The interaction of 2 diseases: diabetes mellitus and cystic fibrosis

We have reviewed the hospital records of 24 patients with cystic fibrosis-associated diabetes, and 2 groups of CF patients (1 with normal and the other with abnormal oral glucose tolerance tests) who did not develop symptomatic fasting hyperglycemia, to define the clinical characteristics of the diabetes and to study its effects on the progression of the pulmonary disease, changes in sputum organisms, and mortality. Although maximum blood glucoses ranged from 322 to 1160 mg/dl with a median of 579 mg/dl, only 1 of 24 diabetic patients developed ketoacidosis. This patient developed diabetes 12 years prior to the diagnosis of CF and may have had type 1 diabetes. In contrast, hypoglycemia was frequent and 4 patients were hospitalized with serious neurologic manifestations. Two patients were found to have diabetic retinopathy, 1 with macular edema required laser photocoagulation to improve vision, and the other had multiple microaneurysms. CF-associated diabetes did not influence the deterioration of clinical scores, chest x-ray scores, pulmonary function tests, the number of hospital admissions, the type of organisms found in the sputum, or mortality rates. The development of diabetes in our CF patients was not related to the severity of pulmonary dysfunction, clinical, or chest x-ray scores. Thus, although the development of diabetes is an additional encumbrance upon the already therapeutically burdened existence of a CF patient, it does not appear to affect the course of the disease. Despite the demonstration of diabetic retinopathy in this study, most patients with CF-associated diabetes still do not live long enough to develop microvascular complications from the diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Diagnosis, objective assessment of severity, and management of acute pancreatitis. Santorini consensus conference.

BACKGROUND: The diagnosis, early assessment, and management of severe acute pancreatitis remain difficult clinical problems. This article presents the consensus obtained at a meeting convened to consider the evidence in these areas. The aim of the article is to provide outcome statements to guide clinical practice, with an assessment of the supporting evidence for each statement. METHOD: Working groups considered the published evidence in the areas of diagnosis, assessment of severity, nonoperative treatment, and surgical treatment of severe acute pancreatitis. Outcome statements were defined to summarize the conclusions on each point considered. The findings were discussed and agreed on by all participants. A careful assessment was made of the strength of the available evidence (proven, probable, possible, unproven, or inappropriate). FINDINGS AND CONCLUSIONS: There is reliable evidence to support much current practice. Clear guidance can be given in most areas examined, and several areas were identified where further investigation would be helpful. Diagnosis using plasma concentrations of pancreatic enzymes is reliable. Rapid advances are taking place in the assessment of severity. Several new therapeutic strategies show real promise for the reduction of morbidity and mortality rates. Surgical debridement is required for infected pancreatic necrosis, but is less often necessary for sterile necrosis.     

Microvascular complications in cystic fibrosis-related diabetes mellitus: a case report

CONTEXT, The prevalence of cystic fibrosis-related diabetes mellitus is increasing and is associated with increased survival from cystic fibrosis. CASE REPORT, This study describes a case of the premature onset of disabling and widespread microvascular complications resulting from cystic fibrosis-related diabetes mellitus. Previously asymptomatic retinopathy was diagnosed on recognition of diabetic nephropathy. CONCLUSIONS, The treatment of pulmonary exacerbations has become more complex due to the nephrotoxic potential of intravenous aminoglycoside drugs which are frequently used to control chronic Pseudomonas infection in cystic fibrosis.     

Prevalence of diabetes mellitus and impaired glucose tolerance in cystic fibrosis

Summary The aim of this study was to evaluate the prevalence of impaired glucose tolerance or diabetes mellitus in 99 patients (53 M, 46 F; mean age 10.5±6.9 years), with cystic fibrosis. Glucose tolerance was evaluated in all patients without overt diabetes using the oral glucose tolerance test (OGTT). Six patients showed a pathological OGTT and 2 patients had insulin-requiring diabetes mellitus. The mean age of the patients with impaired glucose tolerance was significantly higher than that of the subjects with normal glucose metabolism (p<0.0001). Patients with overt diabetes mellitus were the oldest subjects in the study group. Preliminary results of this study were presented at the XX European Pancreatic Club, August 29–31, 1988. Budapest, Hungary and published in Digestion40, 72, 1988.     

