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.     

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.     

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.     

Glycosylated haemoglobin and glucose intolerance in cystic fibrosis.

Sixty four patients, age range 1-20 years, with cystic fibrosis had their tolerance to glucose assessed according to their glycosylated haemoglobin (HbA1) concentrations. Raised concentrations were found in 24 (37.5%). Oral glucose tolerance tests were performed on 21 patients with raised HbA1 and 13 patients with normal HbA1 concentrations. C peptide responses were also measured to assess islet cell function. Patients with normal HbA1 had normal glucose tolerance and C peptide response. Seven of 21 patients with raised HbA1 concentrations were glucose intolerant. The remaining 14 patients with raised HbA1 concentrations had normal glucose tolerance but a reduced C peptide response, suggesting impaired islet cell function. There were no appreciable differences in the incidence of chest infections, respiratory function, and chest x-ray scores among patients with normal HbA1 concentrations, raised HbA1 concentrations, and normal oral glucose tolerant tests, and patients who were glucose intolerant. No correlation was found between HbA1 concentration and age or Shwachman score. Measuring HbA1 concentrations periodically is useful in detecting and monitoring glucose intolerance in patients with cystic fibrosis.     

Pancreatic alpha and beta cell functions in cystic fibrosis.

Insulin and glucagon secretions were studied during oral glucose tolerance testing and arginine infusion in 13 patients with cystic fibrosis. Two groups of patients were identified; Group I (N=6) whose OGTT was entirely normal and Group II (N=7) who had some abnormality in glucose during OGTT. In each group basal glucagon concentrations were normal and supressed appropriately (p less than 0.05) after glucose; insulin responses were attenuated and the peak responses delayed. During arginine stimulation, insulin secretion was impaired in each group. However, glucagon secretion was diminished only in Group II. Thus, insulinopenia was found in both groups and hyperglucagonemia was not found as a contributory factor to the hyperglycemia in Group II.     

Hyperglycemia and hypoinsulinemia in patients with Fanconi-Bickel syndrome

Fanconi-Bickel syndrome (FBS) is a rare autosomal recessive disorder characterized by the combination of hepatorenal glycogen accumulation and Fanconi-type nephropathy. Mutations in GLUT2, the gene for facilitative glucose transporter protein 2 (GLUT2), cause FBS. AIM: To evaluate glucose and insulin responses to oral glucose load in patients with FBS. METHODS: Ten children (7.3 +/- 4.8 years) diagnosed with FBS in early infancy underwent a standard oral glucose tolerance test (OGTT); plasma glucose (PG) and serum insulin concentrations were measured at 30-min intervals for 2 hours. HbA1c, insulin-like growth factor-I, and fasting lipid profiles were also measured. RESULTS: Mean fasting and 2-h PG concentrations were 3.8 +/- 0.9 mmol/l and 8.6 +/- 3.0 mmol/1, respectively. 2-hour PG levels were above 11.1 mmol/l in two patients (20%) and between 7.75 and 11.1 mmol/ in four patients (40%). HbA1c was normal in all the patients with a mean of 5.4 +/- 0.3%. Mean fasting and peak serum insulin levels were 8.7 +/- 0.8 pmol/ and 98.6 +/- 43.0 pmol/l, respectively, and did not differ between the patients with normal and abnormal OGTT. Patients with abnormal OGTT were younger (4.8 +/- 3.2 vs 11.0 +/- 4.8 yr; p = 0.04). Fasting PG increased with age (r = 0.80, p < 0.01). Total and LDL cholesterol as well as triglyceride concentrations were elevated. CONCLUSIONS: Most but not all patients with FBS have impaired glucose tolerance/diabetes range hyperglycemia after OGTT while maintaining normal HbA1c. Patients with FBS are relatively hypoinsulinemic. Both fasting hypoglycemia and post-OGTT hyperglycemia seem to improve with age.     

The abnormalities of carbohydrate metabolism in Turner syndrome: analysis of risk factors associated with impaired glucose tolerance

An oral glucose tolerance test (OGTT) was performed in 103 patients with Turner syndrome (TS) who had normal fasting and postprandial glucose levels. The plasma glucose, insulin, C-peptide and proinsulin levels were measured every 30 min during the test. Using a homeostatic model assessment (HOMA) and a quantitative insulin sensitivity check index (QUICKI), the insulin resistance in TS patients was investigated. Diabetes mellitus and impaired glucose tolerance (IGT) were newly diagnosed in two and 18 patients respectively. There was a significant increase in mean plasma glucose, insulin, C-peptide and proinsulin reponse during an OGTT in the IGT group in contrast to the normal glucose tolerance (NGT) group ( P <0.05). There was a significant decrease in the quantitative insulin sensitivity check index (QUICKI) in the IGT group in contrast to the NGT group ( P <0.05). The fasting insulin and triglyceride levels strongly predicted the 2 h glucose level during the OGTT ( P <0.05). Conclusion:The oral glucose tolerance test is superior to the fasting and postprandial plasma glucose test for the early detection of abnormalities of carbohydrate metabolism in patients with Turner syndrome.     

