Should liver function tests be included in definitions of metabolic syndrome? Evidence from the association between liver function tests, components of metabolic syndrome and prevalent cardiovascular disease.

AIMS: The definition of metabolic syndrome (MS) continues to be debated and does not include abnormal liver function tests (LFTs). This study aims to determine: (1) the association between the five ATP3 MS diagnostic components and different LFTs, and (2) the association between raised LFTs and prevalent cardiovascular disease (CVD). METHODS: A total of 1357 patients, without alcoholism or known liver disease, from randomly selected households from rural Victoria, Australia, attended for biomedical assessment. Receiver operating characteristic (ROC) areas under the curve (AUC) were determined for associations between the ATP3 diagnostic components, and between LFTs and ATP3 diagnostic components. RESULTS: The range of ROC AUC for ATP3 diagnostic components was 0.60-0.77. Waist had the strongest association and blood pressure the weakest. The strength of association between ATP3 diagnostic components and gamma GT (GGT) was similar (0.63-0.72), but was less for alanine transaminase and aspartate transaminase. Using the ROC-derived GGT cut-off (men 27 IU, women 20 IU), those with MS and a high GGT had more CVD than those with MS and a low GGT, and those without MS (18% vs. 10% vs. 7%, respectively; P < 0.001). Among those with MS, after adjusting for covariates, the odds ratio of CVD was 2.66 (1.18-5.96) for a high GGT compared to a low GGT. CVD was not significantly more prevalent in MS patients with a low GGT compared to non-MS patients. CONCLUSIONS: We suggest that including a raised GGT in the criteria for MS could increase its predictive nature for CVD. Prospective studies are needed to confirm this finding.

Variability in hydrocortisone plasma and saliva pharmacokinetics following intravenous and oral administration to patients with adrenal insufficiency.

OBJECTIVE: The best method for determining hydrocortisone replacement therapy is not well defined. This study aimed to assess interindividual variability in cortisol pharmacokinetics and to investigate whether measurement of salivary cortisol provides a useful alternative to plasma concentration measurements. DESIGN: Intravenous (IV) and oral crossover. PATIENTS: Twenty-seven patients with primary or secondary adrenal insufficiency who had been on stable replacement therapy for at least 3 months. MEASUREMENTS: Plasma and salivary concentrations of cortisol were measured up to 8 h following administration of hydrocortisone. RESULTS: After IV administration, Cmax ranged from 715 to 8313 nmol/l, area under the curve (AUC) from 1112 to 12 177 nmol h/l and cortisol clearance had a median (range) of 0.267 (0.076-0.540) l/h/kg. After oral administration, Cmax ranged from 422 to 1554 nmol/l, AUC 1081-5471 nmol h/l and oral clearance had a median (range) of 0.267 (0.081-0.363) l/h/kg. There was no clear relationship between paired saliva and plasma cortisol concentrations after IV or oral dosing. Plasma and salivary AUC(2-8 h) after IV administration were highly correlated (r2 = 0.77) but differences between predicted and measured plasma AUCs ranged from 3% to 90%. There was a poor correlation between plasma and saliva AUC(2-6 h) after oral administration (r2 = 0.16). CONCLUSIONS: The wide interindividual variability in plasma and salivary profiles of cortisol following the administration of IV and oral hydrocortisone to patients with adrenal insufficiency and the poor correlation between salivary and plasma measurements suggest that salivary cortisol measurements cannot be used for individual hydrocortisone dosage adjustment.

Acquisition of linguistic and cognitive skills by children with cleft palate.

This study compared the early cognitive and linguistic development of young children with cleft palate (N = 28) to that of noncleft children (N = 29). Measures included the Mental scale of the Bayley Scales of Infant Development, the Minnesota Child Development Inventory, Mean Length of Utterance, and words acquired by 24 months. Children with cleft palate, although well within the normal range, performed significantly below the children in the control group on the Mental Scale of the Bayley Scales of Infant Development, some subscales of the Minnesota Child Development Inventory, and words acquired by 24 months. Differences observed in the cognitive development of children with and without cleft palate were verbal as opposed to nonverbal (i.e., linguistic in nature) and were related to hearing status at 12 months and velopharyngeal adequacy.