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Validity and Reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and Mcauley’S Indices in Patients with Hypertension and Type II Diabetes

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Validity and Reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and Mcauley’S Indices in Patients with Hypertension and Type II Diabetes Journal of Human Hypertension (2007) 21, 709–716 & 2007 Nature Publishing Group All rights reserved 0950-9240/07 $30.00 www.nature.com/jhh ORIGINAL ARTICLE Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley’s indices in patients with hypertension and type II diabetes PA Sarafidis1,2, AN Lasaridis1, PM Nilsson3, MI Pikilidou1, PC Stafilas1, A Kanaki1, K Kazakos1, J Yovos1 and GL Bakris2 11st Department of Medicine, AHEPA University Hospital, Aristotle University, Thessaloniki, Greece; 2Hypertension/Clinical Research Center, Department of Preventive Medicine, Rush University Medical Center, Chicago, IL, USA and 3Department of Medicine, Malmo¨ University Hospital, Lund University, Malmo¨, Sweden The aim of this study was to evaluate the validity and subjects’ body weight or fat-free mass and every other reliability of homeostasis model assessment-insulin clamp-derived index. 1/HOMA-IR and QUICKI indices resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), were positively correlated with the M-value (r ¼ 0.342, quantitative insulin sensitivity check index (QUICKI) and Po0.05 and r ¼ 0.456, Po0.01, respectively) and the rest McAuley’s index in hypertensive diabetic patients. In 78 clamp indices. McAuley’s index generally presented less patients with hypertension and type II diabetes glucose, strong correlations (r ¼ 0.317, Po0.05 with M-value). In insulin and triglyceride levels were determined after a multivariate analysis, HOMA-IR was the best fit of clamp- 12-h fast to calculate these indices, and insulin sensi- derived IS. Coefficients of variation between the two tivity (IS) was measured with the hyperinsulinemic visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, euglycemic clamp technique. Two weeks later, subjects 7.8% for QUICKI and 15.1% for McAuley’s index. In had again their glucose, insulin and triglycerides conclusion, HOMA-IR, 1/HOMA-IR and QUICKI are valid measured. Simple and multiple linear regression analy- estimates of clamp-derived IS in patients with hyperten- sis were applied to assess the validity of these indices sion and type II diabetes, whereas the validity of compared to clamp IS and coefficients of variation McAuley’s index needs further evaluation. QUICKI between the two visits were estimated to assess their displayed better reproducibility than the other indices. reproducibility. HOMA-IR index was strongly and in- Journal of Human Hypertension (2007) 21, 709–716; versely correlated with the basic IS clamp index, the M- doi:10.1038/sj.jhh.1002201; published online 19 April 2007 value (r ¼À0.572, Po0.001), M-value normalized with Keywords: insulin resistance; HOMA-IR; QUICKI; McAuley’s index Introduction disturbances.2 In addition, both IR and compensa- tory hyperinsulinemia have been independently The term ‘metabolic’ or ‘insulin-resistance’ syn- associated in longitudinal studies with increased drome refers to a clustering in the same individual risk for CVD.3,4 of disorders that represent risk factors for cardio- In certain individuals, IR can precede the devel- vascular disease (CVD), such as impaired glucose opment of type II diabetes for many years, even tolerance (IGT) or type II diabetes, hypertension, 5,6 1 decades. During this long course compensatory dyslipidaemia and obesity. Insulin resistance (IR) hyperinsulinemia can have harmful consequences was originally proposed to be the central disorder of on many tissues not presenting IR and, through the syndrome, causally related with the other various mechanisms, contribute to the development of other components of the syndrome, that is 7,8 Correspondence: Dr PA Sarafidis, 1st Department of Medicine, hypertension or hypertriglyceridemia. Thus, a AHEPA University Hospital, Aristotle University, St Kiriakidi 1, proportion of subjects with the metabolic syndrome 546 36, Thessaloniki, Greece. can exhibit hypertension long before the develop- E-mail: [email protected] ment of overt type II diabetes. Sources of support: This paper was not supported by any source and represents an original effort on our part. Several methods have been proposed for assess- Received 4 August 2006; revised 16 December 2006; accepted 19 ment of IR, or its reciprocal variable, insulin December 2006; published online 19 April 2007 sensitivity (IS), in humans. Among them the Surrogates of insulin sensitivity in hypertension PA Sarafidis et al 710 hyperinsulinemic euglycemic clamp technique, de- days for the evaluation and five of them did not scribed by DeFronzo et al.9 in 1979, represents undergo the clamp due to difficulties in achieving currently the ‘gold standard’.10 However, due to its stable intravenous access. Therefore, the final study many technical requirements, the clamp technique, group included 78 Caucasian patients (36 men and as well as several other methods for IS measure- 42 women) with complete data set, which were ment, is