-presenting cell (APC) tolerance in vitro and in vivo, resulting in an altered cytokine profile, decreased costimulatory molecule expression, and decreased T-cell proliferation in APC:T-cell assays. TLR4-Ab treatment increases T-regulatory cell (Treg) numbers in both the periphery and the pancreatic islet, predominantly expanding the Helios(+)Nrp-1(+)Foxp3(+) Treg subset. TLR4-Ab treatment in the absence of B cells in NOD.scid mice prevents subsequent T cell-mediated disease, further suggesting a major role for APC tolerization in disease protection. Specific stimulation of the innate immune system through TLR4/MD-2, therefore, can restore tolerance in the aberrant adaptive immune system and reverse new-onset T1D, suggesting a novel immunological approach to treatment of T1D in humans.

  2. Early-Onset Diabetic E1-DN Mice Develop Albuminuria and Glomerular Injury Typical of Diabetic Nephropathy

    PubMed Central

    Hyvönen, Mervi E.; Tienari, Jukka; Lehtonen, Eero; Ustinov, Jarkko; Jalanko, Hannu; Otonkoski, Timo; Miettinen, Päivi J.

    2015-01-01

    The transgenic E1-DN mice express a kinase-negative epidermal growth factor receptor in their pancreatic islets and are diabetic from two weeks of age due to impaired postnatal growth of β-cell mass. Here, we characterize the development of hyperglycaemia-induced renal injury in the E1-DN mice. Homozygous mice showed increased albumin excretion rate (AER) at the age of 10 weeks; the albuminuria increased over time and correlated with blood glucose. Morphometric analysis of PAS-stained histological sections and electron microscopy images revealed mesangial expansion in homozygous E1-DN mice, and glomerular sclerosis was observed in the most hyperglycaemic mice. The albuminuric homozygous mice developed also other structural changes in the glomeruli, including thickening of the glomerular basement membrane and widening of podocyte foot processes that are typical for diabetic nephropathy. Increased apoptosis of podocytes was identified as one mechanism contributing to glomerular injury. In addition, nephrin expression was reduced in the podocytes of albuminuric homozygous E1-DN mice. Tubular changes included altered epithelial cell morphology and increased proliferation. In conclusion, hyperglycaemic E1-DN mice develop albuminuria and glomerular and tubular injury typical of human diabetic nephropathy and can serve as a new model to study the mechanisms leading to the development of diabetic nephropathy. PMID:26000279

  3. Overlap of genetic susceptibility to type 1 diabetes, type 2 diabetes, and latent autoimmune diabetes in adults.

    PubMed

    Basile, Kevin J; Guy, Vanessa C; Schwartz, Stanley; Grant, Struan F A

    2014-01-01

    Despite the notion that there is a degree of commonality to the biological etiology of type 1 diabetes (T1D) and type 2 diabetes (T2D), the lack of overlap in the genetic factors underpinning each of them suggests very distinct mechanisms. A disorder considered to be at the "intersection" of these two diseases is "latent autoimmune diabetes in adults" (LADA). Interestingly, genetic signals from both T1D and T2D are also seen in LADA, including the key HLA and transcription factor 7-like 2 (TCF7L2) loci, but the magnitudes of these effects are more complex than just pointing to LADA as being a simple admixture of T1D and T2D. We review the current status of the understanding of the genetics of LADA and place it in the context of what is known about the genetics of its better-studied "cousins," T1D and T2D, especially with respect to the myriad of discoveries made over the last decade through genome-wide association studies.

  4. Longitudinal changes in medical complications in adults with pediatric-onset spinal cord injury

    PubMed Central

    Hwang, Miriam; Zebracki, Kathy; Chlan, Kathleen M.; Vogel, Lawrence C.

    2014-01-01

    Objectives To determine longitudinal changes in the occurrence of medical complications in adults with pediatric-onset spinal cord injury (SCI). Design Longitudinal study of long-term outcomes. Setting Community. Participants Individuals who had sustained an SCI before age 19, were 23 years of age or older at initial interview, and followed annually between 1996 and 2011. They were classified into four American Spinal Injury Association (ASIA) Impairment Scale (AIS) severity groups: C1–4 AIS ABC, C5–8 AIS ABC, T1–S5 AIS ABC, AIS D. Outcome measures Generalized estimating equation (GEE) models were formulated to obtain the odds ratio (OR) of having a medical complication over time. Results A total of 1793 interviews were conducted among 226 men and 125 women (86% Caucasian; age at baseline, 26.7 ± 3.6 years; time since injury at baseline, 12.9 ± 5.2 years). Odds of complication occurrence over time varied among severity groups, with increased ORs of severe urinary tract infection (1.05, confidence interval (CI) 1.02–1.09), autonomic dysreflexia (AD) (1.09, CI 1.05–1.14), spasticity (1.06, CI 1.01–1.11), pneumonia/respiratory failure (1.09, CI 1.03–1.16), and hypertension/cardiac disease (1.07, CI 1.01–1.15) in the C1-4 ABC group; AD (1.08, CI 1.04–1.13) and pneumonia/respiratory failure (1.09, CI 1.02–1.16) in the C5–8 ABC group; and hypertension/cardiac disease (1.08, CI 1.02–1.14) in the T1–S5 ABC group. Upper extremity joint pain had increased odds of occurrence in all injury severity groups. Conclusion The significantly increased odds of having medical complications over time warrants awareness of risk factors and implementation of preventive measures to avoid adverse consequences of complications and to maintain independence in individuals with pediatric-onset SCI. PMID:24090490

  5. Hereditary leukoencephalopathy with axonal spheroids: a spectrum of phenotypes from CNS vasculitis to parkinsonism in an adult onset leukodystrophy series

    PubMed Central

    Jaunmuktane, Zane; Sheerin, Una-Marie; Phadke, Rahul; Brandner, Sebastian; Milonas, Ionnis; Dean, Andrew; Bajaj, Nin; McNicholas, Nuala; Costello, Daniel; Cronin, Simon; McGuigan, Chris; Rossor, Martin; Fox, Nick; Murphy, Elaine; Chataway, Jeremy; Houlden, Henry

    2016-01-01

    Background Hereditary diffuse leukoencephalopathy with neuroaxonal spheroids (HDLS) is a hereditary, adult onset leukodystrophy which is characterised by the presence of axonal loss, axonal spheroids and variably present pigmented macrophages on pathological examination. It most frequently presents in adulthood with dementia and personality change. HDLS has recently been found to be caused by mutations in the colony stimulating factor-1 receptor (CSF1R) gene. Methods In this study, we sequenced the CSF1R gene in a cohort of 48 patients from the UK, Greece and Ireland with adult onset leukodystrophy of unknown cause. Results Five pathogenic mutations were found, including three novel mutations. The presentations ranged from suspected central nervous system (CNS) vasculitis to extrapyramidal to cognitive phenotypes. The case histories and imaging are presented here, in addition to neuropathological findings from two cases with novel mutations. Conclusion We estimate that CSF1R mutations account for 10% of idiopathic adult onset leukodystrophies and that genetic testing for CSF1R mutations is essential in adult patients presenting with undefined CNS vasculitis or a leukodystrophy with prominent neuropsychiatric signs or dementia. PMID:25935893

  6. Dental visits among dentate adults with diabetes--United States, 1999 and 2004.

    PubMed

    2005-11-25

    One of the major complications of diabetes is periodontal disease, a chronic infection of tissues supporting the teeth and a major cause of tooth loss. Adults with diabetes have both a higher prevalence of periodontal disease and more severe forms of the disease, contributing to impaired quality of life and substantial oral functional disability. In addition, periodontal disease has been associated with development of glucose intolerance and poor glycemic control among adults with diabetes. Regular dental visits provide opportunities for prevention, early detection, and treatment of periodontal disease among dentate adults (i.e., those having one or more teeth); moreover, regular dental cleaning improves glycemic control in patients with poorly controlled diabetic conditions. One of the national health objectives for 2010 is to increase the proportion of persons with diabetes who have an annual dental examination to 71% (revised objective 5-15). To estimate the percentage of dentate U.S. adults aged > or =18 years with diabetes who visited a dentist within the preceding 12 months, CDC analyzed data from the Behavioral Risk Factor Surveillance System (BRFSS) surveys for 1999 and 2004. This report describes the results of that analysis, which indicated that, in 2004, age-adjusted estimates in only seven states exceeded 71% and estimated percentages for four states and District of Columbia (DC) increased significantly from their levels in 1999. The findings underscore the need to increase awareness and support for oral health care among adults with diabetes, including support for national and state diabetes care management programs.

  7. Changes in erythrocyte insulin receptors in normal dogs and keeshond dogs with inheritable, early onset, insulin dependent diabetes mellitus

    SciTech Connect

    Klaassen, J.K.

    1986-01-01

    Validation of a procedure to evaluate insulin receptors on erythrocytes (RBC-IR) in dogs is described. The specific binding of (/sup 125/I)iodoinsulin to RBC-IR of normal dogs is significantly greater than binding in keeshonds with an inheritable form of early onset diabetes mellitus. This decreased binding was due to a significant decrease in RBC-IR affinity in the diabetic keeshonds. To determine the effect on RBC-IR, normal dogs were treated with either dexamethasone (0.1 mg/kg) or prednisone (0.3 mg/kg) for 10 days: concentrations of plasma cortisol, glucose, and insulin, plus binding characteristics of RBC-IR were determined. In the dexamethasone treated group, plasma glucose concentrations were elevated significantly by day 6 and continued through day 10. Insulin concentrations were elevated significantly by day 3 and remained elevated through day 10. In the prednisone treated group, glucose concentrations were elevated significantly by day 3, while insulin concentrations were elevated significantly by day 8. Maximum binding of RBC-IR was unaffected by prednisone and neither affinities nor receptor numbers were significantly different from day 1. No changes in plasma cortisol concentration were seen. Diabetic keeshonds on daily insulin treatment were removed from exogenous insulin therapy for 48 hours. Significant increases in glucose concentrations were observed, but no significant changes in cortisol, insulin, average receptor binding affinity, or RBC-IR number per cell occurred.

  8. Blockade of glucagon signaling prevents or reverses diabetes onset only if residual β-cells persist

    PubMed Central

    Damond, Nicolas; Thorel, Fabrizio; Moyers, Julie S; Charron, Maureen J; Vuguin, Patricia M; Powers, Alvin C; Herrera, Pedro L

    2016-01-01

    Glucagon secretion dysregulation in diabetes fosters hyperglycemia. Recent studies report that mice lacking glucagon receptor (Gcgr-/-) do not develop diabetes following streptozotocin (STZ)-mediated ablation of insulin-producing β-cells. Here, we show that diabetes prevention in STZ-treated Gcgr-/- animals requires remnant insulin action originating from spared residual β-cells: these mice indeed became hyperglycemic after insulin receptor blockade. Accordingly, Gcgr-/- mice developed hyperglycemia after induction of a more complete, diphtheria toxin (DT)-induced β-cell loss, a situation of near-absolute insulin deficiency similar to type 1 diabetes. In addition, glucagon deficiency did not impair the natural capacity of α-cells to reprogram into insulin production after extreme β-cell loss. α-to-β-cell conversion was improved in Gcgr-/- mice as a consequence of α-cell hyperplasia. Collectively, these results indicate that glucagon antagonism could i) be a useful adjuvant therapy in diabetes only when residual insulin action persists, and ii) help devising future β-cell regeneration therapies relying upon α-cell reprogramming. DOI: http://dx.doi.org/10.7554/eLife.13828.001 PMID:27092792

  9. Effects of pregnancy on the onset and progression of diabetic nephropathy and of diabetic nephropathy on pregnancy outcomes.

    PubMed

    Young, Esther Cytrynbaum; Pires, Maria Lucia Elias; Marques, Luiz Paulo José; de Oliveira, José Egídio Paulo; Zajdenverg, Lenita

    2011-01-01

    Controversy exists regarding the effect of pregnancy on the development and course of diabetic nephropathy. This study followed 43 pregnant women with previous diabetes mellitus, 32 without nephropathy (Group I) and 11 with nephropathy (Group II). Urinary albumin excretion (UAE), serum creatinine (Cr) and creatinine clearance (CCr) in the pre-pregnancy (Pre-P), first trimester (1T), third trimester (3T) and 1 year postpartum (PP) were evaluated. In both groups there were an increase in 3T compared to Pre-P of CCr (137 vs. 98 ml/min and 110 vs. 81 ml/min, p=0.0001, respectively) and UAE (7.78 vs. 3.15 mg/24 h and 592 vs. 119 mg/24 h, p=0.0001, respectively). Increase of Cr in the PP compared to 1T in Group II (0.88 vs. 0.70 mg/dL, p=0.031) was observed. There were no difference in UAE, CCr and Cr in the PP when compared to pre-P as well variance over time between groups. Group II showed higher prevalence of chronic hypertension (72.7 vs. 21.9%, p=0.004), preeclampsia (63.6 vs. 6.3%, p=0.0003) and lower gestational age at birth (36 vs. 38 weeks, p=0.003). We conclude that pregnancy was not associated with development and progression of diabetic nephropathy in women with or without mild renal dysfunction. The presence of diabetic nephropathy was associated with increased risk of perinatal complications.

  10. Towards an Earlier and Timely Diagnosis of Type 1 Diabetes: Is it Time to Change Criteria to Define Disease Onset?

    PubMed

    Battaglia, Manuela; Nigi, Laura; Dotta, Francesco

    2015-12-01

    Type 1 diabetes (T1D) is the immune-mediated form of diabetes requiring insulin treatment and affecting both children and adults. The incidence of T1D is increasing dramatically and has doubled in the past 2 decades. In the recent years, significant knowledge on the disease natural history has been gained and, nowadays, diabetes-related autoantibodies make T1D a predictable disease. Despite this great advance in the field of T1D, we still use diagnostic criteria defined by the American Diabetes Association (ADA) in 1997. In other autoimmune endocrine disorders (e.g., Hashimoto's thyroiditis and Addison's disease), that share several features with T1D, diagnosis is made early in the presence of circulating autoantibodies together with subclinical thyroid/adrenal functional impairment and treatments are often provided in the absence of a frank clinical glandular insufficiency. With this review, we propose to anticipate diagnosis also in T1D at the stage in which subjects have circulating multiple islet autoantibodies, are dysglycemic but are still insulin independent. We believe that anticipating T1D diagnosis can lead to better disease management and prevention of secondary complications but can also provide the possibility to perform earlier and likely more effective interventions for a disease that to date has proven controllable but still incurable.

  11. DL-3-n-butylphthalide delays the onset and progression of diabetic cataract by inhibiting oxidative stress in rat diabetic model.

    PubMed

    Wang, Fuxu; Ma, Jia; Han, Fei; Guo, Xiujin; Meng, Li; Sun, Yufeng; Jin, Cheng; Duan, Huijun; Li, Hang; Peng, Ying

    2016-01-13

    DL-3-n-butylphthalide (NBP) is a therapeutic drug used for ischemic stroke treatment. Here, we investigated the impact of NBP on the development of rat diabetic cataract induced by intraperitoneal injection of streptozotocin (STZ). NBP was then administrated by oral gavage for nine weeks. Cataract development was monitored through ophthalmoscope inspections. The levels of blood glucose and serum reactive oxygen species (ROS), malondialdehyde (MDA) and 8-Hydroxydeovexyguanosine (8-OHdG) were measured. Total and soluble protein and oxidative stress parameters, such as 2, 4- dinitrophenylhydrazone (DNP), 4-hydroxynonenal (4-HNE) and MDA in the lenses were determined by Western blot and thiobarbituric acid analyses. The expressions of NF-E2-related factor 2 (Nrf2) and its downstream antioxidant enzymes, thioredoxin (TRX), Catalase and nuclear accumulation of Nrf2 were determined by Western blot and immunohistochemistry analyses. We showed that NBP treatment significantly improved the cataract scores, the levels of DNP, 4-HNE, and MDA in the lens compared to the non-treated groups. NBP also enhanced the expressions of Nrf2, TRX and catalase in the lens of diabetic rats. In addition, NBP treatment also decreased levels of blood glucose, serum MDA and 8-OHdG. These results suggested that NBP treatment significantly delayed the onset and progression of diabetic cataract by inhibiting the oxidative stresses.

  12. Delay between Onset of Symptoms and Seeking Physician Intervention Increases Risk of Diabetic Foot Complications: Results of a Cross-Sectional Population-Based Survey

    PubMed Central

    Gavan, Norina A.; Veresiu, Ioan A.; Vinik, Etta J.; Florea, Bogdan

    2016-01-01

    We present a post hoc analysis of 17,530 questionnaires collected as part of the 2012 screening for neuropathy using Norfolk Quality of Life tool in patients with diabetes in Romania, to assess the impact on foot complications of time between the onset of symptoms of diabetes/its complications and the physician visit. Odds ratios (ORs) for self-reporting neuropathy increased from 1.16 (95% CI: 1.07–1.25) in those who sought medical care in 1–6 months from symptoms of diabetes/its complications onset to 2.27 in those who sought medical care >2 years after symptoms onset. The ORs for having a history of foot ulcers were 1.43 (95% CI: 1.26–1.63) in those who sought medical care in 1–6 months and increased to 3.08 (95% CI: 2.59–3.66) in those who sought medical care after >2 years from symptoms of diabetes/its complications onset. The highest ORs for a history of gangrene (2.49 [95% CI: 1.90–3.26]) and amputations (2.18 [95% CI: 1.60–2.97]) were observed in those who sought medical care after >2 years following symptoms onset. In conclusion, we showed that waiting for >1 month after symptoms onset dramatically increases the risk of diabetic foot complications. These results show the need for accessible educational programs on diabetes and its chronic complications and the need to avoid delays in reporting. PMID:28018920

  13. Stroke prevention by direct revascularization for patients with adult-onset moyamoya disease presenting with ischemia.

    PubMed

    Kim, Tackeun; Oh, Chang Wan; Kwon, O-Ki; Hwang, Gyojun; Kim, Jeong Eun; Kang, Hyun-Seung; Cho, Won-Sang; Bang, Jae Seung

    2016-06-01

    . CONCLUSIONS Direct or combined revascularization for patients with adult-onset moyamoya disease presenting with ischemia can prevent further stroke.

  14. Relations of Behavioral Autonomy to Health Outcomes Among Emerging Adults With and Without Type 1 Diabetes

    PubMed Central

    Reynolds, Kerry A.; Becker, Dorothy; Escobar, Oscar; Siminerio, Linda

    2014-01-01

    Objective To examine the relation of behavioral autonomy to psychological, behavioral, and physical health among emerging adults with and without type 1 diabetes. Methods High school seniors with (n = 118) and without type 1 diabetes (n = 122) completed online questionnaires for three consecutive years. Behavioral autonomy, psychological health, risk behaviors, and diabetes outcomes were assessed. Regression analyses were conducted to predict Time 2 and 3 outcomes, controlling for Time 1 outcomes. Results There were no group differences in behavioral autonomy. Behavioral autonomy predicted better psychological health but only for emerging adults without diabetes. Behavioral autonomy was related to increased risk behavior for both groups. Behavioral autonomy was unrelated to self-care but predicted better glycemic control for females. Conclusions Behavioral autonomy may be beneficial for psychological health, but is related to increased risk behavior. The implications of behavioral autonomy for emerging adults with type 1 diabetes require careful consideration. PMID:25157070

  15. [Adult-onset ataxia-telangiectasia. A clinical and therapeutic observation].

    PubMed

    Gazulla, J; Benavente, I; Sarasa Barrio, M

    2006-10-01

    A case of adult-onset ataxia-telangiectasia (AT) is presented, with debut at the age of 18 years and survival into the fourth decade. The clinical picture included cerebellar ataxia, distal weakness and hypopalesthesia in the lower limbs, oculomotor apraxia, dysarthria, and conjunctival telangiectasiae. Carcinoembrionic antigen was raised in plasma. MR imaging showed atrophy of the cerebellar vermis and thinning of the spinal cord. Deficiencies of gamma-aminobutyric acid and glutamate have been found in the cerebellar cortex in a case of AT. These were attributed to the loss of Purkinje cells and granule cells. In spite of some ataxias having improved with the gabaergic drugs gabapentin and tiagabine, the administration of gabapentin, acetazolamide and a placebo, did not benefit this patient. Pregabalin, 225 mg/day, ameliorated the ataxia unexpectedly, with further improvement after the addition of tiagabine. The authors suggest that the beneficial effect observed might have been due, either to the higher affinity of pregabalin towards alpha2-delta, a subtype of the alpha2-delta subunit which forms part of the voltage-gated calcium channel; either to the profusion of this subtype in the Purkinje cell layer, or to its larger capacity to let calcium into the neuron; or to the combination of these. These differences with gabapentin could explain the higher power of pregabalin in the stimulation of the cerebellar structures, thus justifying the improvement of ataxia in this case of AT. A synergistic effect with pregabalin is proposed as the cause of the improvement obtained with the addition of tiagabine.

  16. Mental health among young adults in prison: the importance of childhood-onset conduct disorder

    PubMed Central

    Anckarsäter, Henrik; Wallinius, Märta; Billstedt, Eva

    2017-01-01

    Background The psychiatric health burden of prisoners is substantial. However, there is a lack of high-quality studies of psychiatric disorders among young adults with a high risk of reoffending. Aims To investigate the lifetime prevalence of psychiatric disorders and use of mental health services among young male violent offenders and the impact of childhood-onset conduct disorder (COCD). Method A nationally representative cohort (n = 270, age 18–25) of male offenders was followed back in medical records and clinically assessed by gold standard methods. Lifetime prevalences are presented together with odds ratios (ORs) as risk estimates in relation to COCD. Results Previous use of psychiatric services among the participants was high but their lifetime psychiatric morbidity was even higher, with 93% meeting criteria for at least one Axis I disorder. The COCD group was overrepresented in most clinical categories and carried five times higher odds (OR = 5.1, 95% CI 2.0–12.8) of a psychotic disorder, three times higher odds (OR = 3.2, 95% CI 1.2–8.5) of a substance use disorder and two times higher odds of a mood disorder (OR = 2.3, 95% CI 1.3–4.0) or anxiety disorder (OR = 2.0, 95% CI 1.1–3.5). Conclusions The mental health burden is substantial among young violent offenders, and COCD is an important indicator of future mental health problems which must be a priority for public health efforts. Declaration of interest None. Copyright and usage © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license. PMID:28357134

  17. Parental smoking in pregnancy and the risks of adult-onset hypertension.

    PubMed

    de Jonge, Layla L; Harris, Holly R; Rich-Edwards, Janet W; Willett, Walter C; Forman, Michele R; Jaddoe, Vincent W V; Michels, Karin B

    2013-02-01

    Fetal exposure to parental smoking may lead to developmental adaptations and promote various diseases in later life. This study evaluated the associations of parental smoking during pregnancy with the risk of hypertension in the daughter in adulthood, and assessed whether these associations are explained by birth weight or body weight throughout life. We used data on 33086 participants of the Nurses' Health Study II and the Nurses' Mothers' Cohort. Cox proportional hazards models were used to examine the associations of maternal and paternal smoking during pregnancy with the nurse daughter, with self-reported physician-diagnosed hypertension from 1989 until 2007. Overall, 8575 (25.9%) mothers and 18874 (57.0%) fathers smoked during pregnancy. During follow-up, 7825 incident cases of adult-onset hypertension were reported. Both maternal and paternal smoking of ≥ 15 cigarettes/d during pregnancy were associated with increased risks of hypertension (rate ratio, 1.19; 95% CI, 1.09-1.29; and rate ratio, 1.18; 95% CI, 1.12-1.25, respectively) in the age-adjusted models. Further adjustment for birth weight did not affect the effect estimates appreciably, whereas additional adjustment for body shape and weight until age 18, or current body mass index, attenuated the associations with both maternal and paternal smoking (rate ratio, 1.07; 95% CI, 0.98-1.16; and rate ratio, 1.06; 95% CI, 1.01-1.12, respectively). The associations of parental smoking during pregnancy with the risk of hypertension in the offspring were largely explained by body weight throughout life, suggesting that these associations may not reflect direct intrauterine mechanisms.

  18. Muscle MRI Findings in Childhood/Adult Onset Pompe Disease Correlate with Muscle Function

    PubMed Central

    Figueroa-Bonaparte, Sebastián; Segovia, Sonia; Llauger, Jaume; Belmonte, Izaskun; Pedrosa, Irene; Alejaldre, Aída; Mayos, Mercè; Suárez-Cuartín, Guillermo; Gallardo, Eduard; Illa, Isabel; Díaz-Manera, Jordi

    2016-01-01

    Objectives Enzyme replacement therapy has shown to be effective for childhood/adult onset Pompe disease (AOPD). The discovery of biomarkers useful for monitoring disease progression is one of the priority research topics in Pompe disease. Muscle MRI could be one possible test but the correlation between muscle MRI and muscle strength and function has been only partially addressed so far. Methods We studied 34 AOPD patients using functional scales (Manual Research Council scale, hand held myometry, 6 minutes walking test, timed to up and go test, time to climb up and down 4 steps, time to walk 10 meters and Motor Function Measure 20 Scale), respiratory tests (Forced Vital Capacity seated and lying, Maximun Inspiratory Pressure and Maximum Expiratory Pressure), daily live activities scales (Activlim) and quality of life scales (Short Form-36 and Individualized Neuromuscular Quality of Life questionnaire). We performed a whole body muscle MRI using T1w and 3-point Dixon imaging centered on thighs and lower trunk region. Results T1w whole body muscle MRI showed a homogeneous pattern of muscle involvement that could also be found in pre-symptomatic individuals. We found a strong correlation between muscle strength, muscle functional scales and the degree of muscle fatty replacement in muscle MRI analyzed using T1w and 3-point Dixon imaging studies. Moreover, muscle MRI detected mild degree of fatty replacement in paraspinal muscles in pre-symptomatic patients. Conclusion Based on our findings, we consider that muscle MRI correlates with muscle function in patients with AOPD and could be useful for diagnosis and follow-up in pre-symptomatic and symptomatic patients under treatment. Take home message Muscle MRI correlates with muscle function in patients with AOPD and could be useful to follow-up patients in daily clinic. PMID:27711114

  19. Successful Management of New-Onset Diabetes Mellitus and Obesity With the Use of Laparoscopic Sleeve Gastrectomy After Kidney Transplantation-A Case Report.

    PubMed

    Chen, J-H; Lee, C-H; Chang, C-M; Yin, W-Y

    2016-04-01

    In kidney transplantation, obesity is associated with poorer graft survival and patient survival. Bariatric surgery may provide benefit for these patients, not only by inducing weight loss, but also via reduction of diabetes. We report a case of morbid obesity, poorly controlled new-onset diabetes mellitus, and gout after kidney transplantation that was treated with laparoscopic sleeve gastrectomy 3 years after kidney transplantation. After 1 year of follow-up, 76% excessive body weight loss was attained. No complications were noted. The operation also provided total remission of diabetes and gout as well as good graft survival. Based on our experience, laparoscopic sleeve gastrectomy may be a feasible treatment for obese patients after renal transplantation to help resolve obesity and control new-onset diabetes. However, the timing of operation and the long-term potential for graft and patient survivals with this operation require further study.

