c-peptide and Cystic-Fibrosis

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have been shown to have a beneficial effect on pulmonary function and nutritional status in patients with cystic fibrosis (CF), but the extent to which they affect glucose tolerance is not fully understood. In the current study, we evaluated the change in glucose tolerance and insulin secretion after first-generation CFTR modulator treatment in adults with CF.. We performed a longitudinal observational study with an oral glucose tolerance test performed at baseline and after three and a half years of follow-up. The test comprised glucose, C-peptide and insulin measured at fasting, 1 h, and 2 h, and HbA1c at fasting. We compared changes in parameters of glucose tolerance and insulin secretion from baseline to follow-up.. Among 55 participants, 37 (67%) were treated with a first-generation CFTR modulator for a median of 21 months. Glucose levels were unchanged in both the treated and untreated group. In the treated group, C-peptide levels declined, yet no significant differences in glucose, insulin, and C-peptide levels were observed between the groups. HbA1c increased in both groups, while no significant change in the insulin sensitivity indices was detected in either group. However, homeostatic model assessment for insulin resistance tended to decline in the treated group, whilst tending towards an increase in the untreated group. The difference between the groups reached statistical significance (p = 0.040).. Treatment with first-generation CFTR modulators, mainly tezacaftor/ivacaftor, did not seem to be associated with glucose tolerance nor insulin secretion in adults with CF. However, CFTR modulators may still have a beneficial effect on insulin sensitivity.

Topics: Adult; Aminophenols; Benzodioxoles; C-Peptide; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Glucose; Glycated Hemoglobin; Humans; Insulin; Insulin Resistance; Mutation

Lumacaftor/Ivacaftor (LUM-IVA), a cystic fibrosis transmembrane conductance regulator (CFTR) protein corrector-potentiator combination, improves lung function and reduces pulmonary exacerbations (PEx) in F508del homozygous CF patients. However, the systemic effects of LUM-IVA outside the respiratory system have not yet been thoroughly investigated.. A prospective, real-world, yearlong study was performed on F508del homozygous adult CF patients who commenced treatment with LUM-IVA. Pancreatic function, bone metabolism, fertility status, nutritional and pulmonary factors were evaluated.. Twelve patients, mean age 28.3 years (18.6-43.9) were recruited. Following 12 months of treatment, no changes were detected in glucose, insulin, c-peptide or BMI values. A significant relative decrease in mean alkaline-phosphatase levels (122.8 U/L vs 89.4, p = 0.002) and a trend toward an increase in calcium levels (9.5 vs 9.9 mg/dL, p = 0.074) were observed. A non-significant improvement in mean DEXA spine t-score after a year of treatment (-2.1 vs -1.6, n = 4, p = 0.11) was detected. Sweat chloride concentrations decreased significantly (-21.4 mEq/L; p = 0.003). Pulmonary outcome revealed improvement in spirometry values during the first three months (FEV. After one year of treatment, stabilization was observed in the pancreatic indices, nutritional status, structure and function of the lungs, with a beneficial effect on bone mineral metabolism and CFTR function. Additional studies should investigate the effect of CFTR modulators on extra-pulmonary manifestations.

Topics: Adolescent; Adult; Anti-Bacterial Agents; C-Peptide; Calcium; Chloride Channel Agonists; Chlorides; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Drug Combinations; Glucose; Humans; Mutation; Prospective Studies; Young Adult

Early detection of cystic fibrosis (CF) related diabetes (CFRD) improves health outcomes and reduces CF-related mortality. The study aims to evaluate the ratio of islet amyloid polypeptide (IAPP) to C-peptide in CF patients with diabetes and without diabetes.. Cross-sectional analysis was carried out in a prospective cohort of 33 participants (CF [n = 16] and CFRD [n = 18]). We examined the association of plasma IAPP:C-peptide ratio with clinical information, including glycated hemoglobin, and lung function markers.. The median (interquartile range) IAPP:C-peptide ratio was significantly (P = 0.004) higher in people with CFRD (4.8 [4.5]) compared with participants without CFRD (12.1 [19.7]). The ratio of IAPP to C-peptide significantly accounted for a 38% variation in the diabetes status in patients with CF (r2 = 0.399, P < 0.001). Islet amyloid polypeptide is strongly correlated with serum ferritin levels (r = 0.683, P = 0.005) and forced expiratory volume in CFRD, but not in nondiabetic participants with CF.. Islet amyloid polypeptide:C-peptide ratio could be a potential marker of CFRD in adults with CF. Further research requires validation of this marker in longitudinal cohort studies to confirm the capability of IAPP:C-peptide to predict CFRD.

Topics: Adult; C-Peptide; Cross-Sectional Studies; Cystic Fibrosis; Diabetes Mellitus; Humans; Islet Amyloid Polypeptide; Longitudinal Studies; Prospective Studies

Post-prandial and oral glucose tolerance test-related hypoglycemia is common in cystic fibrosis (CF); however, the underlying mechanisms are unclear.. To understand the relationship of hypoglycemia with meal-related glucose excursion and insulin secretion, we analyzed plasma glucose, insulin, C-peptide, glucagon and incretins obtained during standardized mixed-meal tolerance tests (MMTT) in non-diabetic adolescents and young adults with pancreatic insufficient CF (PI-CF).. Hypoglycemia, defined as glucose <70 mg/dL, occurred in 9/34 subjects at 150 (range:120-210) minutes following initial meal ingestion. Hypoglycemia[+] and hypoglycemia[-] groups did not differ in gender, age, lung function, HbA1c, or BMI. While 11/14 hypoglycemia[-] individuals displayed normal glucose tolerance (NGT), only 2/9 hypoglycemia[+] had NGT. Peak glucose was higher in hypoglycemia[+] vs hypoglycemia[-]. Compared to hypoglycemia[-] NGT, hypoglycemia[+] exhibited lower early-phase insulin secretion (ISR-AUC. Hypoglycemia is common in PI-CF following MMTT and is associated with early glucose dysregulation (higher peak glucose), more impaired early-phase insulin secretion (lower ISR-AUC