HLA type,islet cell antibodies,and glucose intolerance in cystic fibrosis.

Impaired glucose tolerance, assessed by a raised glycated haemoglobin (HbA1) concentration, was found in 24 (39%) out of 61 patients with cystic fibrosis with an age range of 1-23 years. No correlation between age and HbA1 concentration was found indicating that factors other than progressive pancreatic fibrosis may be important in the aetiology. HLA typing, islet cell antibodies, and autoantibody screen were completed. Eighteen (75%) out of 24 patients with cystic fibrosis who had an impaired glucose tolerance had HLA-DR3 or HLA-DR4 antigens compared with 23 (62%) out of 37 patients with normal glucose tolerance. Islet cell antibodies were present in seven (15%) out of 46 patients with cystic fibrosis; the prevalence in a normal population is 0.5%. Five (25%) of the 20 patients with a raised HbA1 concentration were positive for islet cell antibodies compared with two (8%) out of the 26 with normal glucose tolerance. Six (86%) out of seven patients who were positive for islet cell antibodies had HLA-DR3 or HLA-DR4 antigens. There was no general autoantibody production. Islet cell antibodies may play a part in the development of glucose intolerance in some patients with cystic fibrosis by being produced in those who are genetically predisposed as part of an immune response to damaged pancreatic tissue.     

Oral glucose tolerance test in children and adolescents: positives and pitfalls

Objectives:   To describe the glycaemic status (assessed by an oral glucose tolerance test (OGTT)) and associated comorbidities in a cohort of Australian children and adolescents at risk of insulin resistance and impaired glucose homeostasis (IGH).
Methods:   Twenty-one children and adolescents (three male, 18 female) (18 Caucasian, one Indigenous, two Asian) (20 obese, one lipodystrophy) referred to the Paediatric Endocrinology and Diabetes Clinic underwent a 2-h OGTT with plasma glucose and insulin measured at baseline, + 60 and + 120 min. If abnormal, the OGTT was repeated.
Results:   The mean (SD) age was 14.2 (1.6) years, BMI 38.8 (7.0) kg/m² and BMI-SDS 3.6 (0.6). Fourteen patients had fasting insulin levels >21 mU/L. Type 2 diabetes mellitus was diagnosed in one patient, impaired glucose tolerance (IGT) in four patients and impaired fasting glycaemia (IFG) in one patient. Despite no weight loss, only one patient had a persistently abnormal OGTT on repeat testing. Three patients with IGH were medicated with risperidone at the time of the initial OGTT. One patient who had persistent IGT had continued risperidone. The other two patients had initial OGTT results of IGT and diabetes mellitus type 2. They both ceased risperidone between tests and repeat OGTT showed normal glycaemic status.
Conclusions:   Use of fasting glucose alone may miss cases of IGH. Diagnosis of IGT should not be made on one test alone. Interpretation of glucose and insulin responses in young people is limited by lack of normative data. Larger studies are needed to generate Australian screening recommendations. Further assessment of the potential adverse effects of atypical antipsychotic medication on glucose homeostasis in this at-risk group is important.     

Slow-release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial

Minicucci L, Haupt M, Casciaro R, De Alessandri A, Bagnasco F, Lucidi V, Notarnicola S, Lorini R, Bertasi S, Raia V, Cialdella P, Haupt R. Slow‐release insulin in cystic fibrosis patients with glucose intolerance: a randomized clinical trial. Background: Early stages of glucose metabolism impairment are a period at risk in the long‐term prognosis of cystic fibrosis (CF). Slow‐release synthetic insulin glargine can be a therapeutic tool in this metabolic condition. Methods: In this phase 3 multicenter, controlled, two‐arm, randomized clinical study, glargine was administered up to a dosage of 0.15 U/kg/die for a period of 18 months. Primary endpoint was the improvement of nutritional status [body mass index (BMI) Z score], while glucose tolerance [hemoglobin A1c (HbA1C) and respiratory function (FEV1 predicted] improvement were the secondary endpoints. Results: Thirty‐four subjects (18 in the glargine arm and 16 in the control arm) were evaluated. Adherence to insulin treatment was excellent. No significant adverse events were reported. There were no significant differences in BMI, HbA1C and FEV1 values between the two groups nor within groups, except for HbA1C improvement in the glargine arm at month +18 (p = 0.04). Conclusions: Glargine treatment was well accepted and tolerated. No real efficacy in improving clinical and glycometabolic conditions was demonstrated. Further studies are necessary to test glargine at higher dosage and for a longer follow‐up period.     