  20. Solitary, adult-onset, intraosseous myofibroma of the finger: report of a case and review of literature.

    PubMed

    Ma, Yihong; Siegal, Gene P; Wei, Shi

    2015-09-01

    Myofibroma is a rare benign neoplasm of myofibroblastic origin. It typically occurs in the skin and subcutaneous tissues of the head and neck in infants and young children as multicentric lesions known as infantile myofibromatosis. Intraosseous myofibromas are very rare and are typically destructive lesions that predominantly affect craniofacial bones in the setting of myofibromatosis. Solitary, intraosseous myofibromas in adults are exceedingly rare. Herein, we report a myofibroma involving the middle phalanx of the right index finger in a 58-year-old man who presented with a pathologic fracture. Twelve other cases of adult-onset, intraosseous myofibroma were compiled from the English language literature and integrated with this report.

  1. Heterogeneous Depression Responses to Chronic Pain Onset among Middle-Aged Adults: A Prospective Study

    PubMed Central

    Zhu, Zhuoying; Galatzer-Levy, Isaac R.; Bonanno, George A.

    2014-01-01

    Studies on depression response to chronic pain are limited by lack of clarification of different forms of response patterns and cross-sectional measures. The current study examined heterogeneous long-term patterns of depression response to chronic pain onset using the mixture modeling technique. Depression symptoms prior to and following pain onset over a course of six years were charted in a nationally representative middle-aged sample. Four distinct depression symptom trajectories emerged. The resilience (72.0%) trajectory describes a pattern of no/minimal depression symptoms prior to and following pain onset. The post-pain depression trajectory (11.4%) describes a pattern of low depression at baseline and increasing symptoms following pain onset. The chronic depression (6.8%) trajectory is characterized by persistently high depression symptoms irrespective of pain onset. The prior depression improved (9.8%) trajectory describes a pattern of high depression at baseline and gradually declining symptoms following pain onset. Self-rated health at both baseline and following pain onset predicted the resilience trajectory. Baseline self-rated health distinguished the post-pain depression and chronic depression trajectories. Individuals in the prior depression improved trajectory were older and had more chronic illnesses at baseline but fewer illnesses following pain onset, compared to those in the resilience or post-pain depression trajectory. PMID:24679514

  2. Rationale and design of the Early Sleeve gastrectomy In New Onset Diabetic Obese Patients (ESINODOP) trial.

    PubMed

    Trastulli, Stefano; Desiderio, Jacopo; Grandone, Ilenia; Fontana, Lucia; Paolini, Luisa; Altomare, Maria; D'Angelo, Paola; Palazzi, Mariangela; Cirocchi, Roberto; Leotta, Sergio; Fatati, Giuseppe; Parisi, Amilcare

    2017-03-01

    No randomized clinical trials (RCTs) have yet evaluated the bariatric surgery's efficacy and safety in patients newly diagnosed with type 2 diabetes mellitus (T2DM). The aim of this multicenter RCT is to compare bariatric surgery, particularly laparoscopic sleeve gastrectomy (LSG), with conventional medical therapy (CMT) in obese patients (body mass index between 30 and 42 kg/m(2)) newly diagnosed with T2DM and without any diabetes-related complications at any stage. A total of 100 eligible patients will be randomized at a 1:1 ratio to undergo one of the two planned treatments and will be followed for at least 6 years after randomization. The main objective of the ESINODOP trial is to investigate the efficacy of LSG compared with CMT alone in inducing and maintaining a remission of T2DM (defined as HbA1c levels ≤6.0 %, without active pharmacologic therapy after 1 year). The remission of T2DM will also be evaluated with the criteria provided by the American Diabetes Association (ADA), and the additional parameters such as adverse event rates, micro- and macrovascular complications, weight loss, gastrointestinal hormones, and quality of life will be compared. The study started on September 2015 and the planned recruitment period is 3 years. Patient recruitment and follow-up take place in the two diabetology and nutrition centers participating in the study, which are performed on a national basis. The ESINODOP trial is designed with the intent of comparing the efficacy of CMT alone to that of CMT in conjunction with LSG performed at the time of diabetes diagnosis in mildly obese diabetic patients. Currently, patients with these characteristics are not eligible for bariatric/metabolic surgery.

  3. Effect of Extended-Release Niacin on New-Onset Diabetes Among Hyperlipidemic Patients Treated With Ezetimibe/Simvastatin in a Randomized Controlled Trial

    PubMed Central

    Guyton, John R.; Fazio, Sergio; Adewale, Adeniyi J.; Jensen, Erin; Tomassini, Joanne E.; Shah, Arvind; Tershakovec, Andrew M.

    2012-01-01

    OBJECTIVE To determine the effect of niacin on fasting glucose (FG) and new-onset diabetes in statin/ezetimibe-treated patients. RESEARCH DESIGN AND METHODS This was a prespecified secondary analysis among 942 hyperlipidemic patients randomized to ezetimibe/simvastatin (E/S; 10/20 mg) or E/S + extended-release niacin (N; titrated to 2 g) over 64 weeks. RESULTS FG levels peaked by 8–12 weeks, then declined even without antidiabetic medication. At 64 weeks, 3.5% taking E/S+N versus 2.6% taking E/S met criteria for new-onset diabetes (P = 0.66). An additional 1.4% taking E/S+N versus 0.4% taking E/S transiently met criteria for diabetes and then remitted (P = 0.46). Of 28 new-diabetes diagnoses in the E/S+N group, 25 occurred by 24 weeks. Among patients with baseline diabetes, 13.9% taking E/S+N and 11.6% taking E/S underwent antidiabetic treatment modification. CONCLUSIONS Increased FG and new-onset diabetes with E/S+N occurred mainly around the time of initial uptitration of N and often improved or remitted without specific treatment. PMID:22338103

  4. Depressive symptoms, antidepressant medication use and new onset of diabetes in participants of the Diabetes Prevention Program and the Diabetes Prevention Program Outcomes Study

    PubMed Central

    Marrero, David G.; Ma, Yong; de Groot, Mary; Horton, Edward S.; Price, David W.; Barrett-Connor, Elizabeth; Carnethon, Mercedes R.; Knowler, William C.

    2015-01-01

    Objective To assess in participants in the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study (DPP/DPPOS) whether diagnosis of diabetes predicted: elevated depressive symptoms (DS) or antidepressant medicine (ADM) use after diagnosis; diabetes status or duration had significant effect on DS or ADM use; and associations between A1C, fasting plasma glucose (FPG), normalization of FPG and DS or ADM use post diagnosis. Methods DPP participants in 3 treatment arms [intensive lifestyle (ILS), metformin (MET), placebo (PLC)] were assessed semiannually or annually for diabetes, glucose control, ADM use, and DS. DS was measured using Beck Depression Inventory (BDI) questionnaire. Among the total 3234 enrolled participants, 1285 developed diabetes whose levels of depression were measured before and after their diabetes diagnosis. Results Neither DS nor ADM use increased significantly following diabetes diagnosis. After diabetes diagnosis, higher FPG was associated with greater ADM use in the ILS arm independent of potential confounders; a 10 mg/dl higher in FPG is associated with 8.8% more odds of ADM use. Higher FPG, and higher A1C were associated with higher BDI scores in all three arms. On average, a participant with 10 mg/dl higher rise in FPG had a 0.07 increase in BDI score. Similarly, 1% higher A1c was associated with a 0.21 point increase in BDI score. On contrary, normalization of FPG was associated with lower BDI scores. In participants with FPG that had normalized, there was a decrease of 0.30 points in the BDI score compared to those whose FPG had not normalized. Conclusions Contrary to clinical attributions, the diagnosis of diabetes did not show an immediate impact on BDI scores or ADM use. However, higher glucose levels after diagnosis were associated with small but significant higher BDI score and more ADM use. PMID:25775165

  5. Barriers to Eye Care Faced by Adult Hispanics with Diabetes

    ERIC Educational Resources Information Center

    Griffin-Shirley, Nora; Trusty, Sharon; Kelley, Emily; Siew-Jin, Lai Keun; Macias, Eduardo P.

    2004-01-01

    Current diabetes vision care guidelines suggest that people receive at least an annual dilated eye examination 5 years after the diagnosis of Type I diabetes and a dilated eye examination at the time of diagnosis of Type II diabetes, and at least annually thereafter. Hispanics in the United States have a three-fold greater prevalence of diabetes…

  6. Mutation screen and association studies for the fatty acid amide hydrolase (FAAH) gene and early onset and adult obesity

    PubMed Central

    2010-01-01

    Background The orexigenic effects of cannabinoids are limited by activation of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH). The aim of this study was to analyse whether FAAH alleles are associated with early and late onset obesity. Methods We initially assessed association of five single nucleotide polymorphisms (SNPs) in FAAH with early onset extreme obesity in up to 521 German obese children and both parents. SNPs with nominal p-values ≤ 0.1 were subsequently analysed in 235 independent German obesity families. SNPs associated with childhood obesity (p-values ≤ 0.05) were further analysed in 8,491 adult individuals of a population-based cohort (KORA) for association with adult obesity. One SNP was further analysed in 985 German obese adults and 588 normal and underweight controls. In parallel, we screened the FAAH coding region for novel sequence variants in 92 extremely obese children using single-stranded-conformation-polymorphism-analysis and denaturing HPLC and assessed the implication of the identified new variants for childhood obesity. Results The trio analysis revealed some evidence for an association of three SNPs in FAAH (rs324420 rs324419 and rs873978) with childhood obesity (two-sided p-values between 0.06 and 0.10). Although analyses of these variants in 235 independent obesity families did not result in statistically significant effects (two-sided p-values between 0.14 and 0.75), the combined analysis of all 603 obesity families supported the idea of an association of two SNPs in FAAH (rs324420 and rs2295632) with early onset extreme obesity (p-values between 0.02 and 0.03). No association was, however, found between these variants and adult obesity. The mutation screen revealed four novel variants, which were not associated with early onset obesity (p > 0.05). Conclusions As we observed some evidence for an association of the FAAH variants rs2295632 rs324420 with early onset but not adult obesity, we conclude that the

  7. Serum calprotectin--a promising diagnostic marker for adult-onset Still's disease.

    PubMed

    Guo, Qian; Zha, Xicao; Li, Chun; Jia, Yuan; Zhu, Lei; Guo, Jianping; Su, Yin

    2016-01-01

    Calprotectin is a calcium-binding cytosolic protein, mainly expressed in immune cells, such as neutrophils, monocytes, and macrophages. Our study aimed to evaluate the diagnostic value of calprotectin for adult-onset Still's disease (AOSD), by comparing serum calprotectin concentrations in patients with AOSD (n = 46), rheumatoid arthritis (RA, n = 34), primary Sjögren syndrome (pSS, n = 40), systemic lupus erythematosus (SLE, n = 39), osteoarthritis (OA, n = 20), and healthy controls (HCs, n = 49). Calprotectin concentrations were significantly higher in patients with AOSD (55.26 ± 18.00 ng/ml), compared to patients with RA (39.17 ± 18.90 ng/ml), pSS (35.31 ± 19.47 ng/ml), SLE (32.21 ± 25.01 ng/ml), OA (19.24 ± 10.67 ng/ml), and HCs (8.46 ± 5.17 ng/ml). All the differences were highly significant (p < 0.001). Using receiver-operating characteristic curve, the cut-off value of calprotectin was defined as 45.488 ng/ml, and its sensitivity and specificity for AOSD diagnosis were 63.0 and 80.1%, respectively. The positive rate of calprotectin was significantly higher in AOSD cases compared to patients with other diseases and healthy controls (p < 0.001). Serum calprotectin was positively correlated with ferritin (r = 0.294, p < 0.05), and concentration of hemoglobin was significantly lower in calprotectin-positive patients compared to negative patients in AOSD (103.49 ± 20.21 g/l vs 115.71 ± 15.59 g/l, t = -2.142, p = 0.038). These findings suggest that serum calprotectin may serve as a promising marker for the diagnosis of AOSD and monitor disease activity to a certain extent.

  8. Improving the Transition from Pediatric to Adult Diabetes Healthcare: A Literature Review.

    PubMed

    Wafa, Sarah; Nakhla, Meranda

    2015-12-01

    Effective transition to adult care is a significant component of an emerging adult's diabetes care. Poor transition places them at risk for disengagement with the health care system and for poor diabetes-related outcomes. The purpose of this paper was to review the literature to date on existing methods of transition care delivery for emerging adults with diabetes. We conducted a literature review using MEDLINE via OvidSP and searching the grey literature. Papers published in English between January 1, 2000 and March 25, 2015 that evaluated transition care programs for emerging adults with diabetes were included. 16 original studies, 1 study protocol and 1 technical brief describing transition programs were reviewed. Common components of care included transition care coordination, young adult clinics, transition preparation, familiarity with adult health care providers and support groups. Overall, when emerging adults are supported during the transition period, clinic attendance and glycemic control can be maintained or improved, and diabetes-related complications reduced. Despite widespread support in the literature for the need for structured transition care delivery, methodologically strong research evaluating transition care services remains limited. The literature to date encompasses a variety of care models that lack consistency in outcome measurements as well as lacking frameworks describing the interventions, which impedes comparison across studies. Further research, using a consistent framework for transition care program design, delivery and evaluation as well as reporting of outcomes, is needed to inform how best to deliver transition care services to this vulnerable population.

  9. Variation in genes related to cochlear biology is strongly associated with adult-onset deafness in border collies.

    PubMed

    Yokoyama, Jennifer S; Lam, Ernest T; Ruhe, Alison L; Erdman, Carolyn A; Robertson, Kathryn R; Webb, Aubrey A; Williams, D Colette; Chang, Melanie L; Hytönen, Marjo K; Lohi, Hannes; Hamilton, Steven P; Neff, Mark W

    2012-09-01

    Domestic dogs can suffer from hearing losses that can have profound impacts on working ability and quality of life. We have identified a type of adult-onset hearing loss in Border Collies that appears to have a genetic cause, with an earlier age of onset (3-5 years) than typically expected for aging dogs (8-10 years). Studying this complex trait within pure breeds of dog may greatly increase our ability to identify genomic regions associated with risk of hearing impairment in dogs and in humans. We performed a genome-wide association study (GWAS) to detect loci underlying adult-onset deafness in a sample of 20 affected and 28 control Border Collies. We identified a region on canine chromosome 6 that demonstrates extended support for association surrounding SNP Chr6.25819273 (p-value = 1.09 × 10(-13)). To further localize disease-associated variants, targeted next-generation sequencing (NGS) of one affected and two unaffected dogs was performed. Through additional validation based on targeted genotyping of additional cases (n = 23 total) and controls (n = 101 total) and an independent replication cohort of 16 cases and 265 controls, we identified variants in USP31 that were strongly associated with adult-onset deafness in Border Collies, suggesting the involvement of the NF-κB pathway. We found additional support for involvement of RBBP6, which is critical for cochlear development. These findings highlight the utility of GWAS-guided fine-mapping of genetic loci using targeted NGS to study hereditary disorders of the domestic dog that may be analogous to human disorders.

  10. Earlier Age of Onset of Chronic Hypertension and Type 2 Diabetes Mellitus After a Hypertensive Disorder of Pregnancy or Gestational Diabetes Mellitus.

    PubMed

    Heida, Karst Y; Franx, Arie; van Rijn, Bas B; Eijkemans, Marinus J C; Boer, Jolanda M A; Verschuren, Monique W M; Oudijk, Martijn A; Bots, Michiel L; van der Schouw, Yvonne T

    2015-12-01

    A prospective cohort study was conducted to assess the impact of a history of hypertensive disorder of pregnancy (HDP) or gestational diabetes mellitus (GDM) on the risk and age of onset of hypertension, type 2 diabetes mellitus (T2D), and cardiovascular disease (CVD) later in life, independent of hypertension and T2D. Between 1993 and 1997, 22 265 ever-pregnant women were included from the European Prospective Investigation into Cancer and Nutrition-NL study, aged 20 to 70 years at baseline. Details on complications of pregnancy and known hypertension were obtained by questionnaire. Blood pressure was measured at enrollment. Participants were followed for the occurrence of CVD events. Data were analyzed using ANCOVA, multivariable logistic regression, and Cox proportional hazard (with HDP and GDM as time-dependent variables for T2D and CVD) models. At enrollment, women with a HDP reported diagnosis of hypertension 7.7 years earlier (95% confidence interval [CI] 6.9-8.5) and women with GDM reported diagnosis of T2D 7.7 years earlier (95% CI 5.8-9.6) than women without pregnancy complications. After adjustment for potential confounders, HDP was associated with presence of hypertension at enrollment (odds ratio 2.12, 95% CI 1.98-2.28) and onset of CVD later in life (hazard ratio 1.21, 95% CI 1.10-1.32). After including the intermediates hypertension and T2D in the model, the risk of CVD later in life decreased (hazard ratio 1.09, 95% CI 1.00-1.20). GDM was associated with an increased risk of developing T2D later in life (hazard ratio 3.68, 95% CI 2.77-4.90), but not with risk of CVD. HDP and GDM have a substantial impact on the risk of CVD and are potentially important indicators for preventive cardiovascular risk management.

  11. The future of treating youth-onset type 2 diabetes: focusing upstream and extending our influence into community environments.

    PubMed

    Amed, Shazhan

    2015-03-01

    Type 2 diabetes (T2D) in youth is on the rise and many of these youth already have comorbidity at disease onset. The TODAY trial clearly demonstrated the challenges of treating this disease. Obesity is a key risk factor in the development of youth-onset T2D, and its prevention can mitigate the risk for developing T2D. However, childhood obesity prevention efforts to date have shown only modest effectiveness. Considering the larger, complex socioeconomic and cultural contexts that influence health behaviors among children and their families can enhance prevention efforts. Community-based participatory, multi-component, multi-setting childhood obesity prevention initiatives designed using the socio-ecological model and systems theory have been effective in sustainably decreasing childhood overweight and obesity. To advance our progress in treating and preventing T2D in youth, we must apply this new knowledge on community-wide childhood obesity prevention to enhance the impact of individual-level therapeutic strategies such as the TODAY intervention.

  12. Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset.

    PubMed

    Cabrera, Susanne M; Wang, Xujing; Chen, Yi-Guang; Jia, Shuang; Kaldunski, Mary L; Greenbaum, Carla J; Mandrup-Poulsen, Thomas; Hessner, Martin J

    2016-04-01

    It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1α and IL-1β additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials.

  13. New-onset diabetes after transplantation--role of oral glucose tolerance test for diagnosis and study of risk factors.

    PubMed

    Sahay, Manisha; Sahay, Rakesh K; Narayan, Girish

    2013-09-01

    To determine the role of the oral glucose tolerance test in the early detection of new-onset diabetes after transplantation (NODAT) and to compare the various risk factors and insulin kinetics in the transplant patients, we studied 41 live-related renal allograft recipients who were not diabetic before transplantation. Immunosuppression included triple drug therapy (cyclosporine, azathioprine and steroids) and rejection episodes were treated with methyl prednisolone (30 mg/kg IV × 3 days). All the study patients were subjected to an oral glucose tolerance test (OGTT) at Day 90 post-transplant and classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and NODAT as per the World Health Organization guidelines. Insulin levels were also determined at 0, ½ hour, 1 hour and 2 hours during OGTT. NODAT was noted in 29.2% of the study patients, IFG in 4.8% of the study patients and NGT in 65.8% of the study patients. All the groups had normal fasting plasma glucose, but higher than normal insulin levels, suggesting insulin resistance. The patients with overt NODAT had, in addition, low fasting insulin (insulin secretory defect). OGTT may be used for the early detection of NODAT. Although insulin resistance is detected in the majority of post-transplant patients, NODAT also reveals also an insulin secretory defect.

  14. Glutathione-s-transferase M1 and T1 polymorphisms and associations with type 1 diabetes age-at-onset.

    PubMed

    Bekris, Lynn M; Shephard, Cindy; Peterson, Morgan; Hoehna, Jana; Van Yserloo, Brian; Rutledge, Elizabeth; Farin, Federico; Kavanagh, Terrance J; Lernmark, Ake

    2005-12-01

    Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction involving auto-reactive T-cells, pro-inflammatory cytokines, reactive oxygen species (ROS) and loss of insulin. Monozygotic twin studies show a 20-60% concordance with T1D indicating there may be an environmental component to the disease. Glutathione (GSH) is the major endogenous antioxidant produced by the cell. GSH participates directly in the neutralization of free radicals and plays a role in the immune response. Glutathione-s-transferases (GSTs) conjugate GSH to free-radicals or xenobiotics. GST activity depletes GSH levels and may either detoxify or enhance the toxicity of a compound. Glutathione-s-transferase mu 1 (GSTM1) and glutathione-s-transferase theta 1 (GSTT1) have polymorphic homozygous deletion (null) genotypes resulting in complete absence of enzyme activity. GSTM1 and GSTT1 null genotypes in Caucasian populations have frequencies of approximately 40-60% and 15-20%, respectively. GST null genotypes have been associated with susceptibility to cancer and protection against chronic pancreatitis. The aim of this study was to investigate associations with GSTM1 and GSTT1 polymorphisms in a group T1D patients and control subjects 0-35 years old who participated in the Combined Swedish Childhood Diabetes Registry and Diabetes Incidence Study (1986-1988). Results show that the presence of the GSTM1 and not the null genotype (OR, 2.13 95% CI, 1.23-3.70, p-value, 0.007, Bonferroni corrected p-value, 0.035) may be a susceptibility factor in T1D 14-20 years old. These results suggest that the GSTM1 null genotype is associated with T1D protection and T1D age-at-onset and that susceptibility to T1D may involve GST conjugation.

  15. Carbohydrate nutrition differs by diabetes status and is associated with dyslipidemia in Boston Puerto Rican adults without diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Puerto Rican adults have a greater prevalence of type 2 diabetes (T2D) and lower HDL-cholesterol (HDL-C) than the general U.S. population. Carbohydrate nutrition may play a role in this disparity. Cross-sectional analyses included data from 1219 Puerto Ricans aged 45-75 y enrolled in the Boston Puer...

  16. Disease progression and search for monogenic diabetes among children with new onset type 1 diabetes negative for ICA, GAD- and IA-2 Antibodies

    PubMed Central

    2010-01-01

    Background To investigate disease progression the first 12 months after diagnosis in children with type 1 diabetes negative (AAB negative) for pancreatic autoantibodies [islet cell autoantibodies(ICA), glutamic acid decarboxylase antibodies (GADA) and insulinoma-associated antigen-2 antibodies (IA-2A)]. Furthermore the study aimed at determining whether mutations in KCNJ11, ABCC8, HNF1A, HNF4A or INS are common in AAB negative diabetes. Materials and methods In 261 newly diagnosed children with type 1 diabetes, we measured residual β-cell function, ICA, GADA, and IA-2A at 1, 6 and 12 months after diagnosis. The genes KCNJ11, ABCC8, HNF1A, HNF4A and INS were sequenced in subjects AAB negative at diagnosis. We expressed recombinant K-ATP channels in Xenopus oocytes to analyse the functional effects of an ABCC8 mutation. Results Twenty-four patients (9.1%) tested AAB negative after one month. Patients, who were AAB-negative throughout the 12-month period, had higher residual β-cell function (P = 0.002), lower blood glucose (P = 0.004), received less insulin (P = 0.05) and had lower HbA1c (P = 0.02) 12 months after diagnosis. One patient had a heterozygous mutation leading to the substitution of arginine at residue 1530 of SUR1 (ABCC8) by cysteine. Functional analyses of recombinant K-ATP channels showed that R1530C markedly reduced the sensitivity of the K-ATP channel to inhibition by MgATP. Morover, the channel was highly sensitive to sulphonylureas. However, there was no effect of sulfonylurea treatment after four weeks on 1.0-1.2 mg/kg/24 h glibenclamide. Conclusion GAD, IA-2A, and ICA negative children with new onset type 1 diabetes have slower disease progression as assessed by residual beta-cell function and improved glycemic control 12 months after diagnosis. One out of 24 had a mutation in ABCC8, suggesting that screening of ABCC8 should be considered in patients with AAB negative type 1 diabetes. PMID:20863361

  17. Familial Young-Onset Diabetes, Pre-Diabetes and Cardiovascular Disease Are Associated with Genetic Variants of DACH1 in Chinese

    PubMed Central

    Tam, Claudia Ha Ting; Ho, Janice Siu Ka; Zhao, Hai-Lu; Guan, Jing; Kong, Alice Pik Shan; Lau, Eric; Zhang, Guozhi; Luk, Andrea; Wang, Ying; Tsui, Stephen Kwok Wing; Chan, Ting Fung; Hu, Cheng; Jia, Wei Ping; Park, Kyong Soo; Lee, Hong Kyu; Furuta, Hiroto; Nanjo, Kishio; Tai, E. Shyong; Ng, Daniel Peng-Keat; Tang, Nelson Leung Sang; Woo, Jean; Leung, Ping Chung; Xue, Hong; Wong, Jeffrey; Leung, Po Sing; Lau, Terrence C. K.; Tong, Peter Chun Yip; Xu, Gang; Ng, Maggie Chor Yin; So, Wing Yee; Chan, Juliana Chung Ngor

    2014-01-01

    In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57–3.96, P = 8.4×10−5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02–1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07–2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19–9.19, P = 0.0214) and 3.27(1.25–11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese. PMID:24465431

  18. Perinatal triphenyl phosphate exposure accelerates type 2 diabetes onset and increases adipose accumulation in UCD-type 2 diabetes mellitus rats.

    PubMed

    Green, Adrian J; Graham, James L; Gonzalez, Eduardo A; La Frano, Michael R; Petropoulou, Syrago-Styliani E; Park, June-Soo; Newman, John W; Stanhope, Kimber L; Havel, Peter J; La Merrill, Michele A

    2017-03-01

    Triphenyl phosphate (TPhP) is a flame retardant additive frequently found in consumer products and household dust. We administered 170μg of TPhP in maternal food from gestational day 8.5 to weaning and evaluated metabolic phenotypes of 3.5 month old male and female rats, and weight-matched males up to 6 months, to assess the development of obesity and type 2 diabetes mellitus (T2DM), respectively. Perinatal TPhP exposure increased body and fat mass in 3.5 month old male and female rats, while leptin and cumulative energy intake were elevated in males and females, respectively. Independent of body mass, perinatal TPhP exposure accelerated T2DM onset in males and increased plasma non-esterified- fasting fatty acids. These observations suggest that perinatal exposure to TPhP exacerbates the development of obesity in male and female UCDavis-T2DM rats and accelerates T2DM onset in male UCD-T2DM rats.

