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Biomedical subjects

John A Tayek

Publications and source records attributed to John A Tayek.

8 recordsLinked to original sources
PubMed2003

A decrease in glucose production is associated with an increase in plasma citrulline response to oral arginine in normal volunteers.

Acute arginine administration (30 g) increases insulin secretion and reduces glucose production (GP). A slower administration of L-arginine may have direct effect on the liver without increasing C-peptide or insulin secretion. We tested the direct effect of oral L-arginine on fasting GP in 15 normal-weight volunteers and compared these to a group of L-alanine-treated controls (placebo). Volunteers were admitted to the General Clinical Research Center for a 3-day stay. Three grams of freebase arginine or alanine was ingested hourly between 4 am and 2 pm. Neither arginine nor alanine had an effect on C-peptide or insulin concentration. Oral arginine, but not alanine, increased plasma arginine, citrulline, and ornithine concentrations. Arginine-treated volunteers had a greater fall in GP as compared to the alanine-treated group (16.2% +/- 1.9% v 9.7% +/- 3.6%, respectively; P<.05). Five volunteers treated with arginine had less than a 30% increase in citrulline concentration (26 +/- 2 to 32 +/- 2 micromol/L, mean +/- SEM) and 10 volunteers had equal to or greater than a 30% increase in plasma citrulline concentration (29 +/- 2 to 49 +/- 4 micromol/L, P<.05). Since citrulline is generated in the conversion of arginine to nitric oxide (NO), the failure of oral arginine to increase citrulline concentration suggests that NO generation may be varied in different individuals. The increased plasma citrulline group reduced GP by 18.2% +/- 1.9% over the final 4 hours of arginine administration (2.00 +/- 0.08 to 1.64 +/- 0.07 mg/kg/min; P<.01). In contrast, GP only decreased by 12.4% +/- 3.9% (1.97 +/- 0.13 to 1.73 +/- 0.13 mg/kg/min; not significant [NS]) in those who had little to no increase in plasma citrulline concentration. The 12% decrease in GP in the hyporesponders was similar to the 10% decrease seen in the alanine-treated normal volunteers (9.7% +/- 3.6%). Individuals may have a variable NO response from an oral arginine administration. GP is suppressed in those who have a greater increase in plasma citrulline concentration.

Adult↗
PubMed2003

Low-dose oral glyburide reduces glucose production rates in patients with impaired fasting glucose.

Impaired fasting glucose (IFG) is commonly seen in the US population. Approximately 20% of patients with IFG can progress to develop type 2 diabetes mellitus (DM-2) within 1 year. In the recent diabetes prevention study, lifestyle changes reduced the progression to only 8% per year, and metformin reduced the progression from IFG to DM-2 from 20% to 11% per year. Sulfonylurea therapy in DM-2 increases beta-cell function and fails to accelerate the 4% loss in function observed per year. Low-dose sulfonylurea therapy for IFG may be an effective treatment to delay the onset of type 2 diabetes if the treatment does not cause hypoglycemia. A very low dose of glyburide (20 microg/kg body weight) was given orally to 15 nondiabetic volunteers in an attempt to describe its effects on glucose production rates (GPR), blood glucose concentrations, and conterregulatory hormone profile. Six of the volunteers had IFG (mean +/- SEM, 115 +/- 1.8 mg/dL), and 9 had a normal fasting glucose (NFG) (94 +/- 2.3 mg/dL). Fasting blood glucose (FBG) decreased more in IFG after glyburide when compared with the NFG group (29% +/- 2.4% v 17% +/- 3.5%, P <.05). Patients with IFG had a larger insulin response to glyburide than those with NFG (17.7 +/-3 v 10.7 +/- 2.9 microU/mL; P <.05). The IFG patients also had a greater decrease in GPR (19% +/- 4%) than seen with the normals (12% +/- 3%, P <.05). The steeper decrease in GPR may have been due to a greater insulin response to oral glyburide in those with IFG. Low-dose glyburide increases insulin's effect on the liver.

Adult↗
PubMed2003

Glucocorticoid insufficiency in patients who present to the hospital with severe sepsis: a prospective clinical trial.

