If you don't remember your password, you can reset it by entering your email address and clicking the Reset Password button. You will then receive an email that contains a secure link for resetting your password
If the address matches a valid account an email will be sent to __email__ with instructions for resetting your password
We used insulin pump therapy in three patients (two males and one female; age 5.5, 21 and 28.2 years, respectively) with CFRD and we reported the experience of 2 years of follow-up.
In all the patients during the CSII treatment, the annual mean level of HbA1c reduced and the annual mean level of BMI increased, respected, the year before starting the CSII (in MDI treatment with 4 injections/day). The insulin requirements decreased during the CSII treatment and respected MDI treatment. During the CSII treatment, none of the patients exhibited episodes of DKA or severe hypoglycaemia. Only two episodes of lipohypertrophy and a slight local cutaneous inflammation were reported.
Conclusions
The use of CSII in our patients with CFRD improves the metabolic control of diabetes and the nutritional status with no concomitant problems related to this treatment.
]. Other long-term complications have become apparent as more patients with cystic fibrosis survive into adulthood. The most significant of these complications is cystic fibrosis-related diabetes (CFRD) which appears in 10–25% of individuals with cystic fibrosis [
]. Good glycometabolic control is important not only to improve the clinical and nutritional status of these patients, but also to prevent or delay the appearance of long-term microvascular complications linked to the diabetic disease [
Continuous subcutaneous insulin infusion (CSII) is being increasingly adopted in adults and children affected by type 1 diabetes, where it has been shown to be a valid alternative to multiple daily injections (MDI) and able to improve glycometabolic control and the quality of life of these patients [
]. At our centre, we used CSII in three patients with CFRD and we report below the experience of 2 years of follow-up.
2. Patient report 1
A 7.5-year-old male with Cystic Fibrosis, diagnosed at 2 months of age (sweat test: Cl=88 meq/l) and CFRD diagnosed at 3.5 years of age, started the insulin pump therapy (H-Tron plus, Disetronic) at the age of 5.5 years using a rapid-acting insulin analogue (Aspart, Novonordisk).
Insulin therapy was started at the diagnosis of CFRD, and in the year before CSII therapy, the patient was receiving 4 insulin injections/day as follows: a regular (R) insulin and an intermediate (NPH) insulin before breakfast, a rapid-acting insulin analogue before lunch and dinner, an NPH insulin at bed-time.
The annual mean level of HbA1c in the year before starting CSII (measured every 3 months) was 9.5% while HbA1c at the start of this therapy (baseline) was 9.7%. The annual mean level of HbA1c decreased during the years of CSII treatment (7.9% in the first year and 8% in the second year of CSII treatment) (Fig. 1).
Fig. 1Annual mean values of HbA1c in the year pre-CSII and the 2 years of CSII treatment.
The annual mean level of body mass index (BMI) (measured every 3 months), which was 15.1 in the year preceding the start of CSII, increased during insulin pump treatment (respectively, 15.6 in the first year of therapy with CSII and 15.8 in the second year) (Fig. 2). The BMI level at the start of CSII (baseline) was 14.9.
Fig. 2Annual mean values of BMI in the year pre-CSII and the 2 years of CSII treatment.
Compared to insulin requirement (0.69 U/kg/day) prior to CSII treatment, the insulin requirement decreased to 0.47, 0.51 and 0.49 U/kg/day at 1, 12 and 24 months after CSII was started.
Basal insulin made up 44–51% of the daily quantity of insulin (44% at the first month, 51% at the 12th month and 50% at the 24th month of insulin pump therapy). Basal nocturnal insulin made up around 9–11% of the total basal (10% at the first month, 9% at the 12th month and 11% at the 24th month) (Table 1).
Table 1Insulin requirements, basal/bolus report and nocturnal basal prior and during the CSII treatment
During the 2 years of CSII therapy, no episodes of diabetic ketoacidosis (DKA) or severe hypoglycaemia (defined as any hypoglycemic event requiring assistance from another person or resulting in seizure or coma) occurred; there was one episode of mild lipohypertrophy of the glutei (insertion site of the cannula) and one episode of slight cutaneous inflammation which needed no local antibiotic treatment.
3. Patient report 2
A female of 32.3 years with CF which was diagnosed at 4 years of age. At 23.2 years of age, CFRD was diagnosed and began oral hypoglycemic treatment (Glibenclamide). After 2 years of treatment with oral diabetes agent, she started insulin therapy with 4 injections/day.
Insulin pump therapy (Minimed 508) was started using rapid-acting insulin analogues (Humalog, Elly-Lilly) at the age of 28.2 years. Before starting the CSII therapy, the treatment was as follows: an R insulin before breakfast, lunch and dinner and an NPH insulin at bed-time.
During insulin pump treatment there was a reduction in the annual mean level of HbA1c: 7.8% in the year preceding CSII, 6.2% and 6.4% in the first and second year of CSII treatment. The HbA1c level was 7.6% at the star of CSII treatment (Fig. 1).
The increase in the annual mean level of BMI (measured every 3 months) indicates an improvement in the nutritional state (20.1% in the year preceding CSII, 21.9 in the first year of CSII and 22.1 in the second year). At the start of CSII, the BMI level was 20.0 (Fig. 2).
The insulin requirement decreased from 0.82 U/kg/day before CSII to 0.47 U/kg/day at 1 month (basal/bolus 50%/50%, nocturnal basal 13% of total basal), 0.35 U/kg/day at 12 months (basal/bolus 40/60%, nocturnal basal 18% of total basal), 0.40 U/kg/ day at 24 months of CSII (basal/bolus 52/48%, nocturnal basal 12% of total basal) (Table 1).
