Pancreatic islets in older patients with cystic fibrosis with and without diabetes mellitus: morphometric and immunocytologic studies

Forty patients with cystic fibrosis (CF), including 34 who died above age 10 years without having developed clinical diabetes mellitus and 6 who died with both cystic fibrosis and diabetes mellitus, were studied. The mean age of the female patients with CF but not diabetes was 15.8 +/- 5.6 years; of males without diabetes, 17.2 +/- 6.4 years; of female patients with CF and diabetes mellitus, 20.2 +/- 6.9 years; and of males with CF and diabetes, 21.3 +/- 6.6 years. The mean number of pancreatic islets in microscopic sections for patients with cystic fibrosis but not diabetes was 4.18 +/- 2.76/mm2, and the value for patients with both cystic fibrosis and diabetes mellitus was 2.61 +/- 2.07/mm2. The lowest density of pancreatic islets (1.69 +/- 0.48/mm2) for cystic fibrosis was found in patients with the latest-stage pathologic lesion. Nesidioblastosis (presence of ductuloinsular complexes) was identified in 14 of 38 cystic fibrosis patients, both with and without diabetes mellitus. The pancreatic islets of both diabetic and nondiabetic patients with CF showed hypertrophy; the mean volume of the three largest pancreatic islets for CF only was 0.0117 +/- 0.00657 mm3 and that for cystic fibrosis and diabetes was 0.00795 +/- 0.00599 mm3, both values being larger than normal. Ratios of the amounts of islet endocrine cells, A cells, B cells, and D cells, were determined by peroxidase--anti-peroxidase labeled antibody staining. The B cells composed 43.0% of endocrine cell mass in cystic fibrosis alone and 30.1% in cystic fibrosis with diabetes mellitus, which were lower than normal proportions. The D cell values, 11.9% in cystic fibrosis and 15.1% in cystic fibrosis with diabetes mellitus, on the other hand, were greater than normal ratios.     

Pancreatic Islets in Older Patients with Cystic Fibrosis with and without Diabetes Mellitus: Morphometric and Immunocytologic Studies

Forty patients with cystic fibrosis (CF), including 34 who died above age 10 years without having developed clinical diabetes mellitus and 6 who died with both cystic fibrosis and diabetes mellitus, were studied. The mean age of the female patients with CF but not diabetes was 15.8± 5.6 years; of males without diabetes, 17.2± 6.4 years; of female patients with CF and diabetes mellitus, 20.2± 6.9 years; and of males with CF and diabetes, 21.3± 6.6 years. The mean number of pancreatic islets in microscopic sections for patients with cystic fibrosis but not diabetes was 4.18± 2.76/mm², and the value for patients with both cystic fibrosis and diabetes mellitus was 2.61± 2.07/mm². The lowest density of pancreatic islets (1.69± 0.48/mm²) for cystic fibrosis was found in patients with the latest-stage pathologic lesion. Nesidioblastosis (presence of ductuloinsular complexes) was identified in 14 of 38 cystic fibrosis patients, both with and without diabetes mellitus. The pancreatic islets of both diabetic and nondiabetic patients with CF showed hypertrophy; the mean volume of the three largest pancreatic islets for CF only was 0.0117± 0.00657³ mm and that for cystic fibrosis and diabetes was 0.00795± 0.00599 mm³, both values being larger than normal. Ratios of the amounts of islet endocrine cells, A cells, B cells, and D cells, were determined by peroxidase-anti-peroxidase labeled antibody staining. The B cells composed 43.0% of endocrine cell mass in cystic fibrosis alone and 30.1% in cystic fibrosis with diabetes mellitus, which were lower than normal proportions. The D cell values, 11.9% in cystic fibrosis and 15.1% in cystic fibrosis with diabetes mellitus, on the other hand, were greater than normal ratios.     

