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.

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.

frequency of multiple primary cancers: 1952-2004

To evaluate the frequency rate and site of origin of multiple primary malignancies [MPM] in Bahrain from 1952 to 2004. Retrospective study. Pathology Department, Salmaniya Medical Complex, Bahrain. Confirmed malignancies diagnosed in Bahraini patients from 1952 - 2004. The diagnosis are based on histopathology and hematology archives of the government, private hospitals and clinics. Six thousand nine hundred and nineteen cancer patients were found in the archives, 122 [1.7%] had MPM; 31 [25%] had synchronous and 91 [75%] had metachronous lesions, the annual frequency rate was 2.3 patients/year. Equal M:F ratio was found, but males had more synchronous while females had more metachronous, double and triple cancers lesions. Sixty percent of all cancer patients were above the age of 50 years compared to 69% in all MPM patients, [74%] in synchronous, [67%] in first age metachronous and [77%] in second age metachronous lesions. The three most common metachronous MPM occurred in association with cancers of breast [21%], urinary tract [17%] and prostate [8%]. Amongst males the commonest combinations occurred in association with cancers of urinary tract [28%], prostate [16.3%] and kidney [7%]. Amongst female breast [38%], thyroid [10.4%] and urinary tract [6.3%] were the most common

Cardiovascular responses to tonic pain in REM sleep-deprived rats. Role of melatonin and beta endorphin

Chronic pain is associated with increased incidence of hypertension. Sleep deprivation, common in patients with chronic pain, is associated with increased blood pressure and heart rate. This study was designed to determine whether sleep deprivation induces increased cardiovascular responses to pain. In addition; we examined the role of melatonin and endorphins in mediating these responses. The study was conducted in Sprague-Dawely rats divided into a control group [n=8] and Rapid Eye Moment sleep deprived [REMSD] group [n=8]. REM sleep deprivation was done for three days using the inverted flowerpot technique. Systolic BP and HR were recorded at baseline as well as 5, 10 and 30 minutes after intra-plantar formalin injection. In addition, serum melatonin and endorphin levels were determined. Under basal conditions, BP and HR and following acute pain [1[st] phase of formalin injection] were comparable with non-sleep deprived [non-SD] state. In contrast, the REMSD rats showed significantly greater increases in HR and BP during the 2[nd] phase of formalin pain as compared to non-SD state. These changes were associated with significant reductions in serum melatonin and endorphin levels in REMSD rats. These data indicate that exaggerated blood pressure and HR responsiveness to pain in sleep deprivation could be mediated through reductions in melatonin and endorphin