  19. Diabetes and pancreatic exocrine dysfunction due to mutations in the carboxyl ester lipase gene-maturity onset diabetes of the young (CEL-MODY): a protein misfolding disease.

    PubMed

    Johansson, Bente B; Torsvik, Janniche; Bjørkhaug, Lise; Vesterhus, Mette; Ragvin, Anja; Tjora, Erling; Fjeld, Karianne; Hoem, Dag; Johansson, Stefan; Ræder, Helge; Lindquist, Susanne; Hernell, Olle; Cnop, Miriam; Saraste, Jaakko; Flatmark, Torgeir; Molven, Anders; Njølstad, Pål R

    2011-10-07

    CEL-maturity onset diabetes of the young (MODY), diabetes with pancreatic lipomatosis and exocrine dysfunction, is due to dominant frameshift mutations in the acinar cell carboxyl ester lipase gene (CEL). As Cel knock-out mice do not express the phenotype and the mutant protein has an altered and intrinsically disordered tandem repeat domain, we hypothesized that the disease mechanism might involve a negative effect of the mutant protein. In silico analysis showed that the pI of the tandem repeat was markedly increased from pH 3.3 in wild-type (WT) to 11.8 in mutant (MUT) human CEL. By stably overexpressing CEL-WT and CEL-MUT in HEK293 cells, we found similar glycosylation, ubiquitination, constitutive secretion, and quality control of the two proteins. The CEL-MUT protein demonstrated, however, a high propensity to form aggregates found intracellularly and extracellularly. Different physicochemical properties of the intrinsically disordered tandem repeat domains of WT and MUT proteins may contribute to different short and long range interactions with the globular core domain and other macromolecules, including cell membranes. Thus, we propose that CEL-MODY is a protein misfolding disease caused by a negative gain-of-function effect of the mutant proteins in pancreatic tissues.

  20. Association between reductions in low-density lipoprotein cholesterol with statin therapy and the risk of new-onset diabetes: a meta-analysis

    PubMed Central

    Wang, Shaohua; Cai, Rongrong; Yuan, Yang; Varghese, Zac; Moorhead, John; Ruan, Xiong Z.

    2017-01-01

    A recent meta-analysis demonstrated that statin therapy was associated with a risk of diabetes. The present study investigated whether the relative reduction in low-density lipoprotein cholesterol (LDL-c) was a good indicator of the risk of new-onset diabetes. We searched the PubMed, Embase, Cochrane Central Register, Lilacs, Food and Drug Administration, and European Medicines Agency databases for randomized controlled trials of statins. Fourteen trials were included in the study. Eight trials with target LDL-c levels ≤100 mg/dL (2.6 mmol/L) or LDL-c reductions of at least 30% were extracted separately. The results showed that the overall risk of incident diabetes increased by 11% (OR = 1.11; 95% CI 1.03–1.20). The group with intensive LDL-c-lowering statin had an 18% increase in the likelihood of developing diabetes (OR = 1.18; 95% CI, 1.10–1.28). Furthermore, the risks of incident diabetes were 13% (OR = 1.13; 95% CI 1.01–1.26) and 29% (OR = 1.29; 95% CI 1.13–1.47) in the subgroups with 30–40% and 40–50% reductions in LDL-c, respectively, suggesting that LDL-c reduction may provide a dynamic risk assessment parameter for new-onset diabetes. In conclusion, LDL-c reduction is positively related to the risk of new-onset diabetes. When LDL-c is reduced by more than 30% during lipid-lowering therapy, blood glucose monitoring is suggested to detect incident diabetes in high-risk populations. PMID:28071756

  1. Intrathecal antibody production against Epstein-Barr and other neurotropic viruses in pediatric and adult onset multiple sclerosis.

    PubMed

    Pohl, Daniela; Rostasy, Kevin; Jacobi, Christian; Lange, Peter; Nau, Roland; Krone, Bernd; Hanefeld, Folker

    2010-02-01

    Epstein-Barr virus (EBV) has been implicated in the pathogenesis of multiple sclerosis (MS). Recent reports proposed an increased EBV-targeted humoral immune response in MS, which appears to be more pronounced in pediatric patients. However, little is known about the CNS-derived antibody production against EBV in patients with MS. The objective of this study was to assess the frequency and intensity of intrathecal antibody production against EBV as compared to other neurotropic viruses in pediatric and adult onset MS. In cohorts of 43 childhood, 50 adult onset MS patients, 20 children and 12 adults with other CNS disorders, paired CSF and serum samples were studied. Frequency and intensity of intrathecal antibody production against EBV as compared to measles, rubella, varicella zoster (VZV) and herpes simplex virus (HSV) were analyzed by determination of virus-specific CSF-to-serum Antibody Indices (AI). Intrathecally synthesized EBV antibodies were detectable in 26% pediatric and 10% adult onset MS patients, compared to frequencies ranging in both groups from 10 to 60% for the other viruses. Median AIs for EBV were lower than those for all other viruses, with more than twofold higher median AI for measles, rubella and VZV. The EBV-targeted humoral immune response in the CNS is only part of the intrathecal polyspecific antibody production in MS, directed against various neurotropic viruses. Our results do not rule out the possibility that EBV is involved in the pathogenesis of MS by triggering diverse cellular immune mechanisms, but they argue against a direct pathogenic role of EBV-targeted humoral immune response within the CNS.

  2. Obesity-related abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D.

    PubMed

    Nguyen, K Hoa; Ande, Sudharsana R; Mishra, Suresh

    2016-01-29

    The incidence of adult-onset T1D in low-risk non-HLA type has increased several folds, whereas the contemporaneous incidence in high-risk HLA-type remains stable. Various factors behind this selective increase in T1D in young adults remain unclear. Obesity and its associated abnormalities appear to be an important determinant; however, the underlying mechanism involved is not understood. Recently, we have developed two novel transgenic obese mice models, Mito-Ob and m-Mito-Ob, by expressing a pleiotropic protein prohibitin (PHB) and a phospho mutant form of PHB (Y114F-PHB or m-PHB) from the aP2 gene promoter, respectively. Both mice models develop obesity in a sex-neutral manner, independent of diet; but obesity associated chronic low-grade inflammation and insulin resistance in a male sex-specific manner. Interestingly, on a high fat diet (HFD) only male m-Mito-Ob mice displayed marked mononuclear cell infiltration in pancreas and developed insulitis that mimic adult-onset T1D. Male Mito-Ob mice that share the metabolic phenotype of male m-Mito-Ob mice, and female m-Mito-Ob that harbor m-PHB similar to male m-Mito-Ob mice, did not develop insulitis. Thus, insulitis development in male m-Mito-Ob in response to HFD requires both, obesity-related abnormalities and m-PHB. Collectively, this data provides a proof-of-concept that obesity-associated abnormalities couple environmental triggers with genetic susceptibility in adult-onset T1D and reveals PHB as a potential susceptibility gene for T1D.

  3. Dental caries prevalence among type II diabetic and nondiabetic adults attending a hospital

    PubMed Central

    Malvania, Ekta A.; Sheth, Sona A.; Sharma, Ashish S.; Mansuri, Saloni; Shaikh, Faizan; Sahani, Saloni

    2016-01-01

    Objectives: Diabetes mellitus (DM) is a common chronic metabolic disorder which affects millions of people. At present, India has the highest incidence of diabetes worldwide. Several oral lesions and conditions are associated with diabetes. However, there is a lack of consensus among researchers regarding the relationship between DM and dental caries. Hence, the present study was carried out to assess the dental caries prevalence among type II diabetic and nondiabetic adults attending a hospital in Ahmedabad city. Materials and Methods: A hospital-based cross-sectional study was conducted. One hundred and twenty diabetics individuals attending the diabetic Outpatient Department (OPD) and age and sex-matched 120 nondiabetic individuals from general OPD were included in the study. The data were gathered through semi-close-ended questionnaire and clinical examination. Dental caries was assessed by using the World Health Organization's 2013 proforma. Data was analyzed by applying Student's independent t-test or one-way analysis of variance. Results: Dental caries prevalence among the diabetic group was 73.33% and 33.33% among the nondiabetic group. Dental caries prevalence and mean dental caries was significantly higher among uncontrolled diabetic individuals than that among controlled diabetic individuals. Duration of the disease and dental caries prevalence did not show any significant difference. Conclusion: Dental caries prevalence was significantly high among diabetic individuals compared with nondiabetic individuals. Close collaboration between the patients, healthcare units, and oral health professionals could be a way of improving diabetic patients' general and oral health. PMID:28217542

  4. Polymorphism on Chromosome 9p21.3 Is Associated with Severity and Early-Onset CAD in Type 2 Diabetic Tunisian Population.

    PubMed

    Abid, Kaouthar; Mili, Donia; Kenani, Abderraouf

    2015-01-01

    Multiple association studies found that the human 9p21.3 chromosome locus is a risk factor for atherosclerosis. The purpose of this study was to investigate the association of the severity and early-onset of coronary artery disease with variant rs1333049 on chromosome 9p21.3 polymorphism and the impact of this variant on cardiovascular risk factors in type 2 diabetic patients. The study population consisted of a control CAD group (101 patients) and 273 consecutive type 2 diabetic patients. Severity and extent of coronary atherosclerosis were scored numerically using the Gensini scoring system. The diabetic population was divided into three groups according to Gensini score: Group 1: no stenosis; Group 2: moderate CAD; Group 3, severe CAD. The homozygous CC genotype of rs1333049 was significantly associated with CAD in Group 2 (OR: 1.36; p = 0.02) and Group 3 (OR: 5.77, p < 0.001) compared to Group 1 (OR: 0.18; p = 0.2) and control group (OR: 0.22; p = 0.21). Among diabetic patients with early-onset CAD, CC genotype carriers had significantly higher Gensini scores than non-CC genotype carriers (49 ± 21.3 versus 14.87 ± 25.22; p < 0.001). The homozygous CC genotype of rs1333049 confers a magnified risk of early-onset and severe CAD in type 2 diabetic Tunisian population.

  5. Supplementation with D-serine prevents the onset of cognitive deficits in adult offspring after maternal immune activation

    PubMed Central

    Fujita, Yuko; Ishima, Tamaki; Hashimoto, Kenji

    2016-01-01

    Prenatal maternal infection contributes to the etiology of schizophrenia, with D-serine, an endogenous co-agonist of the N-methyl-D-aspartate (NMDA) receptor, playing a role in the pathophysiology of this disease. We examined whether supplementation with D-serine during juvenile and adolescent stages could prevent the onset of cognitive deficits, prodromal and the core symptoms of schizophrenia in adult offspring after maternal immune activation (MIA). Juvenile offspring exposed prenatally to poly(I:C) showed reduced expression of NMDA receptor subunits in the hippocampus. Supplementing drinking water with D-serine (600 mg/L from P28 to P56) prevented the onset of cognitive deficits in adult offspring after MIA, in a significant manner. This study shows that supplementing offspring with D-serine during juvenile and adolescent stages could prevent the onset of psychosis in adulthood, after MIA. Therefore, early intervention with D-serine may prevent the occurrence of psychosis in high-risk subjects. PMID:27853241

  6. The midlife cognitive profiles of adults at high risk of late-onset Alzheimer's disease: The PREVENT study.

    PubMed

    Ritchie, Karen; Carrière, Isabelle; Su, Li; O'Brien, John T; Lovestone, Simon; Wells, Katie; Ritchie, C W

    2017-03-29

    Although biomarker studies of late-onset Alzheimer's disease suggest pathology to be present decades before diagnosis, little is known about cognitive performance at this stage. A sample of 210 adults (aged 40-59) of whom 103 have a parent diagnosed with dementia (family history subgroup) underwent computerized cognitive testing. ApoE status was determined, and 193 subjects had magnetic resonance imaging. Distance from dementia onset was estimated in relation to age of parental diagnosis, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia Risk Scores were calculated. Lower hippocampal volumes (P = .04) were associated with poorer spatial location recall and higher Dementia Risk Scores with poorer visual recognition (P = .0005), and lower brain and hippocampal volume (P < .0001, P = .04, respectively). Family history subgroup participants closer to dementia onset had lower scores on visual working memory (P = .05), whereas those with an ApoE ε4 allele performed better on form perception (P = .005). Middle-aged adults at risk of dementia show evidence of poorer cognitive performance, principally in visuospatial functions.

  7. Consumers' Perspectives on Effective Orientation and Mobility Services for Diabetic Adults Who Are Visually Impaired

    ERIC Educational Resources Information Center

    Griffin-Shirley, Nora; Kelley, Pat; Matlock, Dwayne; Page, Anita

    2006-01-01

    The authors interviewed and videotaped diabetic adults with visual impairments about their perceptions of orientation and mobility (O&M) services that they had received. The visual impairments of these middle-aged adults ranged from totally blind to low vision. The interview questions focused on demographic information about the interviewees, the…

  8. Lifestyle change and mobility in obese adults with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients. We randomly assigned 5145 overweight or obese adults between the ages o...

  9. Lifestyle change and mobility in obese adults with type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background Adults with type 2 diabetes mellitus often have limitations in mobility that increase with age. An intensive lifestyle intervention that produces weight loss and improves fitness could slow the loss of mobility in such patients. Methods We randomly assigned 5145 overweight or obese adults...

  10. Grip Strength as a Marker of Hypertension and Diabetes in Healthy Weight Adults

    PubMed Central

    Mainous, Arch G.; Tanner, Rebecca J.; Anton, Stephen D.; Jo, Ara

    2015-01-01

    Introduction Muscle strength may play a role in cardiometabolic disease. We examined the relationship between hand grip strength and diabetes and hypertension in a sample of healthy weight adults. Methods In 2015, we analyzed the National Health and Nutrition Examination Survey 2011–2012 for adults aged ≥20 years with healthy BMIs (between 18.5 and <25 kg/m2) and no history of cardiovascular disease (unweighted n=1,469; weighted n=61,672,082). Hand grip strength was assessed with a dynamometer. Diabetes was based on hemoglobin A1c level and reported diabetes diagnosis. Hypertension was based on measured blood pressure and reported hypertension diagnosis. Results Individuals with undiagnosed diabetes compared with individuals without diabetes had lower grip strength (51.9 vs 69.8, p=0.0001), as well as among individuals with diagnosed diabetes compared with individuals without diabetes (61.7 vs 69.8, p=0.008). Mean grip strength was lower among individuals with undiagnosed hypertension compared with individuals without hypertension (63.5 vs 71.5, p=0.008) as well as among individuals with diagnosed hypertension compared with those without hypertension (60.8 vs 71.5, p<0.0001). In adjusted analyses controlling for age, sex, race, smoking status, and first-degree relative with disease, mean grip strength was lower for undiagnosed diabetes (β= −10.02, p<0.0001) and diagnosed diabetes (β= −8.21, p=0.03) compared with individuals without diabetes. In adjusted analyses, grip strength was lower among individuals with undiagnosed hypertension (β= −6.6, p=0.004) and diagnosed hypertension (β= −4.27, p=0.04) compared with individuals without hypertension. Conclusions Among healthy weight adults, combined grip strength is lower in individuals with diagnosed and undiagnosed diabetes and hypertension. PMID:26232901

  11. Metabolic co-morbidities revealed in patients with childhood-onset adult GH deficiency after cessation of GH replacement therapy for short stature.

    PubMed

    Fukuda, Izumi; Hizuka, Naomi; Yasumoto, Kumiko; Morita, Junko; Kurimoto, Makiko; Takano, Kazue

    2008-12-01

    GH therapy was approved in 2006 for treatment of adult growth hormone deficiency (GHD) in Japan. Until then, GH was used only to treat short stature in children with GHD and the treatment was stopped when the final height was reached. In the present study, we investigated metabolic co-morbidities experienced by adults with childhood-onset (CO) GHD after the cessation of GH. Forty-two patients with COGHD (M/F 22/20, age at follow up when the retrospective analysis was carried out: 18-52 yr) treated with GH in childhood were studied. We reviewed the medical records of these patients to determine the metabolic co-morbidities that developed after cessation of GH. The median age was 19 yrs (range: 14-38) at cessation of GH, and the following co-morbidities were observed: hypertriglyceridemia in 15 (41%) patients, non-alcoholic fatty liver disease (NAFLD) in 11 (29%) patients, hypercholesterolemia in 10 (26%) patients, diabetes mellitus (DM) in 4 (10%) patients, and hypertension in 1 (2.4%) patient. The median BMI when these complications became overt was 23.5 kg/m(2) for those with hypertriglyceridemia, 26.0 kg/m(2) for those with NAFLD, 20.9 kg/m(2) for those with hypercholesterolemia, and 27.2 kg/m(2 ) for those with DM. More than two co-morbidities were experienced by 32% of men and 30% of women. In conclusion, adults with COGHD after the cessation of GH have multiple metabolic co-morbidities. Lifelong GH replacement might be important for improving the overall metabolic profiles in these patients.

  12. Association Analyses of Variants in the DIO2 Gene with Early-Onset Type 2 Diabetes Mellitus in Pima Indians

    PubMed Central

    Muller, Yunhua Li; Ortega, Emilio; Kobes, Sayuko; Bogardus, Clifton; Baier, Leslie J.

    2012-01-01

    Background The type 2 deiodinase gene (DIO2) encodes a deiodinase that converts the thyroid prohormone, thyroxine, to the biologically active triiodothyronine. Thyroid hormones regulate energy balance and may also influence glucose metabolism. Therefore, we hypothesized that variations in DIO2 could contribute to obesity or type 2 diabetes mellitus (T2DM) in Pima Indians. Methods Sequencing of the DIO2 gene in DNA from 83 Pima Indians identified 12 single-nucleotide polymorphisms (SNPs). Several of these SNPs were in perfect genotypic concordance among the 83 samples that were sequenced, and all 12 could be divided into five linkage disequilibrium groups. One representative SNP from each group (Thr92Ala, rs225011, rs225015, rs6574549, and a rare 5′ flanking SNP) was selected for further genotyping for association analyses. In this study, the five selected variants in DIO2, as described above, were genotyped in three groups of Pima Indians: (i) a case (n=150)/control (n=150) group for early-onset T2DM (onset age <25 years); (ii) a case (n=362)/control (n=127) group for obesity; (iii) a large (n=1,311, cases n=810/controls n=501) family-based group, of which 256 nondiabetic subjects had undergone detailed metabolic phenotyping. Results The Thr92Ala variant common in Pima Indians, rs225011, and rs225015 were modestly associated with early-onset T2DM (p=0.01–0.04) in the case–control study, but were not associated with obesity in the obesity case–control study, nor associated with T2DM (at any age) or body–mass index (BMI; as a quantitative trait) in the family-based analysis. Thr92Ala, rs225011, rs225015, and rs6574549 were also nominally associated with hepatic glucose output (p=0.02). rs6574549 was associated with fasting insulin (p=0.02), insulin action (p=0.04), and energy expenditure (p=0.02). None of these nominal associations remained statistically significant after corrections for multiple testing. Conclusions We propose that variation in DIO2 may

  13. Impact of statins on risk of new onset diabetes mellitus: a population-based cohort study using the Korean National Health Insurance claims database

    PubMed Central

    Lee, Jimin; Noh, Yoojin; Shin, Sooyoung; Lim, Hong-Seok; Park, Rae Woong; Bae, Soo Kyung; Oh, Euichaul; Kim, Grace Juyun; Kim, Ju Han; Lee, Sukhyang

    2016-01-01

    Statin therapy is beneficial in reducing cardiovascular events and mortalities in patients with atherosclerotic cardiovascular diseases. Yet, there have been concerns of increased risk of diabetes with statin use. This study was aimed to evaluate the association between statins and new onset diabetes mellitus (NODM) in patients with ischemic heart disease (IHD) utilizing the Korean Health Insurance Review and Assessment Service claims database. Among adult patients with preexisting IHD, new statin users and matched nonstatin users were identified on a 1:1 ratio using proportionate stratified random sampling by sex and age. They were subsequently propensity score matched further with age and comorbidities to reduce the selection bias. Overall incidence rates, cumulative rates and hazard ratios (HRs) between statin use and occurrence of NODM were estimated. The subgroup analyses were performed according to sex, age groups, and the individual agents and intensities of statins. A total of 156,360 patients (94,370 in the statin users and 61,990 in the nonstatin users) were included in the analysis. The incidence rates of NODM were 7.8% and 4.8% in the statin users and nonstatin users, respectively. The risk of NODM was higher among statin users (crude HR 2.01, 95% confidence interval [CI] 1.93–2.10; adjusted HR 1.84, 95% CI 1.63–2.09). Pravastatin had the lowest risk (adjusted HR 1.54, 95% CI 1.32–1.81) while those who were exposed to more than one statin were at the highest risk of NODM (adjusted HR 2.17, 95% CI 1.93–2.37). It has been concluded that all statins are associated with the risk of NODM in patients with IHD, and it is believed that our study would contribute to a better understanding of statin and NODM association by analyzing statin use in the real-world setting. Periodic screening and monitoring for diabetes are warranted during prolonged statin therapy in patients with IHD. PMID:27785041

  14. Clinical relevance of epigenetics in the onset and management of type 2 diabetes mellitus.

    PubMed

    Sommese, Linda; Zullo, Alberto; Mancini, Francesco Paolo; Fabbricini, Rossella; Soricelli, Andrea; Napoli, Claudio

    2017-01-06

    Epigenetics is involved in the altered expression of gene networks that underlie insulin resistance and insufficiency. Major genes controlling β-cell differentiation and function, such as PAX4, PDX1, and GLP1 receptor, are epigenetically controlled. Epigenetics can cause insulin resistance through immunomediated pro-inflammatory actions related to several factors, such as NF-kB, osteopontin, and Toll-like receptors. Hereafter, we provide a critical and comprehensive summary on this topic with a particular emphasis on translational and clinical aspects. We discuss the effect of epigenetics on β-cell regeneration for cell replacement therapy, the emerging bioinformatics approaches for analyzing the epigenetic contribution to type 2 diabetes mellitus (T2DM), the epigenetic core of the transgenerational inheritance hypothesis in T2DM, and the epigenetic clinical trials on T2DM. Therefore, prevention or reversion of the epigenetic changes occurring during T2DM development may reduce the individual and societal burden of the disease.

  15. Fever of unknown origin and leukemoid reaction as initial presentation of adult-onset Still's disease.

    PubMed

    Pardo-Cabello, Alfredo José; Manzano-Gamero, Victoria; Javier-Martínez, Rosario

    2014-01-01

    Adult Still's Disease has been reported as cause of Fever of Unknown Origin. Leukocytosis has been described as a common haematological abnormality in Adult Still's Disease. In some rare cases, leukemoid reaction has been reported associated to Still's Disease. We report the case of Adult Still's Disease presenting as Fever of Unknown Origin and leukemoid reaction in a patient with Down Syndrome. The patient needed high dosage of corticosteroids to control the disease and haematological findings.

  16. Characteristics of American Young Adults With Increased Risk for Type 2 Diabetes

    PubMed Central

    Cha, EunSeok; Umpierrez, Guillermo; Kim, Kevin H.; Bello, Morenike K.; Dunbar, Sandra B.

    2013-01-01

    Purpose The purpose of the study was to examine the characteristics of American young adults with increased risk for type 2 diabetes (T2D). Methods Participants ages 18 to 29, overweight/obese, and sedentary were recruited from the metro Atlanta area in the United States. Variables included demographics, anthropometric and clinical variables, and physical activity. Of 107 participants, 3 participants had undiagnosed diabetes and 1 participant did not complete the modifiable activity questionnaire. Thus, 103 young adults remained for the final data analysis. Results Most participants were females and African Americans. About 30% of participants had prediabetes, either impaired fasting glucose, an A1C of 5.7% to 6.4%, or both. Overall, prediabetes young adults were heavier and did less physical activity than Diabetes Prevention Program (DPP) trial participants. In addition, these young adults had a higher prevalence of parental T2D history and lower level of physical activity compared to young adults with normoglycemia. Conclusions Physical activity and parent T2D history are key risk factors for identifying young adults with prediabetes. Multilevel strategies are necessary to raise awareness of diabetes risk and to prevent T2D in young adults. PMID:23640300

  17. Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

    PubMed

    Lin, Yu-Ju; Lo, Kuan-Wu; Yang, Li-Kuang; Gau, Susan Shur-Fen

    2015-12-01

    The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment.

  18. Explaining the Association between Early Adversity and Young Adults' Diabetes Outcomes: Physiological, Psychological, and Behavioral Mechanisms.

    PubMed

    Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

    2017-01-31

    Previous studies have documented that early adversity increases young adults' risk for diabetes resulting in morbidity and comorbidity with adverse health conditions. However, less is known about how inter-related physiological (e.g., body mass index [BMI]), psychological (e.g., depressive symptoms), and behavioral mechanisms (e.g., unhealthy eating and sedentary behavior) link early adversity to young adults' diabetes outcomes, although these mechanisms appear to stem from early stressful experiences. The current study tested the patterning of these longitudinal pathways leading to young adults' diabetes using a nationally representative sample of 13,286 adolescents (54% female) over a period of 13 years. The findings indicated that early adversity contributed to elevated BMI, depressive symptoms, and stress-related health behaviors. The impact of these linking mechanisms on hierarchical diabetes outcomes (i.e., prediabetes and diabetes) remained significant after taking their associations with each other into account, showing that these mechanisms operate concurrently. The findings emphasize the importance of early detection for risk factors of young adults' diabetes in order to minimize their detrimental health effects.

  19. Adult-onset focal expression of mutated human tau in the hippocampus impairs spatial working memory of rats.

    PubMed

    Mustroph, Martina L; King, Michael A; Klein, Ronald L; Ramirez, Julio J

    2012-07-15

    Tauopathy in the hippocampus is one of the earliest cardinal features of Alzheimer's disease (AD), a condition characterized by progressive memory impairments. In fact, density of tau neurofibrillary tangles (NFTs) in the hippocampus strongly correlates with severity of cognitive impairments in AD. In the present study, we employed a somatic cell gene transfer technique to create a rodent model of tauopathy by injecting a recombinant adeno-associated viral vector with a mutated human tau gene (P301L) into the hippocampus of adult rats. The P301L mutation is causal for frontotemporal dementia with parkinsonism-17 (FTDP-17), but it has been used for studying memory effects characteristic of AD in transgenic mice. To ascertain if P301L-induced mnemonic deficits are persistent, animals were tested for 6 months. It was hypothesized that adult-onset, spatially restricted tau expression in the hippocampus would produce progressive spatial working memory deficits on a learned alternation task. Rats injected with the tau vector exhibited persistent impairments on the hippocampal-dependent task beginning at about 6 weeks post-transduction compared to rats injected with a green fluorescent protein vector. Histological analysis of brains for expression of human tau revealed hyperphosphorylated human tau and NFTs in the hippocampus in experimental animals only. Thus, adult-onset, vector-induced tauopathy spatially restricted to the hippocampus progressively impaired spatial working memory in rats. We conclude that the model faithfully reproduces histological and behavioral findings characteristic of dementing tauopathies. The rapid onset of sustained memory impairment establishes a preclinical model particularly suited to the development of potential tauopathy therapeutics.