Topics: Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Glucagon; Glucose Intolerance; Glucose Tolerance Test; Humans; Hypoglycemia; Incretins; Insulin; Insulin Secretion; Male; Young Adult

Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established.. To delineate the mechanism(s) underlying OGTT-related hypoglycemia.. We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose <65 mg/dL. We hypothesized that CF-Hypo[+] would demonstrate impaired early phase insulin secretion and persistent late insulin effect compared with control-Hypo[+], and explored the contextual counterregulatory response.. OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas under the curve (AUC) between 0 and 30 minutes (early) and between 120 and 180 minutes (late), and Δglucagon120-180min and Δfree fatty acids (FFAs)120-180min were compared between individuals with CF and control participants with Hypo[+].. Hypoglycemia occurred in 15/23 (65%) patients with CF (43% female, aged 24.8 [14.6-30.6] years) and 8/15 (55%) control participants (33% female, aged 26 [21-38] years). The CF-Hypo[+] group versus the control-Hypo[+] group had higher 1-hour glucose (197 ± 49 vs 139 ± 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 ± 7 vs 59 ± 4 mg/dL; P < 0.01), while insulin, C-peptide, and ISR-AUC0-30 min results were lower and insulin and C-peptide, and AUC120-180min results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared with the control-Hypo[+] group (P < 0.01).. OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFAs. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Case-Control Studies; Child; Cystic Fibrosis; Female; Glucagon; Glucose Tolerance Test; Humans; Hypoglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Male; Time Factors; Young Adult

To investigate the incretin axis in people with cystic fibrosis.. Adults with cystic fibrosis-related diabetes, cystic fibrosis without diabetes, and controls (adults without cystic fibrosis and without diabetes) underwent an oral glucose tolerance test and then a closely matched isoglycaemic i.v. glucose infusion. On each occasion, glucose, insulin, C-peptide, total and active glucagon-like peptide-1 and gastric inhibitory polypeptide responses were recorded and incremental areas under curves were calculated for 60 and 240 min.. Five adults with cystic fibrosis-related diabetes, six with cystic fibrosis without diabetes and six controls, matched for age and BMI, completed the study. Glucose during oral glucose tolerance test closely matched those during isoglycaemic i.v. glucose infusion. The calculated incretin effect was similar in the control group and the cystic fibrosis without diabetes group (28% and 29%, respectively), but was lost in the cystic fibrosis-related diabetes group (cystic fibrosis-related diabetes vs control group: -6% vs 28%; p=0.03). No hyposecretion of glucagon-like peptide-1 or gastric inhibitory polypeptide was observed; conversely, 60-min incremental area under the curve for total glucagon-like peptide-1 was significantly higher in the cystic fibrosis-related diabetes group than in the control group [1070.4 (254.7) vs 694.97 (308.1); p=0.03] CONCLUSIONS: The incretin effect was lost in cystic fibrosis-related diabetes despite adequate secretion of the incretin hormones. These data support the concept that reduced incretin hormone insulinotropic activity contributes significantly to postprandial hyperglycaemia in cystic fibrosis-related diabetes.

Topics: Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Hyperglycemia; Incretins; Infusions, Intravenous; Insulin; Male

Diabetes is associated with worse cystic fibrosis (CF) outcomes. The CFTR potentiator ivacaftor is suggested to improve glucose homeostasis in individuals with CF.. To test the hypothesis that clinically indicated ivacaftor would be associated with improvements in glucose tolerance and insulin and incretin secretion.. Oral glucose tolerance tests, mixed-meal tolerance tests, and glucose-potentiated arginine tests were compared preivacaftor initiation and 16 weeks postivacaftor initiation in CF participants with at least one CFTR gating or conductance mutation. Meal-related 30-minute (early phase) and 180-minute incremental area under the curves were calculated as responses for glucose, insulin, C-peptide, and incretin hormones; glucagon-like peptide-1; and glucose-dependent insulinotropic polypeptide. First-phase insulin secretion, glucose potentiation of arginine-induced insulin secretion, and disposition index were characterized by glucose-potentiated arginine stimulation tests.. Insulin secretion improved following 4 months of clinically indicated ivacaftor therapy in this relatively young group of patients with CF with normal to mildly impaired glucose tolerance, whereas incretin secretion remained unchanged.

Topics: Adolescent; Adult; Aminophenols; Blood Glucose; C-Peptide; Child; Cystic Fibrosis; Female; Follow-Up Studies; Glucose Tolerance Test; Humans; Incretins; Insulin; Male; Quinolones; Young Adult

Cystic fibrosis-related diabetes (CFRD) is the most frequent extrapulmonary complication of cystic fibrosis (CF).. We report the first combined pancreatic islet-lung-liver transplantation in a 14-year-old adolescent. CFTR was analyzed by Sanger sequencing. Further genes were analyzed by high-throughput sequencing.. The patient was diagnosed with CF at the age of 14 months. Nine years later, after diagnosis of CFRD, the patient's BMI and lung function began to decline. Bilateral lung transplantation with simultaneous liver transplantation was performed at the age of 14.5 years. The first islet transplantation (IT) was carried out 10 days later. Six months later, C-peptide secretion after arginine stimulation showed peak values of 371 pmol/L (vs. 569 pmol/L before IT) and insulin doses had slightly increased (1.40 vs. 1.11 units/kg/day before IT). A second IT was performed at the age of 15 years, a third at 16 years. Two years after the first IT, arginine-stimulated C-peptide secretion increased to 2,956 pmol/L and insulin doses could be reduced to 0.82 units/kg/day. HbA1c decreased from 7.3% (57.4 mmol/mol) to 5.9% (41.0 mmol/mol).. IT following lung and liver transplantation, with injection of islets into a transplanted organ, is feasible. It improves C-peptide secretion, decreases insulin needs, and lowers HbA1c.

