Cystic fibrosis-related diabetes mellitus: clinical impact of prediabetes and effects of insulin therapy* (original) (raw)
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Once daily insulin detemir in cystic fibrosis with insulin deficiency
Archives of Disease in Childhood, 2011
The aim of this study was to determine if once daily insulin detemir reverses decline in weight and lung function in patients with cystic fi brosis (CF). 12 patients with early insulin defi ciency and six with CF related diabetes (aged 7.2-18.1 years) were treated for a median of 0.8 years. Changes in weight and lung function following treatment were compared to pretreatment changes. Before treatment, the change in weight SD score (ΔWtSDS), percentage of predicted forced expiratory volume in 1 s (Δ%FEV 1) and percentage of predicted forced vital capacity (Δ%FVC) declined in the whole study population (−0.45±0.38, −7.9±12.8%, −5.8±14.3%) and in the subgroup with early insulin defi ciency (−0.41±0.43, −9.8±9.3%, −6.8±10.3%). Following treatment with insulin ΔWtSDS, Δ%FEV 1 and Δ%FVC signifi cantly improved in the whole study population (+0.18±0.29 SDS, p=0.0001; +3.7±10.6%, p=0.007; +5.2±12.7%, p=0.013) and in patients with early insulin defi ciency (+0.22±0.31 SDS, p=0.003; +5.3±11.5%, p=0.004; +5.8±13.4%, p=0.024). Randomised controlled trials are now needed.
European Journal of Endocrinology, 2005
Objective: To evaluate insulin-secretion kinetics and insulin sensitivity in cystic fibrosis (CF) patients with normal glucose tolerance (CF-NGT), impaired glucose tolerance (CF-IGT) or CF-related diabetes (CFRD), and the potential effects of moderate hyperglycemia on clinical and nutritional status. Design and methods: Cross-sectional study including 50 outpatients with CF. Patients underwent both oral (OGGT) and intravenous (IVGTT) glucose tolerance tests in order to assess insulin secretion and peripheral insulin sensitivity. Homeostasis assessment model and OGGT were used to investigate insulin sensitivity. Forced expiratory volume in the first second (FEV 1 ) and forced vital capacity (FVC) were measured to evaluate pulmonary function. Body mass index (BMI) was determined to assess nutritional status. Results: Insulin secretion was significantly decreased (and delayed at OGTT) in the CFRD group (n ¼ 9) versus the CF-IGT group (n ¼ 10) and the CF-IGT versus the CF-NGT group (n ¼ 31). Insulin sensitivity was significantly different in the CF-IGT and CFRD groups versus the CF-NGT group. FEV 1 , FVC and BMI presented a significant linear correlation with plasma glucose value at 120 min at OGTT and were significantly lower in both CF-IGT and CFRD versus the CF-NGT group, whereas no differences were found between the CF-IGT and CFRD groups. Conclusions: CF patients with IGT present diminished insulin secretion and increased peripheral insulin resistance, correlating with a worse clinical status, undernutrition and impaired pulmonary function. These findings open the question of whether early treatment of mild alterations of glucose metabolism with insulin secretagogues or short-action insulin may lead to improvement of clinical status in CF patients.
[Insulin therapy in patients with cystic fibrosis in the pre-diabetes stage: a systematic review]
Revista paulista de pediatria : orgao oficial da Sociedade de Pediatria de Sao Paulo, 2016
to elucidate whether insulin is effective or not in patients with cystic fibrosis before the diabetes mellitus phase. The study was performed according to the Prisma method between August and September 2014, using the PubMed, Embase, Lilacs and SciELO databases. Prospective studies published in English, Portuguese and Spanish from 2002 to 2015, evaluating the effect of insulin on weight parameters, body mass index and pulmonary function in patients with cystic fibrosis, with a mean age of 17.37 years before the diabetes mellitus phase were included. Eight articles were identified that included 180 patients undergoing insulin use. Sample size ranged from 4 to 54 patients, with a mean age ranging from 12.4 to 28 years. The type of follow-up, time of insulin use, the dose and implementation schedule were very heterogeneous between studies. There are theoretical reasons to believe that insulin has a beneficial effect in the studied population. The different methods and populations asses...