  20. The changes in the hypothalamo-pituitary-gonadal axis of streptozotocin-treated male rats depend from age at diabetes onset.

    PubMed

    Pitton, I; Bestetti, G E; Rossi, G L

    1987-01-01

    The influence of age at diabetes onset and of capillary microangiopathy on the severity and evolution of hypothalamo-pituitary-gonadal changes was studied morphologically and morphometrically in male rats 4 and 8 months after streptozotocin injection. At each time period we studied 2 groups of rats, one made diabetic before (age 1 month), the other after puberty (age 3 months), and compared them with corresponding controls. The size of hypothalamic axons, numerical density and size of pituitary gonadotrophs, size of testicular tubules, and basement membrane thickness of retinal capillaries were measured. Major differences were found at 8 months. Changes of pituitary glands (i.e. small and numerous gonadotrophs) and testes (i.e. small tubular size) were more important in pre- than in postpubertal diabetic rats. This was a consequence of the aggravating prepubertal diabetes between 4 and 8 months. On the contrary, these changes partially regressed in postpubertal diabetic animals. Pituitary and testicular changes were correlated. Other lesions, such as swollen axonal processes in the hypothalamus, increased thickness of seminiferous epithelium and of capillary basement membranes, though very evident in diabetics, were independent from age at induction. Neither microangiopathy nor glycemia were correlated with any other change which confirmed their secondary role in diabetic neuroendocrine disorders. Thus, two types of diabetic disorders of the hypothalamo-pituitary-gonadal axis could be distinguished: 1) those with irreversible effects on immature yet partially reversible effects on mature structures; and 2) those independent from age at induction.

  1. Risks and Population Burden of Cardiovascular Diseases Associated with Diabetes in China: A Prospective Study of 0.5 Million Adults

    PubMed Central

    Bragg, Fiona; Li, Liming; Yang, Ling; Guo, Yu; Chen, Yiping; Bian, Zheng; Chen, Junshi; Collins, Rory; Peto, Richard; Dong, Caixia; Pan, Rong; Xu, Xin; Chen, Zhengming

    2016-01-01

    681,202) cardiovascular deaths annually in China. Conclusions Among Chinese adults, diabetes is associated with significantly increased risks of major cardiovascular diseases. The increasing prevalence and younger age of onset of diabetes foreshadow greater diabetes-attributable disease burden in China. PMID:27379518

  2. Recent Advances in Understanding Depression in Adults with Diabetes

    PubMed Central

    Lustman, Patrick J.; Penckofer, Sue M.; Clouse, Ray E.

    2013-01-01

    The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance. PMID:17425915

  3. Recent Advances in Understanding Depression in Adults With Diabetes

    PubMed Central

    Lustman, Patrick J.; Penckofer, Sue M.; Clouse, Ray E.

    2013-01-01

    The authors review the science linking depression with diabetes. Some recent heuristic research is identified that highlights progress in the field and is directing future research. Issues in the management of depression in diabetes are outlined, including interactions of depression and insulin resistance. PMID:18980733

  4. Ethnic Disparities in Glycemic Control Among Rural Older Adults with Type 2 Diabetes

    PubMed Central

    Quandt, Sara A.; Bell, Ronny A.; Snively, Beverly M.; Smith, Shannon L.; Stafford, Jeanette M.; Wetmore, Lindsay K.; Arcury, Thomas A.

    2006-01-01

    Glycemic control is a predictor of diabetes-related morbidity and mortality. However, little is known about how well older adults in rural communities, with limited access to self-care resources and specialty care practitioners, control their diabetes. Even less is known about whether minority, older, rural adults are at increased risk for poor glycemic control. We analyzed data from a cross-sectional survey of randomly selected older (≥65 years) adults with type 2 diabetes in rural North Carolina. Participants (N=693) were men and women from three ethnic groups: African American, Native American, and White. Capillary blood samples were collected for HbA1C analysis. HbA1C levels (<7%, 7%–<8%, and ≥8%) were compared across ethnic and gender groups. Two multiple logistic regression models (model 1: personal characteristics; model 2: personal and health characteristics) were used to evaluate potential predictors of HbA1C ≥7%. Overall, 36.4% had HbA1C ≥7%. Native Americans and African-American men had the highest proportion at levels of poor glycemic control (≥7%), and African-American women and White men had the lowest. In bivariate analysis, ethnicity, living arrangements, use of medications for diabetes, having a diabetes-related healthcare visit in the past year, and duration of diabetes were significantly associated with glycemic control. In multivariate analysis (model 1), being Native American, having low income without Medicaid, and being married were associated with poor glycemic control. Adding health characteristics (model 2), longer diabetes duration and diabetes medication therapy were significant predictors. These data indicate that older ethnic minorities in rural communities are at increased risk for diabetes complications and need diabetes management strategies to improve glycemic control. PMID:16259490

  5. Protective Connections and Educational Attainment among Young Adults with Childhood-Onset Chronic Illness

    ERIC Educational Resources Information Center

    Maslow, Gary; Haydon, Abigail A.; McRee, Annie-Laurie; Halpern, Carolyn T.

    2012-01-01

    Background: Youth with childhood-onset chronic illness (COCI) are at risk of poor educational attainment. Specific protective factors that promote college graduation in this population have not been studied previously. In this study, we examine the role protective factors during adolescence play in promoting college graduation among young adults…

  6. The History and Timing of Depression Onset as Predictors of Young Adult Self-Esteem

    ERIC Educational Resources Information Center

    Gayman, Mathew D.; Lloyd, Donald A.; Ueno, Koji

    2011-01-01

    Depression often emerges early in the lifecourse and is consistently shown to be associated with poor self-esteem. The 3 main objectives of the current study are to (1) evaluate the association between a history major depression and self-esteem in young adulthood, (2) assess the relationship between timing of depression onset and young adult…

  7. Adult-onset nemaline rods in a patient treated for suspected dermatomyositis: study with two-dimensional electrophoresis

    SciTech Connect

    Danon, M.J.; Giometti, C.S.; Manaligod, J.R.; Perurena, O.H.; Skosey, J.L.

    1981-12-01

    A 65-year-old woman with progressive muscle weakness and a diffuse rash of three years' duration was examined. Muscle tissue was studied with histochemical techniques, phase-contrast microscopy, electron microscopy, and two-dimensional electrophoresis. Histochemical studies showed numerous nemaline rods, with a normal ratio of types I and II fibers. Two-dimensional electrophoresis revealed abnormalities in the myosin light chain and tropomyosin protein patterns when compared with normal and diseased muscle biopsy samples, including those from two patients with adult-onset dermatomyositis.

  8. Ethical and legal dilemmas arising during predictive testing for adult-onset disease: the experience of Huntington disease.

    PubMed Central

    Huggins, M; Bloch, M; Kanani, S; Quarrell, O W; Theilman, J; Hedrick, A; Dickens, B; Lynch, A; Hayden, M

    1990-01-01

    The goal of predictive testing is to modify the risk for currently healthy individuals to develop a genetic disease in the future. Such testing using polymorphic DNA markers has had major application in Huntington disease. The Canadian Collaborative Study of Predictive Testing for Huntington Disease has been guided by major principles of medical ethics, including autonomy, beneficence, confidentiality, and justice. Numerous ethical and legal dilemmas have arisen in this program, challenging these principles and occasionally casting them into conflict. The present report describes these dilemmas and offers our approach to resolving them. These issues will have relevance to predictive-testing programs for other adult-onset disorders. PMID:1971997

  9. [Recurrent effusive pericarditis in the course of adult-onset Still's disease--case reports of two patients].

    PubMed

    Bilska, Anna; Wilińska, Ewelina; Szturmowicz, Monika; Wawrzyńska, Liliana; Fijałkowska, Anna; Oniszh, Karina; Swiatowiec, Andrzej; Wsół, Agnieszka; Torbicki, Adam

    2011-01-01

    Pericardial effusion is caused by various pathological agents. In differential diagnosis infectious as well as non-infectious factors have to be considered. Adult-onset Still disease (AOSD)--relatively uncommon systemic inflammatory disorder of unknown etiology--is among possible diagnosis. The disease typically affects patients in the age between 16-35 years and is characterized by spiking fever, arthralgia, evanescent salmon rash with other abnormalities including pharingitis, serositis (especially pleuritis and pericarditis) and leucocytosis as well as increased serum levels of inflammatory indicators. We present two patients with recurrent pericardial effusion in the course of AOSD.

  10. Prevalence and Associated Factors of Diabetes and Impaired Fasting Glucose in Chinese Hypertensive Adults Aged 45 to 75 Years

    PubMed Central

    Zhang, Yan; Ma, Wei; Fan, Fangfang; Wang, Binyan; Xing, Houxun; Tang, Genfu; Wang, Xiaobin; Xu, Xin; Xu, Xiping; Huo, Yong

    2012-01-01

    Objective This study examined the prevalence of impaired fasting glucose (IFG) and diabetes and their associated factors in 17,184 Chinese hypertensive adults aged 45–75 years. Methods A cross-sectional investigation was carried out in a rural area of Lianyungang, China. Previously undiagnosed diabetes [fasting plasma glucose (FPG) ≥7.0mmol/l] and IFG (6.1–6.9mmol/l) were defined based on FPG concentration. Previously diagnosed diabetes was determined on the basis of self-report. Total diabetes included both previously diagnosed diabetes and previously undiagnosed diabetes. Results The prevalence of previously diagnosed diabetes, undiagnosed diabetes, and IFG were 3.4%, 9.8%, and 14.1%, respectively. About 74.2% of the participants with diabetes had not previously been diagnosed. In the multivariable logistic-regression model, older age, men, antihypertensive treatment, obesity (BMI ≥25kg/m2), abdominal obesity (waist circumference ≥90cm for men and ≥80cm for women), non-current smoking, a family history of diabetes, higher heart rate, lower physical activity levels, and inland residence (versus coastal) were significantly associated with both total diabetes and previously undiagnosed diabetes. Furthermore, methylene- tetrahydrofolate reductase (MTHFR) 677 TT genotype was an independent associated factor for total diabetes, and current alcohol drinking was an independent associated factor for previously undiagnosed diabetes. At the same time, older age, men, abdominal obesity, non-current smoking, current alcohol drinking, a family history of diabetes, higher heart rate, and inland residence (versus coastal) were important independent associated factors for IFG. Conclusion In conclusion, we found a high prevalence of diabetes in Chinese hypertensive adults. Furthermore, about three out of every four diabetic adults were undiagnosed. Our results suggest that population-level measures aimed at the prevention, identification (even if only based on the FPG

  11. The association between types of eating behaviour and dispositional mindfulness in adults with diabetes. Results from Diabetes MILES. The Netherlands.

    PubMed

    Tak, Sanne R; Hendrieckx, Christel; Nefs, Giesje; Nyklíček, Ivan; Speight, Jane; Pouwer, François

    2015-04-01

    Although healthy food choices are important in the management of diabetes, making dietary adaptations is often challenging. Previous research has shown that people with type 2 diabetes are less likely to benefit from dietary advice if they tend to eat in response to emotions or external cues. Since high levels of dispositional mindfulness have been associated with greater awareness of healthy dietary practices in students and in the general population, it is relevant to study the association between dispositional mindfulness and eating behaviour in people with type 1 or 2 diabetes. We analysed data from Diabetes MILES - The Netherlands, a national observational survey in which 634 adults with type 1 or 2 diabetes completed the Dutch Eating Behaviour Questionnaire (to assess restrained, external and emotional eating behaviour) and the Five Facet Mindfulness Questionnaire-Short Form (to assess dispositional mindfulness), in addition to other psychosocial measures. After controlling for potential confounders, including demographics, clinical variables and emotional distress, hierarchical linear regression analyses showed that higher levels of dispositional mindfulness were associated with eating behaviours that were more restrained (β = 0.10) and less external (β = -0.11) and emotional (β = -0.20). The mindfulness subscale 'acting with awareness' was the strongest predictor of both external and emotional eating behaviour, whereas for emotional eating, 'describing' and 'being non-judgemental' were also predictive. These findings suggest that there is an association between dispositional mindfulness and eating behaviour in adults with type 1 or 2 diabetes. Since mindfulness interventions increase levels of dispositional mindfulness, future studies could examine if these interventions are also effective in helping people with diabetes to reduce emotional or external eating behaviour, and to improve the quality of their diet.

  12. Type 2 diabetes and its correlates in a first nationwide study among Cypriot adults.

    PubMed

    Andreou, Eleni; Papandreou, Dimitrios; Hajigeorgiou, Photos; Kyriakou, Katia; Avraam, Thalia; Chappa, Georgia; Kallis, Procopis; Lazarou, Christalleni; Philippou, Christiana; Christoforou, Christoforos; Kokkinofta, Rebecca; Dioghenous, Christos; Savva, Savvas; Kafatos, Antony; Zampelas, Antonios

    2017-04-01

    Obesity rates in Cyprus are very high and epidemiological information on type 2 diabetes mellitus is limited. The correlates of type 2 diabetes among adults remain unknown in the Cypriot population. Thus, the purpose of this study is to provide the first national estimate of the prevalence of type 2 diabetes and investigate its correlates. A randomly stratified nationally sample of 1001 adults aged 18-80 participated in the study. Only 950 subjects completed the study. All subjects were free of any diseases (known diabetes, kidney, liver), medication and supplementation. The overall prevalence of diabetes and pre-diabetes based on WHO criteria was 9.2% and 16.3%, respectively. After adjusting for age, energy intake, smoking and physical activity participants with obesity (BMI) (OR=2.00, P<0.001), waist circumference (WC) (OR=2.08, P<0.001), hypertension (HT) (OR=1.99, P<0.001) and hypercholesterolemia (HC) (OR=2.07, P<0.007) were most likely to develop T2DM compared with the normal ones. The odds of having diabetes were also found significant between subjects with high levels of triglycerides (TG) (OR=1.49, P<0.007), compared with the normal ones and between subjects with low levels of HDL (OR=1.44, P<0.008) compared with the ones with high levels of HDL. The prevalence of type 2 diabetes in Cyprus is relatively medium-high. However, the pre-diabetes rates are very high showing a promising increase toward total rates of type 2 diabetes. Obesity, HT, WC, TG, HC and low HDL are all strong correlates of type 2 diabetes. Healthy education programs should be initiated for young and older-aged people and those with described abnormal risk factors.

  13. Regulatory T cell-associated activity in photopheresis-induced immune tolerance in recent onset type 1 diabetes children

    PubMed Central

    Jonson, C-O; Pihl, M; Nyholm, C; Cilio, C M; Ludvigsson, J; Faresjö, M

    2008-01-01

    Extracorporeal photochemotherapy (ECP) has demonstrated immunological effects. The proposed cytotoxic lymphocyte antigen 4 (CTLA-4) involvement, together with forkhead box P3 (FoxP3) and transforming growth factor (TGF)-β are associated with regulatory T cell activity. The aim of the study was to evaluate the regulatory T cell-associated effect of ECP in recent onset type 1 diabetic (T1D) children. Children (n = 20) with T1D received photopheresis 8-methoxypsoralen + ECP or placebo + shampheresis. Peripheral blood mononuclear cells (PBMC) collected pretreatment (day 1) and post-treatment (day 90) were stimulated with phytohaemagglutinin (PHA) and T1D-associated glutamic acid decarboxylase 65 (GAD65) peptide a.a. 247–279. CTLA-4, sCTLA-4, FoxP3 and TGF-β mRNA transcription was quantified. Photopheresis-treated individuals' relative mRNA expression was generally maintained during the course of the study. Placebo individuals increased in spontaneous CTLA-4 mRNA (P< 0·05) but decreased in expression after stimulation with GAD65-peptide (P< 0·05) and PHA (P< 0·05). Spontaneous TGF-β (P< 0·05) increased whereas PHA- (P< 0·01) and GAD65-peptide (P< 0·01)-induced TGF-β expression decreased in the placebo group, whereas it was maintained in the treated group. Without intervention, expression of CTLA-4 and TGF-β, stimulated with PHA and GAD65 peptide, decreased with time, with a parallel reduction of GAD65-peptide and PHA-stimulated TGF-β expression. These parameters were counteracted by ECP. In conclusion, our results indicate that ECP maintains regulatory T cell-associated activity in recent-onset T1D. PMID:18549445

  14. Life Course Socioeconomic Transition and its Association with Early Onset Type 2 Diabetes: Protocol for a Sequential Exploratory Mixed Method Study

    PubMed Central

    Raman, V Kutty; Nochikattil, Santhosh Kumar

    2016-01-01

    Introduction The prevalence of early onset type 2 diabetes (Diabetes below the age of 45 years) is increasing worldwide. Transition in socio-economic position–i.e. Life Course Socio-Economic Transition (LSET) - may contribute to the development of early onset T2D through complex processes involving economic and occupational opportunities as well as individual life style choices. Aim To develop and validate the life course socioeconomic transition questionnaire and to know the association between life courses socioeconomic transition and early onset type 2 diabetes. Materials and Methods This study follows sequential exploratory mixed method study design. It consists of one qualitative strand followed by two quantitative strands. Qualitative strand consist of in- depth interview among the community dwellers to develop a tool for measuring LSET. Two quantitative strands consist of the validation of the questionnaire by conducting cross-sectional survey among 200 randomly selected community dwellers and a hospital based case control study using the same questionnaire. Results Those who have a history of lower SEP during his childhood period and enjoying higher SEP during his adulthood period have an increased risk for developing type 2 diabetes at their younger age (18-45 years). Conclusion This study will help to develop a validated life course socioeconomic transition questionnaire and application of that tool in an epidemiological study. PMID:27504317

  15. Diabetes

    MedlinePlus

    ... version of this page please turn Javascript on. Diabetes What is Diabetes? Too Much Glucose in the Blood Diabetes means ... high, causing pre-diabetes or diabetes. Types of Diabetes There are three main kinds of diabetes: type ...

  16. Walking and type 2 diabetes risk using CANRISK scores among older adults.

    PubMed

    Johnson, Steven T; Eurich, Dean T; Lytvyak, Ellina; Mladenovic, Ana; Taylor, Lorian M; Johnson, Jeffrey A; Vallance, Jeff K

    2017-01-01

    The objective of this study was to determine the association between pedometer-assessed steps and type 2 diabetes risk using the Public Health Agency of Canada-developed 16-item Canadian Diabetes Risk Questionnaire (CANRISK) among a large population-based sample of older adults across Alberta, Canada. To achieve our study objective, adults without type 2 diabetes (N = 689) aged 55 years and older provided demographic data and CANRISK scores through computer-assisted telephone interviews between September and November 2012. Respondents also wore a step pedometer over 3 consecutive days to estimate average daily steps. Logistic regression was used to assess the association between achieving 7500 steps/day and risk of diabetes (low vs. moderate and high). Overall, 41% were male, average age was 63.4 (SD 5.5) years, body mass index was 26.7 (SD 5.0) kg/m(2), and participants averaged 5671 (SD 3529) steps/day. All respondents indicated they were capable of walking for at least 10 min unassisted. CANRISK scores ranged from 13-60, with 18% in the low-risk category (<21). After adjustment, those not achieving 7500 steps/day (n = 507) were more than twice as likely to belong to the higher risk categories for type 2 diabetes compared with those walking ≥7500 steps/day (n = 182) (73.6% vs. 26.4%; odds ratio: 2.37; 95% confidence interval: 1.58 - 3.57). Among older adults without diabetes, daily steps were strongly and inversely associated with diabetes risk using the CANRISK score. Walking remains an important modifiable risk factor target for type 2 diabetes and achieving at least 7500 steps/day may be a reasonable target for older adults.

  17. Statin therapy reduces the likelihood of suboptimal blood pressure control among Ugandan adult diabetic patients

    PubMed Central

    Lumu, William; Kampiire, Leaticia; Akabwai, George Patrick; Kiggundu, Daniel Ssekikubo; Kibirige, Davis

    2017-01-01

    Background Hypertension is one of the recognized risk factors of cardiovascular diseases in adult diabetic patients. High prevalence of suboptimal blood pressure (BP) control has been well documented in the majority of studies assessing BP control in diabetic patients in sub-Saharan Africa. In Uganda, there is a dearth of similar studies. This study evaluated the prevalence and correlates of suboptimal BP control in an adult diabetic population in Uganda. Patients and methods This was a cross-sectional study that enrolled 425 eligible ambulatory adult diabetic patients attending three urban diabetic outpatient clinics over 11 months. Data about their sociodemographic characteristics and clinical history were collected using pre-tested questionnaires. Suboptimal BP control was defined according to the 2015 American Diabetes Association standards of diabetes care guideline as BP levels ≥140/90 mmHg. Results The mean age of the study participants was 52.2±14.4 years, with the majority being females (283, 66.9%). Suboptimal BP control was documented in 192 (45.3%) study participants and was independently associated with the study site (private hospitals; odds ratio 2.01, 95% confidence interval 1.18–3.43, P=0.01) and use of statin therapy (odds ratio 0.5, 95% confidence interval 0.26–0.96, P=0.037). Conclusion Suboptimal BP control was highly prevalent in this study population. Strategies to improve optimal BP control, especially in the private hospitals, and the use of statin therapy should be encouraged in adult diabetic patients. PMID:28260908

  18. Prevalence of Type 2 Diabetes among High-Risk Adults in Shanghai from 2002 to 2012

    PubMed Central

    Hou, Xuhong; Lu, Huijuan; Shen, Yixie; Chen, Ruihua; Fang, Pingyan; Yu, Hong; Li, Ming; Zhang, Feng; Chen, Haibing; Yu, Haoyong; Zhou, Jian; Liu, Fang; Bao, Yuqian; Jia, Weiping

    2014-01-01

    Objective The objective of this study was to evaluate the trend and prevalence of prediabetes and diabetes among high-risk adults in Shanghai from 2002 to 2012. Methods From 2002 to 2012, 10043 subjects with known risk factors for diabetes participated in the diabetes-screening project at the Shanghai Sixth People’s Hospital of Shanghai Jiao Tong University. All participants were asked to complete a nurse-administered standard questionnaire concerning age, sex, smoking status, and personal and family histories of diabetes, cardiovascular disease, stroke, hypertension and other diseases. The participants’ body mass index scores, blood pressures and blood glucose levels at 0, 30, 60, 120 and 180 min were measured in response to a 75 g oral glucose tolerance test. Results The overall prevalence of diabetes increased from 27.93% to 34.78% between 2002 and 2012 in high-risk subjects. The study also showed that the prevalence increased much faster in male compared to female subjects. Specifically, an increased rate was seen in middle-aged men, with no change observed in middle-aged females over the eleven-year period. Conclusion This study showed that sex, age, parental diabetic history, and being overweight were associated with an increased risk for diabetes in high-risk people. Therefore, as prediabetes and diabetes are highly prevalent in people with multiple diabetes risk factors in Shanghai, screening programs targeting these individuals may be beneficial. PMID:25047241

  19. Early prediction of new-onset diabetes mellitus by fifth-day fasting plasma glucose, pulse pressure, and proteinuria.

    PubMed

    Rodrigo, E; Santos, L; Piñera, C; Quintanar, J A; Ruiz, J C; Fernández-Fresnedo, G; Palomar, R; Gómez-Alamillo, C; Arias, M

    2011-01-01

    Renal transplant recipients are at high risk of cardiovascular disease (CVD). New-onset diabetes mellitus after transplantation (NODAT) contributes to the risk of CVD, reducing graft and patient survival. To improve outcome of kidney transplant recipients, it is of great interest to identify those patients who will develop NODAT. The aim of our study was to explore the predictive value of fifth-day fasting plasma glucose (FPG), third-month proteinuria, and pulse pressure (PP) for NODAT development. We analyzed 282 non-previously-diabetic kidney transplants in our center. Fifth-day FPG, PP, and third-month 24-hour proteinuria were collected. NODAT was defined at month 12 according to the "consensus guidelines": symptoms of diabetes plus casual glucose concentrations ≥ 200 mg/dL or FPG ≥ 126 mg/dL. Some 46 patients (16.3%) developed NODAT at month 12. Fifth-day FPG (133 ± 35 vs 108 ± 16 mg/dL, P < .001) and PP (57 ± 17 vs 49 ± 15 mm Hg, P = .007) were significantly higher in patients at risk for NODAT, but there was no difference in third-month proteinuria (652 ± 959 vs 472 ± 1336 mg, P = .390). A multivariate regression model showed an increased risk for NODAT associated with recipient age, body mass index, smoking habit, and a fifth-day FPG ≥ 126 mg/dL (relative risk 4.784, 95% confidence interval 2.121-10.788, P = .0002). The negative predictive value of a fifth-day FPG ≥ 126 mg/dL for predicting 1-year NODAT was 89.4%. Fifth-day FPG was independently related to NODAT development. The detection of a fifth-day FPG ≥ 126 mg/dL increases the risk of suffering NODAT more than 4 times. Fifth-day FPG < 126 mg/dL allows us to identify a transplant population with a low risk (near 10%) for NODAT.

  20. Timing of onset of evening activity of adult chinese rose beetles (Coleoptera: Scarabaeidae)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adult Chinese rose beetles, Adoretus sinicus (Burmeister) (Coleoptera: Scarabaeidae: Adoretini), present in China, Taiwan, Indonesia, Cambodia, Laos, Singapore, Thailand, Vietnam, the Marianas Islands, the Caroline Islands, and the Hawaiian Islands, are nighttime defoliators that feed on a wide vari...

