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 receivedsubcutaneous 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.
RCT Entities:
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.
Authors: Richard I G Holt; J Hans DeVries; Amy Hess-Fischl; Irl B Hirsch; M Sue Kirkman; Tomasz Klupa; Barbara Ludwig; Kirsten Nørgaard; Jeremy Pettus; Eric Renard; Jay S Skyler; Frank J Snoek; Ruth S Weinstock; Anne L Peters Journal: Diabetologia Date: 2021-12 Impact factor: 10.122
Authors: Adam Mulka; Brianne E Lewis; Li Mao; Roshanak Sharafieh; Shereen Kesserwan; Rong Wu; Donald L Kreutzer; Ulrike Klueh Journal: ACS Pharmacol Transl Sci Date: 2021-04-26