Dissertation/Thesis Abstract

Lactate, a novel marker of disordered energy homeostasis in the metabolic derangements of obesity
by Crawford, Stephen Owen, Ph.D., The Johns Hopkins University, 2009, 171; 3340035
Abstract (Summary)

Background. Type 2 diabetes is a major public health problem as a result of the growing obesity epidemic. Accumulating evidence suggests that decreased oxidative capacity may play a central role in the development of insulin resistance, type 2 diabetes, and, perhaps, hypertension. However, clinical research on oxidative capacity as a mediator of obesity's physiologic effects has been limited by the absence of a simple, noninvasive technique to measure oxidative capacity. We considered plasma lactate as an indirect indicator of insufficient oxidative capacity among obese and type 2 diabetic subjects.

Methods. We first analyzed plasma lactate among 40 obese subjects with the metabolic syndrome (Ob-MS), 40 obese subjects without the metabolic syndrome, and 20 lean controls. Change in lactate and other metabolic factors were assessed among 40 Ob-MS entered into a very low calorie diet weight loss intervention. We then examined the association of plasma lactate and type 2 diabetes among 2066 older adults participating in the Atherosclerosis Risk in Communities (ARIC) Carotid MRI Study. Stratified random sampling was utilized to oversample subjects with plaque and maintain generalizable inferences to the ARIC base-population.

Results. In our first analysis, lactate was two-fold higher among obese compared to lean participants. Following significant weight loss among Ob-MS subjects (mean = -14.7 kg), change in lactate remained associated with change in diastolic (p=0.024) and mean arterial ( p=0.04) pressures after adjustment for change in body mass index. In the second analysis, lactate was independently associated with markers of insulin resistance, type 2 diabetes, and diabetes treatment, particularly in whites. The adjusted relative odds of type 2 diabetes among whites, rose with increasing lactate quartile: 1.84 (95% CI: 0.98, 3.45), 2.76 (95% CI: 1.50, 5.09), and 3.69 (95% CI: 2.06, 6.62).

Conclusion. Our results suggest that lactate is independently associated with insulin resistance and type 2 diabetes, particularly among older white adults. Change in lactate following rapid weight loss may also be associated with change in blood pressure among obese subjects. Additional work must be conducted to better understand the direct association between lactate, oxidative capacity, and the metabolic derangements of obesity.

Indexing (document details)
Advisor: Young, J. Hunter
Commitee:
School: The Johns Hopkins University
School Location: United States -- Maryland
Source: DAI-B 69/12, Dissertation Abstracts International
Source Type: DISSERTATION
Subjects: Public health, Physiology, Epidemiology
Keywords: Diabetes, Disordered energy, Insulin resistance, Lactate, Obesity
Publication Number: 3340035
ISBN: 9780549940197
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