Clinical trial NCT01083043: Continuous Glucose Monitoring in Type 2 Diabetes Mellitus
Official title: Glycemic Variability Predicts Endothelial Dysfunction
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Vascular Complications
Keywords: Glycemic Variability
Endothelial Dysfunction
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2010-03-09
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult subjects with Type 2 Diabetes Mellitus from an outpatient Endocrinology Practice

Brief summary: It is well known that lowering average blood glucose decreases the risk of diabetic complications involving the small vessels, such as those found in the eyes, nerves and kidney. It is less clear however, if controlling fluctuations in blood glucose will further help to prevent such complications.

The purpose of this study is to examine the relationship between extreme fluctuations in glucose and damage to the blood vessel lining.

Detailed description: Studies have shown that glycemic variability is associated with oxidative stress which in turn has been correlated with endothelial damage. Further, endothelial damage has been identified as a critical event lending way to the vascular complications seen in many disease states.

The specific aim of this study is to investigate the relationship between short-term glycemic variability and biomarkers of endothelial dysfunction while analyzing the influence of different variables and adjusting for covariates.

Data obtained from a continuous glucose monitoring system(CGMS), a device that continuously records interstitial glucose for a 72 hour period, is used to calculate glycemic variability. Serology for the determination of endothelial dysfunction biomarkers is obtained on day three.

Pearson and Spearman Rank Order correlations are utilized to determine whether there are any significant correlations between measures of glycemic variability and biomarker levels of endothelial dysfunction. Multiple regression analysis would also determine if glycemic variability predicts elevated biomarker levels even after controlling for other variables.

Provided the high prevalence of diabetic complications and their staggering socioeconomic costs, it is important to elucidate the relationship between glycemic variability and endothelial dysfunction.

Eligibility criteria: Inclusion Criteria:

* Adult subjects with Type 2 Diabetes Mellitus and glycosylated hemoglobin \<8.0%

Exclusion Criteria:

* Age \<18 or \>65
* BMI \>35
* Pregnant
* Baseline glycosylated hemoglobin \<6.0% or \>8.0%
* Winthrop University Hospital Employee or Staff member
* Vulnerable subject
* Uncontrolled hypertension(defined as systolic blood pressure \>130 or diastolic blood pressure \>80mmHg)
* Uncontrolled dyslipidemia (defined as LDL \>130mg/dL; HDL \<30mg/dL or triglycerides \>199mg/dL)
* Current smoker or significant smoke exposure(defined as greater than 2 hours of exposure to second-hand smoke within the preceding 48hrs)
* Sympathomimetic use within the past week
* History of cardiovascular disease
* History of paroxysmal nocturnal hemoglobinuria
* History of thrombotic thrombocytopenic purpura
* History of stage II-V Chronic Kidney Disease

Primary outcomes:
measure: Serum levels of endothelial dysfunction biomarkers and glycemic variability
timeFrame: Day 3 of study enrollment
Secondary outcomes:
measure: Metabolic parameters and glycemic variability
timeFrame: Day 3 of study enrollment
Other outcomes:
Locations:
city: Mineola
country: United States
facility: Winthrop University Hospital
state: New York
Study officials:
affiliation: Winthrop University Hospital
name: Lawrence E Shapiro, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C. Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA. 2006 Apr 12;295(14):1681-7. doi: 10.1001/jama.295.14.1681.
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citation: Albertini JP, Valensi P, Lormeau B, Aurousseau MH, Ferriere F, Attali JR, Gattegno L. Elevated concentrations of soluble E-selectin and vascular cell adhesion molecule-1 in NIDDM. Effect of intensive insulin treatment. Diabetes Care. 1998 Jun;21(6):1008-13. doi: 10.2337/diacare.21.6.1008.
citation: Krzyzanowska K, Mittermayer F, Wolzt M, Schernthaner G. Asymmetric dimethylarginine predicts cardiovascular events in patients with type 2 diabetes. Diabetes Care. 2007 Jul;30(7):1834-9. doi: 10.2337/dc07-0019. Epub 2007 Apr 24.
citation: Schram MT, Chaturvedi N, Schalkwijk C, Giorgino F, Ebeling P, Fuller JH, Stehouwer CD; EURODIAB Prospective Complications Study. Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study. Diabetes Care. 2003 Jul;26(7):2165-73. doi: 10.2337/diacare.26.7.2165.
citation: Meigs JB, Hu FB, Rifai N, Manson JE. Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus. JAMA. 2004 Apr 28;291(16):1978-86. doi: 10.1001/jama.291.16.1978.