Topics: Adolescent; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Glycated Hemoglobin; Humans; Insulin; Islets of Langerhans Transplantation; Liver Transplantation; Lung Transplantation; Male

Patients with pancreatic-insufficient cystic fibrosis (PI-CF) are at increased risk for developing diabetes. We determined β-cell secretory capacity and insulin secretory rates from glucose-potentiated arginine and mixed-meal tolerance tests (MMTTs), respectively, in pancreatic-sufficient cystic fibrosis (PS-CF), PI-CF, and normal control subjects, all with normal glucose tolerance, in order to identify early pathophysiologic defects. Acute islet cell secretory responses were determined under fasting, 230 mg/dL, and 340 mg/dL hyperglycemia clamp conditions. PI-CF subjects had lower acute insulin, C-peptide, and glucagon responses compared with PS-CF and normal control subjects, indicating reduced β-cell secretory capacity and α-cell function. Fasting proinsulin-to-C-peptide and proinsulin secretory ratios during glucose potentiation were higher in PI-CF, suggesting impaired proinsulin processing. In the first 30 min of the MMTT, insulin secretion was lower in PI-CF compared with PS-CF and normal control subjects, and glucagon-like peptide 1 and gastric inhibitory polypeptide were lower compared with PS-CF, and after 180 min, glucose was higher in PI-CF compared with normal control subjects. These findings indicate that despite "normal" glucose tolerance, adolescents and adults with PI-CF have impairments in functional islet mass and associated early-phase insulin secretion, which with decreased incretin responses likely leads to the early development of postprandial hyperglycemia in CF.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Exocrine Pancreatic Insufficiency; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucose; Glucose Tolerance Test; Humans; Incretins; Insulin; Insulin-Secreting Cells; Male; Middle Aged; Pancreas; Proinsulin; Young Adult

In cystic fibrosis, abnormal glucose tolerance is associated with decreased lung function and worsened outcomes. Translational evidence indicates that abnormal glucose tolerance may begin in early life.. To determine whether very young children with cystic fibrosis have increased abnormal glucose tolerance prevalence compared with control subjects. The secondary objective was to compare area under the curve for glucose and insulin in children with cystic fibrosis with control subjects.. This is a prospective multicenter study in children ages 3 months to 5 years with and without cystic fibrosis.. Oral glucose tolerance testing with glucose, insulin, and C-peptide was sampled at 0, 10, 30, 60, 90, and 120 minutes. Twenty-three children with cystic fibrosis and nine control subjects had complete data. All control subjects had normal glucose tolerance. Nine of 23 subjects with cystic fibrosis had abnormal glucose tolerance (39%; P = 0.03). Of those, two met criteria for cystic fibrosis-related diabetes, two indeterminate glycemia, and six impaired glucose tolerance. Children with cystic fibrosis failed to exhibit the normal increase in area under the curve insulin with age observed in control subjects (P < 0.01), despite increased area under the curve glucose (P = 0.02).. Abnormal glucose tolerance is notably prevalent among young children with cystic fibrosis. Children with cystic fibrosis lack the normal increase in insulin secretion that occurs in early childhood despite increased glucose. These findings demonstrate that glycemic abnormalities begin very early in cystic fibrosis, possibly because of insufficient insulin secretion.

Topics: Blood Glucose; C-Peptide; Case-Control Studies; Child, Preschool; Cystic Fibrosis; Female; Glucose Tolerance Test; Humans; Infant; Insulin; Male; Prospective Studies

Exhaled breath analysis is able to identify biomarkers of respiratory and systemic diseases. It was hypothesized that markers of pancreatic function would be identified in the breath of those with diabetes mellitus and cystic fibrosis. Children aged 6-18 years old with diabetes mellitus (DM), cystic fibrosis (CF), cystic fibrosis related diabetes (CFRD) and healthy controls (C) contributed exhaled breath condensate (EBC), with concurrent blood glucose measurements taken from a subset. EBC C-peptide, glucose, sodium concentrations and conductivity were subsequently measured.A total of 104 children were recruited (DM = 56, CF = 26, CFRD = 5, C = 17). C-peptide was detected in EBC: CF 19.6  ±  11.7 pmol L(-1); DM: 9.66  ±  8.27 pmol L(-1); CFRD: 11.9  ±  9.23 pmol L(-1) which was significantly higher than in the control group (0.987  ±  2.26 pmol L(-1)) (p < 0.0001). No statistically significant difference was seen between the three groups for glucose, conductivity or sodium concentration.Glucose was not reliably found in EBC, but C-peptide was found to be higher in CF EBC. This may represent inflammation and a change in airway integrity, rather than increased secretion of this peptide.

Topics: Adolescent; Analysis of Variance; Biomarkers; Blood Glucose; Breath Tests; C-Peptide; Case-Control Studies; Child; Cystic Fibrosis; Diabetes Mellitus; Electric Conductivity; Exhalation; Female; Humans; Ions; Male; Pancreas; Sodium

To assess the major determinants of glucose tolerance between age, genotype, and clinical status in cystic fibrosis (CF) patients, and study if defects of insulin secretion and insulin sensitivity were associated with the onset of CF-related diabetes (CFRD).. One hundred and nineteen patients, in stable clinical condition were studied. They were subdivided into 3 groups based on age, and 2 groups based on Schwachman-Kulczycki clinical score. All patients were genotyped, and subsequently divided into 3 groups. Ninety-four healthy normal-weight controls, comparable for sex and age were also studied. All subjects had baseline blood samples taken for glucose and insulin, C-peptide, and glycated hemoglobin. Homeostasis model assessment of insulin resistance (HOMA-IR), fasting glucose/insulin ratio (FGIR) were calculated as indices of IR and insulinogenic index as a marker of pancreatic β-cell function. All patients underwent an oral glucose tolerance test, and 57 underwent an IVGTT for the calculation of first-phase (FPIR) and acute insulin responses (AIR).. The F508del homozygous patients had an increased chance of developing impaired glucose tolerance (IGT) and significantly lower FPIR, decreased HOMA-IR, and insulinogenic index. Heterozygote F508del patients had an increased chance of having normal glucose tolerance. HOMA-IR, FGIR, and insulinogenic index did not change with age or clinical score. HOMAIR correlated with FPIR. FPIR correlated positively with insulinogenic index. AIR correlated negatively with FGIR, and positively with C-reactive protein. In multiple linear regression analyses, glucose tolerance was related to the agegroup, and to the HOMA-IR and insulinogenic indexes.. IGT and CFRD were related mainly to genotype, although, as expected, the prevalence increased with age. The data suggested a possible combined contribution of insulin deficiency, β-cell function, and reduced insulin sensitivity to the onset of CFRD; however, further studies are warranted to better elucidate this aspect.

