Clinical trial NCT03229850: Dynamics of Insulin Absorption in Subclinical Lipohypertrophy Using the Euglycemic Clamp Technique
Official title: Dynamics of Insulin Absorption in Subclinical Lipohypertrophy Using the Euglycemic Clamp Technique
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Diabetes Mellitus
Lipohypertrophy
Keywords: Diabetes
Insulin
Lipohypertrophy
Euglycemic Clamp
Lead sponsor: University of British Columbia
Sponsor class: OTHER
First posted: 2017-07-26
Enrollment: 0
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Insulin Levels
timeFrame: 2 months
Secondary outcomes:
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: University of British Columbia - Gerontology Research Lab
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Graydon Meneilly, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.