P. J. Anderson

Factor analysis of the metabolic syndrome: obesity vs insulin resistance as the central abnormality.

OBJECTIVES: To evaluate whether there is one central abnormality contributing to the conditions associated with the metabolic syndrome (MES), or whether one abnormality is contributing on multiple levels.METHODS: We recruited 145 Chinese subjects aged 17–68 y with varying degrees of insulin-sensitivity (IS): 33 healthy, 59 with type 2 diabetes mellitus, 32 essential hypertensives and 21 dyslipidaemics. IS was evaluated by the short insulin sensitivity test using a 0.1 U/kg intravenous bolus dose of insulin. Blood pressure, anthropometric measures and biochemical parameters associated with IS were also measured. Exploratory factor analyses (EFA) were performed in the entire group of 145 subjects and in the 76 with normal glucose tolerance.RESULTS: EFA in all 145 subjects defined three distinct, independent factors. Factor 1 was interpreted as general and central adiposity, impaired IS and glucose intolerance, Factor 2 was associated with hypertension and general and central obesity, whilst Factor 3 was strongly related to low HDL-cholesterol and high triglyceride concentrations and weakly to waist circumference. In patients with impaired glucose tolerance, only two factors were identified; factor 1 related to reduced IS, impaired glucose tolerance, dyslipidaemia and general and central adiposity, and factor 2 which was related to blood pressure and general and central adiposity.CONCLUSIONS: These models suggest that the clustering of variables in MES is a result of multiple factors linked by adiposity and not a single aetiology. Furthermore, increases in blood pressure are related to obesity in these Chinese subjects rather than decreased IS per se.

Visceral Fat and Cardiovascular Risk Factors in Chinese NIDDM Patients

OBJECTIVE The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kongs Chinese population, in whom increasing affluence has coincided with a marked increase in the prevalence of NIDDM. We designed a pilot study to examine the relationships between visceral fat and cardiovascular risk factors in Chinese NIDDM patients. RESEARCH DESIGN AND METHODS We studied 21 Chinese NIDDM patients whose visceral fat was quantified by magnetic resonance imaging. Cardiovascular risk factors including plasma lipids and 24-h ambulatory blood pressure (BP) were measured. In addition, insulin resistance was determined by a short insulin tolerance test (SITT). RESULTS Increased visceral adiposity was significantly correlated with plasma triglycerides (r = 0.63, P = 0.004), the total cholesterol/HDL cholesterol ratio (r = 0.61, P = 0.008), the urinary albumin/creatinine ratio (r = 0.49, P = 0.04), and decreased insulin sensitivity as measured by the SITT (r = 0.47, P = 0.03). When the data were analyzed by tertiles, increasing visceral fat area was associated with higher plasma triglycerides, lower HDL cholesterol, and a smaller plasma glucose decrement during the SITT. In addition, the diurnal rhythm in BP and heart rate tended to be best preserved in those with the least visceral obesity. CONCLUSIONS This pilot study demonstrates that visceral fat accumulation is associated with dyslipidemia, hypertension, insulin resistance, and albuminuria in Chinese patients with NIDDM.

Selective liver enzyme induction by carbamazepine and phenytoin in Chinese epileptics

Objective:Anticonvulsant drugs are known inducers of cytochrome P450 liver enzymes and it has been suggested that this induction increases susceptibility to paracetamol-induced hepatotoxicity.Methods:We measured the percentage urinary recovery of paracetamol and its metabolites after a dose of 20 mg kg−1, and the excretion of 6ß-hydroxycortisol as a ratio to urinary free cortisol(6ßOHF/F) in Chinese epileptic patients maintained on long term therapy with carbamazepine (n = 6) or phenytoin (n = 6).Results:Compared to the healthy controls (n = 20), patients on phenytoin had significantly lower recoveries of mercapturic acid, cysteine and sulphate metabolites, but a higher recovery of glucuronide metabolites of paracetamol. The recoveries of paracetamol metabolites in patients on carbamazepine were not different from controls. In contrast, the 6ßOHF/F was signi ficantly higher in patients on carbamazepine (3-fold) or phenytoin (2-fold) compared to controls.Healthy control Chinese subjects metabolised paracetamol in a similar way to that reported in Caucasians, indicating that the risk for hepatotoxicity would be the same. Our findings in a group of Chinese patients on phenytoin were also similar to those previously reported in Caucasians on this drug. The apparent differences in the pattern of isoenzyme induction between the groups on phenytoin and carbamazepine require verification in larger studies. The data do not suggest an increased risk of paracetamol-induced hepatotoxicity in Chinese patients on anticonvulsants.