Topics: Adolescent; Adult; Age Factors; Body Mass Index; C-Peptide; Child; Cystic Fibrosis; Female; Genotype; Glucose Tolerance Test; Homeostasis; Humans; Inflammation; Insulin; Insulin Resistance; Insulin-Secreting Cells; Lung; Male; Young Adult

Impaired growth and nutritional status in CF may be related to progressive insulin deficiency before CF-Related Diabetes has established. Aim of this study was to analyse the association of circulating insulin with nutritional status and lung function in CF patients with normal glucose tolerance (NGT).. We performed OGTT in 152 consecutive CF patients aged 8-20 years: 115 of them had NGT and were included in the study. Areas under the curves (AUC) of glucose, insulin and c-peptide after 120 min were calculated. Quartiles (Q) of increasing fasting insulin (fINS-Q) and c-peptide (fCP-Q) levels were calculated in CF patients. Respiratory function parameters (FEV1, FVC), Standard Deviation Scores (SDS) of height, weight and BMI were compared between Q1 and the three higher Q. Multiple regression analysis was used to analyse the association of fasting insulin, c-peptide or OGTT derived indices with nutritional or respiratory parameters.. Compared to patients in fINS-Q4 or fCP-Q4, those in fINS-Q1 or in fCP-Q1 respectively showed lower levels of insulin AUC or c-peptide AUC (both P < 0.0001), weight-SDS (P = 0.013, P = 0.007), BMI-SDS (P = 0.010, P = 0.002), FEV1 (P = 0.076, P = 0.013) and FVC (P = 0.101, P = 0.009). Age- and gender-adjusted regression analysis showed significant associations of fINS and fCP with SDS of BMI (P = 0.023 and P = 0.001 respectively), fCP was significant associated with FEV1 (P = 0.01). AUC insulin/AUC glucose ratio (P < 0.0001) and AUC c-peptide/AUC glucose ratio (P = 0.0001) were significantly associated with FEV1.. Insulin deficiency in CF patients with NGT has a significant impact on clinical outcomes.

Topics: Adolescent; Area Under Curve; Blood Glucose; C-Peptide; Child; Cystic Fibrosis; Fasting; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Linear Models; Male; Nutritional Status; Respiration; Retrospective Studies; Young Adult

Glucagon like peptide 1 (GLP-1) is an incretin hormone released as a bioactive peptide from intestinal L-cells in response to eating. It acts on target cells and exerts several functions as stimulating insulin and inhibiting glucagon. It is quickly deactivated by the serine protease dipeptidyl peptidase IV (DPP-IV) as an important regulatory mechanism. GLP-1 analogues are used as antidiabetic drugs in patients with type 2 diabetes. We served patients with cystic fibrosis (CF, n=29), cystic fibrosis related diabetes (CFRD, n=19) and healthy controls (n=18) a standardized breakfast (23 g protein, 25 g fat and 76 g carbohydrates) after an overnight fasting. Blood samples were collected before meal as well as 15, 30, 45 and 60 min after the meal in tubes prefilled with a DPP-IV inhibitor. The aim of the study was to compare levels of GLP-1 in patients with CF, CFRD and in healthy controls. We found that active GLP-1 was significantly decreased in patients with CF and CFRD compared to in healthy controls (p<0.01). However, levels in patients with CFRD tended to be lower but were not significantly lower than in patients with CF without diabetes (p=0.06). Total GLP-1 did not differ between the groups, which points to that the inactive form of GLP-1 is more pronounced in CF patients. The endogenous insulin production (measured by C-peptide) was significantly lower in patients with CFRD as expected. However, levels in non-diabetic CF patients did not differ from the controls. We suggest that the decreased levels of GLP-1 could affect the progression toward CFRD and that more studies need to be performed in order to evaluate a possible treatment with GLP-1 analogues in CF-patients.

Topics: Adult; C-Peptide; Comorbidity; Cystic Fibrosis; Diabetes Mellitus; Disease Progression; Female; Glucagon-Like Peptide 1; Humans; Male; Middle Aged; Postprandial Period; Young Adult

Cystic fibrosis (CF)-related diabetes is a leading complication of CF and is associated with pulmonary and nutritional deterioration, years before an evident hyperglycemia, possibly because of insulin deficiency and resistance.. To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population.. A total of 165 CF subjects (80 females) aged 17±5 years and 18 age- and sex-matched healthy controls (CON) received an oral glucose tolerance test with glucose, insulin and C-peptide determinations. Insulin sensitivity was defined on the basis of glucose and insulin concentrations using the oral glucose insulin sensitivity index, whereas β-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration.. Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. β-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6  pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7  pmol/min per m(2) per mM per year (confidence interval (CI) -4.5 to -0.82), i.e. almost 4% yearly. The early insulin secretion index was also reduced. Insulin sensitivity was similar to CON. CF patients who attained glucose tolerance comparable to CON had lower β-cell function and higher insulin sensitivity.. The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining β-cell function, consisting of delayed and reduced responsiveness to hyperglycemia, that in CF patients with normal glucose tolerance may be compensated by an increased insulin sensitivity.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Glucose Intolerance; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Insulin Secretion; Male