Diabetic microangiopathy in patients with cystic fibrosis

Individuals with cystic fibrosis have a 1% to 7% incidence of insulin-dependent diabetes mellitus. The occurrence of diabetic microangiopathy in patients with cystic fibrosis has been reported recently. From 1978 to 1987, 19 patients with cystic fibrosis and diabetes mellitus were followed up. Four patients (21%) had evidence of diabetic microangiopathy. In one, peripheral neuropathy developed 5 years after the onset of diabetes mellitus, and the other 3 patients each had complications of retinopathy, nephropathy, and neuropathy which developed 10 years after the onset of diabetes mellitus. All were poorly compliant in their medical care. Significant morbidity was seen in the 3 patients with multisystem involvement--blindness, glaucoma, hypertension, and renal failure. The combination of long-standing diabetes mellitus, poor glycemic control, plus pathophysiologic features associated with cystic fibrosis may have contributed to the development of microangiopathy. The use of steroids in 4 other patients and dextrose infusions (as part of hyperalimentation) in another 4 patients precipitated or exacerbated diabetes. The data indicate that diabetic microangiopathy can occur in the individual with cystic fibrosis. Routine screening for diabetes and its complications in the population with cystic fibrosis, as well as optimal control of hyperglycemia, is warranted.     

Glucose intolerance in cystic fibrosis patients

Diabetes mellitus has evolved as a complication because of increased longevity of patients with cystic fibrosis (CF). CF-related diabetes (CFRD) is associated with increased morbidity and mortality, therefore, prompt diagnosis and aggressive management are important.The prevalence of CFRD increases with age with an age-dependent incidence rate of 5% per year; at 30 years 50% of patients are diabetic. CFRD develops insidiously. Screening by measurements of fasting, random plasma glucose or glycated haemoglobin A(1c), alone or in combination, do not reliably identify CFRD as compared with the 2-hour plasma glucose value measured during an oral glucose tolerance test.Reasons for the development of CFRD are not fully understood. Generally, patients are characterised by the presence of a class I, II or III CF mutation, exocrine pancreatic insufficiency, impaired and delayed insulin secretion, impaired glucagon secretion, normal insulin sensitivity and an increased insulin clearance rate. One can speculate that for endocrine dysfunction to deteriorate from normal to impaired glucose tolerance and then to CFRD, there must be an additional diabetes mellitus-related genetic defect.CFRD leads to deterioration of overall clinical CF status but insulin therapy can revert this. Late diabetic complications may develop as in other types of diabetes although macrovascular complications are rare. CFRD patients have an increased mortality compared to non-diabetic CF patients. Insulin therapy is the preferred treatment.     

Good glycemic control remains crucial in prevention of late diabetic complications – the Linköping Diabetes Complications Study

Background:  Several intervention studies have convincingly demonstrated the importance of good glycemic control to avoid long-term diabetic complications, but the importance of other risk factors remains controversial. We previously reported a markedly reduced incidence of severe retinopathy and nephropathy during the past decades in an unselected population of type 1 diabetes mellitus diagnosed in childhood. The aim of the present study was to analyze possible risk factors, which could explain the improved prognosis.
Methods:  In this longitudinal population-based cohort study, we followed all 269 patients in whom type 1 diabetes mellitus was diagnosed in childhood 1961–1985 in a well-defined geographical area in Sweden. The patients were followed until the end of 1990s. Multivariable regression models were used to analyze the importance of hemoglobin A1c (HbA_1c), diabetes duration, blood pressure, cardiovascular risk factors and persisting C-peptide secretion for the development of diabetic retinopathy and nephropathy.
Results:  Beside longer duration and higher HbA_1c, blood pressure and lipid values were higher and cardiovascular disease and smoking were more common in patients with severe complications. However, multivariable analysis abolished these associations. Diabetes duration and long-term HbA_1c were the only significant independent risk factors for both retinopathy and nephropathy. The risk of overt nephropathy increased substantially when HbA_1c was above 9.6% [Diabetes Control and Complications Trial (DCCT) corrected value], while the risk of severe retinopathy increased already when HbA_1c exceeded 8.6%.
Conclusion:  In this unselected population, glycemic control was the only significant risk factor for the development of long-term complications.     

