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Impaired fasting glucose in cystic fibrosis.

Frohnert BI, Ode KL, Moran A, Nathan BM, Laguna T, Holme B, Thomas W - Diabetes Care (2010)

Bottom Line: Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04-0.9]).IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29-1.48]).Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.

ABSTRACT

Objective: While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

Research design and methods: Data were retrieved from the University of Minnesota CF database on oral glucose tolerance tests (OGTTs) performed in 1996-2005. Subjects were identified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CF-related diabetes without fasting hyperglycemia (CFRD FH-). Patients with fasting hyperglycemia were excluded. The presence of IFG was assessed within each category. In a separate case-control cohort study, subjects with IFG were matched to CF control subjects by age, sex, and OGTT class to explore outcomes.

Results: For the total population (n = 310), the prevalence of IFG was 22%, and by OGTT class was NGT 14%, IGT 31%, CFRD FH- 53%. Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04-0.9]). IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29-1.48]). Lung function was better in pediatric IFG subjects with IGT and not significantly worse in adults with IGT or adults and children with NGT and CFRD FH-. BMI was not significantly different in IFG subjects versus control subjects.

Conclusions: Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.

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Related in: MedlinePlus

Model for fasting blood glucose and IFG in CF. A: In the normal population, fasting HGP is balanced by total body glucose utilization (GU). B: Inflammation, undernutrition, and perhaps the CF gene defect increase GU in CF patients. HGP is elevated for reasons that are not understood very well, but fasting glucose levels are normal when HGP and GU are in balance. C: In healthier CF patients, HGP is similarly elevated but GU is reduced, leading to IFG.
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Figure 1: Model for fasting blood glucose and IFG in CF. A: In the normal population, fasting HGP is balanced by total body glucose utilization (GU). B: Inflammation, undernutrition, and perhaps the CF gene defect increase GU in CF patients. HGP is elevated for reasons that are not understood very well, but fasting glucose levels are normal when HGP and GU are in balance. C: In healthier CF patients, HGP is similarly elevated but GU is reduced, leading to IFG.

Mentions: In CF, euglycemic clamp studies demonstrate normal peripheral insulin sensitivity in nondiabetic CF patients and only mild peripheral insulin resistance in those with diabetes (17). For reasons that are unclear, in contrast to peripheral skeletal muscle, hepatic insulin resistance with increased HGP is found even in nondiabetic CF patients with completely NFG levels (17–20). Glucose-mediated glucose uptake is normal (17). Because elevated HGP correlates with resting energy expenditure (18), we and others (17,18) have hypothesized that NFG levels are seen in the face of increased HGP because of an adaptive physiologic balance between high glucose utilization and elevated glucose production. The current study supports this hypothesis since healthier, better nourished CF patients would be expected to have lower resting energy needs in the fasting state, thus less ability to metabolize extra glucose produced by the liver and leading to IFG (Fig. 1).


Impaired fasting glucose in cystic fibrosis.

Frohnert BI, Ode KL, Moran A, Nathan BM, Laguna T, Holme B, Thomas W - Diabetes Care (2010)

Model for fasting blood glucose and IFG in CF. A: In the normal population, fasting HGP is balanced by total body glucose utilization (GU). B: Inflammation, undernutrition, and perhaps the CF gene defect increase GU in CF patients. HGP is elevated for reasons that are not understood very well, but fasting glucose levels are normal when HGP and GU are in balance. C: In healthier CF patients, HGP is similarly elevated but GU is reduced, leading to IFG.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2992208&req=5

Figure 1: Model for fasting blood glucose and IFG in CF. A: In the normal population, fasting HGP is balanced by total body glucose utilization (GU). B: Inflammation, undernutrition, and perhaps the CF gene defect increase GU in CF patients. HGP is elevated for reasons that are not understood very well, but fasting glucose levels are normal when HGP and GU are in balance. C: In healthier CF patients, HGP is similarly elevated but GU is reduced, leading to IFG.
Mentions: In CF, euglycemic clamp studies demonstrate normal peripheral insulin sensitivity in nondiabetic CF patients and only mild peripheral insulin resistance in those with diabetes (17). For reasons that are unclear, in contrast to peripheral skeletal muscle, hepatic insulin resistance with increased HGP is found even in nondiabetic CF patients with completely NFG levels (17–20). Glucose-mediated glucose uptake is normal (17). Because elevated HGP correlates with resting energy expenditure (18), we and others (17,18) have hypothesized that NFG levels are seen in the face of increased HGP because of an adaptive physiologic balance between high glucose utilization and elevated glucose production. The current study supports this hypothesis since healthier, better nourished CF patients would be expected to have lower resting energy needs in the fasting state, thus less ability to metabolize extra glucose produced by the liver and leading to IFG (Fig. 1).

Bottom Line: Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04-0.9]).IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29-1.48]).Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.

ABSTRACT

Objective: While glucose tolerance abnormalities are common in cystic fibrosis (CF), impaired fasting glucose (IFG) has scarcely been explored. No studies have examined the relation between IFG and clinical status.

Research design and methods: Data were retrieved from the University of Minnesota CF database on oral glucose tolerance tests (OGTTs) performed in 1996-2005. Subjects were identified as normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or CF-related diabetes without fasting hyperglycemia (CFRD FH-). Patients with fasting hyperglycemia were excluded. The presence of IFG was assessed within each category. In a separate case-control cohort study, subjects with IFG were matched to CF control subjects by age, sex, and OGTT class to explore outcomes.

Results: For the total population (n = 310), the prevalence of IFG was 22%, and by OGTT class was NGT 14%, IGT 31%, CFRD FH- 53%. Within the cohort study, mortality was significantly reduced in IFG (two vs. nine deaths, odds ratio [OR] = 0.2 [95% CI 0.04-0.9]). IFG did not confer increased risk of progression to diabetes (OR 0.66 [0.29-1.48]). Lung function was better in pediatric IFG subjects with IGT and not significantly worse in adults with IGT or adults and children with NGT and CFRD FH-. BMI was not significantly different in IFG subjects versus control subjects.

Conclusions: Contrary to expectations in patients with CF, IFG appeared to be associated with improved survival and was not associated with worse nutritional or pulmonary status or increased progression to fasting hyperglycemia.

Show MeSH
Related in: MedlinePlus