Patients with end-stage cystic fibrosis (CF) and severe CF-related diabetes (CFRD) may benefit from combined lung-pancreatic islet transplantation. In the present study, we report the long-term follow-up of four end-stage CF patients treated with combined bilateral lung and pancreatic islet transplantation from the same donor. All patients were C-peptide negative (<0.5 microg/L) and inadequately controlled despite intensive insulin treatment. One patient was transplanted with 4 019 +/- 490 islet equivalent/kg injected into the transverse colic vein using a surgical approach. In the remaining three patients, islets were cultured for 3-6 days and transplanted by percutaneous transhepatic catheterization of the portal vein. In all patients, islet allograft recovery was recognized by elevation in the plasma level of C-peptide (>0.5 microg/L). At 6 months after transplantation, one patient showed multiple episodes of acute lung transplant rejection and a progressive decline in pancreatic islet cell function. Three out of four patients experienced an improved control of glucose levels with a HbA1c of 5.2%, 7% and 6% respectively at 1.5, 2 and 15 years follow-up. Compared with the pretransplant period, there was a 50% reduction in mean daily insulin needs. Pulmonary function remained satisfactory in all patients. In conclusion, our cases series shows that combined bilateral lung and pancreatic islet transplantation may be a viable therapeutic option for patients with end-stage CF and CFRD.

Topics: Adolescent; Adult; Age of Onset; C-Peptide; Combined Modality Therapy; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Diabetes Complications; Forced Expiratory Volume; Humans; Islets of Langerhans Transplantation; Lung Transplantation; Male; Mutation; Sequence Deletion; Transplantation, Homologous; Treatment Outcome; Vital Capacity; Young Adult

The determination of endocrine and exocrine pancreatic function in cystic fibrosis patients is clinically important. Recently, a new non-invasive test, in which pancreatic stimulation by a Lundh meal is followed by sequential serum lipase measurements, was found to be a good indicator of exocrine pancreatic status. Since the Lundh meal also contains glucose, the present study assessed whether it also might be suitable for evaluation of the pancreatic endocrine axis. After an overnight fast, 10 healthy non-diabetic subjects and 14 cystic fibrosis patients ingested a Lundh meal. Glucose, insulin, and C peptide levels were measured at various time intervals following the meal. For purposes of comparison, the oral glucose tolerance test was also performed on the cystic fibrosis patients. All healthy subjects demonstrated an increase in glucose levels post Lundh meal, peaking at 45 min (mean 140+/-21 mg/dl) and then gradually declining and reaching the normal range at 120 min. Concordant peaks of insulin (46.3+/-20 IU/ml) and C peptide (5.8+/-1. 5 ng/ml) levels were noted at 60 min. All 14 cystic fibrosis patients had normal basal glucose levels: in 8, the pattern of glucose, insulin, and C peptide post Lundh meal was similar to that of the healthy controls. These 8 patients also had a normal oral glucose tolerance test, and their hemoglobin A(1C) levels were within the normal range. The other 6 cystic fibrosis patients demonstrated glucose levels above 200 mg/dl 30-60 min post Lundh meal, and all also had an impaired oral glucose tolerance test. Of these 6, 4 had high levels of hemoglobin A(1C). This study demonstrates that the Lundh meal challenges the endocrine pancreas as well as the oral glucose tolerance test. Thus, determination of both exocrine and endocrine pancreatic status can be achieved by a single non-invasive test.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Case-Control Studies; Cystic Fibrosis; Diet; Evaluation Studies as Topic; Female; Glucose Tolerance Test; Humans; Insulin; Islets of Langerhans; Male; Pancreas; Pancreatic Function Tests; Time Factors

Impaired glucose tolerance and secondary diabetes are frequent in older patients with cystic fibrosis (CF), associated with increased frequency of infections and reduced life expectancy. Studies on the pathophysiology of islet cell secretion in CF are a prerequisite for a scientifically based therapeutic approach.. Oral glucose tolerance tests were performed in 71 patients (14.2 +/- 0.5 years; mean +/- SE) and 56 control subjects (16.5 +/- 0.9 years). Glucose, insulin, C-peptide, and proinsulin were measured every 30 min.. Glucose tolerance in CF patients was classified as normal (NGT, n = 48), impaired (IGT, n = 14), or diabetic (DM, n = 9). Even in CF patients with NGT, blood glucose was significantly elevated at 30, 60, and 90 min of the test. Surprisingly, the secretory responses of insulin and C-peptide were not reduced in CF patients with IGT or DM compared with both healthy controls or CF patients with normal glucose tolerance. However, peak insulin concentration was reached at 90 min in CF-IGT or CF-DM patients compared with 30 min in controls. The ratio of glucose to insulin, an indicator of insulin resistance, increased in CF patients with progression of carbohydrate intolerance. Proinsulin was significantly reduced in all CF patients compared with controls (p < 0.001; Wilcoxon's rank sum test).. In CF patients with impaired glucose tolerance or diabetes, integrated insulin release is not diminished, indicating that insulin resistance is likely to contribute to hyperglycemia in CF patients with IGT or DM. Reduced proinsulin levels in CF patients are compatible either with enhanced conversion of proinsulin to insulin in compensation for reduced beta-cell mass, or enhanced clearance of proinsulin.

