Younger Disease Onset Research Articles

Diabetes and Noncommunicable Disease

In this issue of JAMA, Xu et al1 provide 2010 estimates of the prevalence of diabetes and prediabetes in China. This is the first large survey to use the latest American Diabetes Association criteria, which include glycated hemoglobin A1c (HbA1c), fasting plasma glucose, and 2-hour glucose during a 75-g oral-glucose tolerance test. The study was a substantial undertaking, striving for representation across 31 provinces and performing all 3 glucose measures in 98 658 Chinese adults. The authors report a prevalence of 11.6% for diabetes (4.5% by fasting plasma glucose ≥125 mg/dL and 4.6% by HbA1c ≥6.5%) and 50.1% for prediabetes (35.4% by HbA1c ≥5.7%-6.4% and 27.2% by fasting plasma glucose ≥100-125 mg/dL, ). Among those with diabetes, only 30% had been previously diagnosed and only 26% were treated. Among those treated, only 40% had HbA1c concentrations lower than 7%.1 Despite the widely publicized report of 9.7% for diabetes and 15.5% for prediabetes byYang et al2 in the 2007China survey, the findings reported by Xu et al1 indicate that the epidemic of diabetes andprediabetes inChinahas shownno sign of abating. In examining the testing patterns bywhich the diabetes and prediabetes diagnoses weremade, the 2-hour glucosemeasure contributed the least to these diagnoses, uniquely establishing the diagnosis in only 15%of thosewith newly diagnoseddiabetes and 4% of those with prediabetes. This finding has 2 important ramifications. First, the increased prevalence of obesity may have affected the testing characteristics of the population with diabetes or prediabetes. In contrast to this report, themajority of adults with diabetes or prediabetes in the mid 1990-2000s had high post– glucose loading plasma glucose levels.3 In the 2010 survey, 1 in3Chineseadultshadeither centralorgeneralobesity.Among theobeseparticipants, 1 in 2hadprediabetes and1 in5haddiabetes. Furthermore, there were associations between diabetes andprediabeteswithother cardiometabolic risk factors includingdyslipidemia andhighbloodpressure.1 Second, these data support a high diagnostic yield from the combination of themore easily obtained fasting plasma glucose andHbA1c in the Chinese population. Inadditionto thevalueof fastingplasmaglucoseandHbA1c in diabetes screening, these diagnostic tests also have prognostic value in predicting the onset of chronic disease. In the Emerging Risk Factors Collaboration involving 97 prospectivestudiesof820 900peoplewithanaccrualof 123 205deaths, peoplewithdiabeteshada 1.3to 3-fold increased riskofdeath due to multiple causes including cardiovascular disease, renal failure,mental illnesses, all-site cancer, hepatobiliary disease, and sepsis. Overall, diabetes was associated with reduced life expectancy of 6 years, especially in persons with young onset of disease. Importantly, there were linear relationships between fastingplasmaglucose andhazard ratios of all vascular, cancer, nonvascular, andnoncancer events starting from a threshold plasma glucose value of 90 to 108 mg/ dL. These hazards were attenuated with adjustment of fasting plasma glucose only, supporting the causal nature of glucotoxicity inmultipleorgandysfunction.4Similarly, thenear linear relationships between HbA1c and risk of diabetes, cardiovasculardisease5 andcancer6havebeen reported inpeople withorwithoutdiabetes. Inadequate control of fastingplasma glucose andHbA1c inChinaherald a looming andmassive epidemicof chronicdiseases, if promptpreventiveactionsarenot taken. Given themagitude of the problem,what are the priorities in preventive actions? According to the study, 50% of Chinese men were current smokers. Although Xu et al found negative associations of diabetes and prediabeteswith smoking, which might be due to reverse causality, the dose-response associationbetweensmokinganddiabeteshasbeenreported inametaanalysis of prospective studies.7 Although it remains to be proven whether tobacco control would reduce the diabetesprediabetes epidemic, smoking cessation shouldhelpmitigate the amplifying effects of tobacco on the adverse effects of glucotoxicityonorgandamage.Asiahas thehighestpopulationof tobaccousers.Although the levels of development, systemsof government, and population size differ greatly among countries, there have been successful reports of tobacco control through strong political will and restrictive policies in some areas, such as in New Zealand and Hong Kong.8 In the study by Xu et al,1 5% to 8% of those in the 18to 40-year age group had diabetes and 40% to 50% had prediabetes. Apart from phenotypic and genotypic heterogeneity, which pose therapeutic challenges, these young adults are at high risk of prematuremortality and cardiovascular-renal disease during the prime of life. Yet, in part, due to the nonurgent nature of the condition and competing priorities, these young to middle-aged persons often have high rates of nonadherence, default, and suboptimal risk factor control.9 For such populations, a life course and proactive approach starting with protecting maternal and childhood health, promotingahealthy lifestyle, andavoidingobesity fromchildhoodand by launchingoutreachawareness anddetectionprograms targeting theworkforce and early intervention of high-risk individuals with prediabetes, notably those with gestational diabetes and family history of diabetes, are measures that are in linewith theWorldHealthOrganization (WHO)Global Planof Action for Control and Prevention of Noncommunicable Diseases.10 Diabetes is a societal and a health care challenge due to complex interplays amonggenetic, perinatal, lifestyle, andenvironmental factors, to name but a few. Rapidmodernization has resulted in an obesogenic environment characterized by food abundance, physical inactivity, and psychosocial stress. Related article 948 Opinion Editorial