The short insulin tolerance test : Feasibility study using venous sampling

The short insulin tolerance test (ITT) is both a simple and valid method of quantifying insulin sensitivity although arterialization of samples and the risk of hypoglycaemia remain as potential difficulties. We examined the safety and reproducibility of using venous sampling with insulin doses of 0.1U kg−1 and 0.05 U kg−1 in healthy subjects. Whole blood glucose concentrations were measured contemporaneously and the rate of plasma glucose decline (mmol l−1 min−1) for each test was estimated from unlogged venous plasma glucose concentrations measured at 1 min intervals. The mean rates of plasma glucose decline for the 0.1 U kg−1 and 0.05 U kg−1 insulin doses were 0.26 mmol l−1 min−1 (n = 11, range = 0.17–0.41, intrasubject coefficient of variation (CV) = 9.4%) and 0.25 mmol l−1 min−1 (n = 6, range 0.19–0.46, intrasubject CV = 15.9%), respectively. Reversal of significant hypoglycaemia was necessary in one subject before 15 min post‐insulin. We found that: (1) venous sampling provides a reproducible measure of glucose uptake after insulin, (2) contemporaneous bedside glucose sampling identifies those at risk of significant hypoglycaemia during the ITT, and (3) the 0.1 U kg−1 dose response is more reproducible and no less safe than the half dose response. We conclude that the current ITT protocol would be made safer and simpler with the above modifications although further studies comparing venous with arterialized sampling are needed.

A Sibling-Pair Analysis of Fasting Lipids and Anthropometric Measurements and Their Relationship to Hypertension

Fifty non-diabetic, young Chinese hypertensives were compared to their normotensive siblings with respect to body fat distribution and fasting lipid and glucose (FPG) profiles. Sitting BP in hypertensives met conventional hypertension criteria after a 4-week washout period on placebo. Hypertensives had greater body mass index (BMI), subscapular skin-fold thickness (SFT), waist circumference (W), waist-to-height (WHtR) and waist-to-hip ratio (WHR), p<0.0001 for all. Higher triglycerides (p=0.004) and lower HDL-cholesterol (p=0.015) concentrations were also observed. Weight, W, WHtR and BMI were higher in hypertensives in both male (n=9) and female gender-concordant sibling pairs (n=21). Higher WHR, hip circumference and subscapular SFT were only seen in the male hypertensives. Hypertension is associated with central adiposity and adverse lipid profiles in this group of young hypertensives, supporting the hypothesis that obesity, particularly central, is closely associated with hypertension in Chinese as in other ethnic groups.

Non-invasive continuous arterial pressure, heart rate and stroke volume measurements during graded head-up tilt in normal man

The haemodynamic effects of head-up tilt (HUT) at different tilt angles were investigated non-invasively in eight normal male subjects. Mean arterial pressure (MAP; by Ohmeda Finapres 2300), stroke volume (SV) and heart rate (HR; by BoMed NCCOM3-R7S) were continuously recorded whilst performing a series of HUTs (55°, 10°, 20°, 30° and 55°) lasting 3 min each. The response to HUT was proportional to the sine of the tilt angle. The magnitude of the response varied between subjects. HUT to 55° resulted in mean (95% confidence limits) increases in MAP by 16 (±16)% and HR by 11 (±24)% and a decrease in SV by −25 (±22)%. These results were repeatable after 30 min. At small tilt angles, i.e. ≤20°, MAP did not change and HR decreased by −3 (±4)%. A detailed analysis revealed immediate dynamic (0–30 s), late dynamic (30–90 s) and plateau (after 90 s) phases in the response to HUT. In conclusion, HUT produces reproducible haemodynamic effects, although differences exist among subjects. A detailed analysis of these effects can be successfully performed using non-invasive methods.The haemodynamic effects of head-up tilt (HUT) at different tilt angles were investigated non-invasively in eight normal male subjects. Mean arterial pressure (MAP; by Ohmeda Finapres 2300), stroke volume (SV) and heart rate (HR; by BoMed NCCOM3-R7S) were continuously recorded whilst performing a series of HUTs (55°, 10°, 20°, 30° and 55°) lasting 3 min each. The response to HUT was proportional to the sine of the tilt angle. The magnitude of the response varied between subjects. HUT to 55° resulted in mean (95% confidence limits) increases in MAP by 16 (±16)% and HR by 11 (±24)% and a decrease in SV by −25 (±22)%. These results were repeatable after 30 min. At small tilt angles, i.e. ≤20°, MAP did not change and HR decreased by −3 (±4)%. A detailed analysis revealed immediate dynamic (0–30 s), late dynamic (30–90 s) and plateau (after 90 s) phases in the response to HUT. In conclusion, HUT produces reproducible haemodynamic effects, although differences exist among subjects. A detailed analysis of these effects can be successfully performed using non-invasive methods.

