title: Insulin Injection Into Lipohypertrophic Tissue: Blunted and More Variable Insulin Absorption and Action and Impaired Postprandial Glucose Control.
abstract: Lipohypertrophy (LHT) is common in insulin-treated patients but its exact impact on insulin absorption and action is unclear.
  
  
  
  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.
  
  
  
  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.
  
  
  
  Insulin absorption and action are blunted and considerably more variable with LHT injection, leading to profound deterioration in postprandial glucose control.
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Famulla
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Hövelmann
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Annelie
authors.initials: A
authors.lastname: Fischer
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Hans-Veit
authors.initials: HV
authors.lastname: Coester
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Lidia
authors.initials: L
authors.lastname: Hermanski
authors.affiliation: Gemeinschaftspraxis Kaltheuner, Leverkusen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kaltheuner
authors.affiliation: Gemeinschaftspraxis Kaltheuner, Leverkusen, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Kaltheuner
authors.affiliation: Profil, Neuss, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Heinemann
authors.affiliation: Profil, Neuss, Germany tim.heise@profil.com.
authors.forename: Tim
authors.initials: T
authors.lastname: Heise
authors.affiliation: Becton, Dickinson and Company Diabetes Care, Franklin Lakes, NJ.
authors.forename: Laurence
authors.initials: L
authors.lastname: Hirsch
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007003:Hypoglycemia / Q000139:chemically induced; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007279:Injections, Subcutaneous; D007328:Insulin / Q000378:metabolism*; D061268:Insulin Lispro / Q000008:administration & dosage* / Q000009:adverse effects; D008060:Lipodystrophy / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro