الفهرس 
DIABETES MELLITUSOnly 14 pages are availabe for public view
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Abstract
Type 1 diabetes is characterized by autoimmune destruction of pancreatic islet cells that results in an inability to produce insulin and a need for daily insulin administration to sustain life. Individuals with type 1 diabetes require insulin that can be administered using a range of insulin types (e.g., rapid, short, intermediate, and long-acting) and delivery methods [e.g., subcutaneous injection, continuous subcutaneous insulin infusion (CSII)] to prevent life threatening ketosis, to maintain normoglycemia without inducing significant hypoglycemia, to maintain normal body weight and promote normal growth and development in children.
Tight glycemic control with intensive insulin therapy reduces the risk of the microvascular and macrovascular complications of diabetes, while resulting hypoglycemic episodes can be a source of significant distress and anxiety to patients and a barrier to achieving tight glycemic control. This difficulty led to the development of more physiological basal and mealtime (prandial) insulins that, when used together, mimic normal pancreatic function, In addition, the development of continuous subcutaneous insulin infusion (CSII) via a pump provided another means to deliver insulin in a more physiological manner. Thus today, patients receive intensive insulin therapy as three or more daily insulin injections (i.e., multiple daily injections [MDI]) or by the use of the external CSII.
Physicians currently recommend CSII for patients with type 1 diabetes who are not achieving glycemic goals despite an adherence to a maximal MDI regimen particularly when patients have wide and erratic glycemic excursions, frequent severe hypoglycemia and/or hypoglycemia unawareness, or marked dawn phenomenon (pre-breakfast rise in blood glucose seen when bedtime basal insulin effect diminishes).
Compared with MDI, CSII has the advantage of providing a constant delivery of basal insulin, permitting a peakless insulin profile that is adjustable throughout the day and decreasing glycemic variability by allowing controlled delivery of small insulin doses. While CSII eliminates the need for multiple daily needle injections compared to MDI, it is more costly than MDI therapy, increases the patient’s risk for developing diabetic ketoacidosis if there is a pump malfunction due to the absence of long acting basal insulin and requires significant patient involvement to manage CSII procedures. MDI therapy using insulin analogs can achieve more predictable and constant blood insulin levels and is cheaper, easier to use, not subject to malfunction and requires less staff supervision than CSII.
Given new technologies in insulin delivery, clinicians are now faced with determining which patient populations benefit most from the use of CSII in terms of improved glycemic, clinical and patient reported outcomes. Because this technology is expensive and requires extensive training and oversight by health care professionals, it is critical to determine how to select patients for use it.
Our systematic review summarizes the current state of the evidence on the effectiveness and safety of methods for intensive insulin delivery(continuous subcutaneous insulin infusion (CSII) and multiple daily injections [MDI]) used in clinical practice in term of diabetes-related clinical outcomes in children and adolescents with type 1diabetes mellitus to facilitate clinical decision making regarding appropriate modes of insulin delivery so that therapeutic options can be selected that result in improved outcomes.
Our systematic review of the comparative effectiveness of CSII and MDI included studies using rapid acting insulin analogs in the CSII intervention groups, requiring the MDI groups to be receiving at least three injections per day” the current standard for intensive insulin therapy” . We included only RCTs in our combined estimates for HbA1c.
We examined glycemic (HbA1c, frequency of hypoglycemia, hyperglycemia and diabetic ketoacidosis) and nonglycemic outcomes, including weightgain, total daily insulin dose and QOL).Unfortunately, for some of these outcomes, the evidence was insufficient to draw definitive conclusions about the comparative effectiveness of CSII versus MDI.
The current study revealed that:
1- Continuous subcutaneous insulin infusion showed no improvement over multiple daily insulin injections regarding HbA1c with no significant difference in children and adolescents with type1 diabetes mellitus. Our estimates are based on RCTs using rapidacting analogs in the CSII arms and at least three daily injections in the MDI arms, making them comparable in intensity to CSII.
2- Continuous subcutaneous insulin infusion showed improvement over multiple daily insulin injections regarding reduction of total daily insulin dose with significant difference in children and adolescents with type1 diabetes mellitus supporting the more physiological action of the pump.
3- Continuous subcutaneous insulin infusion showed an improvement over multiple daily insulin injections regarding BMI reduction in children and adolescents with type 1 DM, with significant difference between both methods of insulin administration.
4- Continuous subcutaneous insulin infusion therapy did not show any improvement over multiple daily insulin injections regarding frequency of mild hypoglycemic events in children and adolescents with type 1 DM, with no significant difference between both methods of insulin administration.
5- The evidence was insufficient to draw definitive conclusions about the comparative effectiveness of CSII versus MDI regarding frequency of severe hypoglycemic events in children and adolescents with type 1 DM, results for severe hypoglecemic events were not enough for pooling (studies did not provide SD or 95% confidence intervals) and definitions of severe hypoglycemia used in studies varied preventing us from combining data to determine effect estimates for this outcome.
6- Continuous subcutaneous insulin infusion therapy did not show any improvement over multiple daily insulin injections regarding frequency of hyperglycemic events in children and adolescents with type 1 DM patients, with no significant difference between both methods of insulin administration
7- The evidence was insufficient to draw definitive conclusions about the comparative effectiveness of CSII versus MDI regarding frequency of diabetic ketoacidosis events in children and adolescents with type 1 DM, continuous subcutaneous insulin infusion therapy could not be compared with multiple daily insulin injections regarding diabetic ketoacidosis events, because original studies did not facilitate enough data for pooling the results.
8- Multiple daily insulin injections showed an improvement over continuous subcutaneous insulin infusion regarding numberof ketotic events in children and adolescents with type 1 DM, with significant difference between both methods of insulin administration
9- The evidence was insufficient to draw definitive conclusions about the comparative effectiveness of CSII versus MDI regarding improvement in quality of life in children and adolescents with type 1 DM, the studies were heterogeneous useing different scales for measuring, assessing and reporting QOL outcomes, which prevented us from quantifying the effects of insulin delivery on QOL. However, multiple daily insulin injections showed better improvement over continuous subcutaneous insulin infusion regarding diabetes quality of life in children and adolescents with type 1 DM, with significant difference between both methods of insulin administration
10- Continuous subcutaneous insulin infusion therapy showed an improvement over multiple daily insulin injections regarding total satisfaction score in in children and adolescents with type 1 DM patients, with significant difference between both methods of insulin administration.
The strength of evidence examining the comparative effectiveness of CSII versus MDI was moderate for HbA1c, and low for daytime and nocturnal hypoglycemia, severe hypoglycemia, and weight gain, general and disease-specific quality of life due to the small number of studies addressing these outcomes.
Risk of bias was medium for the outcomes of HbA1c, severe hypoglycemia, daytime and nocturnal hypoglycemia, and weight gain and high for mild hypoglycemia and hyperglycemia.
The majority of studies in children and adolescents with type 1 diabetes were small focused on adolescents, with fewer studies in children 12 years of age or less and most RCTs were fair or poor quality showing the true need for more studies on this topic with larger number of patients and sufficient extractable data.