  1. Glomerular Filtration Rate and Urine Albumin to Creatinine Ratio Associated With Hearing Impairment Among Korean Adults With Diabetes

    PubMed Central

    Cho, Yunji; Kim, Do Hoon; Choi, June; Lee, Joo Kyung; Roh, Yong-Kyun; Nam, Hyo-Yun; Nam, Ga-Eun; Kim, Dong-Won; Lee, Seung-Hyun; Lee, Chung-Woo; Han, Kyungdo; Park, Yong-Gyu

    2016-01-01

    Abstract The objective of this study was to examine the association of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR) with hearing impairment among diabetic adults in Korea. The study was based on data from Korea National Health and Nutrition Examination Survey 2011 to 2012. Participants were 1206 diabetic adults, aged over 19 years, who completed audiometric testing supervised by nationally certified clinicians. Hearing impairment was defined in three grades: no hearing impairment (pure-tone average 0–25 dB), slight hearing impairment (26–40 dB), and disabling hearing impairment (>40 dB) in the better ear at frequencies 0.5, 1, 2, 3, 4 and 6 kHz. Using logistic regression, risk of hearing impairment was assessed after having controlled for confounding factors. Higher levels of ACR and lower levels of eGFR correlated with an increase in percentage of disabling hearing impairment both unilaterally and bilaterally (P < 0.001). Controlling for possible confounding covariates, odds ratios for hearing impairment showed tendency to increase in higher ACR groups (P for trend = 0.029). Similar pattern was examined between eGFR and hearing impairment (P for trend = 0.006). Odds ratios were 1.981 (1.146, 3.424) for ACR Q4 and 2.773 (1.286, 5.983) for eGFR < 60 mL/min. Fall in eGFR and rise in ACR correlated with severity of hearing impairment. The association existed independently of age, sex, body mass index (BMI), smoking, drinking, exercise, new onset of diabetes, education, income, mental stress, noise exposure, and metabolic syndrome. PMID:27124027

  2. A Rare Case of Adult Onset Intussusception Complicated By Narcotic Dependence

    PubMed Central

    Khan, Saira J; Desmarais, Ashley M; Joseph, Bellal

    2017-01-01

    This report describes a rare case of adult intussusception in a patient with a history of a Roux-en-Y gastric bypass procedure; complicated by a history of narcotic abuse, methadone dependence, and methamphetamine abuse. Adult patients who have undergone a Roux-en-Y gastric bypass procedure may be at an increased risk of developing intussusception, and clinicians involved in their care should be aware of this potential complication. PMID:28191368

  3. Longitudinal analysis of hepatic transcriptome and serum metabolome demonstrates altered lipid metabolism following the onset of hyperglycemia in spontaneously diabetic biobreeding rats

    PubMed Central

    Hessner, Martin J.; Jia, Shuang; Åkesson, Lina; Stenlund, Hans; Moritz, Thomas; La Torre, Daria; Lernmark, Åke

    2017-01-01

    Type 1 diabetes is associated with abberations of fat metabolism before and after the clinical onset of disease. It has been hypothesized that the absence of the effect of insulin in the liver contributes to reduced hepatic fat synthesis. We measured hepatic gene expression and serum metabolites before and after the onset of hyperglycemia in a BioBreeding rat model of type 1 diabetes. Functional pathway annotation identified that lipid metabolism was differentially expressed in hyperglycemic rats and that these pathways significantly overlapped with genes regulated by insulin. 17 serum metabolites significantly changed in concentration. All but 2 of the identified metabolites had previously been reported in type 1 diabetes, and carbohydrates were overall the most upregulated class of metabolites. We conclude that lack of insulin in the liver contributes to the changes in fat metabolism observed in type 1 diabetes. Further studies are needed to understand the clinical consequences of a lack of insulin in the liver in patients with type 1 diabetes. PMID:28192442

  4. Inadvertent Skipping of Steroids in Septic Shock Leads to a Diagnosis of Adult Onset Still’s Disease

    PubMed Central

    Sethuraman, Vinoth K; Balasubramanian, Kavitha; Aghoram, Rajeswari

    2017-01-01

    Adult onset Still’s disease is uncommon in middle-aged and elderly individuals and can rarely present with shock; shock is usually associated with disseminated intravascular coagulation, multiorgan dysfunction syndrome or acute respiratory distress syndrome. We report a post-menopausal woman with arthritis, fever, pneumonitis and hypotension which was managed as septic shock. Steroids were inadvertently missed during the second day of hospitalization in the intensive care unit. Persistence of hypotension on inotropes, with normal renal, hepatic and neurological function and recurrence of fever when steroids were skipped, led to suspicion of an inflammatory disorder. A diagnosis of Still’s disease may be entertained in postmenopausal women with polyarthritis, rash, and fever with leukocytosis. Sepsis is mimicked, and multiple antibiotics use is common before the diagnosis of such an entity is made. Shock is rare in adult onset Still’s disease and is not necessarily associated with disseminated intravascular coagulation, acute respiratory distress syndrome, or multiorgan dysfunction. PMID:28191382

  5. GC-MS metabolomic analysis reveals significant alterations in cerebellar metabolic physiology in a mouse model of adult onset hypothyroidism.

    PubMed

    Constantinou, Caterina; Chrysanthopoulos, Panagiotis K; Margarity, Marigoula; Klapa, Maria I

    2011-02-04

    Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.

  6. Adult-Onset Still’s Disease: Still a Serious Health Problem (a Case Report and Literature Review)

    PubMed Central

    Agha-Abbaslou, Mojgan; Bensaci, Ana Maria; Dike, Oluchi; Poznansky, Mark C.; Hyat, Arooj

    2017-01-01

    Patient: Female, 53 Final Diagnosis: Adult-onset Still’s Disease Symptoms: Abdominal pain • fever Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare disease Background: Adult-onset Still’s Disease (AOSD) is a rare systemic inflammatory disease accompanied by a triad of spiking fever, maculopapular exanthema, and arthralgia. To date, there is no definite laboratory or imaging test available for diagnosing AOSD, and the diagnosis is one of exclusion, which can be very challenging. Case Report: We report on the case of a 53-year-old female who presented with fever, arthralgia, and abdominal pain. Her initial laboratory tests showed elevated AST and ALT, and normal leukocytes with bandemia. During her hospitalization, we evaluated the patient for other potential differential diagnoses. After an extensive workup, the patient was diagnosed with AOSD based on Yamaguchi criteria. Her serum ferritin levels were measured and found to be markedly elevated, which is a non-specific finding in AOSD patients. Conclusions: This case highlights the important role of a detailed history and physical examination for timely diagnosis of AOSD to prevent complications and improve patient’s prognosis. PMID:28154368

  7. Prevalence and risk factors of diabetes mellitus among adults in Jaffna District.

    PubMed

    Amarasinghe, S; Balakumar, S; Arasaratnam, V

    2015-09-01

    A cross sectional descriptive study was carried out to determine the prevalence and risk factors of diabetes mellitus among adults in Jaffna District. Multistage stratified cluster sampling technique was employed to select 544 participants. An interviewer administrated questionnaire was used. Anthropometric and blood pressure (BP) measurements were recorded and biochemical parameters were analysed. Response rate was 95.3%. Of them, 224 (43.8%) were male. The prevalence of diabetes mellitus was 16.4% (95% CI: 13.3- 19.9); in males 19.6% (95% CI: 14.6-25.4) and in females 13.9% (95% CI: 10.1-18.5). Of the diabetics, 27.4% were previously undiagnosed. In the final multivariable model, participants with family history of diabetes were 3.5 times (p<0.001) more likely and those with high waist hip ratio were 2 times (p=0.009) more likely to develop diabetes mellitus.

  8. The impact of cytomegalovirus infection on new-onset diabetes mellitus after kidney transplantation: a review on current findings

    PubMed Central

    Einollahi, Behzad; Motalebi, Mohsen; Salesi, Mahmood; Ebrahimi, Mehrdad; Taghipour, Mehrdad

    2014-01-01

    Context: New onset diabetes mellitus after transplantation (NODAT) increases the risk of cardiovascular disease, rate of infections, graft rejection and graft loss as well as decreases patient and graft survival rates. There is a controversy surrounding the impact of cytomegalovirus (CMV) infection in the development of NODAT. This meta-analysis aims to identify the role of CMV infection leading to the development of NODAT in kidney recipient patients. Evidence Acquisitions: We searched several electronic databases, including PubMed, Embase, Medline, Scopus, Trip Database and Google Scholar for studies that completely fulfill our criteria between January 1990 and January 2014 Results: Seven studies with 1389 kidney transplant patients were included in this metaanalysis.The mean age of patients ranged from 42.8 to 48.8 years and males made up 53% to 75% of patients in the cohort studies. The incidence of NODAT varies from 14.3% to 27.1% in these studies. Overall adj OR was 1.94 [exp (0.66)] with a 95% CI of 1.26-2.98 [exp (0.23) and (1.09)]. There was no significant publication bias based on the Begg’s and Egger’s test (p value = 0.17 and 0.54, respectively). Conclusions: Our study showed that CMV infection is a risk factor for increasing incidence of NODAT. Thus, prophylaxis against CMV infection after kidney transplantation is strongly suggested. However, further clinical trials and cohorts are needed to confirm this association. PMID:25374883

  9. Genome-Wide Association Study Identifies Pharmacogenomic Loci Linked with Specific Antihypertensive Drug Treatment and New-Onset Diabetes

    PubMed Central

    Chang, Shin-Wen; McDonough, Caitrin W.; Gong, Yan; Johnson, Todd A.; Tsunoda, Tatsuhiko; Gamazon, Eric R.; Perera, Minoli A.; Takahashi, Atsushi; Tanaka, Toshihiro; Kubo, Michiaki; Pepine, Carl J.; Johnson, Julie A.; Cooper-DeHoff, Rhonda M.

    2016-01-01

    We conducted a discovery genome-wide association study with expression quantitative trait loci (eQTL) annotation of new-onset diabetes (NOD) among European Americans, who were exposed to a calcium channel blocker-based strategy (CCB strategy) or a β-blocker-based strategy (β-blocker strategy) in the INternational VErapamil SR Trandolapril STudy. Replication of the top signal from the SNP*treatment interaction analysis was attempted in Hispanic and African Americans, and a joint meta-analysis was performed (total 334 NOD cases and 806 matched controls). PLEKHH2 rs11124945 at 2p21 interacted with antihypertensive exposure for NOD (meta-analysis p=5.3×10−8). rs11124945 G allele carriers had lower odds for NOD when exposed to the β-blocker strategy compared with the CCB strategy [OR=0.38 (0.24-0.60), p=4.0×10−5], while A/A homozygotes exposed to the β-blocker strategy had increased odds for NOD compared with the CCB strategy [OR=2.02 (1.39-2.92), p=2.0×10−4]. eQTL annotation of the 2p21 locus provides functional support for regulating gene expression. PMID:27670767

  10. Phenotypic and environmental factors associated with elevated autoantibodies at clinical onset of paediatric type 1 diabetes mellitus

    PubMed Central

    Ponsonby, Anne-Louise; Pezic, Angela; Cameron, Fergus J.; Rodda, Christine; Ellis, Justine A.; Kemp, Andrew S.; Carlin, John; Dwyer, Terence

    2012-01-01

    To examine possible determinants of autoantibody levels at type 1 diabetes mellitus (T1DM) onset. We assessed levels of glutamic acid decarboxylase 65 islet cell antigen (GADA) and anti-insulin antibodies (IAA) in 247 incident T1DM cases presenting <15 years of age in Melbourne from 1st March 2008 to 30th June 2010. 58.9% (142/241) of cases were GADA seropositive and 42.3% (94/222) were IAA seropositive. Factors associated with elevated IAA antibodies included younger age and red hair phenotype. Factors associated with elevated GAD antibodies included lower birthweight and recent eczema. Intriguingly, low recent or past sun exposure was only associated with elevated GADA levels among children presenting at age <5 years, not older (difference in effect, p<0.05 for 4 of 5 associations). These findings show that environmental and phenotypic factors are associated with autoantibody levels at time of presentation for T1DM. We recommend such environmental and phenoytypic factors should be examined in further detail. PMID:24371576

  11. Biochemical characterization of novel glucokinase mutations isolated from Spanish maturity-onset diabetes of the young (MODY2) patients.

    PubMed

    Estalella, Itziar; Garcia-Gimeno, Maria Adelaida; Marina, Alberto; Castaño, Luis; Sanz, Pascual

    2008-01-01

    Mature-onset diabetes of the young, type 2 (MODY2) is associated with mutations in the glucokinase (GCK) gene that result in impaired glucokinase activity. Although more than 200 inactivating GCK mutations have been reported, only less than 20% of these mutations have been functionally characterized. In this work, we describe the biochemical characterization of six missense glucokinase mutations associated with MODY2 from Spanish patients, namely, Y61S, V182L, C233R, E265K, A379V, and K420E. All these mutations produced enzymes that presented reduced enzymatic activity in various degrees, from a mild affectation (K420E) to a more severe effect (C233R). Mutation severity correlated with the importance of the structural changes introduced by the mutations. For example, C233R affected a critical residue of the active center of the enzyme and rendered a protein with undetectable enzymatic activity. These data add new information on the structure-function relationship of human glucokinase.

  12. Mechanisms of diabetic autoimmunity: I--the inductive interface between islets and the immune system at onset of inflammation.

    PubMed

    Askenasy, Nadir

    2016-04-01

    The mechanisms of autoimmune reactivity onset in type 1 diabetes (T1D) remain elusive despite extensive experimentation and discussion. We reconsider several key aspects of the early stages of autoimmunity at four levels: islets, pancreatic lymph nodes, thymic function and peripheral immune homeostasis. Antigen presentation is the islets and has the capacity to provoke immune sensitization, either in the process of physiological neonatal β cell apoptosis or as a consequence of cytolytic activity of self-reactive thymocytes that escaped negative regulation. Diabetogenic effectors are efficiently expanded in both the islets and the lymph nodes under conditions of empty lymphoid niches during a period of time coinciding with a synchronized wave of β cell apoptosis surrounding weaning. A major drive of effector cell activation and expansion is inherent peripheral lymphopenia characteristic of neonates, though it remains unclear when is autoimmunity triggered in subjects displaying hyperglycemia in late adolescence. Our analysis suggests that T1D evolves through coordinated activity of multiple physiological mechanisms of stimulation within specific characteristics of the neonate immune system.

  13. Cross-sectional study of glycemic control among adults with type 2 diabetes.

    PubMed

    Amarasekara, Amarasekara Appuhamillage Thamara Dilhani; Fongkaew, Warunee; Wimalasekera, Savithri Wasundara; Turale, Sue; Chanprasit, Chawapornpan

    2015-06-01

    Type 2 diabetes mellitus is a chronic condition, a global concern, and a serious issue in Sri Lanka, where there is little data regarding the influence of dietary control, exercise, and adherence to medication behaviors among adults diabetes. In this cross-sectional, descriptive study, we identified current factors influencing glycemic control and glycemic control behavior among adults with diabetes. A total of 230 people attending diabetes clinics in a tertiary hospital and a primary care institute were administered the self-report Diabetes Information Form, assessing their socioeconomic and medical information and glycemic control behaviors. Data were analyzed by frequency distribution, percentages, mean scores, and standard deviation. The results indicated that most participants had not achieved the recommended fasting blood glucose level (< 126 mg/dL). Although dietary control was practised by 72%, regular exercise was not practised by 85%, and while 77% reported adhering to regular medication, they still had poor glycemic control. The findings highlight the need for health professionals to adopt new strategies for diabetes education to overcome issues related to misconceptions and barriers in providing diabetes care in Sri Lanka.

  14. Latent autoimmune diabetes in adults: definition, prevalence, beta-cell function, and treatment.

    PubMed

    Stenström, Gunnar; Gottsäter, Anders; Bakhtadze, Ekaterine; Berger, Bo; Sundkvist, Göran

    2005-12-01

    Latent autoimmune diabetes in adults (LADA) is a disorder in which, despite the presence of islet antibodies at diagnosis of diabetes, the progression of autoimmune beta-cell failure is slow. LADA patients are therefore not insulin requiring, at least during the first 6 months after diagnosis of diabetes. Among patients with phenotypic type 2 diabetes, LADA occurs in 10% of individuals older than 35 years and in 25% below that age. Prospective studies of beta-cell function show that LADA patients with multiple islet antibodies develop beta-cell failure within 5 years, whereas those with only GAD antibodies (GADAs) or only islet cell antibodies (ICAs) mostly develop beta-cell failure after 5 years. Even though it may take up to 12 years until beta-cell failure occurs in some patients, impairments in the beta-cell response to intravenous glucose and glucagon can be detected at diagnosis of diabetes. Consequently, LADA is not a latent disease; therefore, autoimmune diabetes in adults with slowly progressive beta-cell failure might be a more adequate concept. In agreement with proved impaired beta-cell function at diagnosis of diabetes, insulin is the treatment of choice.

  15. Impact of behavioral interventions in the management of adults with type 2 diabetes mellitus.

    PubMed

    Cox, Daniel J; Gill Taylor, Ann; Dunning, Elizabeth S; Winston, Mary C; Luk Van, Ingrid L; McCall, Anthony; Singh, Harsimran; Yancy, William S

    2013-12-01

    Research on the role of behavior change as an efficacious intervention for adults with type 2 diabetes is evolving. Searching PubMed and Ovid Medline, we identified and reviewed primarily randomized controlled trials from 2010 to 2013 of adults managing type 2 diabetes without insulin. All studies are evaluated in terms of the rigor of their design and their impact on glycosylated hemoglobin. The most efficacious interventions appear to be low-carbohydrate/glycemic load diets, combined aerobic and resistance training, and self-monitoring of blood glucose, which educates patients about the impact of their food selections and physical activity on their blood glucose.

  16. Adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia: report of five cases and a new mutation.

    PubMed

    Kleinfeld, Kirk; Mobley, Bret; Hedera, Peter; Wegner, Adam; Sriram, Subramaniam; Pawate, Siddharama

    2013-02-01

    The objective of this work is to report on a series of five patients with adult-onset leukoencephalopathy with neuroaxonal spheroids and pigmented glia (ALSP). ALSP is a rare adult-onset leukodystrophy, which encompasses hereditary diffuse leukoencephalopathy with axonal spheroids and pigmentary orthochromatic leukodystrophy. This was a retrospective chart review and literature review. Five previously healthy women presented with a rapidly progressive neurological disorder at ages 39, 37, 40, 30, and 47, respectively. All five individuals were initially diagnosed as suffering from multiple sclerosis. The clinical courses of the five patients were dominated by progressive spastic quadriparesis (patient 5, newly diagnosed, has paraparesis at this time) and dementia. Brain magnetic resonance imaging (MRI) showed diffuse cerebral atrophy, corpus callosal atrophy, and diffuse T2 hyperintensities in the subcortical and periventricular white matter with no gadolinium enhancing lesions. Three patients showed involvement of pyramidal tracts from motor cortex to the brainstem. Cerebrospinal fluid was normal in all cases. Diagnosis of ALSP was established by biopsy (two cases) and autopsy (two cases). Histopathology showed the presence of neuroaxonal spheroids in all four cases and pigmented glia in three. In the fifth case, diagnosis was established by genetic analysis alone that showed a disease-causing mutation in the colony-stimulating factor 1 receptor (CSF1R) gene. Genetic analysis was done in three patients with available DNA, and identified the disease-causing mutation in all three, including a novel mutation F828S. ALSP may be suspected in adults with rapid to subacute progression of neurological disease when (1) MRI shows corpus callosal atrophy on a background of generalized brain atrophy and diffuse white matter disease without postcontrast enhancement, (2) CSF studies are normal, and (3) studies for systemic inflammatory diseases and specific leukodystrophies are

  17. Pulmonary Langerhans Cell Histiocytosis in an Adult Male Presenting with Central Diabetes Insipidus and Diabetes Mellitus: A Case Report.

    PubMed

    Choi, Yeun Seoung; Lim, Jung Soo; Kwon, Woocheol; Jung, Soon-Hee; Park, Il Hwan; Lee, Myoung Kyu; Lee, Won Yeon; Yong, Suk Joong; Lee, Seok Jeong; Jung, Ye-Ryung; Choi, Jiwon; Choi, Ji Sun; Jeong, Joon Taek; Yoo, Jin Sae; Kim, Sang-Ha

    2015-10-01

    Pulmonary Langerhans cell histiocytosis is an uncommon diffuse cystic lung disease in adults. In rare cases, it can involve extrapulmonary organs and lead to endocrine abnormalities such as central diabetes insipidus. A 42-year-old man presented with polyphagia and polydipsia, as well as a dry cough and dyspnea on exertion. Magnetic resonance imaging of the hypothalamic-pituitary system failed to show the posterior pituitary, which is a typical finding in patients with central diabetes insipidus. This condition was confirmed by a water deprivation test, and the patient was also found to have type 2 diabetes mellitus. Computed tomographic scanning of the lungs revealed multiple, irregularly shaped cystic lesions and small nodules bilaterally, with sparing of the costophrenic angles. Lung biopsy through video-assisted thoracoscopic surgery revealed pulmonary Langerhans cell histiocytosis. On a follow-up visit, only 1 year after the patient had quit smoking, clinical and radiological improvement was significant. Here, we report an uncommon case of pulmonary Langerhans cell histiocytosis that simultaneously presented with diabetes insipidus and diabetes mellitus.

  18. Acute post-disaster medical needs of patients with diabetes: emergency department use in New York City by diabetic adults after Hurricane Sandy

    PubMed Central

    Lee, David C; Gupta, Vibha K; Carr, Brendan G; Malik, Sidrah; Ferguson, Brandy; Wall, Stephen P; Smith, Silas W; Goldfrank, Lewis R

    2016-01-01

    Objective To evaluate the acute impact of disasters on diabetic patients, we performed a geospatial analysis of emergency department (ED) use by New York City diabetic adults in the week after Hurricane Sandy. Research design and methods Using an all-payer claims database, we retrospectively analyzed the demographics, insurance status, and medical comorbidities of post-disaster ED patients with diabetes who lived in the most geographically vulnerable areas. We compared the patterns of ED use among diabetic adults in the first week after Hurricane Sandy's landfall to utilization before the disaster in 2012. Results In the highest level evacuation zone in New York City, postdisaster increases in ED visits for a primary or secondary diagnosis of diabetes were attributable to a significantly higher proportion of Medicare patients. Emergency visits for a primary diagnosis of diabetes had an increased frequency of certain comorbidities, including hypertension, recent procedure, and chronic skin ulcers. Patients with a history of diabetes visited EDs in increased numbers after Hurricane Sandy for a primary diagnosis of myocardial infarction, prescription refills, drug dependence, dialysis, among other conditions. Conclusions We found that diabetic adults aged 65 years and older are especially at risk for requiring postdisaster emergency care compared to other vulnerable populations. Our findings also suggest that there is a need to support diabetic adults particularly in the week after a disaster by ensuring access to medications, aftercare for patients who had a recent procedure, and optimize their cardiovascular health to reduce the risk of heart attacks. PMID:27547418

  19. Does Inflammation Mediate Relationships Between Racial Identity and Onset of Menopause Among US Adults?

    PubMed

    Nowakowski, Alexandra C H; Graves, Katelyn Y

    2016-12-06

    We assess how well differences in ethnoracial background may predict timing of menopause among females in the USA and whether or not inflammatory biomarker levels appear to mediate these overall associations. We use data from the National Social Life, Health, and Aging Project (NSHAP) to model apparent net effects from race on menopausal onset, as well as possible mediating influences from the inflammatory biomarker C-reactive protein (CRP). Using continuous time event history analysis, we assess and frame overall relationships between race and menopausal age. We use structural equation modeling to assess potential mediating effects from CRP and to estimate direct and indirect components of these apparent effects. Our findings suggest that on average, black females experience menopause earlier than their peers of other racial backgrounds, and have higher inflammatory biomarker levels. Both black race and higher CRP have negative and significant direct associations with menopausal age. CRP appears to partially mediate the overall association between black race and earlier menopause. This apparent mediation persists with statistical controls for income, education, and body mass index. Our study concludes with recommendations for future research on racial identity, inflammation, and menopausal onset. We focus our recommendations on intersectional forms of inequality that may affect black females in later life.

  20. Nutrition label use is associated with lower longer-term diabetes risk in US adults.

    PubMed

    Kollannoor-Samuel, Grace; Shebl, Fatma M; Hawley, Nicola L; Pérez-Escamilla, Rafael

    2017-03-29

    Background: Regular nutrition label use may have important long-term health implications. To our knowledge, the role of nutrition label use in protecting against the development of chronic diseases was unexplored prospectively before this study.Objective: We tested the association between nutrition label use and risk of a future diabetes diagnosis in a multiethnic US cohort.Design: Data from the ongoing National Longitudinal Survey of Youth-1979 (NLSY79) were analyzed. From 2002 (baseline) to 5 follow-up time points (2004-2012), 7150 diabetes-free, multiethnic young adults were prospectively followed for a diagnosis of incident diabetes. Nutrition label use, diabetes diagnosis, time to diabetes diagnosis, and all covariates were self-reported.Results: Between January 2002 and September 2013, 430 participants (6.0%) were diagnosed with diabetes. A weighted, multivariable, extended Cox regression was conducted, which suggested that in nutrition label users, the HR of diabetes diagnosis risk decreased significantly with time (P-nutrition label use × time interaction < 0.05) compared with risk in nutrition label nonusers.Conclusions: There is an association between nutrition label use and diabetes risk in the longer term. However, additional longitudinal research with a robust dietary intake assessment is needed to test this hypothesis.

  1. Fatal enteritis necroticans (pigbel) in a diabetic adult.

    PubMed

    Gui, Lizhen; Subramony, Charu; Fratkin, Jonathan; Hughson, Michael D

    2002-01-01

    Enteritis necroticans is a segmental necrotizing infection of the jejunum and ileum caused by Clostridium perfringens, Type C. The disease occurs sporadically in parts of Asia, Africa, and the South Pacific, where it primarily affects children with severe protein malnutrition. The disease is extremely rare in developed countries, where it has been seen primarily in diabetics. Two cases have previously been reported in the United States, one in a child with poorly controlled Type 1 diabetes. A 66-year-old woman with a 12-year history of Type 2 diabetes mellitus developed severe abdominal pain and bloody diarrhea after eating a meal of turkey sausage. She died unattended at home. An autopsy showed peritonitis and segmental necrosis of the jejunum and ileum. Microscopic examination showed Gram-positive club-shaped bacilli consistent with Clostridia coating a necrotic mucosa. Products of cpa and cpb genes of C. perfringens, Type C were identified in the necrotic jejunum by polymerase chain reaction amplification.

  2. Effects of early-onset voluntary exercise on adult physical activity and associated phenotypes in mice.

    PubMed

    Acosta, Wendy; Meek, Thomas H; Schutz, Heidi; Dlugosz, Elizabeth M; Vu, Kim T; Garland, Theodore

    2015-10-01

    The purpose of this study was to evaluate the effects of early-life exercise on adult physical activity (wheel running, home-cage activity), body mass, food consumption, and circulating leptin levels in males from four replicate lines of mice selectively bred for high voluntary wheel running (High Runner or HR) and their four non-selected control (C) lines. Half of the mice were given wheel access shortly after weaning for three consecutive weeks. Wheel access was then removed for 52 days, followed by two weeks of adult wheel access for all mice. A blood sample taken prior to adult wheel testing was analyzed for circulating leptin concentration. Early-life wheel access significantly increased adult voluntary exercise on wheels during the first week of the second period of wheel access, for both HR and C mice, and HR ran more than C mice. During this same time period, activity in the home cages was not affected by early-age wheel access, and did not differ statistically between HR and C mice. Throughout the study, all mice with early wheel access had lower body masses than their sedentary counterparts, and HR mice had lower body masses than C mice. With wheel access, HR mice also ate significantly more than C mice. Early-life wheel access increased plasma leptin levels (adjusted statistically for fat-pad mass as a covariate) in C mice, but decreased them in HR mice. At sacrifice, early-life exercise had no statistically significant effects on visceral fat pad, heart (ventricle), liver or spleen masses (all adjusted statistically for variation in body mass). Results support the hypothesis that early-age exercise in mice can have at least transitory positive effects on adult levels of voluntary exercise, in addition to reducing body mass, and may be relevant for the public policy debates concerning the importance of physical education for children.

