Effects of Insulin on Hypotension and Sarcopenia

Diabetes Clinical Trial

Official title:

Effects of Insulin on Hypotension and Sarcopenia

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03248271
• Other study ID #: H17-01663
• Status: Withdrawn
• Start date: October 1, 2017
• Est. completion date: January 10, 2023

Study information

• Verified date: January 2023
• Source: University of British Columbia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

In this study investigator's aim to determine the impact of insulin therapy on hypotension and sarcopenia

Description:

Diabetes is common in the elderly. By the age of 70, approximately 25% of the population has diabetes and another 25% is at risk for diabetes. Elderly patients with diabetes are at increased risk for disability and reduction in their instrumental and basic activities of daily living. The prevalence of frailty is higher in people with diabetes that with age matched controls without diabetes. One of the major contributing factors to frailty is sarcopenia.

Insulin is an important anabolic hormone that prevents protein breakdown and to a lesser extent stimulates protein synthesis. There is some evidence that the ability of insulin to stimulate anabolic processes may be reduced in diabetes.

Insulin has cardiovascular properties, resulting in simultaneous adrenergic and vasodilatory responses that have opposing influences on blood pressure. Epidemiological studies have demonstrated that the use of insulin is a risk factor for syncope.

The investigators will study 30 older adults age 65 and older with type 2 diabetes who have never taken insulin to manage their diabetes but now need insulin to manage their diabetes. Data will be compared pre insulin start and 3 and 6 months after starting insulin.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: January 10, 2023
• Est. primary completion date: January 10, 2023
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• 65 years of age or older

• Type 2 diabetes for at least 5 years

• Insulin naive

• now needs insulin to manage diabetes

Exclusion Criteria:

• anemia as defined by serum hematocrit

• abnormal liver function tests

• elevated serum creatinine

• smoked within last 5 years

• musculoskeletal or neurological condition that would preclude tilt table testing or orthostatic vitals

• aortic stenosis

Related Conditions & MeSH terms

• Diabetes
• Hypotension
• Hypotension, Orthostatic
• Sarcopenia

Intervention

Drug:
• Insulin Lispro
Insulin

Locations

Country	Name	City	State
Canada	University of British Columbia - Gerontology Research Lab	Vancouver	British Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Kenneth Madden

Country where clinical trial is conducted

Canada, 

References & Publications (22)

Bassil MS, Gougeon R. Muscle protein anabolism in type 2 diabetes. Curr Opin Clin Nutr Metab Care. 2013 Jan;16(1):83-8. doi: 10.1097/MCO.0b013e32835a88ee. — View Citation

Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Meneilly GS, Knip A, Tessier D. Diabetes in the elderly. Can J Diabetes. 2013 Apr;37 Suppl 1:S184-90. doi: 10.1016/j.jcjd.2013.01.045. Epub 2013 Mar 26. No abstract available. — View Citation

de Kanter M, Lilja B, Elmstahl S, Eriksson KF, Sundkvist G. A prospective study of orthostatic blood pressure in diabetic patients. Clin Auton Res. 1998 Aug;8(4):189-93. doi: 10.1007/BF02267780. — View Citation

Del Rosso A, Ungar A, Bartoli P, Cellai T, Mussi C, Marchionni N, Masotti G; Gruppo Italiano di Studio Della Sincope Dell'anziano. Usefulness and safety of shortened head-up tilt testing potentiated with sublingual glyceryl trinitrate in older patients with recurrent unexplained syncope. J Am Geriatr Soc. 2002 Aug;50(8):1324-8. doi: 10.1046/j.1532-5415.2002.50351.x. — View Citation

Gin H, Rigalleau V, Perlemoine C. Insulin therapy and body weight, body composition and muscular strength in patients with type 2 diabetes mellitus. J Nutr Metab. 2010;2010:340570. doi: 10.1155/2010/340570. Epub 2009 Oct 21. — View Citation

Gupta V, Lipsitz LA. Orthostatic hypotension in the elderly: diagnosis and treatment. Am J Med. 2007 Oct;120(10):841-7. doi: 10.1016/j.amjmed.2007.02.023. — View Citation

Leenders M, Verdijk LB, van der Hoeven L, Adam JJ, van Kranenburg J, Nilwik R, van Loon LJ. Patients with type 2 diabetes show a greater decline in muscle mass, muscle strength, and functional capacity with aging. J Am Med Dir Assoc. 2013 Aug;14(8):585-92. doi: 10.1016/j.jamda.2013.02.006. Epub 2013 Mar 26. — View Citation

Lipsitz LA, Mukai S, Hamner J, Gagnon M, Babikian V. Dynamic regulation of middle cerebral artery blood flow velocity in aging and hypertension. Stroke. 2000 Aug;31(8):1897-903. doi: 10.1161/01.str.31.8.1897. — View Citation

Lipsitz LA, Pluchino FC, Wei JY, Rowe JW. Syncope in institutionalized elderly: the impact of multiple pathological conditions and situational stress. J Chronic Dis. 1986;39(8):619-30. doi: 10.1016/0021-9681(86)90187-6. — View Citation

Madden KM, Tedder G, Lockhart C, Meneilly GS. Euglycemic hyperinsulinemia alters the response to orthostatic stress in older adults with type 2 diabetes. Diabetes Care. 2008 Nov;31(11):2203-8. doi: 10.2337/dc08-1058. Epub 2008 Aug 20. — View Citation