Antibiotic therapy against Pseudomonas aeruginosa in cystic fibrosis: a European consensus.

Cystic fibrosis (CF) is the most common lethal hereditary disorder with autosomal recessive heredity in caucasians. The majority of CF patients suffer from chronic respiratory infection with the opportunistic bacterial pathogen Pseudomonas aeruginosa. No consensus among clinicians has been reached so far concerning antibiotic treatment against P. aeruginosa in CF patients. Consensus answers to 24 important questions in this context, based on current evidence, are presented, given by a panel of 34 European experts. Questions addressed and answered are: The diagnosis of P. aeruginosa lung colonization in CF; The impact of P. aeruginosa on the clinical state of CF patients; The assessment of P. aeruginosa susceptibility against antibiotics and the importance of these results for the clinician; The use of monotherapy versus combination therapy; The development of microbial resistance; The achievement of optimal airway concentrations; The effects of subinhibitory concentrations of antibiotics on P. aeruginosa; Statements on the pharmacokinetics of antibiotics in CF patients; Recommendations for doses and dosing intervals and length of treatment regimens; and Toxic side effects due to repeated antibiotic therapy was addressed. The expert panel answered further questions on the use of fluoroquinolones in children with CF, on the administration of nebulized antibiotics and whether prevention of P. aeruginosa lung colonization is possible in CF using antibiotic therapy. Problems of antibiotic therapy at home and in the hospital were addressed, a consensus statement on regular maintenance treatment, or treatment on demand, was given and different routes of administration of antibiotics were recommended for different clinical situations. Finally, the factors which determine the choice of the antibiotic, the dosage, and the duration of the treatment in cystic fibrosis patients were addressed and the design of future antibiotic studies in the context of Pseudomonas aeruginosa lung infection in cystic fibrosis patients were recommended.     

New criteria for impaired fasting glucose and screening for diabetes in cystic fibrosis.

Cystic fibrosis-related diabetes mellitus (CFRD) is the most frequent comorbidity in cystic fibrosis. Its clinical relevance is stressed by the association with increased mortality, and decreased pulmonary and nutritional status. An annual oral glucose tolerance test (OGTT) is recommended as a screening test for CFRD, but this is often not realised because of its time- and resource-consuming nature. Therefore, alternative approaches are welcome. In 2003, the American Diabetes Association (ADA) lowered the cut-off point separating normal from elevated fasting plasma glucose from <6.1 mmol x L(-1) to <5.6 mmol x L(-1), suggesting the performance of an OGTT only in those with impaired fasting glucose (IFG; range 5.6-6.0 mmol x L(-1)). The current authors tested whether this approach was reliable for the early identification of patients with CFRD. OGTTs from 1,128 patients (53% males; 47% females; median age 17.1 yrs) were available for analysis. A total of 101 (8.9%) OGTTs were classified as diabetic. The new ADA criteria for IFG increased the sensitivity to 82% (versus 65%) and decreased the specificity to 70% (versus 94%) compared with the old criteria used to identify patients with diabetic OGTTs. In conclusion, the American Diabetes Association approach of using impaired fasting glucose as an indication for performing selective oral glucose tolerance tests is definitely unsuitable when aiming at the early identification of patients with cystic fibrosis-related diabetes mellitus, and it cannot replace annual oral glucose tolerance tests.     

Guidelines for the diagnosis and therapy of diabetes mellitus in cystic fibrosis

Diabetes is a common complication of cystic fibrosis. Because it is associated with increased morbidity and mortality, prompt diagnosis and aggressive management of cystic fibrosis-related diabetes is important. The Cystic Fibrosis Foundation held a consensus conference in 1998 to define the standards of care for patients with this disease [1[symbol: see text]]. In this article, pathophysiology and management of cystic fibrosis-related diabetes are reviewed.     

The management of chronic viral hepatitis: a Canadian consensus conference 2004.

