Date of Graduation

5-2019

Document Type

Dissertation

Degree Name

Doctor of Philosophy in Kinesiology (PhD)

Degree Level

Graduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Kavouras, Stavros A.

Committee Member

Ganio, Matthew S.

Second Committee Member

Greene, Nicholas P.

Third Committee Member

Mulvenon, Sean W.

Keywords

AVP; Copeptin; Glucose Metabolism; Hypertonic Saline

Abstract

Diabetes is currently affecting 30 million Americans. To combat disease onset, lifestyle interventions have been focused on. Low water intake, alongside elevated concentrations of circulating copeptin, has been linked to increased risk for. However, it is unknown whether this effect on glucose regulation is acute or chronic. Furthermore, no study to date assessed the effects of copeptin independent of the renin-angiotensin-aldosterone system (RAAS). Purpose: The purpose of these studies was therefore two-fold: 1) to establish high endogenous copeptin concentrations independent of RAAS, and 2) to assess glucose metabolism following a standardized oral glucose tolerance test (OGTT) during high concentrations of c copeptin. Methods: 60 subjects participated in this randomized, crossover design study. On two trial days, subjects were infused for 120-min with either 0.9 % sodium chloride (NaCl, ISO) or 3.0 % NaCl (HYPER) (Study 1). Post infusion, a 240-min oral glucose tolerance test (OGTT, 75 g) was administered (Study 2). Changes in plasma volume (ΔPV), plasma osmolality (POsm), electrolyte, copeptin, glucose, insulin, glucagon, crh, acth and cortisol concentrations were measured every 30 min. Results: During HYPER, plasma osmolality (POsm) and copeptin increased (P0.05) at baseline and during the 120-min of infusion. During the OGTT the positive integer of the area under the curve (AUC) for glucose was greater during HYPER (401.5±190.5 mmol·L-1·min) vs. the ISO trial (354.0±205.8 mmol·L-1·min, P< 0.05). The positive integer of the AUC for insulin during OGTT did not differ between trials (HYPER: 55,850±36,488 vs. ISO: 57,205±31,119 pmol·L-1·min). Baseline values of serum glucagon were not different between the two trials, however, the AUC of glucagon during the OGTT was also significantly greater in HYPER (19,303±3,939 ng·L-1·min) vs. the ISO trial (18,600±3,755 ng·L-1·min; P < 0.05). Conclusion: The present data indicate that acute osmotic stimulation of copeptin induced greater hyperglycemic responses during the oral glucose challenge possibly due to greater glucagon levels.

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