  3. Analysis of the glucokinase gene in Mexican families displaying early-onset non-insulin-dependent diabetes mellitus including MODY families.

    PubMed

    del Bosque-Plata, L; García-García, E; Ramírez-Jiménez, S; Cabello-Villegas, J; Riba, L; Gómez-León, A; Vega-Hernández, G; Altamirano-Bustamante, N; Calzada-León, R; Robles-Valdés, C; Mendoza-Morfín, F; Curiel-Pérez, O; Tusié-Luna, M T

    1997-11-12

    Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes, affecting 5% of the general population. Genetic factors play an important role in the development of the disease. While in other populations NIDDM is usually diagnosed after the fifth decade of life, in Mexico a large proportion of patients develop the disease at an early age (between the third and the fourth decade). In Caucasian population, mutations in the glucokinase gene, the TCF1, and TCF14 genes, have been identified in a subgroup of early-onset NIDDM patients denominated MODY (maturity-onset diabetes of the young), which show an autosomal dominant pattern of inheritance. As a first step in the molecular characterization of Mexican families displaying early-onset NIDDM we searched for mutations in the glucokinase gene through SSCP analysis and/or direct sequencing in 26 individuals from 22 independent families, where at least four can be classified as MODY. No mutations were detected in the exons or the intron-exon boundaries of the gene in any of the screened individuals. The phenotype and clinical profile of some of the studied patients is compatible with that of patients carrying mutations in the TCF1 or TCF14 genes, while others may carry mutations in different loci. Through computer simulation analysis we identified at least four informative families which will be used for further linkage studies.

  4. Association between Serum 25-hydroxyvitamin D Levels and Type 2 Diabetes in Korean Adults

    PubMed Central

    Nam, Hyun; Choi, Jin-Su; Kweon, Sun-Seog; Lee, Young-Hoon; Nam, Hae-Sung; Park, Kyeong-Soo; Ryu, So-Yeon; Choi, Seong-Woo; Oh, Su-Hyun; Kim, Sun A; Shin, Min-Ho

    2017-01-01

    Previous studies have suggested that a vitamin D deficiency increases the risk of type 2 diabetes. This study evaluated the association between serum vitamin D levels and type 2 diabetes in Korean adults. This study included 9,014 subjects (3,600 males and 5,414 females) aged ≥50 years who participated in the Dong-gu Study. The subjects were divided into groups in whom the serum vitamin D level was severely deficient (<10 ng/mL), deficient (10 to <20 ng/mL), insufficient (20 to <30 ng/mL) and sufficient (≥30 ng/mL). Type 2 diabetes was defined by a fasting blood glucose level of ≥126 mg/dL and/or an HbA1c proportion of ≥6.5% and/or self-reported current use of diabetes medication. Multiple logistic regression was performed to evaluate the association between vitamin D status and type 2 diabetes. The age- and sex-adjusted prevalence of type 2 diabetes was 22.6%, 22.5% and 18.4% and 12.7% for severely deficient, deficient, insufficient, and sufficient, respectively. Multivariate modeling revealed that subjects with insufficient or sufficient vitamin D levels were at a lower risk of type 2 diabetes than were subjects with deficient vitamin D levels [odds ratio (OR), 0.82; 95% confidence interval (CI), 0.71–0.94 and OR, 0.51; 95% CI, 0.35–0.74, respectively]. Higher serum vitamin D levels were associated with a reduced risk of diabetes in Korean adults, suggesting that vitamin D may play a role in the pathogenesis of diabetes. PMID:28184342

  5. Predictors of Adherence to Multiple Clinical Preventive Recommendations among Adults with Diabetes in Spain

    PubMed Central

    Jimenez-Trujillo, Isabel; Jiménez-García, Rodrigo; Esteban-Hernández, Jesus; Hernández-Barrera, Valentin; Carrasco Garrido, Pilar; Salinero-Fort, Miguel A.; Cardenas-Valladolid, Juan; López-de-Andrés, Ana

    2015-01-01

    Objective This study aims to describe adherence to seven clinical preventive services among Spanish adults with diabetes, to compare adherence with people without diabetes and to identify predictor of adherence to multiple practices among adults with diabetes. Design Cross-sectional study based on data obtained from the European Health Survey for Spain 2009 and the Spanish National Health Survey 2011. We analyzed those aged 40-69 years (n= 20,948). Diabetes status was self-reported. The study variables included adherence to blood pressure (BP) checkup, cholesterol measurement, influenza vaccination, dental examination, fecal occult blood test (FOBT), mammography and cytology. Independent variables included socio-demographic characteristics, variables related to health status and lifestyle factors. Results The study sample included 1,647 subjects with diabetes and 19,301 without. Over 90% had measured their BP and cholesterol in the last year, 44.4% received influenza immunization, 36.4% had a dental checkup within the year and only 8.1% underwent a FOBT. Among diabetic women 75.4% had received a mammography and 52.4% a cytology in the recommended periods. The adherence to BP and cholesterol measurements and influenza vaccination was significantly higher among those suffering diabetes and cytology and dental checkup were lower. Only 63.4% of people with diabetes had fulfilled half or more of the recommended practices. Female sex, higher educational level, being married or cohabiting, higher number of chronic conditions and number of physician visits increased the adherence to multiple preventive practices. For each unhealthy lifestyle reported the probability of having a higher adherence level decreased. Conclusions Acceptable adherence is found for BP and cholesterol checkups and mammography. Unacceptably low rates were found for influenza vaccine, dental care, cytology and FOBT. Moreover, preventive services are provided neither equitably nor efficiently so future

  6. Structure of the human glucokinase gene and identification of a missense mutation in a Japanese patient with early-onset non-insulin-dependent diabetes mellitus

    SciTech Connect

    Sakura, Hiroshi; Eto, Kazuhiro; Ueno, Hirohisa; Yazaki, Yoshio; Kadowaki, Takashi ); Kadowaki, Hiroko; Simokawa, Kotaro; Akanuma, Yasuo ); Koda, Naoya; Fukushima, Yoshimitsu )

    1992-12-01

    Glucokinase is thought to play a glucose-sensor role in the pancreas, and abnormalities in its structure, function, and regulation can induce diabetes. The authors isolated the human glucokinase gene, and determined its genomic structure including exon-intron boundaries. Structure of the glucokinase gene in human was very similar to that in rat. Then, by screening Japanese diabetic patients using polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) and direct-sequencing strategies, they identified a missense mutation substituting ariginine (AGG) for glycine (GGG) at position 261 in exon 7 of the glucokinase gene in a patient with early-onset non-insulin-dependent diabetes (NIDDM). 12 refs., 3 figs., 2 tabs.

  7. ATP1A3 Mutation in Adult Rapid-Onset Ataxia

    PubMed Central

    Sweadner, Kathleen J.; Toro, Camilo; Whitlow, Christopher T.; Snively, Beverly M.; Cook, Jared F.; Ozelius, Laurie J.; Markello, Thomas C.; Brashear, Allison

    2016-01-01

    A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the α3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid-onset dystonia-parkinsonism (RDP) with a similar age and speed of onset, as well as severe diseases of infancy. The patient’s ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4), a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1) deletes a motif with multiple copies and is unlikely to be causative. PMID:26990090

  8. ATP1A3 Mutation in Adult Rapid-Onset Ataxia.

    PubMed

    Sweadner, Kathleen J; Toro, Camilo; Whitlow, Christopher T; Snively, Beverly M; Cook, Jared F; Ozelius, Laurie J; Markello, Thomas C; Brashear, Allison

    2016-01-01

    A 21-year old male presented with ataxia and dysarthria that had appeared over a period of months. Exome sequencing identified a de novo missense variant in ATP1A3, the gene encoding the α3 subunit of Na,K-ATPase. Several lines of evidence suggest that the variant is causative. ATP1A3 mutations can cause rapid-onset dystonia-parkinsonism (RDP) with a similar age and speed of onset, as well as severe diseases of infancy. The patient's ATP1A3 p.Gly316Ser mutation was validated in the laboratory by the impaired ability of the expressed protein to support the growth of cultured cells. In a crystal structure of Na,K-ATPase, the mutated amino acid was directly apposed to a different amino acid mutated in RDP. Clinical evaluation showed that the patient had many characteristics of RDP, however he had minimal fixed dystonia, a defining symptom of RDP. Successive magnetic resonance imaging (MRI) revealed progressive cerebellar atrophy, explaining the ataxia. The absence of dystonia in the presence of other RDP symptoms corroborates other evidence that the cerebellum contributes importantly to dystonia pathophysiology. We discuss the possibility that a second de novo variant, in ubiquilin 4 (UBQLN4), a ubiquitin pathway component, contributed to the cerebellar neurodegenerative phenotype and differentiated the disease from other manifestations of ATP1A3 mutations. We also show that a homozygous variant in GPRIN1 (G protein-regulated inducer of neurite outgrowth 1) deletes a motif with multiple copies and is unlikely to be causative.

  9. Adult-onset cystic hygroma: A case report of rare entity

    PubMed Central

    Bahl, Sumit; Shah, Vandana; Anchlia, Sonal; Vyas, Siddharth

    2016-01-01

    Cystic hygroma is a benign congenital malformation of the lymphatic system that occurs in infant or children younger than 2 years of age. Although cystic hygroma is well recognized in pediatric practice, it seldom presents de novo in adulthood. These are commonly present in head and neck but can be present anywhere. Cystic hygroma is very rare in adults, but it should be considered in the differential diagnosis of adult neck swellings. Patients presenting with a painless, soft, fluctuant, and enlarging neck mass should have a careful history and physical examination along with radiological imaging to assist with diagnosis. Surgical intervention is the treatment of choice for this rare condition. Here, we are reporting a case of cystic hygroma in a 32-year-old male patient in the neck region. The objectives of this case report are to discuss the clinical presentation, diagnosis, histopathological findings and management of this malformation. PMID:27134456

  10. Adult-onset cystic hygroma: A case report of rare entity.

    PubMed

    Bahl, Sumit; Shah, Vandana; Anchlia, Sonal; Vyas, Siddharth

    2016-01-01

    Cystic hygroma is a benign congenital malformation of the lymphatic system that occurs in infant or children younger than 2 years of age. Although cystic hygroma is well recognized in pediatric practice, it seldom presents de novo in adulthood. These are commonly present in head and neck but can be present anywhere. Cystic hygroma is very rare in adults, but it should be considered in the differential diagnosis of adult neck swellings. Patients presenting with a painless, soft, fluctuant, and enlarging neck mass should have a careful history and physical examination along with radiological imaging to assist with diagnosis. Surgical intervention is the treatment of choice for this rare condition. Here, we are reporting a case of cystic hygroma in a 32-year-old male patient in the neck region. The objectives of this case report are to discuss the clinical presentation, diagnosis, histopathological findings and management of this malformation.

  11. A course on the transition to adult care of patients with childhood-onset chronic illnesses.

    PubMed

    Hagood, James S; Lenker, Claire V; Thrasher, Staci

    2005-04-01

    Children with special health care needs born today have a 90% chance of surviving into adulthood, making their transition to adult systems of care an issue that will affect almost all physicians. However, many adult generalists and specialists are not familiar with the management of chronic diseases that begin in childhood. While the public health system has made transition to appropriate adult care a priority, and many specialty organizations have endorsed this concept, there are no published studies addressing how the concept of transition can be taught to medical students or residents. The authors describe a one-week course for medical students, begun in 2001 at their institution, that addresses the transition for youth with special health care needs, emphasizing patient and family-centered care, cultural competence, and decision making in end-of-life issues. Cystic fibrosis, a common genetic disease with increasing life expectancy, is used as the model for the course. Involvement of interdisciplinary faculty, interviews with youth with special health care needs and family caregivers, readings from academic and nonacademic literature, and group discussions are presented as teaching methods. Key insights based on experience with the course are the need to include the voices of patients and families, the use of faculty from various professions and specialties to model interdisciplinary care, and the insight that problems specific to transition offer into contemporary health care financing. Future studies should measure the impact of such courses on students' knowledge of transition issues, and determine essential information required for physicians in practice.

  12. Invisible Victims: Delayed Onset Depression among Adults with Same-Sex Parents

    PubMed Central

    Sullins, D. Paul

    2016-01-01

    The relationship of elevated depression risk recently discovered among adult persons raised by same-sex parents with possible precipitating conditions in childhood has not previously been acknowledged. This study tests whether such inattention is supportable. Logistic regression based risk ratios were estimated from longitudinal measures of mental health outcomes observed in three waves (at ages 15, 22, and 28) of the US National Survey of Adolescent to Adult Health (n = 15,701). At age 28, the adults raised by same-sex parents were at over twice the risk of depression (CES-D: risk ratio 2.6, 95% CI 1.4–4.6) as persons raised by man-woman parents. These findings should be interpreted with caution. Elevated risk was associated with imbalanced parental closeness and parental child abuse in family of origin; depression, suicidality, and anxiety at age 15; and stigma and obesity. More research and policy attention to potentially problematic conditions for children with same-sex parents appears warranted. PMID:27313882

  13. Diagnosis and management of type 2 diabetes in adults: a review of the ICSI guideline.

    PubMed

    Gavi, Shai; Hensley, Jennifer

    2009-06-01

    Diabetes is a complex chronic disease that affects approximately 25% of people above the age of 60 in the United States. This poses a significant challenge to primary care physicians to provide optimal treatment plans to improve metabolic control and to minimize debilitating complications. This article provides a summary of the recent guideline published by the Institute for Clinical Systems Improvement (ICSI) for the Diagnosis and Management of Type 2 Diabetes Mellitus in Adults. The purpose of this guideline is to provide a comprehensive approach to the diagnosis and management of prediabetes and type 2 diabetes in adults. Management strategies from the evidence-based guideline will include recommendations for nutrition therapy, physical activity, self-management approaches, and pharmacologic agents.

  14. Food Insecurity and Food Choices in Rural Older Adults with Diabetes Receiving Nutrition Education via Telemedicine

    ERIC Educational Resources Information Center

    Homenko, Daria R.; Morin, Philip C.; Eimicke, Joseph P.; Teresi, Jeanne A.; Weinstock, Ruth S.

    2010-01-01

    Objective: To evaluate differences between rural older adults with diabetes reporting the presence or absence of food insecurity with respect to meal planning, preparation, shopping, obesity, and glycemic control after receiving nutrition counseling through telemedicine. Methods: Food insecurity data were obtained by telephone survey (n = 74).…

  15. Adults Living with Type 2 Diabetes: Kept Personal Health Information Items as Expressions of Need

    ERIC Educational Resources Information Center

    Whetstone, Melinda

    2013-01-01

    This study investigated personal information behavior and information needs that 21 adults managing life with Type 2 diabetes identify explicitly and implicitly during discussions of item acquisition and use of health information items that are kept in their homes. Research drew upon a naturalistic lens, in that semi-structured interviews were…

  16. Metals in Urine and Diabetes in U.S. Adults

    PubMed Central

    Guallar, Eliseo; Cowie, Catherine C.

    2016-01-01

    Our objective was to evaluate the relationship of urine metals including barium, cadmium, cobalt, cesium, molybdenum, lead, antimony, thallium, tungsten, and uranium with diabetes prevalence. Data were from a cross-sectional study of 9,447 participants of the 1999–2010 National Health and Nutrition Examination Survey, a representative sample of the U.S. civilian noninstitutionalized population. Metals were measured in a spot urine sample, and diabetes status was determined based on a previous diagnosis or an A1C ≥6.5% (48 mmol/mol). After multivariable adjustment, the odds ratios of diabetes associated with the highest quartile of metal, compared with the lowest quartile, were 0.86 (95% CI 0.66–1.12) for barium (Ptrend = 0.13), 0.74 (0.51–1.09) for cadmium (Ptrend = 0.35), 1.21 (0.85–1.72) for cobalt (Ptrend = 0.59), 1.31 (0.90–1.91) for cesium (Ptrend = 0.29), 1.76 (1.24–2.50) for molybdenum (Ptrend = 0.01), 0.79 (0.56–1.13) for lead (Ptrend = 0.10), 1.72 (1.27–2.33) for antimony (Ptrend < 0.01), 0.76 (0.51–1.13) for thallium (Ptrend = 0.13), 2.18 (1.51–3.15) for tungsten (Ptrend < 0.01), and 1.46 (1.09–1.96) for uranium (Ptrend = 0.02). Higher quartiles of barium, molybdenum, and antimony were associated with greater HOMA of insulin resistance after adjustment. Molybdenum, antimony, tungsten, and uranium were positively associated with diabetes, even at the relatively low levels seen in the U.S. population. Prospective studies should further evaluate metals as risk factors for diabetes. PMID:26542316

  17. Does the pancreatic volume reduction rate using serial computed tomographic volumetry predict new onset diabetes after pancreaticoduodenectomy?

    PubMed Central

    Yun, Sung Pil; Seo, Hyung-Il; Kim, Suk; Kim, Dong Uk; Baek, Dong Hoon

    2017-01-01

    Abstract Volume reduction of the pancreatic tissues following a pancreatectomy can lead to the deterioration of glucose homeostasis. This is defined as pancreatogenic diabetes mellitus (DM). The objective of this study was to investigate the occurrence of new-onset DM (NODM) and evaluate the risk factors, including the pancreas volume reduction rate in patients undergoing pancreaticoduodenectomy (PD). Sixty-six patients without preoperative DM underwent PD for periampullary tumors between August 2007 and December 2012 and were included in this analysis. These patients underwent follow-up tests and abdominal computed tomography (CT) scan 7 days, 6 months, 12 months, 24 months, and 36 months after the operation. The pancreas volume reduction rate was calculated by CT volumetry. The patients were divided into 2 groups according to the postoperative development of DM. After PD, newly diagnosed DM occurred in 16 patients (24.2%). The incidence of DM was highest among patients with carcinomas with an advanced T stage. The pancreatic volume reduction rate after 6 and 12 months in the NODM group was significantly higher than the normal glucose group in the univariate analysis. In the multivariate analysis, the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM (P = 0.002). This study suggests that the pancreatic volume reduction rate 6 months after PD was the only significant predictive factor for the development of NODM. CT volumetry of the pancreas may be useful as a predictor of NODM after PD. PMID:28353594

  18. Efficacy of Anakinra in Refractory Adult-Onset Still's Disease: Multicenter Study of 41 Patients and Literature Review.

    PubMed

    Ortiz-Sanjuán, Francisco; Blanco, Ricardo; Riancho-Zarrabeitia, Leyre; Castañeda, Santos; Olivé, Alejandro; Riveros, Anne; Velloso-Feijoo, María L; Narváez, Javier; Jiménez-Moleón, Inmaculada; Maiz-Alonso, Olga; Ordóñez, Carmen; Bernal, José A; Hernández, María V; Sifuentes-Giraldo, Walter A; Gómez-Arango, Catalina; Galíndez-Agirregoikoa, Eva; Blanco-Madrigal, Juan; Ortiz-Santamaria, Vera; del Blanco-Barnusell, Jordi; De Dios, Juan R; Moreno, Mireia; Fiter, Jordi; de los Riscos, Marina; Carreira, Patricia; Rodriguez-Valls, María J; González-Vela, M Carmen; Calvo-Río, Vanesa; Loricera, Javier; Palmou-Fontana, Natalia; Pina, Trinitario; Llorca, Javier; González-Gay, Miguel A

    2015-09-01

    Adult-onset Still's disease (AOSD) is often refractory to standard therapy. Anakinra (ANK), an interleukin-1 receptor antagonist, has demonstrated efficacy in single cases and small series of AOSD. We assessed the efficacy of ANK in a series of AOSD patients. Multicenter retrospective open-label study. ANK was used due to lack of efficacy to standard synthetic immunosuppressive drugs and in some cases also to at least 1 biologic agent. Forty-one patients (26 women/15 men) were recruited. They had a mean age of 34.4 ± 14 years and a median [interquartile range (IQR)] AOSD duration of 3.5 [2-6] years before ANK onset. At that time the most common clinical features were joint manifestations 87.8%, fever 78%, and cutaneous rash 58.5%. ANK yielded rapid and maintained clinical and laboratory improvement. After 1 year of therapy, the frequency of joint and cutaneous manifestations had decreased to 41.5% and to 7.3% respectively, fever from 78% to 14.6%, anemia from 56.1% to 9.8%, and lymphadenopathy from 26.8% to 4.9%. A dramatic improvement of laboratory parameters was also achieved. The median [IQR] prednisone dose was also reduced from 20 [11.3-47.5] mg/day at ANK onset to 5 [0-10] at 12 months. After a median [IQR] follow-up of 16 [5-50] months, the most important side effects were cutaneous manifestations (n = 8), mild leukopenia (n = 3), myopathy (n = 1), and infections (n = 5). ANK is associated with rapid and maintained clinical and laboratory improvement, even in nonresponders to other biologic agents. However, joint manifestations are more refractory than the systemic manifestations.

  19. Congenital and prolonged adult-onset deafness cause distinct degradations in neural ITD coding with bilateral cochlear implants.

    PubMed

    Hancock, Kenneth E; Chung, Yoojin; Delgutte, Bertrand

    2013-06-01

    Bilateral cochlear implant (CI) users perform poorly on tasks involving interaural time differences (ITD), which are critical for sound localization and speech reception in noise by normal-hearing listeners. ITD perception with bilateral CI is influenced by age at onset of deafness and duration of deafness. We previously showed that ITD coding in the auditory midbrain is degraded in congenitally deaf white cats (DWC) compared to acutely deafened cats (ADC) with normal auditory development (Hancock et al., J. Neurosci, 30:14068). To determine the relative importance of early onset of deafness and prolonged duration of deafness for abnormal ITD coding in DWC, we recorded from single units in the inferior colliculus of cats deafened as adults 6 months prior to experimentation (long-term deafened cats, LTDC) and compared neural ITD coding between the three deafness models. The incidence of ITD-sensitive neurons was similar in both groups with normal auditory development (LTDC and ADC), but significantly diminished in DWC. In contrast, both groups that experienced prolonged deafness (LTDC and DWC) had broad distributions of best ITDs around the midline, unlike the more focused distributions biased toward contralateral-leading ITDs present in both ADC and normal-hearing animals. The lack of contralateral bias in LTDC and DWC results in reduced sensitivity to changes in ITD within the natural range. The finding that early onset of deafness more severely degrades neural ITD coding than prolonged duration of deafness argues for the importance of fitting deaf children with sound processors that provide reliable ITD cues at an early age.

  20. Differential onset of infantile deprivation produces distinctive long-term effects in adult ex-laboratory chimpanzees (Pan troglodytes).

    PubMed

    Kalcher, Elfriede; Franz, Cornelia; Crailsheim, Karl; Preuschoft, Signe

    2008-12-01

    Maternal or social deprivation during early infancy inevitably produces social deficiencies in juvenile chimpanzees. Hypothesizing such deficiencies to persist into adulthood (a), and, as in humans, a sensitive period in early infancy for attachment formation (b), we predicted and found behavioral differences in resocialized adult ex-laboratory chimpanzees after about 20 years of solitary confinement depending on their age at onset of deprivation: early deprived (ED; mean: 1.2 years) chimpanzees engaged significantly less in social interactions, spent less time associated, and showed more nonsocial idiosyncrasies than did late deprived (LD; mean: 3.6 years) chimpanzees. In addition to these individual attributes relational qualities, specifically the combination of ED and LD chimpanzees within social groups, have an impact on social recovery. LDs can best exploit their social potential in the company of other LDs and EDs tend to stagnate in their recovery when socialized with other EDs.

  1. A Case of Adult-Onset Acute Rheumatic Fever With Long-Lasting Atrioventricular Block Requiring Permanent Pacemaker Implantation.

    PubMed

    Oba, Yusuke; Watanabe, Hiroaki; Nishimura, Yoshioki; Ueno, Shuichi; Nagashima, Takao; Imai, Yasushi; Shimpo, Masahisa; Kario, Kazuomi

    2015-01-01

    A 45-year-old hypertensive Japanese woman presented with epigastric pain on inspiration, fever, complete atrioventricular block and polyarthritis. Her antistreptolysin O levels were markedly elevated. A diagnosis of rheumatic fever was made according to the modified Jones criteria. She was prescribed loxoprofen sodium, which was partially effective for her extracardiac clinical symptoms. However, she had syncope due to complete atrioventricular block with asystole longer than 10 seconds. Consequently, we implanted a permanent pacemaker. Although we prescribed prednisolone, the efficacy of which was limited for the patient's conduction disturbance, the complete atrioventricular block persisted. In our systematic review of 12 similar cases, the duration of complete heart block was always transient and there was no case requiring a permanent pacemaker. We thus encountered a very rare case of adult-onset acute rheumatic fever with persistent complete atrioventricular block necessitating permanent pacemaker implantation.

  2. Acute pneumonitis in a patient with adult-onset disease after toclizumab treatment with good response to anakinra.

    PubMed

    Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Jara Chinarro, Beatriz; Espinosa Malpartida, María; Barbadillo Mateos, Carmen

    Pulmonary involvement in the form of acute pneumonitis in adult-onset Still's disease (AOSD) is an uncommon manifestation, with few cases reported in the literature. We report the case of a 61-year-old male with 3 years of AOSD evolution, treated with methotrexate (MTX) and half-dose corticosteroids, which debuted with symptoms of fever, dyspnea and dry cough after 3 weeks of receiving the first dose of tocilizumab (TCZ). In the follow-up study showed leukocytosis with left shift, elevated serum ferritin and C-reactive protein standard. The chest CT scan showed ground-glass pattern predominantly in central and upper lobes and the BAL shows an increase in the percentage of lymphocyte with normal subpopulations and negative cultures. MTX and TCM were suspended, prednisone was increased to 30mg/day and within a week Anakinra 100mg/day SC was iniciated, noting in a few days a progressive clinical, analytical and radiological improvement.

  3. Adult-onset presentation of a hyperornithinemia-hyperammonemia-homocitrullinuria patient without prior history of neurological complications.

    PubMed

    Tezcan, Kamer; Louie, Kristal T; Qu, Yong; Velasquez, Jorge; Zaldivar, Frank; Rioseco-Camacho, Natalia; Camacho, José Angel

    2012-01-01

    The Hyperornithinemia-Hyperammonemia-Homocitrullinuria (HHH) syndrome is a disorder of the urea cycle and ornithine degradation pathway caused by mutations in the mitochondrial ornithine transporter, ORNT1 (SLC25A15). In general, the majority of patients with HHH syndrome come to medical attention during infancy or early school years with symptoms such as learning disabilities, changes in cognitive development, spasticity, or liver dysfunction. In this report, we describe a 35-year-old male of Indian descent who was diagnosed with HHH syndrome after he presented to the emergency room with gastroenteritis, disorientation, and slurred speech. Molecular analysis revealed that this patient was heterozygous for two ORNT1 mutations, p.[Gly220Arg(+)Arg275X] (c.[658G>A(+)823C>T]) that had been previously reported in homozygous probands who presented during the first year of life. Cellular studies revealed that the ORNT1 p.Gly220Arg mutation was nonfunctional but targeted to the mitochondria. Given that this patient was a successful college graduate on a vegetarian diet without a prior history of learning or neurological impairment, additional factors such as gene redundancy, environmental, and epigenetic factors may have contributed to the delay in onset of presentation and lack of any previous symptoms. To the best of our knowledge, this is the first reported case of an adult-onset HHH syndrome presentation without a prior history of neurological or cognitive deficiency.

