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Review
. 2012 Mar;41(1):57-87.
doi: 10.1016/j.ecl.2012.03.001. Epub 2012 Apr 17.

Insulin therapy and hypoglycemia

Anthony L McCall  1
Affiliations
Review

Insulin therapy and hypoglycemia

Anthony L McCall. Endocrinol Metab Clin North Am. 2012 Mar.

Abstract

Hypoglycemia is the most important and common side effect of insulin therapy. It is also the rate limiting factor in safely achieving excellent glycemic control. A three-fold increased risk of severe hypoglycemia occurs in both type 1 and type 2 diabetes with tight glucose control. This dictates a need to individualize therapy and glycemia goals to minimize this risk. Several ways to reduce hypoglycemia risk are recognized and discussed. They include frequent monitoring of blood sugars with home blood glucose tests and sometimes continuous glucose monitoring (CGM) in order to identify hypoglycemia particularly in hypoglycemia unawareness. Considerations include prompt measured hypoglycemia treatment, attempts to reduce glycemic variability, balancing basal and meal insulin therapy, a pattern therapy approach and use of a physiological mimicry with insulin analogues in a flexible manner. Methods to achieve adequate control while focusing on minimizing the risk of hypoglycemia are delineated in this article.

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Figures

Fig. 1
Fig. 1
Severe insulin reactions per 100 patient years.
Fig. 2
Fig. 2
Percentage of severe hypoglycemia in 3 studies of intensive control in type 2 DM.
Fig. 3
Fig. 3
Glucose staircase with steep drop: signature of basal > meal imbalance.
Fig. 4
Fig. 4
Insulin levels throughout the day.
Fig. 5
Fig. 5
Insulin regimens for type 1 DM (late type 2).
Fig. 6
Fig. 6
Detection of overnight hypoglycemia with continuous glucose monitoring.
Fig. 7
Fig. 7
The Treat-to-_target Trial was a study of 756 patients with type 2 diabetes mellitus previously treated with 1 or 2 oral agents but inadequately controlled as judged by HgbA1c of >7.5 %. Subjects were randomized to either NPH or insulin glargine at bedtime and underwent a forced weekly titration until they achieved the _target fasting plasma glucose (based on self monitored blood glucose; SMBG) of <100 mg/dL or were prevented from further titration by occurrence of hypoglycemia. As this figure shows, average fasting plasma glucose (FPG on the left) did not achieve the goal but averaged 117 mg/dL in the glargine group and 130 mg/dL in the NPH group at 24 weeks with baseline of 194 mg/dL in the glargine group and 198 mg/dL in the NPH group. The HgbA1c was initially 8.6% in both groups and declined in both to 6.9% on average and the data were not statistically different for either treatment arm.
Fig. 8
Fig. 8
In the Treat-to-_target Trial, although the treatment efficacy was similar with both basal insulin glargine and NPH insulin, increased risk of hypoglycemia (here defined as plasma glucose [PG] ≤72 mg/dL) occurred in both groups starting in the middle of the night (although less with glargine) and continuing on through early morning. Increased risk of hypoglycemia was prominent by 3 AM and continued until before breakfast to a greater degree in the NPH treatment group.
Fig. 9
Fig. 9
Hermansen and colleagues performed a basal insulin titration (with oral agent failure) comparison over one half year with insulin detemir versus NPH insulin. As seen here and similar to results in the Figs. 7 and 8 for the Treat-to-_target trial with insulin glargine, there was equal efficacy in glycemic lowering (left hand panel) based on HgbA1c. Likewise, as shown in the right hand panel, there was substantially reduced incidence overall in all hypoglycemic events (including those only with symptoms).
Fig. 10
Fig. 10
Basal insulin overtreatment.
Fig. 11
Fig. 11
Importance of lag time with meal insulin.
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References

    1. The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358(24):2545–59. - PMC - PubMed
    1. The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with Type 2 diabetes. N Engl J Med. 2008;358(24):2560–72. - PubMed
    1. Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular complications in Veterans with Type 2 diabetes. N Engl J Med. 2009;360(2):129–39. - PubMed
    1. Akram K, Pedersen-Bjergaard U, Carstensen B, et al. Frequency and risk factors of severe hypoglycaemia in insulin-treated type 2 diabetes: a cross-sectional survey. Diabet Med. 2006;23:750–6. - PubMed
    1. Henderson JN, Allen KV, Deary IJ, et al. Hypoglycaemia in insulin-treated type 2 diabetes: frequency, symptoms and impaired awareness. Diabet Med. 2003;20:1016–21. - PubMed

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