Topics: Adolescent; Blood Glucose; C-Peptide; Cohort Studies; Cystic Fibrosis; Diabetes Mellitus, Type 1; Female; Glucose Tolerance Test; Humans; Insulin; Insulin Resistance; Male; Proinsulin; Reference Values; Time Factors

We hypothesized that elevated hepatic glucose output (HGO) may occur in children with cystic fibrosis (CF) as an early sign of declining insulin secretion and that tolbutamide therapy would correct the defect. We studied eight glucose-tolerant CF patients (mean +/- SD, 9.1 +/- 1.9 y) and five healthy controls (9.0 +/- 1.6 y). Fasting glucose, insulin, and insulin-connecting peptide concentrations were not different in the CF and control subjects; however, meal stimulation tests in the CF patients suggested that insulin secretion was defective in the fed state. HGO (mg.kg-1 body weight.min-1) was 26% higher in the CF patients (4.2 +/- 0.7 versus 3.1 +/- 0.6 in HC) (p = 0.016). When normalized for fat-free mass (mg.kg fat-free mass-1.min-1), HGO was 27% higher in CF (4.9 +/- 0.8 versus 3.8 +/- 0.5) (p = 0.015). However, when expressed as a function of resting energy expenditure (mg.kcal-1), HGO was not significantly different in CF (121 +/- 22) versus healthy controls (116 +/- 30). In seven of the CF group, HGO was re-assessed after a 2-h glucose infusion at a rate of 0.90 +/- 0.02 mg.kg-1.min-1. HGO was suppressed (p < 0.05) by an amount equal to 103 +/- 18% of the glucose infusion rate. Finally, in five CF patients, HGO was re-measured after 2 wk of oral therapy with tolbutamide (750 mg/d). Tolbutamide did not affect HGO (fasting or during the glucose infusion). In conclusion, fasting HGO was elevated in the CF patients in proportion to energy expenditure.

Topics: C-Peptide; Child; Cystic Fibrosis; Fasting; Female; Glucose; Humans; Infusions, Intravenous; Insulin; Liver; Male; Tolbutamide

We examined the effect of intravenous (i.v.) tolbutamide administration on glucose and hormone levels in cystic fibrosis (CF) patients with impaired first-phase insulin secretion and oral glucose tolerance (oral glucose tolerance test [OGTT]) and compared them with CF patients with only an impaired first-phase insulin secretion and healthy control subjects. Five CF patients with an impaired OGTT, ie, a serum glucose value of 7.8 mmol/L or greater 120 minutes after an oral glucose load (group I), five CF patients with a normal OGTT, ie, a serum glucose not exceeding 7.8 mmol/L 120 minutes after oral glucose (group II), and five healthy control (CON) subjects underwent IV glucose tolerance tests with glucose alone (IVGTT) and glucose administered in conjunction with tolbutamide ([IVTTT] 25 mg/kg; maximum dose, 1 g). Serum glucose levels were measured using the glucose oxidase method; insulin, C-peptide, and glucagon levels were measured by the double-antibody radioimmunoassay (RIA) technique. Serum immunoreactive trypsin (IRT) and hemoglobin A1 (HbA1) levels and height and weight were measured for each subject, and in addition, pulmonary function was assessed in those with CF. There were no significant differences in the area under the curve (AUC) for glucose or glucose or glucagon levels or the serum glucose disappearance rate (k value) between group I, group II, or CON subjects during the IVGTT. First-phase insulin and C-peptide secretion was abnormal during IVGTT and IVTTT in the CF groups: in group I it was severely impaired, whereas in group II it was between group I and CON values. During the IVTTT serum glucose levels and glucose k values were not significantly altered in any of the three groups as compared with the IVGTT.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Oral; Adolescent; Adult; C-Peptide; Cystic Fibrosis; Female; Glucagon; Glucose; Glucose Tolerance Test; Humans; Infusions, Intravenous; Insulin; Insulin Secretion; Male; Tolbutamide

We have evaluated the metabolic clearance rate (MCR) of insulin and insulin sensitivity in 12 older patients with cystic fibrosis (CF) using the hyperinsulinemic euglycemic clamp method. Compared with a control group matched accurately for age and body mass index (BMI), the MCR of insulin was significantly enhanced in CF CF = 21.85 +/- 1.17 v controls = 16.01 +/- 0.92 mL/kg/min, P < .005), and this difference persisted after correction for lean body mass ([LBM] CF = 26.32 +/- 1.28 v controls = 19.09 +/- 1.09 mL/kg LBM/min, P < .005). Glucose disposal rates (M) were similar in the two groups during the clamp (CF = 7.28 +/- 0.41 v controls = 6.83 +/- 0.60 mg/kg/min, P > .5), but the insulin sensitivity index, M/I x 100 (I = steady-state insulin concentration), was markedly increased in the CF group (CF = 17.62 +/- 1.30 v controls = 11.75 +/- 0.71, P < .005). In conclusion, the MCR of insulin is enhanced in CF, which is in keeping with previous observations on drug metabolism in this disorder. Second, insulin sensitivity is increased in CF, and this points to a compensatory mechanism to counteract the insulinopenia.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Female; Glucose Clamp Technique; Glucose Intolerance; Humans; Insulin; Insulin Resistance; Male; Metabolic Clearance Rate

Immunohistochemical studies of pancreatic tissue from patients with cystic fibrosis associated with diabetes mellitus (CFDM) show increased numbers of somatostatin secreting delta cells. To look for a possible functional correlate to this finding basal and arginine stimulated plasma somatostatin and serum C peptide concentrations in eight insulin treated patients with cystic fibrosis and eight normal male controls were measured. Mean basal somatostatin concentrations were not different in the two groups. Mean peak somatostatin concentrations were significantly higher in the group with CFDM: 11.60 pmol/l v 7.14 pmol/l in controls. Mean peak C peptide concentrations were significantly lower in the group with cystic fibrosis: 0.89 nmol/l v 4.27 nmol/l in controls. This observation provides a physiological correlate to the pathological finding of increased somatostatin content in pancreatic tissue from patients with CFDM. Selective preservation of somatostatin secretion in patients with cystic fibrosis may further complicate pancreatic endocrine insufficiencies through paracrine inhibition of insulin and glucagon secretion.