Estimated Risk of Cross-Infection with Pseudomonas aeruginosa in Danish Cystic Fibrosis Patients

ABSTRACT. During the period 1970–1987 the number of cystic fibrosis (CF) patients treated at the Danish CF Centre increased from 54 to 226. The prevalence of patients with chronic P. aeruginosa infection (CF + P) increased from 35% to 59%, whereafter it decreased to 54%. The yearly incidence of new CF + P patients averaged 8.4% in 1970–1975, 17% in 1976–80, 6.5% in 1981–85, and 3% in 1986–87. These changes correlated to the increased "contact density" between CF + P and non-infected CF patients (CF-P) due to intensified treatment starting in 1976, and the reduced "contact density" due to separation of the two groups starting in 1981. The same trends were observed during an epidemic spread of a multiply resistant P. aeruginosa in the CF + P group, which was also interrupted by separation of two groups of patients, with and without the multiply resistant strain. The observed prevalences of CF + P in different age groups of patients are in accordance with a 20% incidence/year in patients older than three years. The highest probability of aquiring chronic P. aeruginosa infection was calculated to be 2%/day and the lowest 0.09%/day spent in the Centre. By employing a simple mathematical model of the spread of infectious diseases it can be shown, that the highest incidence of CF + P is present when the prevalence of CF + P is 20–80%, and that an increase in the total number of patients also increases the incidence of CF + P unless the patients are divided into smaller groups. The observations in the Danish CF Centre are in accordance with this model.     

Glucose intolerance and diabetes during cystic fibrosis

As a result of the improvement in life-expectancy in cystic fibrosis patients, simultaneous presence of cystic fibrosis and diabetes mellitus is no longer exceptional. In teenagers and young adults with cystic fibrosis, the prevalence of insulin-dependent diabetes mellitus (IDDM) is 7 to 10%. Fifty percent of cystic fibrosis patients have impaired glucose tolerance. These prevalences increase with advancing age. Insulin deficiency is a consistent feature. An endocrine pancreatic deficiency thus exists in addition to the exocrine pancreatic deficiency, as demonstrated by the fall in glucagon and pancreatic polypeptide productions. Development of insulin dependency is associated with deterioration in clinical status and indicates an adverse prognosis. Although in cystic fibrosis patients diabetes mellitus seems to occur as a result of different pathophysiologic mechanisms than those involved in autoimmune IDDM, the risk of degenerative complications is similar in both conditions. It follows that early detection of diabetes mellitus and appropriate insulin treatment are warranted in cystic fibrosis patients.     

Glucose tolerance in cystic fibrosis.

Glucose tolerance was evaluated in 356 living and dead patients with cystic fibrosis who were recorded at the Danish Cystic Fibrosis Centre. Twenty two patients (6%) were treated elsewhere, 25 (7%) were unable, unwilling or too young (age less than 2 years) to participate; 309 patients (87%) were therefore eligible for the study of whom 99 (32%) were dead and 210 (68%) were alive. Of the dead patients, 13 also had diabetes mellitus (13%). Of the living patients (median age 14 years, range 2-40), nine (4%) were known to have diabetes and all were being treated with insulin. In the remaining 201 patients an oral glucose tolerance test (1.75 g/kg body weight, maximum 75 g) was carried out. A total of 155 patients (74%) had normal glucose tolerance, 31 (15%) had impaired glucose tolerance, and 15 (7%) had diabetes mellitus according to the WHO criteria. The percentage of glycated haemoglobin (HbA1c) (reference range 4.1-6.4%) increased significantly as glucose tolerance decreased: when glucose tolerance was normal the median was 5.2%; when it was impaired the figure was 5.5%; in patients whose diabetes was diagnosed by the oral glucose tolerance test it was 5.9%; and in patients already known to have diabetes mellitus it was 8.6%. The incidence and prevalence of impaired glucose tolerance and diabetes mellitus increased with age. From the age of 15 to 30 years the decrease in the prevalence of normal glucose tolerance was almost linear. Within this age span the proportion of patients with cystic fibrosis with normal glucose tolerance was reduced by roughly 5%/year. Only 35% (95% confidence interval (CI) 22 to 48%) of the patients with cystic fibrosis who were alive at the age of 25 years had normal glucose tolerance; 32% (95% CI 14 to 49%) were diabetic. The prevalence of glucose intolerance in cystic fibrosis is rapidly increasing with age; its potentially harmful effect on the prognosis of cystic fibrosis is of increasing importance as the length of survival of these patients increases.     

