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of hypoglycemia, and failure to achieve target HbA1c as compared to basal–
bolus regimen. On the contrary, basal–bolus regimen mimics a near physiologi-
cal insulin profile, and hence glycemic variability is less, and glycemic targets
can be achieved more easily with better quality of life.- Why is there failure to achieve glycemic targets despite intensive insulin ther-
apy in patients with T1DM?
Multiple daily injection or basal–bolus therapy helps to achieve glycemic tar-
gets only in 10–15 % of patients with T1DM, and even with the use of insulin
pump therapy, only 30 % of individuals attain glycemic targets. Absolute insu-
lin deficiency and intra-and interindividual variability in absorption of insulin
are associated with wide swings in blood glucose levels which result in failure
to achieve target HbA1c in these patients. In addition, concurrent comorbidities
like gastroparesis, autonomic neuropathy, and celiac disease may also result in
poor glycemic control due to mismatch between nutrient absorption and insulin
action. Further, deterioration of glycemic control is often seen in adolescents
due to increase in insulin resistance as a result of gonadal steroids-mediated
GH–IGF1 surge.- What are the determinants of intra-and interindividual variability in absorption
of insulin?
The major determinants of intra-and interindividual variability in insulin
absorption include site of administration, type of insulin, and dose of insulin.
The site of insulin administration determines the rate of absorption; however, it
does not influence the extent of absorption. The abdomen is the preferred site
as the rate of absorption is faster and less variable as compared to the thigh and
arm. Other determinants of insulin absorption from injection site include sub-
cutaneous blood and lymph flow and the first-pass catabolism (proteases in
subcutaneous tissue). Regular insulin and rapid-acting insulin analogues do not
have much difference in variability of absorption, whereas long-acting ana-
logues have significant variability in absorption (NPH > glargine > detemir).
Larger doses of insulin administered as a single injection have a greater vari-
ability in absorption as compared to smaller doses of insulin.- Why are patients with T1DM predisposed to hypoglycemia?
Patients with T1DM are predisposed to recurrent and severe hypoglycemia.
The mechanisms for recurrent hypoglycemia include absolute insulin defi-
ciency, impaired regulation of glucagon secretion, and autonomic failure.
The first-line of defense to counteract hypoglycemia is suppression of insu-
lin secretion, which is impaired in patients with T1DM due to absolute insu-
lin deficiency. The second-line of defense against hypoglycemia is
appropriate glucagon secretion. The key regulator of glucagon secretion12 Diabetes in the Young