difficult to apply in everyday clinical included in the analysis. practice or large-scale epidemiologic studies. This is why during the past 20 years numerous simple indices have been developed for IS measurement. Study protocol Some of these indices derive from an oral-glucose Participants were admitted to the Clinical Research tolerance test, whereas others are based only on Laboratory of our Department at 0700 after a 12-h fasting glucose and insulin values,1 and this simpli- overnight fast and without having received their city in obtaining the latter surrogates was the morning hypoglycemic or antihypertensive medica- obvious reason for their wider use. tion. Blood samples were drawn to determine the Among these indices, the most well-known is levels of fasting plasma glucose, insulin and perhaps the homeostasis model assessment-insulin triglycerides and HbA1c. Fasting glucose and insulin resistance (HOMA-IR) index,11 whereas the recipro- values were used to estimate HOMA-IR, 1/HOMA-IR cal of HOMA-IR, as well as a more recently proposed and QUICKI indices and insulin and triglycerides to index, the quantitative insulin sensitivity check estimate the McAuley’s index, as described below. index (QUICKI),12 are increasingly used. The valid- Subjects had also measured their body weight and ity of these estimates in relation to the clamp height to calculate body mass index (BMI). The body technique has been examined in several studies, in composition of each participant was then analysed a wide variety of populations.13–20 However, data on by bioelectrical impedance analysis with the use of their validity in hypertensive populations are gen- the Bodystat1500 device (Bodystat Ltd, Douglas, Isle erally limited. Recently, McAuley et al.21 proposed of Man, British Isles) to estimate the fat-free mass. another index, which uses fasting insulin and Bioelectrical impedance analysis has been shown to triglyceride values, to be a strong predictor of be a simple, valid and reliable method to evaluate clamp-derived IS, but this index was not adequately body composition.23,24 After these procedures, sub- further investigated. In addition, data on the jects had their IS determined with the clamp reproducibility of these surrogate indexes are quite technique. limited11,13,19,22 compared to the data on validity. Two weeks after the first visit, participants Therefore, the aim of the present study was to returned at the Department, again after a 12-h fast determine the comparative validity and the repro- and without having received morning medications ducibility of HOMA-IR, 1/HOMA-IR, QUICKI and to give blood samples for the determination of McAuley’s index in a population consisting of fasting plasma glucose, insulin and triglyceride patients that have initially developed hypertension levels (visit 2). From these values, all surrogate and subsequently type II diabetes. indices were again calculated to evaluate their reproducibility between different time points. All subjects were strictly advised to keep their diet Methods habits and physical activity unchanged during these 2 weeks to avoid major changes in background IR. Subjects Among patients attending the hypertension or diabetes outpatient clinic of the 1st Department of Assessments Medicine, AHEPA Hospital, Thessaloniki, Greece, Hyperinsulinemic euglycemic clamp. The hyper- we selected those with both hypertension and type insulinemic euglycemic clamp was performed as II diabetes that had diagnosis of hypertension before described previously.9,10 In brief, two intravenous the diagnosis of diabetes. We excluded patients infusion lines were placed, one into an antecubital receiving insulin treatment, having glycated hemo- vein for the infusion of insulin and glucose and the globin (HbA1c) 410%, history of secondary hyper- other into a hand or wrist vein by retrograde tension, serum creatinine levels 42 mg/dl, history cannulation for frequent blood sampling. After a of myocardial infarction or unstable angina within 10-min priming infusion, insulin infusion was held the past 6 months, heart failure NYHA class III–IV, constant at 0.6 nmol*mÀ2*minÀ1 for the rest 110 min. malignancy or any other condition with poor Blood glucose concentration was determined every prognosis. From this population we randomly 5 min and it was clamped at the euglycemic level selected 100 individuals, using a computer-gener- (5 mmol/l) by infusion of variable amounts of a 20% ated list. Of these, six were not possible to be dextrose solution. The total body glucose disposal contacted and eight refused to participate. The rate (M-value), the basic clamp-derived IS index, remaining 86 subjects volunteered for the study, was the average value of the glucose infusion providing informed consent after information. Three rate during the final 40 min of the 120-min study of those subjects did not show up at the scheduled (steady-state). As different studies have used various Journal of Human Hypertension Surrogates of insulin sensitivity in hypertension PA Sarafidis et al 711 sub-indices derived from the clamp, the M-value visit 1 and visit 2 and x¯ the pooled mean value for was normalized with body weight (Mbw) and fat-free the two visits.
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