Diabetes mellitus in cystic fibrosis: genetic and immunological markers

Family history, as well as genetic and immunological markers of diabetes mellitus, were studied in cystic fibrosis (CF) patients with and without diabetes mellitus. Positive family history of diabetes mellitus in first-degree relatives was found in only 6 of 210 (3%) CF patients, with no difference between non-diabetic and diabetic patients. The frequency distributions of the HLA types DR3, DR4 and DR3/4, which normally confer susceptibility to insulin-dependent diabetes mellitus and of HLA-DR2, which normally confers resistance to insulin-dependent diabetcs mellitus, were not different in non-diabetic CF patients, diabetic CF patients and normal subjects. The genotypic frequencies of tumor necrosis factor-β and of heat shock protein 70, located within the HLA region on chromosome 6, in CF patients with diabetes were not different from those in patients with insulin-dependent diabetes mellitus, while non-diabetic CF patients and normal subjects shared other patterns. The frequencies of the interleukin-1β alleles, located on chromosome 2, were not different in non-diabetic and diabetic CF patients, insulin-dependent diabetic patients and normal subjects. Islet cell cytoplasmic antibodies. measured before, at and after the diagnosis of diabetes in 33 diabetic CF patients and in 32 matched non-diabetic CF patients, were detected in only 2 of 236 (0.8%) serum samples; m a pre-diabetic patient and in a non-diabetic control patient. Birth weights were not different in diabetic and non-diabetic CF patients, arguing against the importance of the intrauterine environment as a determinant in the transmission of diabetes mellitus in CF patients. We conclude that diabetes mellitus in CF is without family history of diabetes mellitus, HLA-DR association, and serological evidence for autoimmune destruction of the β-cells. The significance of similar frequcncies of tumor necrosis factor-β and heal shock protein 70 alleles in insulin-dependent diabetic patients and diabetic CF patients remains to bc determined.     

Early detection of impaired glucose tolerance in patients with cystic fibrosis and predisposition factors

