The Relationship of Metabolic Syndrome Traits with Beta-Cell Function and Insulin Sensitivity by Oral Minimal Model Assessment in South Asian and European Families Residing in the Netherlands

Hindawi Publishing Corporation Journal of Diabetes Research Volume 2016, Article ID 9286303, 9 pages http://dx.doi.org/10.1155/2016/9286303 Research Article The Relationship of Metabolic Syndrome Traits with Beta-Cell Function and Insulin Sensitivity by Oral Minimal Model Assessment in South Asian and European Families Residing in the Netherlands Thekla Geragotou,1,2 Sjaam Jainandunsing,1 Behiye Özcan,1 Felix W. M. de Rooij,1 Alexander Kokkinos,1 Nicholas Tentolouris,2 and Eric J. G. Sijbrands1 1 Department of Internal Medicine, Erasmus MC-University Medical Center Rotterdam, 3015 CE Rotterdam, Netherlands First Department of Propaedeutic and Internal Medicine, Medical School, National and Kapodistrian of Athens, Laiko General Hospital, 11527 Athens, Greece 2 Correspondence should be addressed to Thekla Geragotou; Received 22 March 2016; Accepted 12 July 2016 Academic Editor: Brunella Capaldo Copyright © 2016 Thekla Geragotou et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background. There are different metabolic syndrome traits among patients with different ethnicities. Methods. We investigated this by studying 44 South Asians and 54 Europeans and classified them in three groups according to the occurrence of metabolic syndrome (MetS) and Type 2 Diabetes (T2D). Insulin sensitivity index (ISI), static, dynamic, and total beta-cell responsivity indices (Φ), and disposition indices (DIs) were calculated with the use of oral minimal model (OMM). Results. In both ethnicities, ISI was lower in the subgroup with MetS and T2D as compared to the subgroup without MetS nor T2D (𝑃 < 0.004). South Asians without MetS were more insulin resistant than Europeans without MetS (𝑃 = 0.033). In the South Asians, ISI, dynamic DI, and static DI were associated significantly (𝑃 < 0.006) with high-density lipoprotein cholesterol and triglycerides. In the Europeans, ISI was associated with waist-to-hip ratio (𝑃 = 0.005) and systolic and diastolic blood pressure (𝑃 < 0.005), while static DI was related to the systolic blood pressure (𝑃 = 0.005). Conclusions. MetS was linked with insulin resistance and reduced capacity to handle glucose regardless of ethnicity. ISI and DIs were associated with lipid traits in South Asians and with blood pressure in Europeans suggesting that insulin resistance enhances different metabolic syndrome traits among different ethnicities. 1. Introduction Overweight and physical inactivity enhance each other and decline the sensitivity to insulin. Resistance to insulin is characteristic of metabolic syndrome (MetS), which is defined as a cluster of the following cardiovascular risk factors: central obesity, impaired glucose tolerance, dyslipidemia, and hypertension. MetS constitutes a major health problem, as it is strongly associated with type 2 diabetes mellitus (T2D) and cardiovascular disease [1–3]. Furthermore, insulin resistance is a consistent finding in T2D and appears to contribute to the development of T2D. However, T2D develops only if there is dysfunction of beta-cells [4]. In the absence of betacell dysfunction individuals can compensate indefinitely for resistance to insulin action with the appropriate hyperinsulinemia. Therefore, many people with remarkable resistance to insulin may never develop T2D [5, 6]. Lifestyle factors clearly underlie MetS incidence, but genetic susceptibility may be important as well [7]. For example, specific ethnic groups are more susceptible to MetS than others [8, 9]. In particular, South Asians are predisposed to develop MetS and subsequently T2D and cardiovascular disease at a younger age [10–12]. They also have a higher prevalence of abdominal obesity, are less sensitive to insulin, and have a lower glucose disposal rate than Europeans [12– 14]. In addition, South Asians have lower plasma levels of HDL and adiponectin and higher levels of glucose, insulin, leptin, complement C3, plasminogen activator inhibitor-1, 2 fibrinogen, and tissue plasminogen activator compared to Europeans [15–20]. However, traditional risk factors such as smoking, hypertension, and dyslipidemia do not explain the increased risk for cardiovascular disease in South Asians [21, 22]. Insulin resistance itself has been held responsible for the high rates of T2D and cardiovascular disease in this ethnic group [10, 12]. Oral minimal modeling is a pharmacokinetic/pharmacodynamic algorithm developed to estimate beta-cell function and insulin sensitivity index (ISI) from dynamic data [23]. In the present study, we used this oral minimal model (OMM) to investigate the relationship between MetS traits and betacell function in South Asian and European families with prevalent T2D. 2. Materials and Methods 2.1. Subjects. The recruitment of patients with T2D and their relatives at our university outpatient clinic has been described in detail previously [24]. In brief, 48 South Asians and 54 Europeans that are residing in the Netherlands were initially recruited for the present study and we used an oral glucose tolerance test (OGTT) to group the subjects in T2D or noT2D according to the WHO criteria. In addition, the International Diabetes Federation (IDF) criteria were used to define MetS [25]. Four South Asians had T2D but not MetS and were excluded from the study as the number of subjects was too small for meaningful analyses and there were no European counterparts for comparison. Hence, 98 subjects were included in our analyses (44 South Asians and 54 Europeans) from 25 families (25 patients with T2D but not on insulin therapy and 73 relatives) and they were distributed among 3 groups; no metabolic syndrome/no type 2 diabetes mellitus (noMetS/noT2D), metabolic syndrome/no type 2 diabetes mellitus (MetS/noT2D), and metabolic syndrome/type 2 diabetes mellitus (MetS/T2D). Written informed consent was obtained from all participants. The Erasmus Medical Ethics Review Board approved the study protocol. 2.2. Physical Examination. Body height and weight were measured in light clothing without shoes and were used to estimate body mass index. Waist circumference was measured halfway between the lowest rib and the iliac crest while the maximum circumference of the hips was measured in the standing position; from these measurements the waist-tohip ratio was calculated. Systolic and diastolic blood pressure were measured in the sitting position with an electronic blood pressure monitor (Datascope Accutorr Plus Inc., Montvale, NJ), after five minutes’ rest. 2.3. Samples and Measurements. All participants underwent a 210 min OGTT. A 75 g glucose load was administered (𝑡 = 0), after an overnight fast, and 11 venous blood samples were acquired at prespecified time intervals (−60 min, −15 min, 15 min, 30 min, 45 min, 60 min, 90 min, 120 min, 150 min, 180 min, and 210 min) for the measurement of (...truncated)