Several government and nongovernment organizations held a consensus conference on the management of acute and chronic viral hepatitis to update previous management recommendations. The conference became necessary because of the introduction of new forms of therapy for both hepatitis B and hepatitis C. The conference issued recommendations on the investigation and management of chronic hepatitis B, including the use of lamivudine, adefovir and interferon. The treatment of hepatitis B in several special situations was also discussed. There were also recommendations on the investigation and treatment of chronic hepatitis C and hepatitis C-HIV coinfection. In addition, the document makes some recommendations about the provision of services by provincial governments to facilitate the delivery of care to patients with hepatitis virus infection. The present document is meant to be used by practitioners and other health care providers, including public health staff and others not directly involved in patient care.     

Diagnosis of cystic fibrosis after newborn screening: the Australasian experience--twenty years and five million babies later: a consensus statement from the Australasian Paediatric Respiratory Group

Newborn screening for cystic fibrosis has been used in Australia and New Zealand for over 20 years. In that time, considerable experience has been developed regarding the early diagnosis of cystic fibrosis after newborn screening. To date, there has not been a consensus on the process of screening and clinical evaluation leading to the diagnosis of cystic fibrosis in infants, many of whom are not symptomatic at time of notification of the screening result. The aim of this paper is to provide some consensus on the important issues of a cystic fibrosis diagnosis arising from newborn screening, based on the experience gained in Australia and New Zealand over the last 20 years.     

No association between the deltaF508 cystic fibrosis mutation and type 2 diabetes mellitus.

Cystic fibrosis (CF) is one of the most common recessively inherited disorders in Caucasian populations and is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. A three base deletion known as deltaF508 occurs on about 70%, of CF chromosomes and accounts for the high prevalence of the disease. Since type 2 diabetes mellitus occurs more frequently in relatives of patients with CF than in the normal population, we addressed the hypothesis whether heterozygosity for deltaF508 might be a genetic risk factor for type 2 diabetes. We screened 301 patients with type 2 diabetes mellitus which had been treated for at least three years from diagnosis by diet or oral antihyperglycemic agents. Healthy controls (n = 282) had no family history for diabetes. The genotype distribution did not differ significantly between patients with type 2 diabetes (2% heterozygotes) and controls (3% heterozygotes). According to these results, we conclude, that the deltaF508 mutation in its heterozygous form does not represent a major genetic risk factor for type 2 diabetes mellitus.     

French consensus conference on hepatitis C: screening and treatment

Correspondence to: Professor J P Galmiche, Hépato-Gastroentérologie, Hôtel Dieu, CHU de Nantes, 44035 Nantes Cedex, France (email: galmiche@easynet.fr).

This consensus conference followed the rules developed by the French Agence Nationale pour le Développement de l'Evaluation Médicale (ANDEM). Briefly, this required an organising committee, a working group whose task was to make a comprehensive critical review of the literature before the conference was held, a panel of experts, and a jury. The conference was held over two days and included (a) a public session with presentations by experts working in areas relevant to the consensus questions, (b) questions and statements from conference attendees, and (c) deliberation by the jury, followed by the drafting of conclusions and recommendations.
(GUT 1998;:892-898)

     

Prevalence of gestational diabetes mellitus: variations related to screening strategy used

OBJECTIVE: To determine the prevalence of gestational diabetes mellitus in a large general obstetric population and its variations depending on the presence of risk factors, and to evaluate how the gestational diabetes screening strategies applied might modify the observed prevalence in the population. DESIGN: A retrospective cohort study. METHODS: The study population was a total of 2574 pregnant women. Information about risk factors, screening and diagnosis of gestational diabetes was obtained. Frequency of risk factors under the American College of Obstetrics and Gynecologists (ACOG) and the American Diabetes Association (ADA) criteria, and observed and expected prevalence of gestational diabetes mellitus were calculated and compared for statistical significance. RESULTS: Age > or = 30 years, family history of diabetes, obesity and previous fetal macrosomia were the most frequent risk factors. Under ACOG recommendations, 45% of our general obstetric population would have been exempt from gestational diabetes mellitus screening, as compared with only 15.5% under ADA guidelines. Sixty-five patients were diagnosed as having gestational diabetes mellitus, giving an overall prevalence of 2.5% (confidence interval 2.0-3.2). Among the low-risk women, prevalence values were 0.6% and 0.5% respectively under ACOG and ADA criteria, whereas for those presenting one or more risk factors rates were 4% and 2.9% respectively. CONCLUSIONS: In our general obstetric population, gestational diabetes mellitus prevalence was found to be approximately six times lower among low-risk gravidae than among the high-risk subjects, suggesting that selective screening might be beneficial. Nevertheless, selective gestational diabetes mellitus screening under ADA criteria seems to entail the same disadvantages as the selective screening strategies without any apparent benefits.     