Meneilly GS, Elliott T, Battistini B, Floras JS. N(G)-monomethyl-L-arginine alters insulin-mediated calf blood flow but not glucose disposal in the elderly. Metabolism. 2001 Mar;50(3):306-10. doi: 10.1053/meta.2001.19493. — View Citation

Morley JE, Malmstrom TK, Rodriguez-Manas L, Sinclair AJ. Frailty, sarcopenia and diabetes. J Am Med Dir Assoc. 2014 Dec;15(12):853-9. doi: 10.1016/j.jamda.2014.10.001. Epub 2014 Nov 20. No abstract available. — View Citation

Rizzo MR, Barbieri M, Fava I, Desiderio M, Coppola C, Marfella R, Paolisso G. Sarcopenia in Elderly Diabetic Patients: Role of Dipeptidyl Peptidase 4 Inhibitors. J Am Med Dir Assoc. 2016 Oct 1;17(10):896-901. doi: 10.1016/j.jamda.2016.04.016. Epub 2016 Jun 2. — View Citation

Rockwood K, Song X, MacKnight C, Bergman H, Hogan DB, McDowell I, Mitnitski A. A global clinical measure of fitness and frailty in elderly people. CMAJ. 2005 Aug 30;173(5):489-95. doi: 10.1503/cmaj.050051. — View Citation

Ruiz GA, Calvar C, Hermes R, Rivadeneira D, Bengolea V, Chirife R, Tentori MC, Gelpi RJ. Insulin sensitivity in young women with vasovagal syncope. Am Heart J. 2003 May;145(5):834-40. doi: 10.1016/S0002-8703(02)94707-1. — View Citation

Salle A, Guilloteau G, Ryan M, Bouhanick B, Ritz P. Effect of insulin treatment on the body composition of Type 2 diabetic patients. Diabet Med. 2004 Dec;21(12):1298-303. doi: 10.1111/j.1464-5491.2004.01335.x. — View Citation

Sergi G, De Rui M, Stubbs B, Veronese N, Manzato E. Measurement of lean body mass using bioelectrical impedance analysis: a consideration of the pros and cons. Aging Clin Exp Res. 2017 Aug;29(4):591-597. doi: 10.1007/s40520-016-0622-6. Epub 2016 Aug 27. — View Citation

Stratton JR, Cerqueira MD, Schwartz RS, Levy WC, Veith RC, Kahn SE, Abrass IB. Differences in cardiovascular responses to isoproterenol in relation to age and exercise training in healthy men. Circulation. 1992 Aug;86(2):504-12. doi: 10.1161/01.cir.86.2.504. — View Citation

Tack CJ, Lenders JW, Willemsen JJ, van Druten JA, Thien T, Lutterman JA, Smits P. Insulin stimulates epinephrine release under euglycemic conditions in humans. Metabolism. 1998 Mar;47(3):243-9. doi: 10.1016/s0026-0495(98)90251-7. — View Citation

Tack CJ, Smits P, Willemsen JJ, Lenders JW, Thien T, Lutterman JA. Effects of insulin on vascular tone and sympathetic nervous system in NIDDM. Diabetes. 1996 Jan;45(1):15-22. doi: 10.2337/diab.45.1.15. — View Citation

Vinik AI, Erbas T. Cardiovascular autonomic neuropathy: diagnosis and management. Curr Diab Rep. 2006 Dec;6(6):424-30. doi: 10.1007/s11892-006-0074-z. — View Citation

Ziegler D, Laux G, Dannehl K, Spuler M, Muhlen H, Mayer P, Gries FA. Assessment of cardiovascular autonomic function: age-related normal ranges and reproducibility of spectral analysis, vector analysis, and standard tests of heart rate variation and blood pressure responses. Diabet Med. 1992 Mar;9(2):166-75. doi: 10.1111/j.1464-5491.1992.tb01754.x. — View Citation

* Note: There are 22 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Body composition	Measured by DEXA Scan	Change from months 0, 3 and 6 months post insulin start
Primary	Grip strength	measured by Hand Dynamometer	Change from months 0, 3 and 6 months post insulin start
Primary	Physical functioning Survey	measured by the Physical Component Summary from the SF-12 Health	Change from months 0, 3 and 6 months post insulin start
Primary	Presence or absence of orthostatic hypotension	Drop in systolic blood pressure of greater than 20 mmHg after 3 minutes of standing	Change from months 0, 3 and 6 months post insulin start
Primary	Nadir of systolic blood pressure during the Tilt Table Test	Lowest systolic blood pressure obtained during the Tilt Table Test	Change from months 0, 3 and 6 months post insulin start
Primary	Nadir of diastolic blood pressure during the Tilt Table Test	Lowest diastolic blood pressure obtained during the Tilt Table Test	Change from months 0, 3 and 6 months post insulin start
Secondary	Nadir of middle cerebral artery velocity as measured by transcranial doppler	Lowest middle cerebral artery velocity obtained during the Tilt Table Test	Change from months 0, 3 and 6 months post insulin start
Secondary	Presence or absence of a positive Tilt Table Test (vasovagal syncope)	Sudden drop in blood pressure and heart rate that leads to fainting	Change from months 0, 3 and 6 months post insulin start