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.     

Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis

Alves C, Lima DS, Cardeal M, Santana A. Low prevalence of glucose intolerance in racially mixed children with cystic fibrosis. Objective: To evaluate glucose tolerance in racially mixed Brazilian youth with cystic fibrosis (CF). Methods: Cross‐sectional study conducted between August and September 2007, at a reference service for CF, evaluating: glycated hemoglobin (HbA1c), blood glucose, and insulin levels, before and 2 h after a glucose overload. Results: There were 46 patients aged between 6 yr and 16 yr and 2 months (median: 9 yr and 10 months) of whom 64% were boys. Of these, 26% were Whites; 54.4% Mulattoes; and 19.6% Blacks. HbA1c was normal in all patients. Only one participant (12‐yr old) had glucose intolerance. Insulin levels ranged from 1 to 23 µIU/mL (median: 4.5 µIU/mL) at baseline and from 3.2 to 192.1 µIU/mL (median: 11 µIU/mL) after a glucose overload. Insulin resistance evaluated by the HOMA index, stratified by sex and age, was present in three patients. The ΔF508 mutation was present in only 4.3% of the sample, all of them being heterozygous. Conclusions: The low prevalence of carbohydrate intolerance in this population is probably a result of their young age. Another possibility is the low frequency of the ΔF508 mutation. Although not conclusive, these data suggest that in addition to age, the genotype:phenotype ratio may influence the development of glucose intolerance in patients with CF.     

Glucose intolerance in children with cystic fibrosis

OBJECTIVE: To evaluate the relations among glucose intolerance, genotype, and exocrine pancreatic status in patients with cystic fibrosis (CF). STUDY DESIGN: Data on 335 patients <18 years of age were from the Toronto CF database. A modified oral glucose tolerance test was given to 94 patients 10 to 18 years of age without recognized CF-related diabetes. CF transmembrane conductance regulator mutations and exocrine pancreatic status were determined for all patients. RESULTS: CF-related diabetes was clinically recognized in 9 of 335 (2.7%) patients <18 years of age, all of whom were pancreatic insufficient, and 8 of 9 had severe (classes I through III) mutations on both alleles. The ninth patient had unidentified mutations. Although all patients given the oral glucose tolerance test were asymptomatic and had normal fasting blood glucose, 16 of 94 (17%) had impaired glucose tolerance and 4 of 94 (4.3%) had CF-related diabetes without fasting hyperglycemia. Abnormal glucose tolerance was associated exclusively with severe mutations and exocrine pancreatic insufficiency. Glycosylated hemoglobin (HbA(1)C) levels did not correlate with glucose tolerance results. CONCLUSIONS: Screening of pancreatic-insufficient, adolescent patients with CF identified more with abnormal oral glucose tolerance than was suspected clinically and is recommended as a routine practice. HbA(1)C was not useful in screening for CF-related glucose intolerance.     

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy

Brufani C, Ciampalini P, Grossi A, Fiori R, Fintini D, Tozzi A, Cappa M, Barbetti F. Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy. Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). Aims: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. Methods: The study group included 510 overweight/obese subjects (3–18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA‐IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta‐cell function was estimated by insulinogenic index. Fat mass was measured by dual‐energy x‐ray absorptiometry. Results: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA‐IR and glucose‐stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA‐IR = 4.4 ± 2.5 vs. 3.4 ± 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. Conclusions: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.     

Efficacy and safety of acarbose in patients with cystic fibrosis and impaired glucose tolerance

Impaired glucose tolerance (IGT) is an increasingly frequent complication of cystic fibrosis (CF). In CF patients, a fast postprandial rise in plasma glucose is typically followed by a delayed but prolonged insulin response. Patients may develop symptoms of both hyper- and hypoglycaemia. The α-glucosidase inhibitor, acarbose, delays the hydrolysis and subsequent absorption of ingested carbohydrates. The aim of this study was to investigate the efficacy of acarbose in CF patients with IGT. During a 2-week inpatient period for treatment of Pseudomonas infection, 12 CF patients with IGT were studied in a double-blinded, randomized crossover trial. Each patient received acarbose (50 mg t.i.d.) for 5 days and placebo for 5 days (days 3–8 and days 10–14, respectively). Glucose, insulin and C-peptide responses to a standardized nutritional load were measured at baseline and at the end of each study period (Days 2, 8 and 14). Treatment with acarbose was associated with significant reductions in the mean value, mean peak values and the area under the curve of plasma glucose, insulin and C-peptide, compared to respective baseline values and placebo. Gastro-intestinal disturbances were recorded in 67% of patients during therapy with acarbose. Conclusion Acarbose has a positive therapeutic effect on glucose tolerance in cystic fibrosis patients, as shown by attenuation of postprandial plasma glucose increase and a significant decrease in insulin secretion response. However, acarbose treatment was associated with adverse gastro-intestinal effects that may prevent patients from accepting long-term therapy. Received: 1 December 1997 / Accepted in revised form: 15 September 1998     

Unexpectedly high prevalence of pretransplant abnormal glucose tolerance in pediatric kidney transplant recipients

Several studies suggested that the incidence of new-onset diabetes following pediatric kidney transplantation has increased markedly in recent years, with reported incidence of up to 20%. However, limited information is available regarding the incidence and features of pretransplant status of abnormal glucose tolerance in pediatric kidney transplant recipients. We assessed the risk of 55 non-diabetic pediatric transplant recipients developing PTDM by performing OGTT prior to transplantation. For post-transplant immunosuppression, each patient received either a CsA- or a TAC-based regimen. However, recipients who had abnormal glucose tolerance in the pretransplant OGTT were allocated to the CsA-based regimen. The mean age of the patients was 9.7 +/- 5.4 yr while mean BMI was 16.5 +/- 3.3 kg/m2. FPG level before transplantation was within the normal limit in all patients, while the mean HbA1C value was 4.5. However, 18 of the 55 patients (32.7%) had abnormal glucose tolerance in the pretransplant OGTT, 13 (23.6%) had impaired glucose tolerance, and 5 (9.4%) had DM. PTDM developed in two patients on the TAC-based regimen with these patients having normal glucose tolerance prior to the transplant. In contrast, the 18 patients with abnormal glucose tolerance did not develop PTDM under CsA-based immunosuppression. Our results demonstrated an unexpectedly high prevalence of abnormal glucose tolerance in pretransplant OGTT even in a pediatric population. We believe that modification of post-transplant immunosuppression by the identification of high-risk patients using the pretransplant OGTT may minimize the development of new onset of PTDM.     

Verbesserung der Glukosetoleranz von Patienten mit Zystischer Fibrose unter pseudomonaswirksamer Chemotherpie

Background. For many patients with cystic fibrosis impaired glucose tolerance or even diabetes mellitus is becoming relevant with growing age. The influence of an anti-Pseudomonas chemotherapy on glucose homeostasis of cystic fibrosis patients was investigated. Patients and methods. In fourteen cystic fibrosis patients aged between 7 and 35 years glucose tolerance was tested by standard oral glucose tolerance test in the beginning and at the end of a routine anti-Pseudomonas chemotherapy of fourteen days. Beside the blood glucose serum insulin was determinated. Results. According to the criteria of the American Diabetes Association three of the fourteen patients had an impaired glucose tolerance and another three had diabetes mellitus when tested at the beginning of anti-Pseudomonas chemotherapy. In four of these six patients glucose tolerance was normal at the end of the chemotherapy. Of the remaining two patients one fulfilled the criteria for impaired glucose tolerance and one for diabetes mellitus. In these patients insulin secretion was lower in the second test. Peak insulin was reached earlier while there was no significant improvement of early insulin response. Conclusion. The treatment of chronic airway infection in cystic fibrosis patients with impaired glucose tolerance or diabetes mellitus results in an improvement of glucose homeostasis by a better insulin sensitivity and less by improvement of early insulin response. In developing diagnostic protocols for screening of cystic fibrosis-related diabetes mellitus the impact of the concomitant therapy on glucose homeostasis should be considered.     

