Continuous subcutaneous insulin infusion

Currently, the most advanced form of insulin therapy is the insulin pump, also referred to as continuous subcutaneous insulin infusion (CSII). Using the short- or rapid-acting insulins only, these pumps are programmed to provide a slow release of small amounts of insulin as the basal portion of therapy, and then larger bolus doses are injected by the patient to account for the consumption of food. 

II.f.1.3. Insulin delivery. Traditionally insulin was given intramuscularly and later subcutaneously. New technology has provided devices for insulin administrations including pen-devices, air powered injectors, external insulin infusion pumps (or continuous subcutaneous insulin infusion, CSII), and implantable insulin infusion pumps. Some novel forms of insulin delivery have been introduced, for example intranasal insulin gives peak insulin concentrations at 10-20 minutes after administration, but most insulin is still administered subcutaneously. 

The standard mode of insulin therapy has traditionally been by subcutaneous injection using disposable needles/syringes. However, other routes of administration, including continuous subcutaneous insulin infusion pumps and inhalation of finely powdered aerosolized insulin, are currently being explored. 

CONTINUOUS SUBCUTANEOUS INSULIN INFUSION DEVICES (CSII, INSULIN PUMPS)... 

In a crossover study, 20 patients with type 2 diabetes were treated for 6 weeks with glucagon-like peptide-1 or saline added to continuous subcutaneous insulin infusion glucagon-like peptide-1 reduced appetite and caused nausea and reduced well-being (3). 

Continuous subcutaneous insulin infusion with fast-acting insulin has been used in two cases. 

A 43-year-old man with type 1 diabetes developed local pruritus, redness, and swelling 4—5 times a week, 15-20 minutes after an injection, subsiding within 1-2 hours (163). Later he had a generalized urticarial reaction 5 minutes after an injection. Insulin lispro did not help. When checked for allergens, he was positive for all types of insulin and negative for additives. With oral mizolastine the local reactions abated for a week, but then reappeared with every injection. Generalized urticaria recurred later. With continuous subcutaneous insulin infusion... 

Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U/ day, because of insulin resistance (168). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U/day. 

A 23-year-old diabetic woman had severe subcutaneous insulin resistance for 11 years (169). Continuous subcutaneous insulin infusion with regular or insulin lispro did not prevent periods of fluctuating responses to insulin. The addition of heparin to insulin lispro in the pump improved serum insulin concentrations and metabolic control. The addition of heparin to regular insulin gave no improvement. 

Continuous subcutaneous insulin infusion (CSII) often gives a better quality of life (189). 

In 132 patients with type 2 diabetes using insulin randomly assigned to continuous subcutaneous insulin infusion (with insulin aspart) or multiple daily injections of insulin aspart and NPH insulin) for 16 weeks, after 8 weeks training to establish optimal dosages (191) there were more episodes of hyperglycemia (blood glucose over 19.4 mmol/1) with multiple daily injections. HbAic was identical. Most of the patients who expressed a view (93%) wanted to stay on the pump. 

In 40 patients aged 4-25 years with type 1 diabetes who were given continuous subcutaneous insulin infusion for 6 months the number of episodes of hypoglycemia was reduced by a half (192). There were two episodes of diabetic ketoacidosis. In 10 patients lipohypertrophy developed at the insertion site and three patients had signs of skin redness, which improved with local antibiotic treatment. 

A 56-year-old man was given a continuous subcutaneous insulin infusion because of frequent episodes of hypoglycemia of which he was unaware and he had four separate episodes of profound ketoacidosis (194). Multiple daily injections produced less flexibility in his mealtimes, more episodes of hypoglycemia, and the need for more injections. However, injecting 60% of his basal needs as insulin glargine once daily in combination with continuous subcutaneous infusion prevented further episodes of diabetic ketoacidosis. 

Continuous subcutaneous insulin infusion (CSII) has been compared with multiple daily injections of insulin in a randomized study in 32 patients, mean age 13 years, over 16 weeks (195). Of the 16 patients who used CSII one returned the pump twice and one returned the pump once, in both cases for pump software errors. Medtronic MiniMed 508 or Paradigm 511 pumps were used in the study. 

Continuous subcutaneous insulin infusion has been reviewed (222,223). Probably more than 100 000 patients... 

Insulin delivery by a pump may be superior to glargine insulin. Continuous subcutaneous insulin infusion was compared with intensive therapy with insulin glargine plus insulin lispro in 19 patients (224). The patients who received insulin glargine were exposed to glucose concentrations under 3.9 mmol/1 overnight for three times as long as those who used continuous subcutaneous insulin infusion. 

