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

NCT ID: NCT03229850

Last Updated: 2025-05-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2021-02-01

Study Completion Date

2025-04-22

Brief Summary

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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.

Detailed Description

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The use of insulin to manage diabetes can cause changes to the skin at sites where insulin is administered. These changes may be felt as lumps under the skin. Insulin injected into these areas may not work as well leading to needing increasing doses of insulin to control blood glucose levels. Hypoglycemia can occur when insulin is injected into normal areas. Previous studies have found that these lipohypertrophic areas can be seen on ultrasound before they can be felt. The Investigators will be using the euglycemic clamp techique to evaluate insulin absorption to see whether tissue with lumps that cannot be felt but are seen on ultrasound affect how insulin is absorbed.

Conditions

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Diabetes Mellitus Lipohypertrophy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Investigators Outcome Assessors
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.

Study Groups

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Subclinical Lipohypertrophy

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

Group Type OTHER

Insulin lispro

Intervention Type 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

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

Group Type OTHER

Insulin lispro

Intervention Type DRUG

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

Interventions

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Insulin lispro

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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)
Minimum Eligible Age

19 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Graydon Meneilly

OTHER

Sponsor Role lead

Responsible Party

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Graydon Meneilly

Professor, UBC Department of Medicine

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Graydon Meneilly, MD

Role: PRINCIPAL_INVESTIGATOR

University of British Columbia

Locations

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University of British Columbia - Gerontology Research Lab

Vancouver, British Columbia, Canada

Site Status

Countries

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Canada

References

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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.

Reference Type BACKGROUND
PMID: 16284443 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11748486 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2076114 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17303282 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6389062 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12919996 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8740933 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23886784 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 2148131 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19236441 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9802742 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27411698 (View on PubMed)

Other Identifiers

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H17-01270

Identifier Type: -

Identifier Source: org_study_id

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