Glucose intolerance in children with cystic fibrosis

[Guest guest]

Hi,

I know I sound like a broken record when it comes to the oral glucose

tolerance test, but since it is still not part of the standard treatment

plan in the USA I feel it is important to inform the parents of teens and

preteens about it. You have to catch glucos intolerance as early as possible

and with the normal fasting blood sugar test you waste valuable time.

Peace

Torsten, dad of Fiona 6wcf

e-mail: torstenkrafft@...

Subject: CF: Glucose intolerance in children with cystic fibrosis

The Journal of Pediatrics, February 2003 . Volume 142

.. Number 2

Original Articles

Glucose intolerance in children with cystic fibrosis

Melinda P. Solomon, MD [MEDLINE LOOKUP]

C. , MD [MEDLINE LOOKUP]

Corey, PhD [MEDLINE LOOKUP]

Daina Kalnins, BSc [MEDLINE LOOKUP]

n Zielenski, PhD [MEDLINE LOOKUP]

Lap-Chee Tsui, PhD [MEDLINE LOOKUP]

Pencharz, MD, PhD [MEDLINE LOOKUP]

Durie, MD [MEDLINE LOOKUP]

Neil B. Sweezey, MD

Abstract TOP

Objective To evaluate the relations among glucose

intolerance, genotype, and exocrine pancreatic status

in patients with cystic fibrosis (CF).

Study design Data on 335 patients <18 years of age

were from the Toronto CF database. A modified oral

glucose tolerance test was given to 94 patients 10 to

18 years of age without recognized CF-related

diabetes. CF transmembrane conductance regulator

mutations and exocrine pancreatic status were

determined for all patients.

Results CF-related diabetes was clinically recognized

in 9 of 335 (2.7%) patients <18 years of age, all of

whom were pancreatic insufficient, and 8 of 9 had

severe (classes I through III) mutations on both

alleles. The ninth patient had unidentified mutations.

Although all patients given the oral glucose tolerance

test were asymptomatic and had normal fasting blood

glucose, 16 of 94 (17%) had impaired glucose tolerance

and 4 of 94 (4.3%) had CF-related diabetes without

fasting hyperglycemia. Abnormal glucose tolerance was

associated exclusively with severe mutations and

exocrine pancreatic insufficiency. Glycosylated

hemoglobin (HbA1C) levels did not correlate with

glucose tolerance results.

Conclusions Screening of pancreatic-insufficient,

adolescent patients with CF identified more with

abnormal oral glucose tolerance than was suspected

clinically and is recommended as a routine practice.

HbA1C was not useful in screening for CF-related

glucose intolerance. (J Pediatr 2003;142:128-32)

The Journal of Pediatrics, February 2003 . Volume 142

.. Number 2

Editorials

Abnormal glucose tolerance in cystic fibrosis: Why

should patients be screened?

Antoinette Moran, MD [MEDLINE LOOKUP]

Milla, MD [MEDLINE LOOKUP]

CF Cystic fibrosis

CFRD CF-related diabetes

Hb Hemoglobin

UM University of Minnesota

Life expectancy for patients with cystic fibrosis (CF)