When continuous subcutaneous insulin infusion and sulfonylureas were compared in nine normolipidemic patients with type 2 diabetes, HbAlc was not different but triglycerides and small LDL particles were reduced by the continuous infusion (226). 

Continuous subcutaneous insulin infusion treatment is feasible in obese patients (BMI over 30 kg/m2) with type 2 diabetes and severe insulin resistance, as has been shown in a study in 10 patients over 40 weeks (227). HbAlc improved from 12 to 9.6% and weight was reduced by 2.5 kg. There were no adverse effects. 

In 95 patients aged 4-18 years with a median follow-up of 28 months, continuous subcutaneous insulin infusion produced no change in medical complications (diabetic ketoacidosis, visit to the emergency department), but there was a reduction in the number of episodes of... 

In 118 children aged 1.5-18 years treated with continuous subcutaneous insulin infusion, HbAic in preschool children fell from 7.1 to 6.5%, in school children from 7.8 to 7.3%, and in adolescents from 8.1 to 7.4% (230). Daily insulin consumption did not increase and the frequency of severe episodes of hypoglycemia fell. 

Catheter malfunction was the most frequent event (obstruction, total occlusion, and peritoneal adhesions 13,10, and 3.1 events per 100 patient-years respectively). Flushing sometimes prevented occlusion. Better tip design had a big effect. Adhesion formation decreased with daily injections of heparin. The frequency of ketoacidosis was comparable to that reported with continuous subcutaneous insulin infusion and was usually related to catheter obstruction. It diminished during the review period. Episodes of severe hypoglycemia were fewer than during intensive subcutaneous therapy. 

When insulin delivery stops during continuous subcutaneous insulin infusion, ketoacidosis can develop rapidly, but it can be easily corrected if ketoacidosis has developed recently, although exceptions occur (240). 

In 103 patients who used continuous subcutaneous insulin infusion for 2 years, the incidence of severe hypoglycemia fell from 0.70 cases/patient/year before treatment to 0.06 cases/patient/year during treatment, and HbAic improved from 7.7 to 7.2% (244). The incidence of abscesses was 0.1 cases/patient/year and of ketoacidosis 0.01 cases/patient/year. The patients with HbAic concentrations above 8.5% had a higher incidence of serious hypoglycemia and abscesses. Quality of life assessments showed great improvements. The reasons for continuous subcutaneous insulin infusion were optimization of metabolic control, greater flexibility, or prevention of severe hypoglycemia. 

In 138 patients treated with continuous subcutaneous insulin infusion for 7 years, there was a fall in the incidence of episodes of serious hypoglycemia (from 0.31 to 0.09 cases/patient/year) and ketoacidosis (from 0.41 to 0.11 cases/patient/year) the number of infections was unchanged (0.2 infections/patient/year) (245). 

Continuous subcutaneous insulin infusion was found to be feasible in 56 children and adolescents (aged 7-23 years) (248). HbAlc improved in 36 and deteriorated in 6. The rate of severe attacks of hypoglycemia fell, but not significantly. Hypoglycemia and seizure frequency were less overall in the group, with better HbAlc concentrations. One patient had a catheter infection and was... 

Insulin lispro is sometimes less beneficial in continuous subcutaneous insulin infusion (250). 

Continuous subcutaneous insulin infusion with insulin lispro has been reported to give variable control (251). 

Continuous subcutaneous insulin infusion has been compared with short-acting insulins plus glargine or isophane as long-acting insulins for 1 year in 32 patients with poor control (252). Four of them had serious attacks of hypoglycemia. There were no differences in HbAic or other metabolic parameters (including lipids). In those treated with continuous subcutaneous insulin infusion, the reduction in the amount of insulin required was larger. 

Naf S, Esmatjes E, Recasens M, Valero A, Halperin I, Levy I, Gomis R. Continuous subcutaneous insulin infusion to resolve an allergy to human insulin. Diabetes Care 2002 25(3) 634-5. 

Colquitt J, Royle P, Waugh N. Are analogue insulins better than soluble in continuous subcutaneous insulin infusion Results of a meta-analysis. Diabetic Med 2003 20 863-6. 

Raskin P, Bode BW, Marks JB, Hirsch IB, Weinstein RL, McGill JB, Peterson GE, Mudaliar SR, Reinhardt RR. Continuous subcutaneous insulin infusion treatment and multiple daily injection therapy are equally effective in type 2 diabetes. Diabetes Care 2003 26 2598-603. 

Sulli N, Shashaj B. Continuous subcutaneous insulin infusion in children and adolescents with diabetes mellitus decreased HbAlc with low risk of hypoglycemia. J Pediatr Endocrinol Metab 2003 16 393-9. 

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