INTRODUCTION: The number of patients with glucose tolerance alterations associated with cystic fibrosis (CF) has increased, probably due to the greater survival rate among sufferers of this disease. We studied impaired glucose tolerance (IGT) in patients with CF and investigated whether its appearance has any relationship with age, sex, genetic mutation and/or the degree of clinical involvement. We assessed the parameters that might allow early detection. PATIENTS AND METHODS: In 28 patients with CF (14 M, 14 F; aged 22 months to 18 years), sex, genetic mutation, nutritional status and the degree of pancreatic and pulmonary involvement were recorded. The metabolic study included glycosylated hemoglobin (HbA1c) determination, oral glucose tolerance test (OGTT) and intravenous glucose tolerance tests (IVGTT). RESULTS: In the patients with CF, 35.71% showed impaired glucose tolerance (IGT) and 3.57% had diabetes mellitus. The patients with IGT and CF were 3.2 years older than those with normal glucose tolerance (NGT; p<0.05), but no significant differences were found regarding sex, anthropometric measurements, percentage of pulmonary gammagraphic involvement, Shwachman-Kulczycki test or HbA1c. In the OGTT, the patients homozygous for the deltaF508 mutation had higher blood glucose values than the heterozygous group (p=0.03), but these values were not higher than those in patients with other mutations. During the OGTT, blood insulin values at 30' were reduced in patients with IGT compared to patients with NGT (p<0.02) and the insulin peak occurred at 100.9+/-24.3 min compared to 65.3+/-21.8, respectively (p<0.05). In the IVGTT, 82.14% of the patients had reduced insulin levels at 1 and 3 min (I1'+3'). No differences in the blood glucose levels during the OGTT were found between patients with normal I1'+3' values and patients with reduced values. CONCLUSIONS: A high percentage of patients with CF also present with IGT. This increases with age and is more common among patients homozygous for the deltaF508 mutation and is not related to clinical status. Alterations in the kinetics of insulin secretion play an important role in the appearance of IGT and CF. We suggest that the OGTT is a more sensitive method than IVGTT for identifying early alterations in CF-related diabetes mellitus.     

Research of factors for glucose intolerance in mucoviscidosis]

Glucose tolerance has been assessed in cystic fibrosis (CF) children using HbA1C and plasma glucose and insulin determinations during an oral glucose tolerance test (OGTT), along with the determination of HLA-DR and islet-cell (ICA) and anti-insulin (IAA) antibodies. Of 49 patients (25 males, 24 females), aged 2 to 21 years (mean = 10.9 years), 29 had normal glucose tolerance (WHO criteria) during OGTT, 14 had impaired glucose tolerance (IGT) and 6 had an isolated hyperglycemia at 120 min. Fasting plasma glucose and HbA1C were significantly higher in IGT than in normoglycemic patients. However, these two parameters showed poor individual predictive value of disturbance in glucose tolerance. Of 14 patients with abnormal OGTT, 7 were aged below 10 years, with 2 as young as 5 years; 8 patients were females. HLA antigens characteristic of type I diabetes tended to be found less frequently in CF patients than in the general population: 9% were DR3, 7% were DR4 and none was DR3/DR4. There were no HLA differences according to glucose tolerance. ICA and IAA were respectively detected in only one patient. Stimulated plasma insulin was low but did not correlate with glucose tolerance. In conclusion, impaired glucose tolerance is common in cystic fibrosis and can be found early in life. Although insulin secretion is decreased in this population, it does not seem to be the only factor responsible for impaired glucose intolerance. The absence of the genetical and immunological characteristics of type I diabetes confirms that glucose intolerance in cystic fibrosis is due to other pathogenetic mechanisms.     

Hyperglycaemia and insulinopenia in a neonate with cystic fibrosis

Abnormal glucose tolerance is a frequent late complication of cystic fibrosis (CF), but the prevalence of CF-related diabetes mellitus (CFRD) in children less than 10 y old is less than 2%. The youngest child with CFRD reported to date was 6 mo of age. Insulinopenia is the primary cause of abnormal glucose tolerance/CFRD, but it is unknown whether it may begin in the neonatal period. We describe a case of a neonate with CF who presented with hyperglycaemia in the diabetic range and marked insulinopenia. Insulinopenia and impaired glucose tolerance were permanent findings at 6 and 15 mo of age. CONCLUSION: This case suggests that abnormal glucose tolerance/diabetes may occur much earlier in the course of CF, even during neonatal age. Careful follow-up and further studies in CF infants could reveal that the real incidence of glucose intolerance and diabetes in this age group has been underestimated.     