OBJECTIVE: To identify the incidence of secondary adrenal insufficiency in severe sepsis. DESIGN: Prospective clinical trial testing 100 patients with a 250-microg adrenocorticotropic hormone (ACTH) stimulation test. SETTING: County-university teaching hospital. PATIENTS: One hundred patients with sepsis and septic shock. Forty patients had bacteremia and 17% shock. INTERVENTIONS: ACTH, cortisol, aldosterone, and electrolyte concentrations were measured at baseline. Cortisol and aldosterone were measured 30 and 60 mins after ACTH (250 microg). MEASUREMENTS AND MAIN RESULTS: Nine of the 100 patients (9%) failed the ACTH stimulation test (all serum cortisol <20 microg/dL). The 91 patients with sepsis began with a serum cortisol at 29.3 +/- 2.5, and it increased to 40.1 +/- 2.6 and 46.9 +/- 2.7 microg/dL at times 30 and 60 mins, respectively. Serum cortisol in nine septic patients who failed the ACTH stimulation test had an initial concentration of 11.3 +/- 1.8 microg/dL, and it increased at time 30 mins to 14.0 +/- 1.9 microg/dL and at 60 mins to 15.7 +/- 1.8 microg/dL. Four of the nine patients had secondary adrenal insufficiency as determined by a normal aldosterone response to ACTH. The remaining five patients had an absent aldosterone response to ACTH and baseline ACTH concentrations that were not elevated, suggesting adrenal dysfunction. Serum sodium (128 +/- 4 vs. 138 +/- 1 mmol/L, p <.05) and glucose concentrations (121 +/- 20 vs. 163 +/- 11 mg/dL, p <.05) were reduced in the nine patients. Of the four patients with secondary adrenal insufficiency, two had a history of amenorrhea after birth of their children many years earlier. CONCLUSIONS: These data demonstrate that 9% of adults with sepsis fail the ACTH stimulation test due to a mixture of etiologies. A reduced sodium or glucose concentration may be helpful in identifying glucocorticoid (adrenal) insufficiency in patients with sepsis.

Adrenal Cortex Function Tests↗
PubMed2002

Oral arginine reduces systemic blood pressure in type 2 diabetes: its potential role in nitric oxide generation.

OBJECTIVES: Arginine is converted in the endothelial cells to nitric oxide (NO) and citrulline. NO is a potent vasodilator in humans, but diabetics may have a reduced generation of NO which results in endothelial dysfunction. The aim of this study was to evaluate the effects of oral arginine on nitric oxide production, counter-regulatory hormones and blood pressure in mildly hypertensive type 2 diabetic patients. METHODS: A prospective, crossover clinical trial was performed over a three-day stay in the General Clinical Research Center. Six patients with type 2 diabetes mellitus and mild hypertension consented and were given orally three grams of arginine per hour for 10 hours on either day 2 or day 3. On both days 2 and 3, blood pressure was monitored between 5 AM and 4 PM and mean pressure determined. RESULTS: Oral arginine increased plasma citrulline from 31.3 +/- 6.0 to 41.5 +/- 6.0 micro mol/L (mean +/- SEM; p < 0.05) which may reflect an increased conversion of arginine into NO and citrulline. Arginine reduced systolic BP from 135 +/- 7 to 123 +/- 8 mmHg; p < 0.05. Diastolic BP fell from 86.9 +/- 1.7 to 80.7 +/- 2.4 mmHg; p < 0.05). The reduction in BP was noted to occur two hours after starting oral arginine, and BP returned to normal within one hour of stopping the arginine. The oral arginine had no effect on C-peptide, insulin or other hormone concentrations. CONCLUSIONS: These data suggest that oral arginine may increase endothelial nitric oxide synthase (NOS) to increase vascular NO and temporally reduce blood pressure in mildly hypertensive type 2 diabetic patients.

Adult↗
PubMed2002

Type 2 diabetic patients may have a mild form of an injury response: a clinical research center study.

