Establishment of reference intervals of clinical chemistry analytes for the adult population in Saudi Arabia: a study conducted as a part of the IFCC global study on reference values.

BACKGROUND: This study is a part of the IFCC-global study to derive reference intervals (RIs) for 28 chemistry analytes in Saudis. METHOD: Healthy individuals (n=826) aged ≥18 years were recruited using the global study protocol. All specimens were measured using an Architect analyzer. RIs were derived by both parametric and non-parametric methods for comparative purpose. The need for secondary exclusion of reference values based on latent abnormal values exclusion (LAVE) method was examined. The magnitude of variation attributable to gender, ages and regions was calculated by the standard deviation ratio (SDR). Sources of variations: age, BMI, physical exercise and smoking levels were investigated by using the multiple regression analysis. RESULTS: SDRs for gender, age and regional differences were significant for 14, 8 and 2 analytes, respectively. BMI-related changes in test results were noted conspicuously for CRP. For some metabolic related parameters the ranges of RIs by non-parametric method were wider than by the parametric method and RIs derived using the LAVE method were significantly different than those without it. RIs were derived with and without gender partition (BMI, drugs and supplements were considered). CONCLUSIONS: RIs applicable to Saudis were established for the majority of chemistry analytes, whereas gender, regional and age RI partitioning was required for some analytes. The elevated upper limits of metabolic analytes reflects the existence of high prevalence of metabolic syndrome in Saudi population.

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population.

BACKGROUND: Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of 'which SNPs in which populations.' The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis. METHODS: Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay. RESULTS: None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region. CONCLUSION: Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects.

BACKGROUND: Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM. METHODS: Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique. RESULTS: Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM. CONCLUSION: The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.