Topics: Adult; C-Peptide; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Female; Humans; Immunohistochemistry; Islets of Langerhans; Male; Pancreas; Somatostatin

Glucose tolerance is often impaired in Cystic Fibrosis. The impact of this condition on enteral nutritional support in case of malnourishment remains to be studied.. In this study the glucose-, C-peptide- and insulin-responses to an OGTT and a standard enteral formula load were investigated in 19 non-diabetic CF-patients. Each test was performed with a carbohydrate load of 1.75 g/kg bodyweight.. 11 patients had a normal OGTT (Group I) and 8 had an impaired glucose tolerance (Group II). After the formula load the glucose concentrations were significantly lower than after the OGTT at 30, 60, and 90 min in both groups and at 120 min in group II only. In group II the glucose values exceeded 6.7 mmol/l at 120 min after both OGTT and formula load and were significantly higher than in group I. The food glycaemic index, a parameter for comparison of glucose response to different diets was calculated. It ranged from 30 to 80% in both groups. An increased C-peptide- and insulin-secretion was found in patients with impaired glucose tolerance.. The condition of impaired glucose tolerance must be considered for enteral hyperalimentation of Cystic Fibrosis-patients. The selection of formulas for nutritional support should be based on the calculation of the Food Glycemic Index because of its high interindividual variability.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Child, Preschool; Cystic Fibrosis; Dietary Carbohydrates; Enteral Nutrition; Female; Food, Formulated; Glucose Tolerance Test; Humans; Insulin; Male

Pancreatic and gut hormone responses to oral glucose, and insulin sensitivity were studied in cystic fibrosis patients with normal (N = 14), impaired (N = 4), and diabetic (N = 12) glucose tolerance, and in 10 control subjects, and beta cell responses to oral glucose and intravenous glucagon were compared. Compared to control subjects, initial insulin and C-peptide responses to oral glucose were lower in all patient groups, and decreased with decreasing glucose tolerance. Insulin sensitivity in patients with impaired and diabetic glucose tolerance was lower than in control subjects. The 6 min post-glucagon C-peptide concentration was positively correlated with the initial insulin response to oral glucose. Fasting levels of pancreatic polypeptide, pancreatic glucagon, total glucagon, glucagon-like peptide-1 7-36 amide, and gastric inhibitory polypeptide were normal in all patient groups. Following oral glucose, pancreatic polypeptide responses were absent in all patients, suppressibility of pancreatic glucagon secretion was increasingly impaired with decreasing glucose tolerance, and gut hormone levels were normal. In conclusion, at cystic fibrosis (a) insulin secretion is impaired even when glucose tolerance and insulin sensitivity are within the normal range, (b) the glucagon test gives valid estimates of residual beta cell function, (c) pancreatic polypeptide response to oral glucose is absent, (d) glucagon suppressibility decreases with decreasing glucose tolerance, and (e) the enteroinsular axis is intact.

Topics: Administration, Oral; Adult; C-Peptide; Cystic Fibrosis; Diabetes Complications; Diabetes Mellitus; Female; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glucagon-Like Peptides; Glucose; Glucose Tolerance Test; Hormones; Humans; Injections, Intravenous; Insulin; Intestinal Mucosa; Intestines; Male; Middle Aged; Pancreas; Pancreatic Polypeptide; Peptide Fragments; Proinsulin; Protein Precursors; Time Factors

Pancreatic endocrine function was studied in 50 patients with cystic fibrosis (CF) and 15 healthy controls by measuring glucose, insulin, C-peptide, glucagon and gastro-inhibitory polypeptide responses to an oral glucose tolerance test (OGTT). Biochemical and clinical parameters were also measured, including glycosylated hemoglobin A1, serum immunoreactive trypsin, fasting urinalysis, pulmonary function, percentage body fat and 3-day dietary records. According to National Diabetes Data Group (NDDG) criteria, 6 CF patients had impaired glucose tolerance (ICF), with elevated serum glucose concentrations and reduced and delayed insulin secretion compared with control (CON) subjects, although none were overtly diabetic. Although the remaining 44 CF patients (NCF) did not meet NDDG criteria for impaired glucose tolerance, mean area under the concentration curve (AUC) for glucose was greater than control values and AUC for insulin diminished. HbA1 levels in the 2 CF groups were greater than that of controls subjects, but there was little difference between ICF and NCF groups. C-peptide levels paralleled those of insulin for the 3 groups throughout OGTT. There was little difference in GIP secretion between groups, and the enteroinsular axis was intact in the control and NCF groups and slightly increased in the ICF group. Basal glucagon concentrations and AUC for glucagon during OGTT were similar for the 3 groups, but glucose-induced glucagon suppressibility i.e., basal to nadir change in each subject, was reduced in the ICF group. Serum IRT concentration was significantly lower in the ICF and NCF groups compared to control subjects, and was lowest in the ICF group. A strong correlation was observed in the ICF group between FEF25-75 and AUC for insulin, as well as HbA1 level and AUC for glucose. The prevalence of impaired glucose tolerance in 50 CF patients was 12%. Despite extensive comparisons of biochemical and clinical parameters with endocrine function in this population, we were unable to define reliable criteria for predicting glucose intolerance.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cystic Fibrosis; Eating; Female; Forced Expiratory Flow Rates; Gastric Inhibitory Polypeptide; Glucagon; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperglycemia; Insulin; Insulin Secretion; Islets of Langerhans; Male; Reference Values; Time Factors

To characterize pancreatic endocrine secretion and to examine interrelationships among alterations in alpha, beta, and pancreatic polypeptide cell function in patients with cystic fibrosis (CF), we studied 19 patients with exocrine insufficiency (EXO), including 9 receiving insulin therapy (EXO-IT); 10 patients with no exocrine insufficiency (NEXO); and 10 normal control subjects. First-phase C-peptide response to intravenously administered glucose was significantly impaired in CF patients with exocrine insufficiency (EXO-IT = 0.02 +/- 0.01; EXO = 0.11 +/- 0.02; NEXO = 0.25 +/- 0.05; control subjects = 0.30 +/- 0.04 nmol/L). Lowering fasting glucose levels with exogenous insulin administration in EXO-IT did not improve beta cell responsivity to glucose. The C-peptide response to arginine was less impaired (EXO-IT = 0.12 +/- 0.02; EXO = 0.15 +/- 0.02; NEXO = 0.23 +/- 0.06; control subjects = 0.28 +/- 0.04 nmol/L). Alpha cell function, measured as peak glucagon secretion in response to hypoglycemia, was diminished in EXO but not NEXO (EXO-IT = 21 +/- 10; EXO = 62 +/- 19; NEXO = 123 +/- 29; control subjects = 109 +/- 12 ng/L). Despite diminished glucagon response, EXO patients recovered normally from hypoglycemia. Peak pancreatic polypeptide response to hypoglycemia distinguished CF patients with exocrine insufficiency from those without exocrine insufficiency (EXO-IT = 3 +/- 2; EXO = 3 +/- 1; NEXO = 226 +/- 68; control subjects = 273 +/- 100 pmol/L). Thus CF patients with exocrine disease have less alpha, beta, and pancreatic polypeptide cell function than CF patients without exocrine disease. These data suggest either that exocrine disease causes endocrine dysfunction in CF or that a common pathogenic process simultaneously and independently impairs exocrine and endocrine function.