Clinical Nutrition, 2012
Background & aims: 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). Methods: We performed OGTT in 152 consecutive CF patients aged 8e20 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. Results: 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 ¼ 0.013, P ¼ 0.007), BMI-SDS (P ¼ 0.010, P ¼ 0.002), FEV1 (P ¼ 0.076, P ¼ 0.013) and FVC (P ¼ 0.101, P ¼ 0.009). Age-and genderadjusted regression analysis showed significant associations of fINS and fCP with SDS of BMI (P ¼ 0.023 and P ¼ 0.001 respectively), fCP was significant associated with FEV1 (P ¼ 0.01). AUC insulin/AUC glucose ratio (P < 0.0001) and AUC c-peptide/AUC glucose ratio (P ¼ 0.0001) were significantly associated with FEV1. Conclusions: Insulin deficiency in CF patients with NGT has a significant impact on clinical outcomes.
Journal of Cystic Fibrosis, 2010
Background: Patients with cystic fibrosis and normoglycemia (CF-NGT) have higher but still "normal" glucose levels in the Oral Glucose Tolerance Test (OGTT). Respiratory exacerbation is associated with metabolic stress. The objective of this study was to assess the glucose metabolism and its relation to the steady state pulmonary function (FEV1) in patients with CF-NGT, specifically during pulmonary exacerbations (PE). Methods: CF-NGT patients who were not on steroids, underwent OGTT and intravenous glucose tolerance tests (IVGTT) during PE and 4 weeks after complete recovery. Results: Of the ten recruited patients two had diabetic OGTT and were excluded. The remaining normoglycemic patients displayed during PE a diabetic glucose tolerance with mean glucose levels of 233 ± 8 and 262 ± 11 mg/dl at 90 and 120 min respectively, compared with normal levels of 154 ± 21and 126 ± 20 mg/dl (p b 0.002) during the steady state. IVGTT showed a tendency to higher first phase insulin release during PE compared with the steady state.(min 3; 305 ± 80 vs. 216 ± 40 pmol\l p = 0.075). Finally, when relating the diabetic status to the general respiratory function we found a negative correlation between baseline FEV1 and glucose levels at 2 h after OGTT during PE (r = − 0.88, p = 0.002). Conclusion: In this pilot study we show that during PE patients with CF and normal glucose tolerance exhibited early latent diabetic glucose intolerance. As this hyperglycemia presents in the later parts of the OGTT it probably results from insufficient second phase insulin secretion during PE. The negative correlation observed here between the diabetic glucose tolerance and FEV1 indicate the need of interventional studies using insulin during PE in non-diabetic patients to determine its potential benefit on the outcome from recurrent PEs.
Clinical importance of cystic fibrosis-related diabetes
Journal of Cystic Fibrosis, 2004
The prevalence of cystic fibrosis-related diabetes (CFRD) and glucose intolerance (IGT) has risen dramatically over the past 20 years as survival has increased for people with cystic fibrosis (CF). Diabetes is primarily caused by pancreatic damage, which reduces insulin secretion, but glucose tolerance is also modified by factors that alter insulin resistance, such as intercurrent illness and infection. CFRD not only causes the symptoms and micro and macrovascular complications seen in type 1 and type 2 diabetes in the general population, but also is associated with accelerated pulmonary decline and increased mortality. Pulmonary effects are seen some years before the diagnosis of CFRD, implying that impaired glucose tolerance may be detrimental. Current practice is to screen for changes in glucose tolerance by regular measurement of fasting blood glucose, by oral glucose tolerance test or a combination of these approaches with symptom review and measurement of HbA 1C. Treatment is clearly indicated for those with CFRD and fasting hyperglycaemia to control symptoms and reduce complications. As nutrition is critical in people with CF to maintain body mass and lung function, blood glucose should be controlled in CFRD by adjusting insulin doses to the requirements of adequate food intake and not by calorie restriction. It is less clear whether blood glucose control will have clinical benefits in the management of patients with CFRD without fasting hyperglycaemia or with impaired glucose tolerance and further studies are required to establish the best treatment for this patient group.
Chapter 2 Cystic Fibrosis – Related Diabetes
2018
Cystic fibrosis–related diabetes (CFRD) results in significant morbidity and mortality for patients with cystic fibrosis (CF). It is the endpoint of a spectrum of progressive insulin deficiency with resulting abnormalities of glucose tolerance. The consequence of glycaemic abnormalities in CF is poorer nutritional status, an increase in respiratory exacerbations with decline in lung function and ultimately greater morbidity and mortality. CFRD can be diagnosed by the standard oral glucose tolerance test (OGTT) usually performed from 10 years of age. However, this may miss early glycaemic abnormalities which appear to be clinically important. Early recognition of CFRD and treatment have been shown to improve outcomes in CF. Novel diagnostic methods such as 30-min sampled OGTT and continuous glucose monitoring (CGM) may prove to be useful in screening for this disorder and in the early identification of glycaemic abnormalities.