oa Comparison of Cardiometabolic Risk Factors in Metabolically Healthy and Pathologically Obese Arabs and Caucasians

Background

Obesity related diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease have become major health problems. Inappropriate insulin production and dyslipidemia are commonly associated with obesity. It is multifactorial and heterogeneous in origin. While 60–80% of obese subjects are insulin resistant (IR) and rapidly develop metabolic diseases, called pathologically obese (PO), a proportion retain sensitivity to the hormone and remain relatively healthy (MHO), either because the progression to disease is slower in these individuals or they have developed pathways that renders them immune. Stratification of this disease, depending on the range of associated pathologies, would help identify mediators, design targeted therapies, in the understanding of mechanisms for this apparent protection. Also some ethnicities, such as South Asians and Arabs, appear susceptible to both obesity and its associated pathologies, perhaps largely determined by lifestyle factors, such as diet and exercise. However weight loss, mainly surgical, is proving to be the most successful means of reducing body weight and improving insulin sensitivity.

Therefore the aims of this study were to compare morbidly obese patients of Caucasian and Arab origin prior to and after weight loss to identify biomarkers of insulin sensitivity and inflammation in Arabs and Caucasians.

Methods

Subjects: Morbidly obese patients of Arab and Caucasian origins awaiting bariatric surgery (gastric bypass, gastric sleeve, or gastric band) were recruited from the pre-operative clinics: Al-Emadi Hospital, Hamad Medical Corporation, (Doha, Qatar) and Whittington Hospital (North London Obesity Surgery Service, Whittington Hospital, London, UK). Morbid obesity was defined as BMI ≥ 40 kg.m^− 2 or BMI ≥ 35 kg.m^− 2 with significant co-morbidities. All studies were approved by the relevant National Ethics Committees.

The studies included both males and females over the age of 18 years. Patients with coronary artery disease, uncontrolled hypertension, malignancy or terminal illness, connective tissue disease or other inflammatory conditions likely to affect cytokine levels, immuno-compromised subjects and those with substance abuse or other causes for poor compliance were excluded.

Anthropometric measurements were recorded: age (years), weight (kg), and height (m) systolic and diastolic blood pressure (mmHg). BMI was calculated (kg.m^− 2). Patient information including demographic data (date of birth, gender, ethnicity), surgery type (gastric bypass, gastric band, gastric sleeve), co-morbidities, current medication, weight loss history, smoking habits and alcohol consumption were recorded from hospital notes.

Samples: Blood samples (EDTA, NaF, no anti-coagulent), following an overnight fast, were drawn from an ante-cubital vein on the day of the operation, immediately after anesthesia. Samples were centrifuged (3000 rpm, 15 minutes, 25°C), and the plasma or serum collected and stored at − 80 °C prior to assay.

Assays: Blood samples were used to determine glucose (hexokinase), lipids (Total Cholesterol, LDL and HDL: Roche) and insulin (ELISA, Mercodia). Adipokines (leptin, adiponectin, interleukin-6, and MCP1) were assayed by ELISA (R&D Systems, Oxon, UK). Insulin resistance was calculated using the homeostatic model assessment where HOMA =  (glucose in mmol/L ×  insulin in miU/ml)/22.5.

The criteria for classification: Subjects were considered MHO if free of T2DM, dyslipidaemia, and cardiovascular disease, and exhibited systolic blood pressure less than 140 mmHg, diastolic blood pressure less than 85 mmHg, fasting plasma glucose less than 6.8 mmol/l and insulin less than 6.5 miU/ml.

Statistics: Data were entered in SPSS version 22.0 for statistical analysis. Parametric tests were used for normally distributed data and non-parametric analysis for skewed data.

Results

Effect of ethnicity on cardiometabolic risk factors.

Despite the Arab cohort being significantly younger, they were hyperglycemic hyperinsulemic and hyperleptinaemic, compared to the Caucasians. This population also had elevated β-cell function and insulin resistance, while insulin sensitivity was lower. However there was no significant difference in blood pressure. Total-, LDL- and HDL-cholesterol were higher, but triglycerides lower, in Arabs. Leptin, a marker of adipose tissue mass and adipocyte hypertrophy, was elevated in Arabs. Furthermore the proinflammatory adipokines (MCP-1, IL-6) were higher and the anti-inflammatory adipokines (adiponectin) lower in this population.

Weight loss

In Caucasians, there was an increase in both HDL- and LDL-cholesterol in the PO group, and in serum adiponectin in both MHO and PO patients, following surgery. However, the insulin levels and HOMA-IR index decreased significantly in the PO group. Fasting plasma glucose did not change after weight loss in either group, whereas the total cholesterol increased in both groups significantly. In Arabs, three months after surgery, both MHO and PO subjects showed significant reduction in BMI, which was accompanied by lower systemic insulin, HOMA-IR and leptin. There was no change in total-, LDL- and HDL-cholesterol, whereas triglycerides were reduced after the weight loss. The inflammatory biomarkers CRP and IL-6 were unchanged.

Conclusion

Despite both populations being equally obese the Arabs had greater prevalence of risk factors for cardio metabolic complications, with fewer having a metabolically healthy phenotype. In non-diabetic Arabs, compared to Caucasians, insulin resistance and inflammation appeared to be predominant lesions. Interestingly higher leptin levels in the BMI-matched Arabs points to adipocyte hypertrophy and adipose tissue dysfunction as causal factors in these lesions. The young age at which Arabs develop obesity perhaps explains the greater susceptibility to its pathological consequences.