has increased dramatically in the last few decades,

with a median survival age of 33 years in 2001.1 With

longer life expectancy and improved treatments for

pulmonary disease, other complications of CF have

become more apparent. CF-related diabetes (CFRD) is

the most common comorbidity affecting the 22,000 CF

patients entered in the CF Foundation Patient

Registry.1

The primary cause of diabetes and impaired glucose

tolerance in CF is insulin deficiency. Obstruction of

the pancreatic ducts by thick viscous exocrine

secretions leads to progressive damage to both the

exocrine and endocrine pancreas and fibroadipose

replacement of the pancreatic tissue. Along with

insulin deficiency, insulin resistance may also play

an important role. The majority of nondiabetic CF

patients, in their usual state of health, appear to be

insulin sensitive.2-5 During bouts of infection or in

severely ill patients, however, insulin resistance is

present.6 We envision in CF patients a continuum of

glucose tolerance ranging from normal glucose

tolerance, to increasingly severe glucose intolerance,

to diabetes without fasting hyperglycemia, and ending

in diabetes with fasting hyperglycemia. Where patients

fall on this spectrum is determined primarily by their

insulin secretory capacity. Chronic loss of pancreatic

islets gradually moves CF patients towards the

diabetes end of the spectrum. During acute infection

or glucocorticoid therapy, or as chronic inflammation

becomes severe, patients become more insulin

resistant, which moves them even further towards

diabetes. Glucose metabolism is also negatively

influenced by factors unique to CF, including

undernutrition, acute episodes of infection

superimposed upon chronic infection, elevated energy

expenditure, glucagon deficiency, malabsorption,

abnormal intestinal transit time, liver dysfunction,

and increased work of breathing. By adulthood, 40% of

CF patients have diabetes and another 30% have

impaired glucose tolerance.7,8

CFRD is often insidious in its onset and may have been

present for years before diagnosis. Potential symptoms

of CFRD include polyuria and polydipsia, failure to

gain or maintain weight despite aggressive nutritional

intervention, poor growth velocity, unexplained

decline in pulmonary function or increased frequency

of exacerbations, and failure to progress normally

through puberty.9 The presence of symptoms alone,

however, has proven to be unreliable in diagnosing

diabetes in adults with CF, the majority of whom are

asymptomatic.10 Likewise, studies in adult patients

have shown that hemoglobin (Hb) A1c level is not an

appropriate screening test for CFRD because it is

usually normal, perhaps because of increased red blood

cell turnover.10-13

In the current issue of The Journal, Solomon et al

from the Toronto CF Center report that 17% of

adolescents with CF had impaired glucose tolerance and

13% had diabetes.14 These numbers are somewhat lower

than those reported in adolescents at the University

of Minnesota (UM), but ~15% of UM patients receive

chronic glucocorticoid therapy, and the UM adolescent

group was older.8 None of the Toronto patients had

symptoms of diabetes, and only two patients had

elevation of HbA1c levels. Thus, as in adults, the

only way to diagnose impaired glucose tolerance or

diabetes without fasting hyperglycemia in adolescents

with CF is to perform an oral glucose tolerance test.

Why is it important to identify CF patients with

abnormal glucose tolerance? One could argue that it is

pointless because there are no clear guidelines for

how to treat their metabolic derangement. There is

reasonable consensus that patients with fasting

hyperglycemia should be treated with insulin. How to

treat patients without fasting hyperglycemia is more

problematic because so few data are available. Because

these patients are at high risk for progression to

fasting hyperglycemia,8 home glucose monitoring is

recommended. They may be at risk for microvascular

complications if they are not treated because the type

2 diabetes literature suggests that patients with

postprandial hyperglycemia have the same risk of

microvascular complications as patients with fasting

hyperglycemia.15 In contrast to patients with type 2

diabetes, however, dietary restriction is never an

appropriate means of treatment for patients with CF

(in whom undernutrition is clearly associated with a

higher likelihood of death), and the data on the

effectiveness of oral diabetes agents are not

promising. Currently in the United States, insulin

therapy is not routinely provided unless symptoms of

diabetes are present, such as poor growth, inability

to maintain normal weight, or an unexpected decline in

pulmonary function.9 A multicenter nationwide study is

currently underway to determine whether insulin

therapy improves nutritional parameters and pulmonary

function in CF patients with diabetes without fasting

hyperglycemia.

Because we are not sure how to best treat abnormal

glucose tolerance in the absence of fasting

hyperglycemia in patients with CF, why bother to

screen for it? We maintain that it is important to

identify and monitor closely these patients because

they are at high risk for clinical deterioration of

their pulmonary status. The additional diagnosis of

diabetes in CF is associated with significantly

increased morbidity and mortality.11,16 Even patients

with less severe abnormalities of glucose tolerance

appear to have an accelerated rate of clinical

decline. In the current Toronto adolescent study,

HbA1c levels were negatively correlated with pulmonary

function, suggesting that the association between

pulmonary decline and glucose metabolism begins early

in the course of abnormal glucose tolerance.14 In a

prospective study of youth and adults with CF, we

found that both the severity of glucose intolerance

and the degree of insulin deficiency correlated with

the future rate of decline in pulmonary function over

a 4-year period in patients who had similar age, sex,

pulmonary function, and respiratory pathogens at

baseline.17 Patients with diabetes without fasting

hyperglycemia had greater deterioration of pulmonary

function than patients with impaired glucose

tolerance, and these in turn had greater deterioration

of pulmonary function than patients with normal

glucose tolerance. The rate of decline was also

correlated with the degree of insulin deficiency at

baseline. We believe that insulin deficiency is the

key pathophysiologic factor behind these detrimental

changes. Insulin deficiency in CF is associated with

abnormal protein catabolism,18,19 and protein

catabolism is related to more severe pulmonary

disease.20,21 Thus, insulin deficiency in CF may

accelerate protein catabolism, negatively affecting

pulmonary function and, ultimately, survival.

Studies in adults with CF and now the current report

on adolescents with CF suggest that identification of

patients with abnormal glucose tolerance is important

because these are the patients at greatest risk for

deterioration of lung function. Whereas the optimal

treatment of their insulin deficient state is

debatable and awaits the completion of ongoing

studies, these high-risk patients warrant close

observation and aggressive treatment of their

pulmonary status by the CF team.