  4. Many faces of monogenic diabetes.

    PubMed

    Schwitzgebel, Valerie M

    2014-03-23

    Monogenic diabetes represents a heterogeneous group of disorders resulting from defects in single genes. Defects are categorized primarily into two groups: disruption of β-cell function or a reduction in the number of β-cells. A complex network of transcription factors control pancreas formation, and a dysfunction of regulators high in the hierarchy leads to pancreatic agenesis. Dysfunction among factors further downstream might cause organ hypoplasia, absence of islets of Langerhans or a reduction in the number of β-cells. Many transcription factors have pleiotropic effects, explaining the association of diabetes with other congenital malformations, including cerebellar agenesis and pituitary agenesis. Monogenic diabetes variants are classified conventionally according to age of onset, with neonatal diabetes occurring before the age of 6 months and maturity onset diabetes of the young (MODY) manifesting before the age of 25 years. Recently, certain familial genetic defects were shown to manifest as neonatal diabetes, MODY or even adult onset diabetes. Patients with neonatal diabetes require a thorough genetic work-up in any case, and because extensive phenotypic overlap exists between monogenic, type 2, and type 1 diabetes, genetic analysis will also help improve diagnosis in these cases. Next generation sequencing will facilitate rapid screening, leading to the discovery of digenic and oligogenic diabetes variants, and helping to improve our understanding of the genetics underlying other types of diabetes. An accurate diagnosis remains important, because it might lead to a change in the treatment of affected subjects and influence long-term complications.

  5. Glycated Hemoglobin and Incident Type 2 Diabetes in Singaporean Chinese Adults: The Singapore Chinese Health Study

    PubMed Central

    Bancks, Michael P.; Koh, Woon-Puay; Yuan, Jian-Min; Gross, Myron D.

    2015-01-01

    Background The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes. Methods Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999–2004) and had no cancer and no reported history of diabetes or cardiovascular disease events. Diabetes was defined as self-report of physician diagnosis, identified at the follow-up II visit (2006–2010). Results Hazard ratios (and 95% confidence intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox regression models and continuous HbA1c with cubic spline analysis. Compared to individuals with an HbA1c ≤ 5.7% (≤39 mmol/mol), individuals with HbA1c 5.8–5.9% (40–41 mmol/mol), 6.0–6.1% (42–43 mmol/mol), 6.2–6.4% (44–47 mmol/mol), and ≥ 6.5% (≥48 mmol/mol) had significantly increased risk for incident diabetes during follow-up. In cubic spline analysis, levels below 5.7% HbA1c were not significantly associated with incident diabetes. Conclusions Our study found a strong and graded association with HbA1c 5.8% and above with incident diabetes in Chinese men and women. PMID:25775375

  6. Self-management of diabetes in children and young adults using technology and smartphone applications.

    PubMed

    Sheehy, Siobhan; Cohen, Georgia; Owen, Katharine R

    2014-01-01

    Treatment compliance and adherence are often a challenge in patients with type 1 diabetes, particularly for adolescent and young adult patients. With the availability of the internet and smart phone applications (apps) there is a hope that such technology could provide a means to encourage treatment adherence in this group of patients. This review focuses on whether telemedicine and smartphone technology in diabetes can influence self-management in young people with diabetes. A large number of smartphone apps are targeted at people with diabetes, but a limited number of well designed evaluation studies have been performed. As our review shows, the evidence base for efficacy of most of these applications is minimal and improvement in hard outcomes such as HbA1c and complication development is largely lacking.

  7. [Fatal cerebral oedema during the treatment of diabetic ketoacidosis in an adult male].

    PubMed

    Dekker, T J A; Janson, J A; Hoorn, E J; Sijpkens, Y W J

    2017-01-01

    Diabetic ketoacidosis is relatively common, but the optimal treatment of this condition is still controversial. Cerebral oedema is a rare, but potentially fatal complication. We present the case of an adult patient who presented with de novo diabetic ketoacidosis that was complicated by cerebral oedema during treatment. In this article we discuss factors that may have played a role in the development of this complication. A prolonged hyperosmolar state in diabetic ketoacidosis may increase the risk of cerebral oedema as a result of cerebral compensatory mechanisms. In this group of patients, liberal doses of insulin, fluids and bicarbonate may lead to a decrease in the effective serum osmolarity which can lead to water shifts in the cerebrum. We suggest several adjustments to current treatment guidelines for patients with diabetic ketoacidosis who have undergone a prolonged period of hyperosmolar derangement, with the aim of decreasing the risk of cerebral oedema.

  8. Mental Health and Risk of Secondary Medical Complications in Adults With Pediatric-Onset Spinal Cord Injury

    PubMed Central

    Zebracki, Kathy

    2014-01-01

    Objective: To investigate mental health problems in adults with pediatric-onset spinal cord injury (SCI) and explore how these problems relate to the risk of negative outcomes over time. Method: The study included 466 adults who sustained an SCI prior to age 19 years and had been injured for at least 1 year. Participants were interviewed on an approximately annual basis using a study-specific questionnaire and standardized measures of depression, anxiety, substance use, and community involvement. Generalized estimating equations were used to assess the risk of negative outcomes across time as a function of depression, anxiety, and substance misuse. Results: Of the participants who reported on each domain of mental health, 26% reported misuse of alcohol or drugs (122/466), 21% reported problems with depression (78/360), and 29% reported problems with anxiety (49/168). Depression was associated with increased odds of pressure ulcers, urinary tract infections, hospitalizations, pain, and smoking and lower levels of economic independence and mobility. Anxiety was associated with increased odds of hospitalization, pain, and smoking. Substance misuse predicted an increased risk of pressure ulcers, pain, and smoking and decreased odds of occupational involvement. When examining the effect of mental health with time, results showed that depression accelerated the risk of urinary tract infections, respiratory complications, and hospitalizations and anxiety and depression accelerated risk for lower occupational independence. Conclusions: The added burden that mental health difficulties pose for medical and psychosocial outcomes highlight the importance of monitoring and treating mental health symptoms in pediatric-onset SCI. PMID:24574817

  9. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan.

    PubMed

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as "carryover patients," who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term "transition" in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children's Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition.

  10. Promotion of the Transition of Adult Patients with Childhood-Onset Chronic Diseases among Pediatricians in Japan

    PubMed Central

    Ishizaki, Yuko; Higashino, Hirohiko; Kaneko, Kazunari

    2016-01-01

    The transition of adult patients with childhood-onset chronic diseases (APCCD) from pediatric to adult health-care systems has recently received worldwide attention. However, Japan is lagging behind European countries and North America as this concept of health-care transition was introduced only 10 years ago. In Japan, before the introduction of this concept, APCCD were referred to as “carryover patients,” who were often considered a burden in pediatric practice. In the late 1990s, groups composed of pediatric nephrologists, developmental and behavioral pediatricians, pediatric nurses, and special education teachers researching the quality of life of adult patients with chronic kidney disease began to discuss the physical and psychosocial problems of APCCD. In 2006, a group of pediatricians first introduced the term “transition” in a Japanese journal. By 2010, a group of adolescent nurses had begun a specialized training program aimed at supporting patients during the transitional period. In 2013, the Ministry of Health, Labour and Welfare in Japan convened a research committee, focusing on issues related to social, educational, and medical support for APCCD, and the Japan Pediatric Society established a committee for the health-care transition of APCCD and summarized their statements. Moreover, in 2013, the Tokyo Metropolitan Children’s Medical Center initiated ambulatory services for APCCD managed by specialized nurses. The concept of health-care transition has rapidly spread over these past 10 years. The purpose of this article is to describe how this concept of health-care transition has advanced in Japan, such that APCCD now experience a positive pediatric to adult health-care transition. PMID:27803894

  11. A multicentre comparative trial of sodium valproate and carbamazepine in adult onset epilepsy. Adult EPITEG Collaborative Group.

    PubMed Central

    Richens, A; Davidson, D L; Cartlidge, N E; Easter, D J

    1994-01-01

    The long-term efficacy and safety of sodium valproate and carbamazepine in adult outpatients with newly diagnosed primary generalised or partial and secondarily generalised seizures were compared in a randomised, open, multicentre study at 22 neurology outpatient clinics. Patients were randomised to oral sodium valproate (Epilim EC enteric coated 200 mg tablets twice daily, n = 149) or oral carbamazepine (100 mg twice daily increasing to 200 mg twice daily in week 2, n = 151) and followed up for three years. If clinically necessary, dosages were regularly increased until seizures were controlled or toxicity developed. Sodium valproate and carbamazepine controlled both primary generalised and partial seizures equally effectively overall. Significantly more patients on sodium valproate than carbamazepine (126/140 (90%) v 105/141 (75%), p = 0.001) remained on randomised treatment for at least six months. Skin rashes occurred significantly more often in carbamazepine recipients than in sodium valproate recipients (11.2% v 1.7%, p < 0.05) and carbamazepine was associated with a higher withdrawal rate because of adverse events (15% v 5% on sodium valproate) in the first six months of treatment. There was no difference between the drugs in the rate of withdrawal because of poor seizure control at any stage, regardless of seizure type. At the end of the three year trial period, over 70% of the available patients were still on randomised treatment or had recently stopped treatment after achieving full seizure control. Sodium valproate and carbamazepine were both associated with a high degree of overall seizure control regardless of seizure type and both have good long-term tolerability in adult patients with newly diagnosed epilepsy. Recommendations are made for a higher initial dosage regime for sodium valproate in partial seizures. PMID:8006647

  12. Inflammatory cues acting on the adult intestinal stem cells and the early onset of cancer (Review)

    PubMed Central

    DE LERMA BARBARO, A.; PERLETTI, G.; BONAPACE, I.M.; MONTI, E.

    2014-01-01

    The observation that cancer often arises at sites of chronic inflammation has prompted the idea that carcinogenesis and inflammation are deeply interwoven. In fact, the current literature highlights a role for chronic inflammation in virtually all the steps of carcinogenesis, including tumor initiation, promotion and progression. The aim of the present article is to review the current literature on the involvement of chronic inflammation in the initiation step and in the very early phases of tumorigenesis, in a type of cancer where adult stem cells are assumed to be the cells of origin of neoplasia. Since the gastrointestinal tract is regarded as the best-established model system to address the liaison between chronic inflammation and neoplasia, the focus of this article will be on intestinal cancer. In fact, the anatomy of the intestinal epithelial lining is uniquely suited to study adult stem cells in their niche, and the bowel crypt is an ideal developmental biology system, as proliferation, differentiation and cell migration are all distributed linearly along the long axis of the crypt. Moreover, crypt stem cells are regarded today as the most likely targets of neoplastic transformation in bowel cancer. More specifically, the present review addresses the molecular mechanisms whereby a state of chronic inflammation could trigger the neoplastic process in the intestine, focusing on the generation of inflammatory cues evoking enhanced proliferation in cells not initiated but at risk of neoplastic transformation because of their stemness. Novel experimental approaches, based on triggering an inflammatory stimulus in the neighbourhood of adult intestinal stem cells, are warranted to address some as yet unanswered questions. A possible approach, the targeted transgenesis of Paneth cells, may be aimed at ‘hijacking’ the crypt stem cell niche from a status characterized by the maintenance of homeostasis to local chronic inflammation, with the prospect of initiating

  13. Prevalence of Mental Health Illness Among Patients with Adult-onset Strabismus

    PubMed Central

    Hassan, Mohamed Basil; Hodge, David O.

    2016-01-01

    Background Children diagnosed with some forms of strabismus were recently found to have an increased risk of developing mental illness by early adulthood. The purpose of this case-controlled study was to determine if adults with non-paralytic forms of strabismus are similarly at an elevated risk for developing mental illness. Methods The medical records of all patients diagnosed as adults (≥ 19 years of age) with convergence insufficiency (CI, n=118), divergence insufficiency (DI, n=80), and small angle hypertropia (HT, n=99) from January 1, 1985, through December 31, 2004, were retrospectively reviewed. Each case was compared with a sex- and birthdate-matched non-strabismic control. The medical records were reviewed for mental health diagnoses, including inpatient and outpatient encounters, psychiatric ER visits, and medication use. Results Mental health disorders were diagnosed in 65 (55.1%) patients with CI compared to 54 (45.8%) controls (p=0.15), in 51 (63.8%) patients with DI compared to 42 (52.5%) controls (p=0.15), and in 63 (63.6%) patients with HT compared to 57 (57.6%) controls (p=0.38). CI patients were not more likely to have mental health disorders than their controls (p=0.15). Mental health hospitalizations (p=0.02), psychiatric medication use (p=0.04), and unspecified anxiety disorders (p=0.03) were higher in DI patients compared to controls. HT patients were found to have more generalized anxiety disorders (p=0.003) than controls. Conclusions Adults with some forms of strabismus (DI and HT) appear to have an increased risk of mental illness and its comorbidities, compared to age- and gender-matched non-strabismic controls. PMID:26559866

  14. The clinical implications of adult-onset henoch-schonelin purpura

    PubMed Central

    2011-01-01

    Henoch-Schonlein Purpura (HSP) is a small vessel vasculitis mediated by IgA-immune complex deposition. It is characterized by the clinical tetrad of non-thrombocytopenic palpable purpura, abdominal pain, arthritis and renal involvement. Pathologically, it can be considered a form of immune complex-mediated leukocytoclastic vasculitis (LCV) involving the skin and other organs. Though it primarily affects children (over 90% of cases), the occurrence in adults has been rarely reported. Management often involves the use of immunomodulatory or immune-suppressive regimens. PMID:21619657

  15. Utility of Childhood Glucose Homeostasis Variables in Predicting Adult Diabetes and Related Cardiometabolic Risk Factors

    PubMed Central

    Nguyen, Quoc Manh; Srinivasan, Sathanur R.; Xu, Ji-Hua; Chen, Wei; Kieltyka, Lyn; Berenson, Gerald S.

    2010-01-01

    OBJECTIVE This study examines the usefulness of childhood glucose homeostasis variables (glucose, insulin, and insulin resistance index [homeostasis model assessment of insulin resistance {HOMA-IR}]) in predicting pre-diabetes and type 2 diabetes and related cardiometabolic risk factors in adulthood. RESEARCH DESIGN AND METHODS This retrospective cohort study consisted of normoglycemic (n = 1,058), pre-diabetic (n = 37), and type 2 diabetic (n = 25) adults aged 19–39 years who were followed on average for 17 years since childhood. RESULTS At least 50% of the individuals who ranked highest (top quintile) in childhood for glucose homeostasis variables maintained their high rank by being above the 60th percentile in adulthood. In a multivariate model, the best predictors of adulthood glucose homeostasis variables were the change in BMI Z score from childhood to adulthood and childhood BMI Z score, followed by the corresponding childhood levels of glucose, insulin, and HOMA-IR. Further, children in the top decile versus the rest for insulin and HOMA-IR were 2.85 and 2.55 times, respectively, more likely to develop pre-diabetes; children in the top decile versus the rest for glucose, insulin, and HOMA-IR were 3.28, 5.54, and 5.84 times, respectively, more likely to develop diabetes, independent of change in BMI Z score, baseline BMI Z score, and total-to-HDL cholesterol ratio. In addition, children with adverse levels (top quintile versus the rest) of glucose homeostasis variables displayed significantly higher prevalences of, among others, hyperglycemia, hypertriglyceridemia, and metabolic syndrome. CONCLUSIONS Adverse levels of glucose homeostasis variables in childhood not only persist into adulthood but also predict adult pre-diabetes and type 2 diabetes and relate to cardiometabolic risk factors. PMID:20009096

  16. Clinical and immunological aspects and outcome of a Brazilian cohort of 414 patients with systemic lupus erythematosus (SLE): comparison between childhood-onset, adult-onset, and late-onset SLE.

    PubMed

    das Chagas Medeiros, M M; Bezerra, M Campos; Braga, F N Holanda Ferreira; da Justa Feijão, M R Melo; Gois, A C Rodrigues; Rebouças, V C do Rosário; de Carvalho, T M Amorim Zaranza; Carvalho, L N Solon; Ribeiro, Át Mendes

    2016-04-01

    The clinical expression of systemic lupus erythematosus (SLE) is influenced by genetic and environmental factors and therefore varies between ethnicities. Information on the epidemiology of SLE in Brazil is scarce and practically limited to studies conducted in socioeconomically developed regions (South and Southeast). The objective of this study was to describe the clinical and immunological aspects and outcome of a cohort of patients with SLE treated at a university hospital in northeastern Brazil and compare patterns related to age at onset: childhood (cSLE), adult (aSLE), and late (lSLE). A random sample of 414 records (women: 93.5%) were reviewed. The mean age at SLE onset and the mean disease duration were 28.9 ± 10.9 years and 10.2 ± 6.6 years, respectively. Most patients had aSLE (n = 338; 81.6%), followed by cSLE (n = 60; 14.5%) and lSLE (n = 16; 3.9%). The female/male ratio was 6.5:1 in cSLE and 16.8:1 in aSLE; in lSLE, all patients were female (p = 0.05). During follow-up, the cSLE group presented higher rates of nephritis (70% vs. 52.9% vs. 12.5%; p = 0.0001) and leuko/lymphopenia (61.7% vs. 43.8% vs. 56.2%; p = 0.02). No significant differences were found for anti-dsDNA, anti-Sm, and antiphospholipid antibodies. Treatment with immunosuppressants was significantly more common, and higher doses of prednisone were used, in cSLE. The prevalence of cardiovascular diseases were more frequent in lSLE (p = 0.03). No significant differences were found between the three groups with regard to mean damage accrual (SDI), remission, and mortality. Although cSLE presented higher rates of nephritis and leuko/lymphopenia, more frequent use of immunosuppressants and higher prednisone doses than aSLE and lSLE, the three groups did not differ significantly with regard to damage accrual, remission, and mortality.

  17. Predictors of type 2 diabetes in a nationally representative sample of adults with psychosis

    PubMed Central

    Foley, Debra L; Mackinnon, Andrew; Morgan, Vera A; Watts, Gerald F; McGrath, John J; Castle, David J; Waterreus, Anna; Galletly, Cherrie A

    2014-01-01

    Antipsychotic drugs such as clozapine and olanzapine are associated with an increased risk for type 2 diabetes, but relatively little is known about the relationship between risk factors for type 2 diabetes established in the general population and type 2 diabetes in people with psychosis. We estimated the prevalence of established risk factors and their association with type 2 diabetes in a nationally representative sample of people with an ICD-10 psychosis (N=1642) who gave a fasting blood sample (N=1155). Logistic regression was used to summarize associations adjusted for age and sex. In this sample, whose mean duration of psychosis was 14.7 years, 12.1% (13.1% of women and 11.5% of men) had type 2 diabetes at age 18–64 years based on current fasting blood glucose levels or treatment with a hypoglycaemic drug. Risk was greatly increased in young adults compared with the general population and peaked in middle age. Risk factors in the general population were common in people with psychosis and strongly associated with type 2 diabetes in those people. Treatment with clozapine was associated with an increased risk and treatment with olanzapine with a decreased risk for type 2 diabetes. The development of diabetes or pre-diabetes may therefore influence the likelihood of treatment with olanzapine over time. The strongest predictors of type 2 diabetes in a multivariate model were a body mass index of at least 40 and treated hypercholesterolemia, followed by a body mass index between 35 and 39.9, a family history of diabetes and treated hypertension. There was minimal to no confounding of the association between type 2 diabetes and current clozapine or olanzapine treatment, but neither association remained significant after adjustment for other predictors. Longitudinal relationships among predictors are likely to be complex, and previous antipsychotic drug treatment may at least partly explain risks associated with severe obesity, dyslipidemia and hypertension. A

  18. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.

    PubMed

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.

  19. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  20. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia.

    PubMed

    Horn, Julia; Schlesier, Michael; Warnatz, Klaus; Prasse, Antje; Superti-Furga, Andrea; Peter, Hans-Hartmut; Salzer, Ulrich

    2010-09-01

    Cartilage hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene. Although its most constant feature is metaphyseal dysplasia with short stature, CHH is associated with extraskeletal defects such as thin hair, anemia, immunodeficiency, and increased incidence of lymphomas. The spectrum of immunologic phenotypes in CHH translates into clinical severity. Whereas T-cell deficiency may remain subclinical or may result in severe combined immunodeficiency or Omenn syndrome, humoral immunodeficiency has only rarely been noted in these patients. Here we report the diagnosis of CHH in a woman who presented with severe short stature and a full-blown antibody deficiency, clinically resembling common variable immunodeficiency. Sequencing of the RMRP gene revealed compound heterozygosity for two novel mutations (g.68_69delinsTT and g.76C>T). Despite the late onset of immunodeficiency in the patient, its clinical course was severe, and the patient died 3 years after the first diagnosis.

  1. Adult-onset demyelinating neuropathy associated with FBLN5 gene mutation.

    PubMed

    Cheng, Si; Lv, He; Zhang, Wei; Wang, Zhaoxia; Shi, Xin; Liang, Wei; Yuan, Yun

    2017-03-23

    Rare forms of autosomal-dominant Charcot-Marie-Tooth disease (AD-CMT) may be associated with mutations in Fibulin-5 (FBLN5) as AD-CMT is genetically heterogeneous. Here, we report the first pathological study of an Asian family. The proband was a 46-year-old man with slowly progressive distal numbness and weakness for 12 years. He had a history of diabetes mellitus for 12 years. His mother was 81 years old and had mild polyneuropathy. His 16-year-old daughter was asymptomatic. The nerve conduction velocities (NCVs) and compound muscular action potential (CMAP) amplitudes were moderately to severely reduced in the proband, and moderately reduced in his daughter and mother. A sensory response could not be elicited in the proband and was moderately to severely decreased in the daughter and mother. Nerve ultrasound indicated a general enlargement of the peripheral nerves in the proband, daughter, and mother. A sural nerve biopsy from the proband demonstrated a pronounced depletion of myelinated fibers, thin myelinated fibers, and onion-bulb formations. A reported heterozygous mutation of c.1117C>T in FBLN5 was identified in the proband, mother, and daughter. These findings confirm a novel subtype of AD-CMT 1 due to a mutation in the FBLN5 gene.
.

  2. Adherence decision making in the everyday lives of emerging adults with type 1 diabetes

    PubMed Central

    Pyatak, Elizabeth A; Florindez, Daniella; Weigensberg, Marc J

    2013-01-01

    Purpose The purpose of this study was to explore motivations underlying nonadherent treatment decisions made by young adults with type 1 diabetes. Methods Eight emerging adults each completed a series of semi-structured interviews concerning their approaches to diabetes care, relationships with clinicians, and everyday activities and routines. A narrative thematic analysis was used to develop initial themes and refine them through continued data collection and review of the research literature. Results Five themes were identified as motivating nonadherence: (1) efforts to mislead health care providers, (2) adherence to alternative standards, (3) treatment fatigue and burnout, (4) social support problems, and (5) emotional and self-efficacy problems. Conclusion Instances of nonadherence generally involved a combination of the five identified themes. Participants reporting nonadherence also described difficulties communicating with care providers regarding their treatment. Nonjudgmental communication between providers and emerging adults may be particularly important in promoting positive health outcomes in this population. PMID:23935361

  3. Orbital sporadic Burkitt lymphoma in an adult diabetic African American female and a review of adult orbital cases

    PubMed Central

    Carmody, John; Misra, Raghunath P; Langford, Marlyn P; Byrd, William A; Ditta, Lauren; Vekovius, Bryan; Texada, Donald E

    2011-01-01

    A case of sporadic Burkitt lymphoma (sBL) presenting with jaw and lid involvement in a diabetic adult African American female and a review of adult orbital Burkitt lymphoma cases are presented. Lid edema, visual loss, ophthalmoparesis, proptosis, and sinusitis progressed over 4 weeks despite antibiotic and steroid treatment. Upper lid biopsy histopathological evaluation and immunophenotyping revealed a homogenous mass of atypical CD10 and CD20-negative B-cells and tingible body macrophages yielding a “starry sky” appearance. Cytogenetic analysis detected a minor variant c-MYC translocation, but no Epstein–Barr virus RNA. Detection of multiple lesions prompted a diagnosis of stage IV disease that totally regressed following radiation and chemotherapy. Review results of the six adult orbital sBL cases support a poor prognosis and a heightened suspicion of variant CD10, CD20 and BCL6 positive sBL in adults presenting with jaw pain and rapidly progressive orbital symptoms, particularly in female, African American, and diabetic patients. PMID:21573040

  4. Heterogeneity and frequency of movement disorders in juvenile and adult-onset Niemann-Pick C disease.

    PubMed

    Anheim, Mathieu; Lagha-Boukbiza, Ouhaïd; Fleury-Lesaunier, Marie-Céline; Valenti-Hirsch, Maria-Paola; Hirsch, Edouard; Gervais-Bernard, Hélène; Broussolle, Emmanuel; Thobois, Stéphane; Vanier, Marie T; Latour, Philippe; Tranchant, Christine

    2014-01-01

    Niemann-Pick type C disease (NPC) is a recessive neurolipidosis. We report five adolescent and adult NPC cases to underscore the frequency and heterogeneity of movement disorders in NPC. Clinical, morphologic, biochemical and genetic study was performed in the five patients. Disease onset was between 8 and 50 years. Movement disorders were present in all cases, were heterogeneous and often combined [cerebellar ataxia (5/5), myoclonus (3/5), dystonia (2/5), chorea (1/5) and tremor (1/5)] and were the first sign in 4/5. Two patients were reported to have no vertical supranuclear gaze palsy (VSGP) at the first examination. Two patients experienced acute neuropsychiatric signs leading to death in one case due to myoclonic storm. Filipin staining was always positive. Two NPC1 mutations were identified in three patients, only one in two siblings. NPC should be considered in case of unexplained movement disorders, even when VSGP or cataplexy are not reported. Filipin staining remains a strong support for the diagnosis. Treatment with miglustat should be considered which is currently the only approved disease-specific treatment of NPC in children and adults.

