E p i d e m i o I o g y / H e a 11 h S e r v i c e s / P s y c h o s o c i a I O R I G I N A L
Research
A R T I C L E
Visceral Fat and Cardiovascular Risk Factors in Chinese NIDDM Patients PATRICIA J. ANDERSON, MPHIL JULIANA C.N. CHAN, FRCP Y.L. CHAN, FRCR BRIAN TOMLINSON, FRCP ROBERT P. YOUNG, MRCP
ZOE S.K. LEE, BSC KENNETH K.C. LEE, MPHIL CONSTANTINE METREWELI, FRCP CLIVE S. COCKRAM, FRCP JULIAN AJ.H. CRITCHLEY, FRCP
OBJECTIVE — The interrelations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance are well recognized. These relationships are of particular interest in Hong Kong's 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 A N D M E T H O D S — 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.
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n the metabolic syndrome, there are close associations between obesity, glucose intolerance, hypertension, dyslipidemia, and insulin resistance (1). Increasing evidence suggests that visceral fat is an important link between the many facets of this syndrome (2). When compared with subcutaneous adipose tissue, visceral adipocytes exhibit increased sensitivity to the lipolytic effects of catecholamines and reduced sensitivity to the antilipolytic effects of insulin (3,4). Increased production of free fatty acids
enhances the production of triglyceride-rich VLDL, reduces the clearance of insulin, increases gluconeogenesis, and induces insulin resistance by reducing glucose uptake in skeletal muscle (5,6). Although indexes of obesity such as BMI and waist-tohip ratio (WHR) have been shown to correlate with cardiovascular risk factors, results are not always consistent. This inconsistency may be partly due to the poor correlations between these anthropometric measurements and the visceral depot of adipose tis-
From the Departments of Clinical Pharmacology (P.J.A.J.C.N.C, B.T., R.P.Y., Z.S.K.L, K.K.C.L.J.AJ.H.C), Diagnostic Radiology and Organ Imaging (Y.L.C., CM.), and Medicine (C.S.C.), The Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong. Address correspondence and reprint requests to Juliana C.N. Chan, FRCP, Department of Clinical Pharmacology, Prince of Wales Hospital, Shatin, New Territories, Hong Kong. E-mail:
[email protected]. Received for publication 28 February 1997 and accepted in revised form 28 August 1997. Abbreviations: ANOVA, analysis of variance; BP, blood pressure; CV, coefficient of variation; dBR diastolic blood pressure; Gj, total glucose decrement expressed as a percentage of baseline plasma glucose; HOMA, homeostasis model assessment; KL> maximal glucose disposal rate; K,, baseline plasma glucose divided by the maximal glucose disposal rate; MR1, magnetic resonance imaging; sBP, systolic blood pressure; SITT, short insulin tolerance test; TC, total cholesterol; WHR, waist-to-hip ratio.
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sue (7). The differentiation between visceral and subcutaneous fat has been made possible with the introduction of such imaging techniques as computed tomography and magnetic resonance imaging (MRI). Several studies using this technology have shown that increased volume of visceral fat is associated with dyslipidemia, characterized by increased triglycerides and low plasma HDL cholesterol concentrations (8,9). As in many nonwhite populations undergoing rapid socioeconomic changes due to increasing affluence and westernization, the prevalence of NIDDM and glucose intolerance have markedly increased in Hong Kong (10,11). In our previous studies of Hong Kong Chinese patients, increased BMI and WHR were shown to be independent predictors for glucose intolerance (11). These indexes also explained most of the variance of blood pressure (BP), plasma glucose, triglycerides, insulin, and to a lesser extent microalbuminuria (12). In white subjects, the adverse effects of visceral fat on metabolism can be significantly reduced through such simple interventions as a brisk daily walk (13). This makes reduction of visceral fat an important goal when treating this complex disease. However, no data are available to show whether visceral fat, accurately quantified, is significantly related to metabolic aberrations and cardiovascular complications in Chinese populations. In this pilot study, we aimed to examine the relationships between visceral fat, as measured by MRI, and various cardiovascular risk factors in a group of Chinese NIDDM patients treated with diet alone.
RESEARCH DESIGN AND M E T H O D S — Twenty-one Chinese patients were recruited consecutively from the diabetes clinic of The Prince of Wales Hospital in Shatin, Hong Kong. All patients had been diagnosed according to the World Health Organization criteria as having NIDDM for at least 3 months (14). None had a history of significant renal, hepatic, or cardiac disease or clinically evident retinopathy or neuropathy. All patients had received therapeutic diabetes education and were treated with diet therapy alone. Blood pressure and glycemic control were stable, as evidenced by no change of either therapy or
DIABETES CARE, VOLUME 20, NUMBER 12, DECEMBER
1997
Anderson and Associates
body weight in the 3 months preceding the study. All patients gave their written informed consent, and the study was approved by the Clinical Research Ethics Committee of the Chinese University of Hong Kong. On the day of the study, the patients visited the study unit, fasting and without having taken their usual morning medications, if any. The patients, wearing light clothing and no shoes, were weighed and measured. Waist measurement was made at the narrowest circumference between the xiphisternum and the umbilicus. Hip measurement was made at the maximum circumference at the level of the femoral trochanters (15). A modified short insulin tolerance test (S1TT) for the measurement of insulin sensitivity was performed (16). Patients underwent cannulation with an unheparinized angiocath in the antecubital fossa, and they remained recumbent for 10 min before blood sampling. Blood samples were then taken for the measurement of routine biochemistry, fasting plasma glucose, insulin, triglycerides, total cholesterol (TC), HDL cholesterol, and HbAlc. Venous blood samples for plasma glucose were taken at —5, —4, —3, —2, — 1, and 0 min (insulin and glucose sample), at which time a weightadjusted (0.1 U/kg) intravenous bolus dose of Human Actrapid insulin (Novo Nordisk, Bagsvaerd, Denmark) was administered and flushed through with 5 ml of normal saline. Sampling for glucose then continued at 1-min intervals from 2 to 20 min after administration of insulin and saline. Whole blood glucose concentrations were monitored at the bedside using a HemoCue B-glucose photometer (HemoCue, Angelholm, Sweden). All blood samples were placed in crushed ice and centrifuged for 10 min at 3,000 rpm and 4°C immediately on completion of the study. The plasma was then separated, and before analysis, it was frozen at — 20°C. Insulin samples were stored at-70°C. Insulin sensitivity was determined according to our previously published methodology (16). Plasma glucose concentration- time curves were first smoothed by nonlinear regression. The mean decrement in plasma glucose per minute between 2 and 20 min was calculated. A least-squares linear regression was then performed on those time points in which the decrement in glucose was greater than the mean decrement. This interval corresponds to the maximum rate of decline of glucose and thus the DIABETES CARE, VOLUME 20, NUMBER 12, DECEMBER
linear part of the curve. The slope of the linear part of the curve (KL [the maximal glucose disposal rate]) was taken as an index of sensitivity to exogenous insulin. In normal subjects, KL is 0.26 ± 0.07 mmol/min with an intrasubject coefficient of variation (CV) of
