Insulin Glargine Vs Standard Insulin Therapy
Insulin Glargine Vs Standard Insulin Therapy
This Study is designed to determine whether treatment of CFRD with glargine insulin will
 improve hemoglobin A1c, weight and muscle mass compared to the traditional regimen of bedtime
 NPH insulin.
The majority of cystic fibrosis (CF) patients now survive beyond childhood, and CF related
 diabetes (CFRD), due to insulin deficiency, is common. CFRD with fasting hyperglycemia occurs
 in about 15% of adult CF patients. Standard insulin therapy has relied primarily on meal
 coverage with rapid-acting insulin. Usually, basal insulin coverage is only provided
 overnight, with modest doses of NPH insulin. The practice of providing minimal basal insulin
 in CFRD is based on the fact that most of these patients, unless they are acutely ill, are
 able to maintain relatively normal blood glucose levels during the day without it. In
 addition, anecdotal experience has suggested that daytime NPH insulin or once to twice daily
 ultralente insulin frequently lead to hypoglycemia in the CFRD patient. This practice, which
 is based on practical clinical considerations, ignores the established relationship between
 insulin deficiency and clinical deterioration in CFRD. BMI and pulmonary function deteriorate
 much more rapidly in CF patients with diabetes than in CF patients with normal glucose
 tolerance. Insulin deficiency leads to increased protein catabolism and fatty acid turnover.
 The resulting loss of weight and lean body mass contributes to pulmonary disease and clinical
 decline.

 We hypothesize that:

 1. Basal insulin coverage with insulin glargine will improve hemoglobin A1c, weight, and
 muscle mass in patients with CFRD with fasting hyperglycemia, compared to traditional
 regimens with less basal insulin.

 2. Because of the peakless action of insulin glargine, this will be accomplished without
 serious hypoglycemia.
1. Inclusion Criteria

 1. CFRD with fasting hyperglycemia (fasting plasma glucose ≥126 mg/dl)

 1. . The diagnosis must be made at a time when the patient is in his/her basal
 state of health with no evidence of acute exacerbation in the preceding two
 months.

 a). Acute exacerbation is defined on page 9.

 2. . For patients with onset of diabetes in the preceding 6 months, the
 hemoglobin A1c must be stable for 3 months prior to study entrance within 5%
 (0.3% A1c increment).

 2. Age ≥18, post-pubertal (done growing, since change in weight is a study endpoint)

 3. Weight stable within 5% during the previous 3 months as measured in CF clinic

 4. Willingness to attend all study visits and to engage in regular phone or e-mail
 contact with the study diabetes nurse

 5. Glucocorticoids can have a profound effect on weight, and thus we wish to
 minimize the occurrence of changing steroid doses during the study period.
 Patients receiving glucocorticoid therapy will be included in the protocol only
 if:

 1. . They have been on the same steroid dose for the preceding six months,

 2. . There are no plans to change their steroid dose in the next eight months.

 2. Exclusion Criteria

 1. Pregnancy or plans to become pregnant in the next eight months (because of the
 changes pregnancy would cause in our study endpoints),

 2. Unwillingness / inability to take multiple injections or to count carbohydrates,

 3. A history of hypoglycemia unawareness (rare in CF),

 4. Plans to start any medication in the next 8 months that might affect weight, such
 as testosterone or Megace. Patients chronically taking these medications may be
 included if:

 1. . They have been on the same dose for the preceding six months

 2. . There are no plans to change their dose in the next eight months