Single-dose pharmacokinetics of paracetamol and its conjugates in Chinese non-insulin-dependent diabetic patients with renal impairment

AbstractObjective: A single oral dose of paracetamol (20 mg · kg−1) was given to 38 Chinese patients with non-insulin-dependent diabetes mellitus (NIDDM) who had either normal renal function or varying degrees of renal impairment, with creatinine clearances ranging from 4 to 123 ml · min−1 · 1.73 m−2. The plasma and urinary concentrations of paracetamol and its major metabolites were measured by high-performance liquid chromatography (HPLC). Results: The absorption and elimination of paracetamol were unaffected by renal impairment. However, the area under the plasma concentration time curve and the elimination half-life of paracetamol metabolites increased significantly with worsening renal insufficiency. Mean renal clearances of paracetamol and its conjugates were significantly reduced in these subjects. There was no evidence of altered metabolic activation with renal impairment. Conclusion: The results demonstrate that paracetamol disposition is minimally affected by diabetic nephropathy; however, extensive accumulation of conjugates may occur.

A comparison of the pharmacokinetics and pharmacodynamics of cilazapril between Chinese and Caucasian healthy, normotensive volunteers

Abstract.Methods: The pharmacokinetics and pharmacodynamics of the angiotensin converting enzyme (ACE) inhibitor cilazapril were studied in 12 Chinese and 13 Caucasian, healthy, normotensive volunteers on their normal diet. Cilazapril was given orally as a single 2.5 mg capsule. Plasma was sampled for assay of the active metabolite, cilazaprilat, plasma renin activity (PRA), aldosterone, angiotensin I (AI) and ACE-activity. Plasma concentrations of the active drug were measured by radioimmunoassay. Blood pressure and heart rate were measured at regular intervals.Results:The pharmacokinetic parameters of cilazaprilat were similar in the two ethnic groups. No significant difference in plasma concentrations was found at any of the time points. However, the weight-adjusted plasma clearance was significantly higher in the Chinese group, which is compatible with their lower body weight.The effects on plasma hormones were also comparable, although there was a somewhat greater rise in PRA and greater fall in aldosterone levels in Chinese than in Caucasians.The effect of cilazapril on blood pressure and heart rate was greater than was previously reported in healthy volunteers. Systolic (SBP) and diastolic (DBP) blood pressure were significantly reduced in both groups, but there was a more prolonged reduction in DBP in Caucasians. In addition, heart rate (HR) was significantly increased from baseline from 5 h onwards in Chinese subjects and significantly higher in comparison with Caucasians at most time points from 1.5 h onwards.The pharmacokinetic parameters of cilazapril were essentially the same in healthy, normotensive Chinese and Caucasians. Cilazapril reduced blood pressure acutely in both groups, with good tolerance. The inhibition of ACE in relationship to time and the plasma concentrations of cilazaprilat were similar in the two groups, although the changes in PRA and aldosterone suggest an ethnic difference in the responses of the renin-angiotensin-aldosterone system.

CHILDHOOD POISONING IN HONG KONG: EXPERIENCE OF THE DRUG AND POISONS INFORMATION BUREAU FROM 1988 TO 1992

Dr Cox (J. Paediatr. Child Health 1994; 30: 191 -2) will be pleased to know that the National Health and Medical Research Council (NH &MRC) has recommended that we adopt a two-dose strategy for measles, mumps, rubella (MMR) vaccine in 1994. The first dose is to be given to all children at the age of 12 months. The second dose will replace the existing rubella vaccination programme for teenage girls and is scheduled for all boys and girls aged 10-1 6 years. The vaccine will be supplied free to the States from July 1994. Some States have already made this change in the schedule, others are waiting to implement it after July 1. In 1993, nearly 4400 cases of measles were notified in Australia. This is by far the highest number for many years. Dr Cox was concerned about the proportion of teenagers among these cases and about the possibility of waning vaccine-induced immunity. While this may be responsible for some cases, by far the majority of cases of measles in Australia occur in children who have never been vaccinated. The introduction of the second dose of vaccine should not divert attention from the importance of increasing compliance for the first dose of MMR, which should be given promptly at the age of 12 months. Measles still has its highest morbidity and mortality in younger children. In the USA, in 1989, although only 37% of cases occurred in children under the age of 5 years, these caused 70% of the deaths.’ The new two-dose strategy for MMR is important and timely. However, we could just complacently revaccinate the vaccinated! More attention must be given to targeting immunization services to children who are disadvantaged. Immunization histories should be checked at every health care visit and deficiencies updated ‘on the spot’2 Health care providers should be familiar with the real contraindications to immunization and should not allow trivial reasons to postpone doses. One-third of the children presenting with measles in recent large measles outbreaks in the USA had had health care visits in the previous 6 weeks in which an opportunity had been missed to immunize them; these cases could have been p r e ~ e n t e d . ~ . ~ It is very likely that this is also occurring in Australia.