Relative increase in IgG antibodies to Pseudomonas aeruginosa 60-kDa GroEL in prediabetic patients with cystic fibrosis

In recent years research has focused on a possible connection between bacterial infection and development of diabetes mellitus. In this study, serum antibody responses against bacterial antigens in diabetic and nondiabetic patients with cystic fibrosis (CF) were evaluated. The first part of the study included 252 CF patients of whom 46 (18 %) had diabetes. This study showed that precipitating antibodies (precipitins) against Pseudomonas aeruginosa and other bacteria in crossed immunoelectrophoresis, and IgG antibodies against a 60-kD GroEL of P. aeruginosa, were highly variable and positively correlated with age. Patient material matched for age and sex showed no significant difference between diabetic and nondiabetic CF patients in precipitins or IgG antibodies to P. aeruginosa GroEL. Two longitudinal studies of 9 and 5 y using retrospectively selected sera from 29 prediabetic and 29 cross-matched nondiabetic CF patients were performed. As to precipitins against P. aeruginosa, we found no difference between the prediabetic and the nondiabetic group of patients during the study period. The study revealed, however, a significant increase of 24.6 % (p = 0.008) of IgG antibodies against P. aeruginosa 60-kD GroEL, 3-12 mo before the onset of diabetes in patients with CF, compared with an overall increase of 5 % to 6 % per year in both groups during the observation period. This study shows that diabetes in CF appears after a peak of serum IgG antibodies against GroEL and indicates that development of diabetes in CF patients may not only be caused by a progressive fibrosis of the pancreatic tissue, but may be augmented by a short-term specific immunologic reaction, initially triggered by an ongoing and progressive pulmonary infection.     

Diabetes mellitus in cystic fibrosis: effect of insulin therapy on lung function and infections

The effect of insulin therapy on lung function and lung infections was studied in a retrospective case-control design in 18 diabetic cystic fibrosis (CF) patients; 18 non-diabetic CF patients, matched for sex, age and presence of chronic Pseudomonas aeruginosa lung infection. served as controls. Parameters of CF clinical status were collected for six years before and two years after the onset of insulin therapy in the diabetic patients. Before onset of insulin therapy, body mass index (BMI) and forced vital capacity (FVC) in (pre)diabetic patients deviated increasingly from those in control patients. Decreases in BMI and lung function during the past three months before onset of insulin therapy were reverted within three months of insulin therapy. From three months to two years after onset of insulin therapy, differences in BMI and lung function diminished between diabetic and control patients. After two years of insulin therapy, BMI was similar in diabetic and non-diabetic patients and the percentage differences in forced expiratory volume in 1s (FEV₁) and FVC between the two groups were similar to those found six years before the onset of insulin therapy. The finding that insulin therapy improves lung function in diabetic CF patients suggests strongly that the insidious decline in lung function seen during the years before the diagnosis of diabetes mellitus results from the pre-diabetic condition. After onset of insulin therapy, the percentages of sputum examinations positive for Haemophilus infuenzae and Streptococcus pneumoniae decreased in the diabetic patients, whereas parameters of lung infections with P. aeruginosa and Staphylococcus aureus remained unchanged. In conclusion, since insulin therapy improves lung function and reduces the number of infections with H. influenzae and S. pneumoniae in diabetic CF patients, we suggest that insulin therapy should be started when diabetes mellitus is diagnosed.     

Continuous glucose monitoring system in the screening of early glucose derangements in children and adolescents with cystic fibrosis

BACKGROUND: In cystic fibrosis (CF), diabetes mellitus (DM) is associated with progression of pulmonary disease and nutritional impairment. AIM: To compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in patients with CF with early glucose derangements. PATIENTS AND METHODS: Thirty-two patients with CF (5-20 years) with intermediate glucose values > 7.7 mmol/l during OGTT received a CGMS registration. Patients were classified into those with normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and DM, according to glucose values at 120 min of OGTT and during CGMS. Furthermore BMI z-scores, forced expiratory volume in 1 second (FEV1%), number of respiratory infections/year, enzyme supplementation, and HbA1c were evaluated. RESULTS: OGTT and CGMS derangements were in agreement in 43.7% of the patients. BMI z-scores, FEV1%, number of respiratory infections/ year, enzyme supplementation, and HbA1c did not differ among the three groups. HbA1c, correlated positively with 120 min OGTT (r = 0.34; p = 0.059), CGMS area (r = 0.35; p = 0.048) and the number of respiratory infections, and negatively with FEV1%. CONCLUSIONS: Intermediate glucose values during OGTT should be considered as a screening test in patients with CF. CGMS can be useful in studying the early occurrence of glucose derangements in selected patients.     

