The Economic Burden of Insulin Injection-Induced Lipohypertophy. Role of Education: The ISTERP-3 Study

Abstract

Introduction: The history of insulin-induced skin lipohypertrophy (LH) runs parallel to that of insulin's 100 years, and an average of 47% of insulin-treated patients still suffer from it today. The metabolic and economic effects of LH are significant, with hypoglycemia being the most striking. The objective of the study was to perform a 52-week follow-up of 713 insulin-treated patients with type 2 diabetes (T2DM) and LH to detect any differences in the occurrence of hypoglycemic events (HYPOs) and related healthcare costs as well as in LH rates and injection habits between an intensive education intervention group (IG) and control group (CG) provided with a single educational session at the starting point.

Methods: All participants were trained in accurately self-monitoring blood glucose and recording all HYPOs for 6 months, which allowed baseline recordings before they were randomized into the IG, comprising 395 insulin-treated subjects undergoing repeated, structured multimodal education on correct injection techniques as a longstanding behavioral rehabilitation strategy, and the CG, comprising 318 subjects receiving the same structured, multimodal educational session, but only initially.

Results: Changes in LH rate and size and in performance were large in the IG and only slight and transient in the CG. A striking difference in the rate of decrease of HYPOs was also apparent between groups. Indeed, estimated costs of health interventions for severe and symptomatic HYPOs, which were on the order of €70,000 and €9300, respectively, in the two groups at baseline decreased by 5.9 times and 13.7 times, respectively, at the end of follow-up in the IG and by only approximately half in the CG. Full details of the changes occurring as a result of intensive education are provided in the text.

Conclusions: The effect of only initial education in the CG was not significant, thus providing evidence of the virtual worthlessness of a single training session on injection techniques, typical of worldwide daily clinical practice, and easily explaining the extremely high prevalence of LH in insulin-treated patients. Conversely, highly positive effects on LH prevalence and size as well as costs expected from decreased HYPO rate were obtained in the IG. To our knowledge, ours is the first 18-month randomized trial in the field. If our experimental model were to be used as an effective, longstanding behavioral rehabilitation strategy and therefore adapted to real-world settings universally, LH prevalence and costs related to their clinical consequences would be drastically reduced. However, only with a strong, relentless commitment of universities, scientific societies, and patient associations can we achieve this ambitious goal, which would provide great institutional savings and improved quality of life for people with diabetes.

Keywords: Diabetes; Economic burden; Education; Hypoglycemia; Lipohypertrophy; Rehabilitation.

Fig. 1

Comparison between the CG (blue bars) and IG (red bars) in terms of percent changes in injection habits, daily insulin doses, and hypoglycemic episodes (severe and symptomatic) occurring after the first 6-month follow-up with respect to baseline (pre-randomization period). All differences between the IG and the CG are statistically significant (p < 0.0001). NR, needle reuse; MR, missing rotation; CII,  cold insulin injection; ILHI, intra LH injection; DID, daily insulin dose; SeH, severe hypoglycemia; SyH, symptomatic hypoglycemia; LHSD, LH size decrease

Fig. 2

Comparison between the first (T+6; blue bars) and second (T+12; red bars) follow-up period in terms of percent changes vs. baseline in injection habits, daily insulin doses, and hypoglycemic episodes (severe and symptomatic) within the only IG, showing that, despite analyzed parameters keeping the same decreasing trend, only LHSD decrease attained statistical significance (**p < 0.01). NR, needle reuse; MR, missing rotation; CII, cold insulin injection; ILHI, intra LH injection; DID, daily insulin dose; SeH, severe hypoglycemia; SyH, symptomatic hypoglycemia; LHSD, LH size decrease

Fig. 3

Percent decrease of severe hypoglycemic events between/within groups in the three study periods. In the IG, it was markedly greater than in the CG (p < 0.0001) during the first follow-up period (B) after randomization (A) and only slightly greater (p < 0.042) in the second one (C). For within-group results, the decrease observed in the IG was already impressive (p < 0.0001) in the first follow-up period (B) after randomization (A) and continued (p < 0.0001) during the second one (C) while the decrease observed in the CG, besides being much smaller than in the IG, followed an opposite trend, being much more prominent (p < 0.01) in the first follow-up period (B) after randomization (A) than in the second one (C) [p < 0.031 vs. A and p < 0.05 vs. B). A = T-6/T0 (pre-randomization period); B = T0/T + 6 (first 6-month follow-up period); C = T + 6/T + 12 (second 6-month follow-up period). *p < 0.05; **p < 0.01; ***p < 0.0001

Fig. 4

Percent decrease of symptomatic hypoglycemic events between/within groups in the three study periods. It was significantly higher in the IG than in the CG (p < 0.0001) during the first follow-up period, despite the further decrease experienced by the IG in the following follow-up period. For within-group results, the decrease observed in the IG was already impressive (p < 0.0001) in the first follow-up period (B) after randomization (A) and continued (p < 0.0001) during the second one (C) while the decrease observed in the CG, besides being much smaller than in the IG, followed an opposite trend, being greater in the first follow-up period (B) after randomization (A) (p < 0.01) and dropping dramatically in the second one (C) (p < 0.01 vs. A and p < 0.01 vs. B, yet). A = T-6/T0 (pre-randomization period); B = T0/T + 6 (first six-month follow-up period); C = T + 6/T + 12 (second six-month follow-up period). **p < 0.01; ***p < 0.0001