  5. Parental psychopathology and reports of the childhood home environment in adults with early-onset dysthymic disorder.

    PubMed

    Lizardi, H; Klein, D N

    2000-02-01

    In previous studies, patients with dysthymic disorder (DD) have reported significantly more adverse early home environments than patients with episodic major depressive disorder (MDD) and normal controls. However, DD is also associated with increased rates of mood and personality disorders in first-degree relatives, raising the possibility that the DD-early adversity relationship may be due to the confounding effects of parental psychopathology. The present study addressed this issue using a sample of 97 adult outpatients with early-onset DD, 45 adult outpatients with episodic MDD, and 45 normal controls, and their first-degree relatives. The early home environment was assessed with semi-structured interviews and self-report inventories. Parental psychopathology was assessed using semi-structured direct and family history interviews, and diagnoses were assigned using the best-estimate procedure. Results indicated that parental mood and personality disorders were strongly associated with probands' reports of early adversity. However, patients with DD continued to differ significantly from patients with episodic MDD and normal controls after controlling for parental psychopathology.

  6. Early Pathogenesis in the Adult-Onset Neurodegenerative Disease Amyotrophic Lateral Sclerosis

    PubMed Central

    van Zundert, Brigitte; Izaurieta, Pamela; Fritz, Elsa; Alvarez, Francisco J.

    2013-01-01

    Amyotrophic lateral sclerosis (ALS) is a devastating paralytic disorder caused by dysfunction and degeneration of motor neurons starting in adulthood. Most of our knowledge about the pathophysiological mechanisms of ALS comes from transgenic mice models that emulate a subgroup of familial ALS cases (FALS), with mutations in the gene encoding superoxide dismutase (SOD1). In the more than 15 years since these mice were generated, a large number of abnormal cellular mechanisms underlying motor neuron degeneration have been identified, but to date this effort has led to few improvements in therapy, and no cure. Here, we consider that this surfeit of mechanisms is best interpreted by current insights that suggest a very early initiation of pathology in motor neurons, followed by a diversity of secondary cascades and compensatory mechanisms that mask symptoms for decades, until trauma and/or aging overloads their protective function. This view thus posits that adultonset ALS is the consequence of processes initiated during early development. In fact, motor neurons in neonatal mutant SOD mice display important alterations in their intrinsic electrical properties, synaptic inputs and morphology that are accompanied by subtle behavioral abnormalities. We consider evidence that human mutant SOD1 protein in neonatal hSOD1G93A mice instigates motor neuron degeneration by increasing persistent sodium currents and excitability, in turn altering synaptic circuits that control excessive motor neuron firing and leads to excitotoxicity. We also discuss how therapies that are aimed at suppressing abnormal neuronal activity might effectively mitigate or prevent the onset of irreversible neuronal damage in adulthood. PMID:22740507

  7. RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy

    PubMed Central

    Reyes, Aurelio; Melchionda, Laura; Nasca, Alessia; Carrara, Franco; Lamantea, Eleonora; Zanolini, Alice; Lamperti, Costanza; Fang, Mingyan; Zhang, Jianguo; Ronchi, Dario; Bonato, Sara; Fagiolari, Gigliola; Moggio, Maurizio; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    Chronic progressive external ophthalmoplegia (CPEO) is common in mitochondrial disorders and is frequently associated with multiple mtDNA deletions. The onset is typically in adulthood, and affected subjects can also present with general muscle weakness. The underlying genetic defects comprise autosomal-dominant or recessive mutations in several nuclear genes, most of which play a role in mtDNA replication. Next-generation sequencing led to the identification of compound-heterozygous RNASEH1 mutations in two singleton subjects and a homozygous mutation in four siblings. RNASEH1, encoding ribonuclease H1 (RNase H1), is an endonuclease that is present in both the nucleus and mitochondria and digests the RNA component of RNA-DNA hybrids. Unlike mitochondria, the nucleus harbors a second ribonuclease (RNase H2). All affected individuals first presented with CPEO and exercise intolerance in their twenties, and these were followed by muscle weakness, dysphagia, and spino-cerebellar signs with impaired gait coordination, dysmetria, and dysarthria. Ragged-red and cytochrome c oxidase (COX)-negative fibers, together with impaired activity of various mitochondrial respiratory chain complexes, were observed in muscle biopsies of affected subjects. Western blot analysis showed the virtual absence of RNase H1 in total lysate from mutant fibroblasts. By an in vitro assay, we demonstrated that altered RNase H1 has a reduced capability to remove the RNA from RNA-DNA hybrids, confirming their pathogenic role. Given that an increasing amount of evidence indicates the presence of RNA primers during mtDNA replication, this result might also explain the accumulation of mtDNA deletions and underscores the importance of RNase H1 for mtDNA maintenance. PMID:26094573

  8. Diabetes Self-care among a Multiethnic Sample of Older Adults

    PubMed Central

    Schoenberg, Nancy E.; Traywick, LaVona S.; Jacobs-Lawson, Joy; Kart, Cary S.

    2011-01-01

    Type 2 diabetes constitutes a leading and increasing cause of morbidity and mortality among older adults, particularly African Americans, Native Americans, Mexican Americans, and rural dwellers. To understand diabetes self-care, an essential determinant of diabetic and overall health outcomes, 80 middle aged and older adults from these four disproportionately affected racial/ethnic/residential groups engaged in in-depth interviews, focusing on approaches to and explanations for diabetes self-care. Certain self-care activities (medication-taking, diet, foot care) were performed regularly while others (blood glucose monitoring, exercise) were practiced less frequently. Despite research suggestions to the contrary, only one in four elders used unconventional diabetes therapies, and only one-third listed someone other than a health care provider as a primary information source. Few self-care differences emerged according to race/ethnicity/residence, perhaps because of the influential and common circumstance of low income. Thematic analyses suggest that inadequate resources, perceived efficacy of medication, great respect for biomedical authority, and lack of familiarity with and concerns about unconventional therapies are influential in establishing these patterns of self-care. We discuss the similarity of self-care practices and perspectives irrespective of race/ethnicity/residence and the predominance of biomedical acceptability. PMID:18369715

  9. Screening for Diabetic Retinopathy in Adults with Learning Disability: Current Uptake and Adjustments to Facilitate Equality of Access

    ERIC Educational Resources Information Center

    Pilling, Rachel F.

    2015-01-01

    Equality of access to health care for adults with learning disability has been in the spotlight in the UK in recent years due to publication of several reports. Adults with learning disability are thought to account for a significant proportion of the diabetic population in the UK. A list of adults known to the learning disability health…

  10. Limb Regeneration is Impaired in an Adult Zebrafish Model of Diabetes Mellitus

    PubMed Central

    Olsen, Ansgar S.; Sarras, Michael P.; Intine, Robert V.

    2010-01-01

    The zebrafish (Danio Rerio) is an established model organism for the study of developmental processes, human disease and tissue regeneration. We report that limb regeneration is severely impaired in our newly developed adult zebrafish model of type I diabetes. Intraperitoneal streptozocin injection of adult, wild type zebrafish results in a sustained hyperglycemic state as determined by elevated fasting blood glucose values and increased glycation of serum protein. Serum insulin levels are also decreased and pancreas immunohistochemisty revealed a lesser amount of insulin signal in hyperglycemic fish. Additionally, the diabetic complications of retinal thinning and glomerular basement membrane thickening (early signs of retinopathy and nephropathy) resulting from the hyperglycemic state were evident in streptozocin injected fish at three weeks. Most significantly, limb regeneration, following caudal fin amputation, is severely impaired in diabetic zebrafish. Nonspecific toxic effects outside the pancreas were not found to contribute to impaired limb regeneration. This experimental system using adult zebrafish facilitates a broad spectrum of genetic and molecular approaches to study regeneration in the diabetic background. PMID:20840523

  11. Liraglutide: a review of its use in adult patients with type 2 diabetes mellitus.

    PubMed

    Scott, Lesley J

    2014-12-01

    Subcutaneous liraglutide (Victoza(®)), a glucagon-like peptide 1 receptor agonist, is approved for the treatment of adult patients with type 2 diabetes mellitus. Once-daily liraglutide, as monotherapy or add-on therapy to other antidiabetic agents (including basal insulin), was an effective and generally well tolerated treatment in adult patients with type 2 diabetes in several well-designed phase III trials and in the real world clinical practice setting. In addition to improving glycaemic control, liraglutide had beneficial effects on bodyweight, systolic blood pressure and surrogate measures of β-cell function in clinical trials, with these benefits maintained during long-term treatment (≤2 years). Liraglutide has a convenient once-daily administration regimen, a low potential for drug-drug interactions and low propensity to cause hypoglycaemia. Thus, liraglutide continues to be a useful option for the management of type 2 diabetes. This article reviews the therapeutic use of liraglutide in adult patients with type 2 diabetes and summarizes its pharmacological properties.

  12. Oral self-care and periodontal health indicators among adults with diabetes in Finland.

    PubMed

    Karikoski, A; Ilanne-Parikka, P; Murtomaa, H

    2001-12-01

    We assessed the effects of oral self-care on periodontal health indicators among adults with diabetes. The sample consisted of 120 dentate individuals, all of whom were regular patients at the Salo Regional Hospital Diabetes Clinic in southwest Finland. Clinical periodontal examination included identification of visible plaque, the presence of calculus, and use of the Community Periodontal Index of Treatment Needs (CPITN). A questionnaire focused on self-treatment, self-prevention, and self-diagnosis of oral diseases, utilization of dental services, and patients' knowledge and attitudes towards oral health. The New Century model of oral health promotion was used as a theoretical framework for analysis of determinants of oral self-care. Although individuals aged 40 years or older were more frequent interdental cleaners, significantly better oral health indicators were found among younger patients. Women reported brushing their teeth more frequently, and differences in plaque and calculus indices were significantly lower than those of men. Self-reported good oral condition was strongly associated with frequent dental visits and less plaque and calculus. No missing teeth and age less than 40 years were predictors of lower plaque, calculus, and CPITN scores. A significant association was found only between frequent dental visits and reduced amount of calculus. Self-reported frequency of oral health habits among adults with diabetes seemed to have little effect on periodontal health indicators. Adults with diabetes should benefit from comprehensive oral self-care, and more attention is needed for improving the quality and outcome of these habits.

  13. Inhibition of GSK-3 Ameliorates Aβ Pathology in an Adult-Onset Drosophila Model of Alzheimer's Disease

    PubMed Central

    Killick, Richard; Augustin, Hrvoje; Gandy, Carina; Allen, Marcus J.; Hardy, John; Lovestone, Simon; Partridge, Linda

    2010-01-01

    Aβ peptide accumulation is thought to be the primary event in the pathogenesis of Alzheimer's disease (AD), with downstream neurotoxic effects including the hyperphosphorylation of tau protein. Glycogen synthase kinase-3 (GSK-3) is increasingly implicated as playing a pivotal role in this amyloid cascade. We have developed an adult-onset Drosophila model of AD, using an inducible gene expression system to express Arctic mutant Aβ42 specifically in adult neurons, to avoid developmental effects. Aβ42 accumulated with age in these flies and they displayed increased mortality together with progressive neuronal dysfunction, but in the apparent absence of neuronal loss. This fly model can thus be used to examine the role of events during adulthood and early AD aetiology. Expression of Aβ42 in adult neurons increased GSK-3 activity, and inhibition of GSK-3 (either genetically or pharmacologically by lithium treatment) rescued Aβ42 toxicity. Aβ42 pathogenesis was also reduced by removal of endogenous fly tau; but, within the limits of detection of available methods, tau phosphorylation did not appear to be altered in flies expressing Aβ42. The GSK-3–mediated effects on Aβ42 toxicity appear to be at least in part mediated by tau-independent mechanisms, because the protective effect of lithium alone was greater than that of the removal of tau alone. Finally, Aβ42 levels were reduced upon GSK-3 inhibition, pointing to a direct role of GSK-3 in the regulation of Aβ42 peptide level, in the absence of APP processing. Our study points to the need both to identify the mechanisms by which GSK-3 modulates Aβ42 levels in the fly and to determine if similar mechanisms are present in mammals, and it supports the potential therapeutic use of GSK-3 inhibitors in AD. PMID:20824130

  14. Self-esteem and illness self-concept in emerging adults with Type 1 diabetes: Long-term associations with problem areas in diabetes.

    PubMed

    Luyckx, Koen; Rassart, Jessica; Aujoulat, Isabelle; Goubert, Liesbet; Weets, Ilse

    2016-04-01

    This long-term prospective study examined whether illness self-concept (or the degree to which chronic illness becomes integrated in the self) mediated the pathway from self-esteem to problem areas in diabetes in emerging adults with Type 1 diabetes. Having a central illness self-concept (i.e. feeling overwhelmed by diabetes) was found to relate to lower self-esteem, and more treatment, food, emotional, and social support problems. Furthermore, path analyses indicated that self-esteem was negatively related to both levels and relative changes in these problem areas in diabetes over a period of 5 years. Illness self-concept fully mediated these associations.

  15. Problem-solving therapy for adults with diabetic retinopathy and diabetes-specific distress: a pilot randomized controlled trial

    PubMed Central

    Rees, Gwyneth; O'Hare, Fleur; Saeed, Marian; Sudholz, Bronwyn; Sturrock, Bonnie A; Xie, Jing; Speight, Jane; Lamoureux, Ecosse L

    2017-01-01

    Objective To provide preliminary evidence for the impact of problem-solving therapy for diabetes (PST-D) in adults with diabetic retinopathy (DR) and diabetes distress. Research design and methods In a pilot randomized controlled trial, 40 participants with DR and diabetes distress were allocated to the PST-D or control groups. Diabetes distress (DDS), depressive symptoms (PHQ-9), self-care activities (SDSCA), and HbA1c were assessed at baseline, and 3 and 6-month follow-ups. Results At the 6-month follow-up, the PST-D group showed significant improvements relative to the control group, in ‘regimen-related distress’ (PST-D: −1.3±1.4; control: −0.4±1.1), depressive symptoms (PST-D: −4.3±6.1; control: −0.3±4.6), and HbA1c (PST-D: −1.2%±1.01; control: 0.2%±1.2%) (all p<0.05). In multiple regression analysis, adjusting for baseline values and sociodemographic factors, PST-D was associated with significant improvement in ‘regimen-related distress’, depressive symptoms, and HbA1c at the 6-month follow-up (p<0.05). Conclusions PST-D is a promising intervention for improving psychological outcomes and glycemic control. A fully powered study is required to confirm these findings and examine mechanisms of change in HbA1c. Trial registration number ACTRN12616001010482; results. PMID:28243448

  16. Reduced physical activity in adults at risk for type 2 diabetes who curtail their sleep.

    PubMed

    Booth, John N; Bromley, Lindsay E; Darukhanavala, Amy P; Whitmore, Harry R; Imperial, Jacqueline G; Penev, Pamen D

    2012-02-01

    Adults with parental history of type 2 diabetes have high metabolic morbidity, which is exacerbated by physical inactivity. Self-reported sleep <6 h/day is associated with increased incidence of obesity and diabetes, which may be mediated in part by sleep-loss-related reduction in physical activity. We examined the relationship between habitual sleep curtailment and physical activity in adults with parental history of type 2 diabetes. Forty-eight young urban adults with parental history of type 2 diabetes (27 F/21 M; mean (s.d.) age 26 (4) years; BMI 23.8 (2.5) kg/m(2)) each completed 13 (2) days of sleep and physical activity monitoring by wrist actigraphy and waist accelerometry while following their usual lifestyle at home. Laboratory polysomnography was used to screen for sleep disorders. The primary outcome of the study was the comparison of total daily activity counts between participants with habitual sleep <6 vs. ≥6 h/night. Secondary measures included daily time spent sedentary and in light, moderate, and vigorous physical activity. Short sleepers had no sleep abnormalities and showed signs of increased sleep pressure consistent with a behavioral pattern of habitual sleep curtailment. Compared to participants who slept ≥6 h/night, short sleepers had 27% fewer daily activity counts (P = 0.042), spent less time in moderate-plus-vigorous physical activity (-43 min/day; P = 0.010), and remained more sedentary (+69 min/day; P = 0.026). Our results indicate that young urban adults with parental history of type 2 diabetes who habitually curtail their sleep have less daily physical activity and more sedentary living, which may enhance their metabolic risk.

  17. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    PubMed

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm(2)). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  18. Diabetes reduces the cognitive function with the decrease of the visual perception and visual motor integration in male older adults.

    PubMed

    Yun, Hyo-Soon; Kim, Eunhwi; Suh, Soon-Rim; Kim, Mi-Han; Kim, Hong

    2013-01-01

    This study investigated the influence of diabetes on cognitive decline between the diabetes and non- diabetes patients and identified the associations between diabetes and cognitive function, visual perception (VP), and visual motor integration (VMI). Sixty elderly men (67.10± 1.65 yr) with and without diabetes (n= 30 in each group) who were surveyed by interview and questionnaire in South Korea were enrolled in this study. The score of Mini-Mental State Examination of Korean version (MMSE-KC), Motor-free Visual Perception Test-Vertical Format (MVPT-V), and Visual-Motor Integration 3rd Revision (VMI-3R) were assessed in all of the participants to evaluate cognitive function, VP, and VMI in each. The score of MMSE-KC in the diabetic group was significantly lower than that of the non-diabetes group (P< 0.01). Participants in the diabetes group also had lower MVPT-V and VMI-3R scores than those in the non-diabetes group (P< 0.01, respectively). Especially, the scores of figure-ground and visual memory among the subcategories of MVPT-V were significantly lower in the diabetes group than in the non-diabetes group (P< 0.01). These findings indicate that the decline in cognitive function in individuals with diabetes may be greater than that in non-diabetics. In addition, the cognitive decline in older adults with diabetes might be associated with the decrease of VP and VMI. In conclusion, we propose that VP and VMI will be helpful to monitor the change of cognitive function in older adults with diabetes as part of the routine management of diabetes-induced cognitive declines.

  19. Transition Readiness in Adolescents and Emerging Adults with Diabetes: The Role of Patient-Provider Communication

    PubMed Central

    Hilliard, Marisa; Sweenie, Rachel; Riekert, Kristin

    2013-01-01

    Transition from pediatric to adult care represents a high risk period for adolescents and emerging adults with diabetes. Fundamental differences between pediatric and adult care delivery models may contribute to increased risk for poor health outcomes. This review provides a brief overview of models of care in pediatric and adult settings and focuses on patient-provider communication content and quality as potential points of intervention to improve transition-related outcomes. This review also highlights disparities in transition and communication for adolescents and emerging adults from racial/ethnic minority groups and discusses recent changes in health care legislation that have significant implications for the transition process. Intervention opportunities include programs to enhance developmentally-appropriate patient-provider interactions and increased attention to promoting transition readiness skills. Improving patient-provider communication may hasten the development of vital self-advocacy skills needed in adult health care systems and, thus, help establish a lasting pattern of positive diabetes self-care. PMID:24014075

  20. Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials.

    PubMed

    Innes, Kim E; Selfe, Terry Kit

    2016-01-01

    A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2.

  1. Yoga for Adults with Type 2 Diabetes: A Systematic Review of Controlled Trials

    PubMed Central

    Innes, Kim E.; Selfe, Terry Kit

    2016-01-01

    A growing body of evidence suggests yogic practices may benefit adults with type 2 diabetes (DM2). In this systematic review, we evaluate available evidence from prospective controlled trials regarding the effects of yoga-based programs on specific health outcomes pertinent to DM2 management. To identify qualifying studies, we searched nine databases and scanned bibliographies of relevant review papers and all identified articles. Controlled trials that did not target adults with diabetes, included only adults with type 1 diabetes, were under two-week duration, or did not include quantitative outcome data were excluded. Study quality was evaluated using the PEDro scale. Thirty-three papers reporting findings from 25 controlled trials (13 nonrandomized, 12 randomized) met our inclusion criteria (N = 2170 participants). Collectively, findings suggest that yogic practices may promote significant improvements in several indices of importance in DM2 management, including glycemic control, lipid levels, and body composition. More limited data suggest that yoga may also lower oxidative stress and blood pressure; enhance pulmonary and autonomic function, mood, sleep, and quality of life; and reduce medication use in adults with DM2. However, given the methodological limitations of existing studies, additional high-quality investigations are required to confirm and further elucidate the potential benefits of yoga programs in populations with DM2. PMID:26788520

  2. A common gene for juvenile and adult-onset primary open-angle glaucomas confined on chromosome 1q

    SciTech Connect

    Morissette, J.; Plante, M.; Raymond, V.

    1995-06-01

    Primary open-angle glaucoma (POAG), which causes progressive loss of the visual fields, was subdivided into two groups according to age at onset: (1) chronic open-angle glaucoma (COAG) diagnosed after 40 years and (2) juvenile open-angle glaucoma (JOAG) diagnosed between 3 years of age and early adulthood. A JOAG gene (GLC1A) was recently mapped to chromosome 1q. We studied 142 members of a huge multigenerational French Canadian family affected with autosomal dominant POAG. Either JOAG or COAG was diagnosed with ocular hypertension (OHT), which may lead to POAG. To localize a common disease gene that might be responsible for both glaucoma subsets, we performed linkage analysis considering JOAG and COAG under the same phenotypic category. JOAG/COAG was tightly linked to seven microsatellite markers on chromosome 1q23-q25; a maximum lod score of 6.62 was obtained with AF-M278ye5. To refine the disease locus, we exploited a recombination mapping strategy based on a unique founder effect. The same characteristic haplotype, composed of 14 markers spanning 12 cM between loci D1S196 and D1S212, was recognized in all persons affected by JOAG, COAG, or OHT, but it did not occur in unaffected spouses and in normal family members >35 years of age, except for three obligatory carriers. Key combination events confined the disease region within a 9-cM interval between loci D1S445 and D1S416/D1S480. These observations demonstrate that the GLC1A gene is responsible for both adult-onset and juvenile glaucomas and suggest that the JOAG and COAG categories within this family may be part of a clinical continuum artificially divided at age 40 years. 49 refs., 4 figs., 2 tabs.

  3. Age-related differences in biomedical and folk beliefs as causes for diabetes and heart disease among Mexican origin adults.

    PubMed

    Palmquist, Aunchalee E L; Wilkinson, Anna V; Sandoval, Juan-Miguel; Koehly, Laura M

    2012-08-01

    An understanding of health beliefs is key to creating culturally appropriate health services for Hispanic populations in the US. In this study we explore age-based variations in causal beliefs for heart disease and diabetes among Mexican origin adults in Houston, TX. This cross-sectional study included 497 adults of Mexican origin. Participants were asked to indicate the importance of biomedically defined and folk illness-related risk factors as causes for heart disease and diabetes. Biomedical risk factors were ranked highest as causes of diabetes and heart disease among all participants. Folk illness-related factors were ranked below biomedical factors as causes of heart disease among all age groups. Susto was ranked above the median as a risk factor for diabetes among older participants. Age-related differences in causal beliefs may have implications for designing culturally appropriate health services, such as tailored diabetes interventions for older Mexican origin adults.

  4. Association Between Sleep Duration and Diabetes in Black and White Adults

    PubMed Central

    Jackson, Chandra L.; Redline, Susan; Kawachi, Ichiro; Hu, Frank B.

    2013-01-01

    OBJECTIVE To examine racial differences in sleep duration and its relationship with diabetes. RESEARCH DESIGN AND METHODS We used data from a nationally representative sample of U.S. adults (n = 130,943) participating in the National Health Interview Survey from 2004 to 2011. Usual sleep duration was self-reported and categorized as <7 h (short), 7 h (optimal), and >7 h (long). Diabetes status was based on self-reported diagnosis from a health professional. RESULTS Participants’ mean age was 50.6 years, 49% were men, and 13% were black. Compared with whites, blacks were more likely to report short sleep (37 vs. 28%) and less likely to get 7 h of sleep (24 vs. 33%). Diabetes (9,643 cases [9%] in whites and 3,612 cases [15%] in blacks) had a U-shaped distribution with sleep in whites (10, 7, and 9%, for short, optimal, and long sleep, respectively) and blacks (16, 13, and 15%). Suboptimal sleep duration was more strongly associated with diabetes in whites than in blacks among short (prevalence ratio 1.49 [95% CI 1.40–1.58] vs. 1.21 [1.09–1.34]) and long (1.32 [1.25–1.40] vs. 1.11 [1.00–1.23]) sleepers on the relative scale. Adjustment for socioeconomic status (SES) attenuated the short sleep–diabetes association in blacks (1.15 [1.02–1.29]), and the racial/ethnic difference in the short sleep–diabetes association became nonsignificant after SES adjustments. CONCLUSIONS Suboptimal sleep duration was positively associated with diabetes in blacks and whites, although diabetes prevalence was higher at any level of sleep in blacks. Socioeconomic factors appear to partly explain the association for short sleep in blacks as well as disparity between racial groups. PMID:24026552

  5. Dominant-Negative Effects of Adult-Onset Huntingtin Mutations Alter the Division of Human Embryonic Stem Cells-Derived Neural Cells

    PubMed Central

    Lopes, Carla; Aubert, Sophie; Bourgois-Rocha, Fany; Barnat, Monia; Rego, Ana Cristina; Déglon, Nicole

    2016-01-01

    Mutations of the huntingtin protein (HTT) gene underlie both adult-onset and juvenile forms of Huntington’s disease (HD). HTT modulates mitotic spindle orientation and cell fate in mouse cortical progenitors from the ventricular zone. Using human embryonic stem cells (hESC) characterized as carrying mutations associated with adult-onset disease during pre-implantation genetic diagnosis, we investigated the influence of human HTT and of an adult-onset HD mutation on mitotic spindle orientation in human neural stem cells (NSCs) derived from hESCs. The RNAi-mediated silencing of both HTT alleles in neural stem cells derived from hESCs disrupted spindle orientation and led to the mislocalization of dynein, the p150Glued subunit of dynactin and the large nuclear mitotic apparatus (NuMA) protein. We also investigated the effect of the adult-onset HD mutation on the role of HTT during spindle orientation in NSCs derived from HD-hESCs. By combining SNP-targeting allele-specific silencing and gain-of-function approaches, we showed that a 46-glutamine expansion in human HTT was sufficient for a dominant-negative effect on spindle orientation and changes in the distribution within the spindle pole and the cell cortex of dynein, p150Glued and NuMA in neural cells. Thus, neural derivatives of disease-specific human pluripotent stem cells constitute a relevant biological resource for exploring the impact of adult-onset HD mutations of the HTT gene on the division of neural progenitors, with potential applications in HD drug discovery targeting HTT-dynein-p150Glued complex interactions. PMID:26863614

  6. A Preclinical Consortium Approach for Assessing the Efficacy of Combined Anti-CD3 Plus IL-1 Blockade in Reversing New-Onset Autoimmune Diabetes in NOD Mice.

    PubMed

    Gill, Ronald G; Pagni, Philippe P; Kupfer, Tinalyn; Wasserfall, Clive H; Deng, Songyan; Posgai, Amanda; Manenkova, Yulia; Bel Hani, Amira; Straub, Laura; Bernstein, Philip; Atkinson, Mark A; Herold, Kevan C; von Herrath, Matthias; Staeva, Teodora; Ehlers, Mario R; Nepom, Gerald T

    2016-05-01

    There is an ongoing need to develop strategic combinations of therapeutic agents to prevent type 1 diabetes</