Spontaneous hypoglycemia in patients with cystic fibrosis

Battezzati, Alberto; Battezzati, Pier Maria; Costantini, D.; Seia, Manuela; Zazzeron, L.; Russo, Maria Chiara; Daccò, Valeria; Bertoli, Simona; Crosignani, Andrea; Colombo, Carla

doi:10.1530/eje.1.02344

Cited by 47 publications

(65 citation statements)

References 40 publications

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“…Although there are reports on hypoglycaemic episodes in patients with CF [15] the role of exercise as trigger of symptomatic hypoglycaemias has not been explored. We found an incidence of exercise-induced symptomatic hypoglycaemia in 0.4% of all patients represented in our caregiver survey and 0.8% in the patient survey.…”

Section: Discussionmentioning

confidence: 99%

Risks associated with exercise testing and sports participation in cystic fibrosis

Ruf

Winkler

Hebestreit

et al. 2010

Journal of Cystic Fibrosis

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Section: Discussionmentioning

confidence: 99%

Risks associated with exercise testing and sports participation in cystic fibrosis

Ruf

Winkler

Hebestreit

et al. 2010

Journal of Cystic Fibrosis

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“…Consistent with this, insulin levels failed to decrease with lower glucose levels in nursing CF kits, while glucose and insulin levels were positively correlated in nursing non-CF kits (Supplemental Figure 3A). These tendencies observed in CF kits toward insulin oversecretion might play a role in the hypoglycemia that is observed in humans with CF (63,64).…”

Section: Figurementioning

confidence: 91%

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

Olivier¹,

Yi²,

Sun³

et al. 2012

J. Clin. Invest.

122

143

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Diabetes is a common comorbidity in cystic fibrosis (CF) that worsens prognosis. The lack of an animal model for CF-related diabetes (CFRD) has made it difficult to dissect how the onset of pancreatic pathology influences the emergence of CFRD. We evaluated the structure and function of the neonatal CF endocrine pancreas using a new CFTR-knockout ferret model. Although CF kits are born with only mild exocrine pancreas disease, progressive exocrine and endocrine pancreatic loss during the first months of life was associated with pancreatic inflammation, spontaneous hyperglycemia, and glucose intolerance. Interestingly, prior to major exocrine pancreas disease, CF kits demonstrated significant abnormalities in blood glucose and insulin regulation, including diminished first-phase and accentuated peak insulin secretion in response to glucose, elevated peak glucose levels following glucose challenge, and variably elevated insulin and C-peptide levels in the nonfasted state. Although there was no difference in lobular insulin and glucagon expression between genotypes at birth, significant alterations in the frequencies of small and large islets were observed. Newborn cultured CF islets demonstrated dysregulated glucose-dependent insulin secretion in comparison to controls, suggesting intrinsic abnormalities in CF islets. These findings demonstrate that early abnormalities exist in the regulation of insulin secretion by the CF endocrine pancreas. IntroductionCystic fibrosis (CF) is caused by defects in the CF transmembrane conductance regulator (CFTR) chloride channel. Cystic fibrosisrelated diabetes (CFRD) is a common complication of CF and affects 20%-25% of adolescents and 40%-50% of individuals over 30 years of age (1,2). CFRD is associated with worsening clinical status, including reduced pulmonary function, increased frequency of pulmonary exacerbations, and a decline in nutritional status (3-7). Furthermore, CFRD leads to increased mortality compared with CF patients without diabetes (4,8). Thus, early diagnosis and treatment are vital to improving clinical outcome of CFRD patients.While the pathophysiology of CFRD is multifactorial, delayed insulin secretion appears to be a key hallmark of disease progression (9-12), and the health of CF patients is improved by insulin therapy prior to and following diagnosis of overt diabetes (13,14). Partial insulin deficiency occurs in part due to islet loss associated with exocrine pancreas disease (15-18). However, CF pancreata at CFRD autopsy demonstrate that remaining islets contain roughly half the number of insulin-positive cells found in non-CF controls (17,18), and this degree of β cell loss is thought to be insufficient to explain diabetes (19). Thus, insulin deficiency in CFRD is relative and not absolute. All stages of CFRD are characterized by abnormalities in circulating insulin levels (10,12,20,21). Impaired first-phase insulin (IFPI) responses are common in CFRD patients, but also occur in approximately 50% of CF children with normal glucose tolerance (9). Cu...

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“…Fasting glycemia is generally lower than in other forms of diabetes and fasting hypoglycemia has been reported (14). Therefore, the categories of 'diabetes without fasting hyperglycemia' (15) and of 'indeterminate glucose tolerance' (isolated hyperglycemia at mid-oral glucose tolerance test (OGTT) or continuous glucose monitoring) were established (16).…”

Section: Introductionmentioning

confidence: 99%

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

Battezzati

Mari

Zazzeron

et al. 2011

European Journal of Endocrinology

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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 17G5 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 b-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. b-cell function was reduced in CF patients compared with CON (70.0G4.1 vs 117.9G11.6 pmol/min per m 2 per mM, P!0.001) and decreased significantly with age by K2.7 pmol/min per m 2 per mM per year (confidence interval (CI) K4.5 to K0.82), 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 b-cell function and higher insulin sensitivity. Conclusion: The major alteration in insulin secretion and insulin sensitivity of CF patients is slowly declining b-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.

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Spontaneous hypoglycemia in patients with cystic fibrosis

Cited by 47 publications

References 40 publications

Risks associated with exercise testing and sports participation in cystic fibrosis

Risks associated with exercise testing and sports participation in cystic fibrosis

Abnormal endocrine pancreas function at birth in cystic fibrosis ferrets

Identification of insulin secretory defects and insulin resistance during oral glucose tolerance test in a cohort of cystic fibrosis patients

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