During the 2 years of treatment, there were no episodes of diabetic ketoacidosis (DKA), severe hypoglycemia or cutaneous infection at the infusion site. During the first year of CSII, there was one episode of lipohypertrophy on the abdomen (insertion site of the cannula).
4. Patient report 3
A 23.1-year-old male was diagnosed with CF at 4 years of age. A diagnosis of CFRD was made at 14.2 years of age and insulin therapy was started with 4 injections/day.
At the age of 21 years, insulin pump therapy (H-Tron plus, Disetronic) was started using rapid-acting insulin analogues (Aspart, Novonordisk). In the year before CSII treatment, the insulin therapy was as follows: a rapid-acting insulin analogues before breakfast and dinner, a rapid-acting insulin analogue+NPH insulin before lunch and a NPH insulin at bed-time.
During the 2 years of CSII treatment, the annual mean HbA1c level decreased compared to the year preceding CSII (7.2% in the first year of CSII and 7.1% in the second year vs. 9.3% in the year before CSII). At the beginning of CSII, HbA1c was 9.8% and 8.8% after 3 months (Fig. 1).
The annual mean BMI level increased both in the first and second year of CSII when compared to the year preceding insulin pump treatment (21.2 in the year before CSII, 22.8 in the first year and 22.6 in the second year of CSII) (Fig. 2).
Insulin requirements decreased from 1.41 U/kg/day before starting CSII to 0.72 U/kg/day in the first month of CSII (basal/bolus 48/52%, nocturnal basal 13% of total basal), 0.93 U/kg/day at 12 months (basal/bolus 38/62%, nocturnal basal 14% of total basal) and 0.87 U/kg/day at 24 months of CSII (basal/bolus 50/50%, nocturnal basal 12% of total basal) (Table 1).
There were no episodes of DKA, severe hypoglycemia, local lipohypertrophy or local skin infections during CSII treatment.
5. Discussion
The achievement and maintenance of a good metabolic control through insulin therapy is an important objective in the treatment of patients affected by CFRD for a variety of reasons: some studies have reported an association between hyperglycaemia and an increase in morbidity and mortality in these patients [
]; with the increase in life expectancy, literature increasingly reports the possibility of the onset and progression of microvascular complications in the CFRD population [
]. Besides controlling the glucidic metabolism, insulin also plays an important role in maintaining a normal body protein status. In patients affected by cystic fibrosis, where there is an increase in protein catabolism, insulin insufficiency could contribute to the worsening of the nutritional state and more generally to deterioration in the base illness [
The use of insulin pumps in all three patients resulted in a significant reduction (between 1.2% and 1.7%) in the HbA1c value, when compared to multiple daily injections (MDI) which the patients had received in their preceding treatment. This reduction remained more or less constant over the 2 years of therapy with CSII, thus demonstrating that this treatment produced good glycometabolic control in both the short and long term.
The increase in the BMI shows that weight increase and more generally that the nutritional state of these patients improved during insulin pump treatment. In guaranteeing good nutritional status, which is a fundamental condition for survival and for the good clinical status of CF patients, the insulin pump offers the following advantages in addition to improving glycaemic control: flexibility in the number, timing and quantity of the meals, without having to resort to additional injections; better management of the length of the meals; improved adjustment of the quantity of insulin to the glucidic input (thanks also to using only rapid-acting insulin analogues); a more precise basal insulin in line with the daily activity and needs of each patient.
Patients with CFRD report an increased risk of hypoglycemia (as a consequence of their impaired counter-regulatory function or poor glucagon response [
]). In our patients, the improvement in glycaemic control during the CSII treatment did not lead to increase in severe hypoglycaemic events. The use of only a rapid-acting insulin analogues and a basal profile which better reflects the needs and the activity of each patient are all factors which could help to prevent episodes of hypoglycaemia.
], using the insulin pump in our patients ,we have seen a significant reduction in insulin requirements when compared with the insulin requirements by the same patients when treated with MDI therapy. Moran reports that little basal insulin is needed in CFRD [
]. These data are not confirmed by our experience; indeed, in our patients the basal represents around 38–52% of the daily insulin requirement. The characteristics of diabetes mellitus in CF differ from other forms of diabetes both as regards the physiopathological and clinical aspects and the management of the insulin therapy [
]. Our study is limited to only three patients and is clear that more experience with the insulin pump in larger number of patients will better clarify the characteristics and the differences of this type of treatment.
Regarding the lipohypertrophy and the local cutaneous infections at the insertion site of the cannula, which are considered as risk factors in insulin pump therapy [
], in our experience, we came across only two mild cases of lipohypertrophy which were resolved by changing the insertion site of the cannula and one episode of a mild local cutaneous infection which required no local antibiotic therapy. However, we believe that these problems are easily preventable by instructing the patient to abide by some simple rules of hygiene and by alternating the insertion site of the cannula.
In addition, insulin pump therapy offers the advantage of fewer injections. The practical importance of this must not be undervalued in patients with FC, who often have a busy and complex daily treatment routine.
In conclusion, the use of CSII in our patients with CFRD resulted in improvements in both the metabolic controls of diabetes and the nutritional status with no concomitant problems. There are some particulars concerning the use of CSII in CFRD which regard the basal/bolus relationship and the nocturnal basal quantity. Further studies with a larger number of patients are required to evaluated the characteristics and the specifics of CSII in patients with CFRD.
References
Cystic Fibrosis Foundation: Annual data base report. Bethesda, MD, Cystic Fibrosis Foundation, 2000.
00118-4&id=gr1.jpg){kind=link}
00118-4&id=gr2.jpg){kind=link}