Hip disease in ankylosing spondylitis

Hip disease occurs in about one-third of patients with ankylosing spondylitis (AS) and can often be disabling, necessitating total hip replacement in young adults. There have been recent articles on a number of aspects of this problem, including the epidemiology and pathology. The most recent studies on diagnosis, prognosis and therapeutic management are reviewed here. Several large studies have evaluated the prevalence and outcome of hip involvement in AS. Hip involvement can be diagnosed clinically, radiologically, by MRI or by ultrasonography. These examinations highlight different aspects of hip disease in AS. Hip disease is more prevalent in patients with a younger disease onset and seems to be associated with more severe axial disease. Antitumour necrosis factor (TNF) agents are helpful for pain relief and improvement of function in patients with active axial and active hip disease. However, it is not clear whether this treatment option can prevent progression of structural damage. In case of end-stage hip disease, total hip replacement should be considered. In patients with AS, the hips should be routinely assessed, at least by clinical examination. Anti-TNF therapy should be considered in patients with NSAID-resistant active axial disease who have concomitant hip disease.

Behavioural disorders, disability and quality of life in Parkinson's disease

although non-motor symptoms of Parkinson's disease (PD) are known to adversely affect disability and health-related quality of life, the impact that specific disorders of reward and motivation have remains unclear. Impulse control disorders are more likely in those with a younger disease onset although there is no strong evidence to date that apathy is related to age of onset or correlated with a longer duration of disease. to examine the effects of apathy and impulse controls disorders on disability and health-related quality of life. a total of 99 non-demented participants with PD (35 with impulse control disorders, 26 with apathy and 38 with neither behavioural complication) were assessed using the Unified Parkinson's Disease Rating Scale (Activities of Daily Living component) and the Schwab-England scale to evaluate disability, and the PDQ (eight items) to assess quality of life. quality of life was reduced in both behavioural groups compared with participants without either condition. Disability was greater in the group with apathy. Variation in disability score (56%, P < 0.001) was explained by greater levels of apathy, depression, motor impairment and longer disease duration. Variation in quality of life score (54%, P < 0.001) was explained by higher levels of impulsivity, depression, dopaminergic load, motor complications, working memory problems and younger age at onset. apathy and impulsivity negatively impact on disability and health-related quality of life, emphasising the importance of effective diagnosis and management of these PD-related behavioural disturbances.

The Lifetime Economic Burden of Keratoconus: A Decision Analysis Using a Markov Model

To estimate the expected incremental lifetime cost of treatment of keratoconus compared to the expected cost of the treatment of myopia. Cost estimate from the patient's perspective using a Markov decision model. We modeled a hypothetical cohort of people with clinically significant incident keratoconus as defined by the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study. We included costs of clinic visits, fitting fees, contact lenses, surgical procedures, and complications. Survival curves of corneal transplants and associated complications were modeled using data from the 2007 Australian Graft Registry. Medical treatment regimens after surgery were defined by expert opinion. The expected value of the lifetime cost of the treatment of keratoconus over myopia was $25 168 with a standard deviation of $16 247 and a median of $17 596. The factors that most influenced the lifetime cost were the probability of initial corneal transplant and a subsequent regraft. The cost of routine care had relatively little influence on the lifetime cost of care. The expected lifetime cost of treatment of keratoconus represents a significant cost to patients and payors. While the cost of routine care for keratoconus is not trivial, the primary factor influencing changes in the cost of care for keratoconus is the probability of corneal transplant. Combined with the significantly impaired vision-related quality of life and the relatively young onset of disease, the economic burden of the treatment of keratoconus represents a significant public health concern.