Patients with type 2 diabetes (DM) demonstrate inadequate insulin release, elevated gluconeogenesis, and diminished nonoxidative glucose disposal. Similar metabolic changes occur during systemic injury caused by infection, trauma, or cancer. Described here are metabolic changes occurring in 16 DM and 11 lung cancer patients (CA) and 13 normal volunteers (NV). After a 10-h overnight fast, all subjects had fasting hormone and substrate concentrations determined, along with rates of glucose production, leucine appearance (LA), and leucine oxidation (LO). Fasting insulin (data not shown) and C-peptide concentrations were elevated in DM and CA compared with weight-matched NV (0.72 +/- 0.09 and 0.64 +/- 0.08 vs. 0.51 +/- 0.03 mg/l, P < 0.05). C-reactive protein concentration was elevated in CA compared with DM and NV (23.3 +/- 6.0 vs. 4.2 +/- 1.4 and 2.1 +/- 0.5 mg/l, P < 0.01). All counterregulatory hormones were normal except for serum cortisol (11.4 +/- 1.0 and 12.1 +/- 1.0 vs. 8.9 +/- 0.7 microg/dl, DM and CA vs. NL, respectively, P < 0.05). Glucose production was increased in DM and CA compared with NV (4.22 +/- 0.6 and 3.53 +/- 0.3 vs. 2.76 +/- 0.2 mg x kg lean body wt(-1) x min(-1), P < 0.01). LO and LA were increased in DM and CA compared with NV (LO: 27.3 +/- 1.5 and 19.7 +/- 1.5 vs. 12.5 +/- 1.1 mmol x kg lean body wt(-1) x min(-1), P < 0.05; LA: 91.9 +/- 6.6 and 90.7 +/- 7.0 vs. 79.1 +/- 6.0 mmol. kg lean body wt(-1) x min(-1), P < 0.01). DM share similar metabolic derangements with CA. The increase in LA may be secondary to an increased glucose production where amino acids are mobilized to provide the liver with adequate substrate to make glucose. The increase in glucose production may also be part of the injury response, or it may represent a form of insulin resistance that exists in both the DM and (non-DM) CA patients.

Acute-Phase Reaction↗
PubMedDate not supplied

Peroxisome proliferator-activated receptor-gamma agonist increases both low-density lipoprotein cholesterol particle size and small high-density lipoprotein cholesterol in patients with type 2 diabetes independent of diabetic control.

OBJECTIVE: To ascertain whether troglitazone, independent of control of diabetes, increases low-density lipoprotein (LDL) particle size. METHODS: We administered 600 mg of troglitazone (a peroxisome proliferator-activated receptor-gamma agonist) daily for 8 weeks to 10 patients with type 2 diabetes (8 of whom completed the study). Then troglitazone therapy was discontinued, and alternative medication for diabetic control was used for another 4 weeks. The LDL, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) concentrations and subpopulations, as well as blood glucose and hemoglobin A1c (HbA1c), were determined at weeks 0, 4, 8, and 12 and analyzed statistically. RESULTS: Small, dense LDL cholesterol is commonly seen in patients with diabetes and is thought to be associated with an increased risk for coronary artery disease. After both 4 and 8 weeks of troglitazone therapy, control of diabetes was significantly improved (mean HbA1c values at baseline, week 4, and week 8 were 8.0 +/- 0.7%, 7.4 +/- 0.5%, and 7.0 +/- 0.7%, respectively; P<0.05). HbA1c (6.5 +/- 0.6% at 12 weeks) and blood glucose levels (126 +/- 19 mg/dL at 8 weeks versus 145 +/- 9 mg/dL at 12 weeks) were not significantly different 4 weeks after troglitazone therapy was discontinued. Troglitazone treatment increased the large LDL particle at 4 and 8 weeks, a change that significantly (P<0.05) enlarged the LDL particle size (20.5 +/- 0.3 nm, 21.2 +/- 0.3 nm, and 21.3 +/- 0.2 nm at baseline, week 4, and week 8, respectively). After 8 weeks of troglitazone therapy, VLDL triglycerides were reduced (195 +/- 37 mg/dL versus 136 +/- 28 mg/dL; P<0.05) and HDL was increased (31.6 +/- 2.4 mg/dL versus 35.5 +/- 2.9 mg/dL; P<0.05). This greater HDL value was due to an increase in the small HDL particles. A decrease in the larger VLDL particles (V5 and V6) resulted in a reduction in the mean VLDL particle size (59 +/- 3 nm versus 46 +/- 2 nm; P<0.05). Despite the fact that control of diabetes remained significantly improved after troglitazone therapy was discontinued, the LDL particle size decreased to the baseline value. This change was due to a reduction in the large LDL cholesterol particle (L3). CONCLUSION: This study shows that troglitazone therapy increases LDL particle size, reduces VLDL particle size, and increases small HDL particles. These changes may lower the risk for coronary artery disease.

Blood Glucose↗