Connective tissue biology and hepatic fibrosis: report of a conference

The past 15 years have seen major advances in the characterization of extracellular matrix proteins and structure of matrix. As a by-product of this work, investigators now have an array of molecular and immunological reagents for monitoring matrix metabolism. Progress in the isolation and culture of individual cell types from liver has made possible direct measurement of matrix protein production and also has opened the way to studies of matrix degradation. The expanding knowledge of soluble mediators of inflammation is being applied to the regulation of matrix protein synthesis and degradation. Finally, experimental models of fibrosis in vivo are available for defining the complexity of matrix metabolism in the intact tissue and for validating the findings from cell culture and in vitro systems.     

Diagnosis and treatment of cystic fibrosis

This review discusses some diagnostic aspects of cystic fibrosis (CF) including direct mutational analysis. Treatment of major disease manifestations is discussed in more detail with an emphasis on lung disease, in particular chronic infection with Pseudomonas aeruginosa which is responsible for the majority of excess morbidity and mortality. Centralised care and aggressive antimicrobial treatment have led to increased life expectancy and this may be even further increased by the demonstration that chronic P. aeruginosa infection may be prevented, or at least postponed for many years in a majority of patients. Adjunct treatment such as the use of local and systemic anti-inflammatory agents and inhalation of human recombinant DNase are also briefly touched upon. It is emphasised that important questions concerning the link(s) between the mutated gene and lung disease are still missing but that current research raises hope of a more causal treatment in the near future.     

Diagnosis and treatment of cystic fibrosis. An update

Cystic fibrosis is the most common fatal inherited disease of Caucasians. At present, cystic fibrosis accounts for most cases of chronic progressive pulmonary disease and for many other clinical features in the first three decades of life. Thus, it is a challenge to both pediatricians and internists, particularly chest physicians. The diagnosis is based on the triad of chronic obstructive pulmonary disease, pancreatic insufficiency, and increased levels of electrolytes in the sweat. The cardinal test for confirmation of the diagnosis is the "sweat test," which is an excellent discriminant for cystic fibrosis, even in adults. Ancillary features of cystic fibrosis may be of diagnostic assistance (eg, nasal polyposis, Pseudomonas aeruginosa in sputum, azoospermia, and others). Treatment of the pulmonary disease must be emphasized. Choice of antibiotics should be based on the results of sputum culture, but P aeruginosa is the most common pathogen. Removal of secretions by regular postural drainage and percussion is an integral part of the program. Pneumothorax, massive hemoptysis, cor pulmonale, and other complications may be encountered. Sinusitis is almost universal, and nasal polyposis is frequently present. Pancreatic insufficiency occurs in over 80 percent of the patients with cystic fibrosis and may result in intestinal malabsorption. Massive salt loss through the sweat in hot weather, a distinctive type of biliary cirrhosis without jaundice, gallbladder abnormalities, cholelithiasis, and diabetes mellitus also may be found. Of special importance are intestinal obstructive complications (meconium ileus in newborn infants with cystic fibrosis and intestinal obstruction due to fecal accumulation or intussusception in adults). Azoospermia is present in 95 percent of men and there is reduced fertility in women; however, pregnancy does occur in cystic fibrosis. This chronic and ultimately fatal disease produces a predictable set of psychosocial complications.