Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control

Diabetes Care. 2016 Sep;39(9):1486-92. doi: 10.2337/dc16-0610. Epub 2016 Jul 13.

Abstract

Objective: Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear.

Research design and methods: In this crossover study, 13 patients with type 1 diabetes received subcutaneous abdominal injections of 0.15 units/kg insulin lispro into LHT (confirmed by examination and ultrasound) and normal adipose tissue (NAT). On one day, a euglycemic clamp was performed with two injections each into LHT and NAT, and on another day one injection per region was given before a standardized mixed meal (75 g carbohydrates), all in randomized order.

Results: Compared with NAT, LHT reduced insulin absorption (mean area under the insulin concentration curve [AUCINS0-4h] 131 vs. 165 h * mU/L [LHT vs. NAT]; Cmax 61 vs. 79 mU/L, P < 0.02, respectively) and effect (areas under glucose infusion rate [GIR] curves [AUCGIR0-4h 625 vs. 775 mg/kg, P < 0.05]) but increased intrasubject variability ([coefficient of variation] AUCINS0-4h 52 vs. 11%, Cmax 55 vs. 15%, AUCGIR0-4h 57 vs. 23%, all P < 0.01). Postprandial blood glucose (BG) concentrations were ≥26% higher with LHT (AUCBG0-5h 731 vs. 513 mg * h/dL, BGmax 199 vs. 157 mg/dL, 2-h BG 150 vs. 104 mg/dL, 5-h BG 145 vs. 81 mg/dL, all P < 0.05) and maximum concentrations occurred later. Hypoglycemia (BG ≤50 mg/dL) occurred numerically less frequently with LHT injection (two vs. six patients), whereas profound hyperglycemia (BG ≥300 mg/dL) only occurred with LHT injection (two patients). Tmax-INS did not differ between LHT and NAT in either study.

Conclusions: Insulin absorption and action are blunted and considerably more variable with LHT injection, leading to profound deterioration in postprandial glucose control.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Cross-Over Studies
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / drug therapy
  • Female
  • Glucose Clamp Technique
  • Humans
  • Hyperglycemia / chemically induced
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Injections, Subcutaneous
  • Insulin / metabolism*
  • Insulin Lispro / administration & dosage*
  • Insulin Lispro / adverse effects
  • Lipodystrophy / etiology
  • Lipodystrophy / metabolism*
  • Male
  • Middle Aged
  • Postprandial Period / drug effects

Substances

  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Insulin Lispro