Factors affecting diabetes mellitus onset in cystic fibrosis: evidence from a 10-year follow-up study

This study reports the results of genotype characterization and of a 10-y prospective evaluation of clinical status, glucose tolerance and insulin secretion in 28 originally normoglycaemic patients with cystic fibrosis (CF). The aim of the study was to assess whether any genetic, clinical or metabolic parameters could identify in advance those patients at risk of developing diabetes mellitus over time. During the follow-up 42.8% of patients became diabetic. Neither gender, age nor clinical parameters were significantly different at entry in the patients who eventually developed diabetes compared with those who did not. Insulin secretion during oral glucose tolerance tests (OGTT) deteriorated over time in both groups, whereas a progressive deterioration of glucose tolerance was only evident in the patients who developed diabetes and increased baseline glucose areas were the only predictive parameter of diabetes onset. Genotype analysis revealed significant differences between patients with and without diabetes: ΔF508 homozygosis was more frequent in the first group and N1303K mutation in the second group. In conclusion, in CF: (i) increased glucose areas during OGTT and deterioration of glucose tolerance over time can predict the evolution towards diabetes; and (ii) ΔF508 homozygosis may predispose to the risk of diabetes, whilst N1303K mutation seems to play a protective role.     

Insulin resistance in overweight cystic fibrosis paediatric patients

AimTo determine the prevalence of overweight in paediatric patients with cystic fibrosis (CF) and to analyse its role as diabetogenic insulin resistance factor and risk of hypertriglyceridaemia.Patients and methodsA total of 109 CF patients (47% males) between 5 and 18 years were divided into 3 groups according to body mass index (BMI): underweight, normal and overweight. Total cholesterol, triglycerides, C- reactive protein (CRP), glycosylated haemoglobin, HOMA-IR and QUICKI index were determined. Insulinogenic index, ISI composite and areas under the curve (AUC) for glucose and insulin were obtained by oral glucose tolerance test (OGTT).ResultsSix patients (5.5%) were overweight. All groups had similar distribution by age, sex and CFTR mutation, although the proportion of pancreatic sufficient (3/6, 50%) was higher in overweight patients (P=.003). The prevalence of glycaemic disorders was similar between groups. Baseline insulin, HOMA-IR, and insulin during the OGTT (peak and AUC) were higher in overweight patients. All patients had a delayed insulin response in OGTT.ConclusionsOverweight CF patients do not have a higher incidence of glycaemic disorders, but their hyperinsulinism and insulin resistance may be additional diabetogenic risk factors.     

Insulin resistance is associated with decreased clinical status in cystic fibrosis

Patients with cystic fibrosis (CF) frequently have impaired glucose tolerance and progression to diabetes (DM) with clinical features of both insulin-dependent and non-insulin-dependent diabetes. One feature of non-insulin-dependent DM is decreased insulin sensitivity, also known as insulin resistance. The goal of this study was to determine whether patients with CF exhibit insulin resistance and to determine the potential effect of insulin resistance on clinical status. We also sought to determine whether insulin resistance is associated with a specific CF genotype. We studied 18 patients with CF (8 with normal glucose tolerance, 5 with impaired glucose tolerance, 5 with DM), and 20 lean control subjects matched for age, weight, and sex. All control subjects had normal glucose tolerance. The clinical status for each CF patient was determined according to a modified National Institutes of Health scoring system. Each subject underwent a three-step hyperinsulinemic euglycemic clamp (insulin doses of 10, 40, 120 mU/m ² per minute). Results from the 120 mU/m ² per minute infusion defined maximal glucose disposal rate (defined in milligrams per kilogram body weight per minute) at steady state with peripheral insulin levels 195 ± 20 mU/ml. Subjects with CF demonstrated insulin resistance (control subjects = 13.6 ± 1.1, patients with CF = 10.2 ± 1.6 mg/kg per minute; p = 0.003). When each subgroup was compared separately with control subjects, all subgroups were statistically insulin resistant (glucose disposal rate, patients with CF and normal glucose tolerance = 10.8; those with impaired glucose tolerance = 8.4; those with DM = 10.1 mg/kg per minute), and the patients with CF with impaired glucose tolerance were the most insulin resistant. When plotted versus glucose disposal rate, a striking positive correlation between worsened clinical status and insulin resistance ( r = 0.85) is demonstrated. Furthermore, there is no correlation between insulin resistance and fasting blood glucose, subject age, or percent ideal body weight (all r values not significant). In conclusion, patients with CF exhibit insulin resistance that is associated with worsened clinical status. We believe it is the combination of insulin resistance and decreased insulin secretion that is responsible for the high incidence of CF-related diabetes. (J Pediatr 1997;130:948-56)