RESUMEN
Objective: Cystic fibrosis (CF)-related diabetes (CFRD) resulting from partial-to-complete insulin deficiency occurs in 40-50% of adults with CF. In people with CFRD, poor glycemic control leads to a catabolic state that may aggravate CF-induced nutritional impairment and loss of muscle mass. Sensor augmented pump (SAP) therapy may improve glycemic control as compared to multiple daily injection (MDI) therapy. Research design and methods: This non-randomized clinical trial was aimed at evaluating the effects of insulin therapy optimization with SAP therapy, combined with a structured educational program, on glycemic control and body composition in individuals with insulin-requiring CFRD. Of 46 participants who were offered to switch from MDI to SAP therapy, 20 accepted and 26 continued the MDI therapy. Baseline demographic and clinical characteristics were balanced between groups using a propensity score-based overlap weighting procedure and weighted mixed-effects regression models were used to estimate changes in study outcomes. Results: After 24 months changes in HbA1c were: -1.1% (-12.1 mmol/mol) (95% CI: -1.5; -0.8) and -0.1% (-1 mmol/mol) (95% CI: -0.5; 0.3) in the SAP and MDI therapy group, respectively, with a between-group difference of -1.0 (-10 mmol/mol) (-1.5; -0.5). SAP therapy was also associated with a decrease in mean glucose (between group difference: -32 mg/dL; 95% CI: -44; -20) and an increase in TIR (between group difference: 19.3%; 95% CI 13.9; 24.7) and in fat-free mass (between group difference: +5.5 Kg, 95% CI: 3.2; 7.8). Conclusion: Therapy optimization with SAP led to a significant improvement in glycemic control, which was associated with an increase in fat-free mass.
Asunto(s)
Fibrosis Quística , Diabetes Mellitus , Insulina , Adulto , Humanos , Composición Corporal , Fibrosis Quística/complicaciones , Fibrosis Quística/tratamiento farmacológico , Control Glucémico , Insulina/uso terapéuticoRESUMEN
BACKGROUND: 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. AIM: To evaluate glucose tolerance, insulin secretion, and insulin sensitivity by a widely applicable method suitable for accurate and prospective measurements in a CF population. METHODS: 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 ß-cell function was determined on the basis of a model relating insulin secretion (C-peptide profile) to glucose concentration. RESULTS: Fifteen percent of CF patients had glucose intolerance and 6% had diabetes without fasting hyperglycemia and 3% had diabetes with fasting hyperglycemia. ß-cell function was reduced in CF patients compared with CON (70.0±4.1 vs 117.9±11.6â pmol/min per m(2) per mM, P<0.001) and decreased significantly with age by -2.7 âpmol/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 ß-cell function and higher insulin sensitivity. CONCLUSION: The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining ß-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.
Asunto(s)
Fibrosis Quística/fisiopatología , Diabetes Mellitus/etiología , Prueba de Tolerancia a la Glucosa , Resistencia a la Insulina/fisiología , Insulina/metabolismo , Adolescente , Adulto , Péptido C/metabolismo , Fibrosis Quística/complicaciones , Femenino , Intolerancia a la Glucosa/etiología , Humanos , Insulina/fisiología , Secreción de Insulina , MasculinoRESUMEN
OBJECTIVE: Diabetes frequently complicates cystic fibrosis (CF) without fasting hyperglycemia or despite spontaneous hypoglycemia (anecdotally ascribed to malnutrition), whose prevalence, clinical meaning, and relationship with glucose tolerance and clinical/nutritional status were not previously investigated. The relationship of CF genotype with insulin secretion control is also unclear. DESIGN AND METHODS: A total of 129 CF patients without stable diabetes received 188 oral glucose tolerance tests. Distribution of fasting plasma glucose (FPG), glucose, insulin and C-peptide responses, clinical/nutritional variables, and their relationships were analyzed. RESULTS: FPG < 60 mg/dl (3.3 mmo/l) was detected in 14% of studies and reactive hypoglycemia (PG < 50 mg/dl (2.8 mmo/l)) in 15%. OGTT-based diabetes frequency was similar in the lowest quartile (Q1) and Q2-3 for FPG (10 and 8%), with higher glucose increment and area under the curve in Q1. Insulin and C-peptide levels were similar among FPG quartiles. Class I cystic fibrosis transmembrane conductance regulator mutation carriers had higher insulin concentrations than class II, especially in Q1 for FPG. Age, sex, nutritional, and anthropometric parameters including fat and lean body mass were unrelated to FPG. Lower FPG was associated with more frequent hospitalization rates (P = 0.002) and lower Shwachman scores (P = 0.041). Steroids weaning was accurately evaluated but then excluded as a possible cause of hypoglycemia. CONCLUSIONS/INTERPRETATION: Fasting asymptomatic hypoglycemia is frequent and possibly related to inappropriate insulin secretion control in class I mutation carriers. Low FPG does not exclude impaired glucose tolerance (IGT) and diabetes in CF and reflects worse clinical status.