Use of Levemir® Improves Metabolic and Clinical Status in Cystic Fibrosis-related Diabetes (CFRD)

Cystic fibrosis (CF) related diabetes (CFRD) and glucose intolerance affects more than
50%-75% of teens and adults with CF. The 1998 North American CF Foundation on CFRD
categorized the disease differently than other types of diabetes: CFRD with fasting
hyperglycemia (FH), CFRD without FH and transient CFRD. The outcome of this consensus
conference was the use of insulin as the only recommended treatment of CFRD. Although the
conference report mandated treatment for CFRD with FH, treatment was not mandated for the
other types of CFRD, the choice to treat was left to the clinician's discretion. However,
insulin was the only recommended therapy for all types of CFRD. Although some clinicians have
used basal bolus regimens as the insulin management, many still use NPH. Given the need for
CF patients to eat many frequent meals and snacks to maintain their weight, use of NPH
insulin rarely renders good glycemic control. A basal bolus regimen is much more physiologic
and would allow good glycemic control even with frequent meals and snacks. To date, there are
no studies documenting safety and efficacy of true basal insulin, or a basal bolus regimen.
Furthermore, protein catabolism and excessive muscle loss has been well documented in CF
patients, both in those with and those without, glucose intolerance. Studies by our group and
others have documented that a major reason for the catabolism is resistance to insulin's
anti-catabolic effects on protein turnover. Thus, there is potential clinical benefit of
improving muscle mass and general health by insulin treatment even for CF patients who do not
have fasting hyperglycemia. A non-peaking basal insulin would be the only reasonable choice,
yet studies are lacking. Our overall goal is to study the safety and efficacy of LevemirTM
for the improvement of glycemic control of patients with CFRD. As a second goal, we will
explore the ability of this basal insulin to improve protein catabolism and muscle mass. The
study will be conducted as a six month trial.

Inclusion Criteria:

- Patients diagnosed with CFRD by oral glucose tolerance test (OGTT) who are medically
stable. Medical stability will be defined as:

- No hospital admission for six weeks or more before the study

- No oral or intravenous antibiotics for at least six weeks preceding the study
(subjects will be allowed to use low doses of inhaled corticosteroids).

Exclusion Criteria:

- Use of oral or intravenous corticosteroid medications within six weeks of the study.

- Evidence of clinically significant liver disease.

- Colonization with Burkholderia cepacia.

- Colonization with Aspergillus.

- Pregnancy.

- Medically unstable (stability defined above).