Rosai–Dorfman disease with factor XII deficiency

A 17-year-old female patient presented with chronic symmetrical oligoarthritis of both knees and ankles, xerostomia, xerophthalmia, multiple bilateral lymphadenopathies in the cervical region, and bilateral parotid enlargement with the histological finding of chronic sialoadenitis. She had been already given methotrexate, chloroquine, and corticosteroids with the diagnosis of rheumatoid arthritis (RA) before referral to our outpatient clinic. Because her complaints and the lumps did not remit and she could be classified as neither RA nor primary Sjögren's syndrome (SS) according to 1987 ACR RA criteria or European preliminary criteria for SS, lymph node biopsy was repeated and revealed the diagnosis of Rosai-Dorfman disease (RDD) with the histological findings of histiocytes, phagocyting lymphocytes in enlarged sinuses, and mature plasma cells infiltrating the pulpa. All the medications were stopped after the pathological diagnosis of RDD and consulting with the Division of Hematology. She was reevaluated with magnetic resonance imaging, which showed dense infiltrative areas around knee and ankle joints, and computed tomography that showed a soft tissue mass surrounding the descending aorta and upper part of the abdominal aorta. Activated partial thromboplastin time was found to be prolonged in prebiopsy examinations, and factor XII deficiency was detected after detailed hematological evaluation. The symptoms of joint involvement were relieved with nonsteroidal antiinflammatory drugs. She has been followed-up without medication without obvious clinical or laboratory change. We herein report a patient with RDD mimicking RA and SS. We consider that RDD should be kept in mind especially in patients with resistant symptoms to conventional therapies, younger disease onset, and predominant parotid and lymph node enlargement.

American Gastroenterological Association Consensus Development Conference on the Use of Biologics in the Treatment of Inflammatory Bowel Disease, June 21–23, 2006

The American Gastroenterological Association (AGA) convened a panel of gastroenterologists expert in the area of inflammatory bowel disease (IBD) that developed this consensus statement based on expert presentations of current scientific knowledge about IBD and through subsequent group discussion. This statement reflects the panel's assessment of medical knowledge available when written. Thus, readers should view this statement in the context of data that will accumulate after its creation. The opinions, conclusions, and recommendations expressed in this report are those of the consensus panel members and may or may not reflect the official opinion of the American Gastroenterological Association Institute. The conference upon which this report is based was funded through an unrestricted educational grant from Abbott Laboratories. Abbott Laboratories representatives did not attend the conference, nor did they participate in any way in the development of this report.

Heterogeneity of Parkinson’s disease in the early clinical stages using a data driven approach

Objective: To investigate the heterogeneity of idiopathic Parkinson’s disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established...

Sinonasal lymphomas in Indonesia: immunophenotype and Epstein-Barr virus association

Sinonasal lymphoma is a rare disease with NK/T-cell (NKTC) or B-cell immunophenotype. Previous study revealed the geographic difference in frequency of NKTC lymphoma (NKTCL) and almost constant association with Epstein-Barr virus (EBV) infection. Through review of 41 cases with sinonasal lymphoproliferative diseases registered in the Department of Anatomical Pathology, University of Indonesia during the period 1994 to 2002, thirty-five were accepted as sinonasal lymphoma. Immunohistochemistry revealed that 20 cases (57%) were NK/T-cell type and 15 (43%) B-cell type with large cell morphology, i.e.,diffuse large B-cell lymphoma. NKTCL showed a marked male preponderance (M/F= 4:1) and younger onset of disease (median age, 37 years), and B-cell lymphoma showed a relative female preponderance (1:1.5) and older disease onset (median age, 49 years). In situ hybridization using EBER-1 probe revealed that 90% of NKTCL were EBV-positive, but none of B-cell lymphoma were EBV-positive. This is the first report on sinonasal lymphoma in Indonesia showing relative predominance of B-cell lymphoma compared to other Asian countries and Peru (14-24%). Lack of EBV-association in Indonesian sinonasal B-cell lymphoma showed a marked contrast to that in other Asian countries (EBV positive rate, 25-41 %). Predominance of sinonasal B-cell lymphoma without EBV genome might suggest presence of specific etiologic factors in Indonesia. (Med J Indones 2004; 13: 71-6) Keywords: sinonasal lymphoma, B-cell, NK/T-cell, Epstein-Barr virus, Indonesia

Association of DR3 with susceptibility to and severity of primary Sjögren's syndrome in a family study.

A study of HLA and primary Sjögren's syndrome (1 degree SS) was performed in 40 index cases and 180 relatives all of whom were Caucasian. The association of DR3 and 1 degree SS was confirmed. In probands, DR3 associated with extraglandular manifestations of 1 degree SS and homozygosity for DR3 associated with younger onset of disease. Familial clustering of 1 degree SS was evident. Definite or probable 1 degree SS (Fox criteria) occurred with a prevalence of 4.4% in the relatives, exclusively in older female first degree relatives and was associated with DR3. The relative risk was greatest in those who expressed anti-nuclear factor, rheumatoid factor or Ro and DR3. We identified a group of young females expressing some criteria for 1 degree SS and the same immunogenetic markers. They may be at risk of full expression of 1 degree SS as they become older. Milder forms of 1 degree SS were common in older relatives but not DR3 associated. 1 degree SS in males was rare and mild irrespective of immunogenetic status. Symptoms of 1 degree SS in relatives were mild or absent. Such individuals will only be identified through a family study or a community survey.