Topics: Adult; Arginine; C-Peptide; Cystic Fibrosis; Fasting; Glucagon; Glucose Tolerance Test; Humans; Hyperglycemia; Hypoglycemia; Insulin; Pancreas; Pancreatic Polypeptide; Time Factors

Beta cell function, peripheral sensitivity to insulin and specific pancreatic autoimmunity were studied in 30 youngsters with cystic fibrosis (CF) accurately selected in order to fulfill the criteria for normal glucose tolerance. With respect to weight-matched controls, patients with CF exhibited a significantly lower glucose tolerance and a globally preserved, although delayed, insulin response to oral glucose tolerance test, while first-phase insulin secretion after i.v. glucose was blunted. Peripheral sensitivity to insulin, assessed in vivo by both the euglycemic clamp technique and the number of insulin receptors, directly measured in circulating monocytes, was superimposable in patients and controls. Serum islet-cell antibodies were not found in any of the patients. In conclusion, disorders of beta cell function may be observed in CF patients even when glucose tolerance is within the normal range. Such abnormalities are not associated with changes in peripheral sensitivity to insulin and do not seem to depend on specific autoimmune events.

Topics: Autoantibodies; Blood Glucose; C-Peptide; Child; Cystic Fibrosis; Female; Glucose Clamp Technique; Glucose Tolerance Test; Humans; Insulin; Insulin Secretion; Islets of Langerhans; Leukocytes, Mononuclear; Male; Receptor, Insulin; Reference Values

The beta-cell response to an oral glucose load was studied in 22 patients with cystic fibrosis (CF) by means of insulin, C-peptide and proinsulin, and the results compared with those from 20 healthy sex and age matched controls. According to WHO criteria two had diabetes mellitus, eight had impaired glucose tolerance and twelve had normal glucose tolerance. All patients showed lower insulin and C-peptide levels than the controls at 30 minutes. However the insulin and C-peptide responses were sustained so that the areas under the curves were comparable between controls, CF patients with normal glucose tolerance, and CF patients with impaired glucose tolerance. By contrast, the area under the proinsulin curve was significantly higher in the CF patients with impaired glucose tolerance compared with both controls (p less than 0.05) and with the CF normal glucose tolerance group (p less than 0.02). In the CF patients with impaired glucose tolerance the proinsulin level was significantly elevated at 120 minutes (median 50 pmol/l) and at 180 minutes (29 pmol/l) as compared with the controls (24 and 19 pmol/l p less than 0.01) and with the CF patients with normal glucose tolerance (21 and 16 pmol/l p less than 0.01). These data confirm that impaired glucose tolerance and diabetes is frequent in cystic fibrosis. The elevated proinsulin immunoreactive material in CF patients with impaired glucose tolerance may partly compensate for the relative insufficient insulin response found in these patients.

Topics: Adolescent; Blood Glucose; C-Peptide; Child; Cystic Fibrosis; Glucose Tolerance Test; Humans; Insulin; Male; Proinsulin; Reference Values

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.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Child; Child, Preschool; Cystic Fibrosis; Diabetes Mellitus, Type 1; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Infant

Immunoreactive Insulin and C-peptide responses to glucose load were estimated in patients with cystic fibrosis and in controls. Both insulin and C-peptide responses were low in cystic fibrosis patients and the changes were more marked in those with glucose intolerance. There appears to be true pancreatic hyposecretion of insulin in patients with cystic fibrosis whereas the peripheral sensitivity of insulin seems to be normal or enhanced.

Topics: Adolescent; Adult; C-Peptide; Child; Cystic Fibrosis; Diabetes Mellitus; Female; Glucose; Glucose Tolerance Test; Humans; Insulin; Male; Reference Values

An assessment of beta cell and exocrine pancreatic reserve based on fasting C peptide and immunoreactive trypsin (IRT) concentrations was carried out in non-diabetic (fasting blood glucose less than 6 mmol/l) patients with cystic fibrosis (CF; n = 20) and their parents (heterozygotes; n = 26). These indices were also measured in comparable control subjects (n = 20) and insulin-dependent diabetics (IDDs). C peptide concentrations in 18 CF patients were markedly lower than those in controls, and in 18 were comparable to those in IDDs (n = 27). Fasting C peptide concentration in heterozygotes was also significantly lower than that in controls and was significantly greater than that in IDDs. IRT concentrations in CF patients and heterozygotes were also significantly lower than those in controls. The frequency of subnormal C peptide concentrations was greater in CF patients with non-measurable IRT than in those who had residual IRT in their sera. These data show for the first time that the diminution in beta cell reserve in CF patients may be of a magnitude similar to that in IDDs in spite of their normal blood glucose and HbA1 concentrations. Therefore, these patients may have enhanced insulin sensitivity. CF heterozygotes too have a significant diminution in endocrine and exocrine pancreatic reserve when compared with the controls.

Topics: Adolescent; Adult; C-Peptide; Cystic Fibrosis; Diabetes Mellitus; Female; Heterozygote; Humans; Islets of Langerhans; Male; Middle Aged; Trypsin