Hospitalization for vascular complications in childhood onset type 1 diabetes – effects of gender and age at onset

Aims: To study the cumulative incidence of hospitalization for severe diabetic vascular complications in childhood onset type 1 diabetes patients with special regards to age at onset and gender.
Methods: The Swedish Childhood Diabetes Register (SCDR) was linked to the Swedish Hospital Discharge Register up to 31 December 2004. The following diagnoses were traced: diabetic kidney disease, myocardial infarction, stroke, lower limb arterial disease and diabetes with multiple complications. Cox proportional hazards survival method was applied with the following covariates: maternal age, birthweight deviation from gestational week standard, age at onset and gender.
Results: Until 31 December 9974 children had been followed for at least 10 years corresponding to 141 839 person years at risk and 103 (7.3 per 1000 person years) had been hospitalized at least once at the maximum duration of follow-up of 26 years. Diabetic kidney disease was the most common cause of hospitalization and 63 patients had more than one diabetic complication. Female gender (RR = 2.02, 95% CI = 1.05–3.89) and age at onset of diabetes (RR = 1.37, 95% CI = 1.20–1.56) were significant risk factors for severe complication.
Conclusions: Hospitalization for severe diabetic complications at a maximum follow-up of 26 years is rather low in Sweden. There is a higher hospitalization rate among females than among males, and also among patients diagnosed with diabetes after 10 years of age than among patients diagnosed before the age of 10 years.     

FREQUENT ANTIBIOTIC THERAPY IMPROVES SURVIVAL OF CYSTIC FIBROSIS PATIENTS WITH CHRONIC PSEUDOMONAS AERUGINOSA INFECTION

ABSTRACT. During the period 1971-75, 51 cystic fibrosis (CF) patients who contracted chronic P. aeruginosa infection were treated at the Danish CF centre with anti-pseudomonas chemotherapy only when their clinical condition deteriorated considerably. During the period 1976–80, 58 CF patients who contracted chronic P. aeruginosa infection were treated at the Danish CF centre with anti-pseudomonas chemotherapy on a regular basis every 3 months. Each routine 24 day-course of chemotherapy consisted of tobramycin in combination with carbenicillin or other β-lactam antibiotics with activity against P. aeruginosa. In case of allergy or resistant strains monotherapy with tobramycin was used. The 5-year survival of CF patients from the time of the onset of the chronic P. aeruginosa infection increased from 54% in the first period to 82 % in the second period ( p <0.05), and lung function (peak expiratory flow rate) also improved significantly. It is concluded that intensive "maintenance" chemotherapy against P. aeruginosa improves survival and quality of life of CF patients although permanent eradication of P. aeruginosa is not accomplished.     

Consensus on the diagnosis and management of changes in carbohydrate metabolism in cystic fibrosis

Abnormal glucose tolerance and diabetes mellitus are a common complication of cystic fibrosis (CF). Cystic fibrosis related diabetes (CFRD) is due to decreased insulin secretion, secondary to pancreatic insufficiency. Patients with CFRD have increased morbidity and mortality and are subject to the same microvascular complications as patients with other types of diabetes. Prompt diagnosis and aggressive management of CFRD is important.A consensus conference on CFRD was held in Madrid in May 2000to define the current standards for the diagnosis and management of this disease in Spain.     

Osteoporosis in Juvenile-Onset Diabetes Mellitus: Morphometric and Comparative Studies

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.     

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

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.