Dynamics of Insulin Absorption in Subclinical Lipohypertrophy Using the Euglycemic Clamp Technique

NCT03229850 | Withdrawn

• 1 other identifier: H17-01270
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This study will use the euglycemic clamp technique to evaluate insulin absorption when insulin is administered subcutaneously in an area of subclinical lipohypertrophy vs an area of normal tissue.

Conditions

Diabetes Mellitus; Lipohypertrophy

Keywords

Diabetes; Insulin; Lipohypertrophy; Euglycemic Clamp

Outcome Measures

Primary Outcomes (1)

• Insulin Levels

  The euglycemic clamp technique will be used. Insulin levels will be analyzed by Eliza assay

  2 months

Study Arms (2)

Subclinical Lipohypertrophy

OTHER

Insulin lispro will be injected in the abdomen into an area of subclinical lipohypertrophy.

Drug: Insulin lispro

No Subclinical Lipohypertrophy

OTHER

Insulin lispro will be injected in the abdomen into an area where there is no subclinical lipohypertrophy.

Drug: Insulin lispro

Interventions

Insulin lispro DRUG

Insulin lispro will be injected into the abdomen into an area of subclinical lipohypertrophy or an area with no subclinical lipohypertrophy

No Subclinical Lipohypertrophy; Subclinical Lipohypertrophy

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participated in Glycemic Variability study
• Type 2 Diabetes for at least 2 years
• Currently using insulin to manage diabetes
• Have used insulin to manage diabetes for at least 2 years
• Age 19 or older
• BMI \< 30 kg/m2
• Confirmed areas of subclinical lipohypertrophic adipose tissue lesions via ultrasound

You may not qualify if:

• Taking other injectable medications (eg liraglutide/Victoza
• Taking systemic steroids (ie prednisone)
• Severe renal insufficiency (eGFR \< 30 ml/min/1.73 m2
• Hypoglycemic unawareness
• Current pregnancy
• Not fluent in speaking and writing English (unless accompanied by a translator)

Sponsors & Collaborators

• Graydon Meneilly: lead

Study Sites (1)

University of British Columbia - Gerontology Research Lab

Vancouver, British Columbia, V5Z 1M9, Canada

Location

Related Publications (12)

• Fujikura J, Fujimoto M, Yasue S, Noguchi M, Masuzaki H, Hosoda K, Tachibana T, Sugihara H, Nakao K. Insulin-induced lipohypertrophy: report of a case with histopathology. Endocr J. 2005 Oct;52(5):623-8. doi: 10.1507/endocrj.52.623.

  PMID: 16284443 BACKGROUND

• Raile K, Noelle V, Landgraf R, Schwarz HP. Insulin antibodies are associated with lipoatrophy but also with lipohypertrophy in children and adolescents with type 1 diabetes. Exp Clin Endocrinol Diabetes. 2001;109(8):393-6. doi: 10.1055/s-2001-18991.

  PMID: 11748486 BACKGROUND

• Schiazza L, Occella C, Bleidl D, Rampini E. Insulin lipohypertrophy. J Am Acad Dermatol. 1990 Jan;22(1):148-9. doi: 10.1016/s0190-9622(08)80037-0. No abstract available.

  PMID: 2076114 BACKGROUND

• Vardar B, Kizilci S. Incidence of lipohypertrophy in diabetic patients and a study of influencing factors. Diabetes Res Clin Pract. 2007 Aug;77(2):231-6. doi: 10.1016/j.diabres.2006.12.023. Epub 2007 Feb 15.

  PMID: 17303282 BACKGROUND

• Young RJ, Hannan WJ, Frier BM, Steel JM, Duncan LJ. Diabetic lipohypertrophy delays insulin absorption. Diabetes Care. 1984 Sep-Oct;7(5):479-80. doi: 10.2337/diacare.7.5.479.

  PMID: 6389062 BACKGROUND

• Chowdhury TA, Escudier V. Poor glycaemic control caused by insulin induced lipohypertrophy. BMJ. 2003 Aug 16;327(7411):383-4. doi: 10.1136/bmj.327.7411.383. No abstract available.

  PMID: 12919996 BACKGROUND

• Hauner H, Stockamp B, Haastert B. Prevalence of lipohypertrophy in insulin-treated diabetic patients and predisposing factors. Exp Clin Endocrinol Diabetes. 1996;104(2):106-10. doi: 10.1055/s-0029-1211431.

  PMID: 8740933 BACKGROUND

• Blanco M, Hernandez MT, Strauss KW, Amaya M. Prevalence and risk factors of lipohypertrophy in insulin-injecting patients with diabetes. Diabetes Metab. 2013 Oct;39(5):445-53. doi: 10.1016/j.diabet.2013.05.006. Epub 2013 Jul 22.

  PMID: 23886784 BACKGROUND

• Thow JC, Johnson AB, Marsden S, Taylor R, Home PD. Morphology of palpably abnormal injection sites and effects on absorption of isophane(NPH) insulin. Diabet Med. 1990 Nov;7(9):795-9. doi: 10.1111/j.1464-5491.1990.tb01494.x.

  PMID: 2148131 BACKGROUND

• Overland J, Molyneaux L, Tewari S, Fatouros R, Melville P, Foote D, Wu T, Yue DK. Lipohypertrophy: does it matter in daily life? A study using a continuous glucose monitoring system. Diabetes Obes Metab. 2009 May;11(5):460-3. doi: 10.1111/j.1463-1326.2008.00972.x. Epub 2009 Feb 19.

  PMID: 19236441 BACKGROUND

• Heinemann L, Weyer C, Rauhaus M, Heinrichs S, Heise T. Variability of the metabolic effect of soluble insulin and the rapid-acting insulin analog insulin aspart. Diabetes Care. 1998 Nov;21(11):1910-4. doi: 10.2337/diacare.21.11.1910.

  PMID: 9802742 BACKGROUND

• Famulla S, Hovelmann U, Fischer A, Coester HV, Hermanski L, Kaltheuner M, Kaltheuner L, Heinemann L, Heise T, Hirsch L. 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.

  PMID: 27411698 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus; Insulin Resistance

Interventions

Insulin Lispro

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Graydon Meneilly, MD

  University of British Columbia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: During one euglycemic clamp study, insulin lispro will be injected subcutaneously into an area of subclinical lipohypertrophy of the abdomen identified by ultrasound, during the other insulin lispro will be injected to an area with no subclinical lipohypertrophy.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, UBC Department of Medicine

Study Record Dates

• First Submitted: June 26, 2017
• First Posted: July 26, 2017
• Study Start: February 1, 2021
• Primary Completion: January 1, 2025
• Study Completion: April 22, 2025
• Last Updated: May 2, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)