Metformin Pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 Polymorphisms on Glycemic Control and HbA1c Levels.

Type 2 diabetes mellitus (T2DM) constitutes a major portion of Jordan's disease burden, and incidence rates are rising at a rapid rate. Due to variability in the drug's response between ethnic groups, it is imperative that the pharmacogenetics of metformin be investigated in the Jordanian population. The objective of this study was to investigate the relationship between twenty-one single nucleotide polymorphisms (SNPs) in the SLC22A1, SLC22A2, and SLC22A3 genes and their effects on metformin pharmacogenetics in Jordanian patients diagnosed with type 2 diabetes mellitus. Blood samples were collected from 212 Jordanian diabetics who fulfilled the inclusion criteria, which were then used in SNP genotyping and determination of HbA1c levels. The rs12194182 SNP in the SLC22A3 gene was found to have a significant association (p < 0.05) with lower mean HbA1c levels, and this association more pronounced in patients with the CC genotype (i.e., p-value was significant before correcting for multiple testing). Moreover, the multinomial logistic regression analysis showed that SNP genotypes within the SLC22A1, SLC22A2, and SLC22A3 genes, body mass index (BMI) and age of diagnosis were significantly associated with glycemic control (p < 0.05). The results of this study can be used to predict response to metformin and other classes of T2DM drugs, making treatment more individualized and resulting in better clinical outcomes.

Diabetes mellitus in two genetically distinct populations in Jordan. A Comparison between Arabs and Circassians/Chechens Living with Diabetes.

OBJECTIVES: To compare clinical, anthropometric, and laboratory characteristics in diabetes type 2 patients of 2 genetically-distinct ethnicities living in Jordan, Arabs and Circassians/Chechens.  Methods: This cross sectional ethnic comparison study was conducted in King Abdullah University Hospital, Irbid and The National Center for Diabetes, Endocrinology, and Genetics, Amman, Jordan between June 2013 and February 2014. A sample of 347 (237 Arab and 110 Circassian/Chechen) people living with diabetes were included in the study. Data were collected through direct interviews with the participants. Clinical data were collected using a questionnaire and anthropometric measurements. Laboratory data were extracted from the patients' medical records. Results: More Arabs with diabetes had hypertension as a comorbidity than Circassians/Chechens with diabetes. Arabs living with diabetes were generally more obese, whereas Circassians/Chechens living with diabetes had worse lipid control. Arabs with diabetes had higher means of glycated haemoglobin (HbA1c) and fasting blood sugar, and more Arabs with diabetes had unsatisfactory glycemic control (60.6%) than Circassians/Chechens with diabetes (38.2%) (HbA1c ≥7.0%). Most participants (88.8%) had at least one lipid abnormality (dyslipidemia).  Conclusion: Multiple discrepancies among the 2 ethnic diabetic populations were found. New diabetes management recommendations and policies should be used when treating people living with diabetes of those ethnicities, particularly in areas of glycemic control, lipid control, and obesity.

Evaluation of Glycemic Control, Lifestyle and Clinical Characteristics in Patients with Type 2 Diabetes Treated at King Abdullah University Hospital in Jordan.

OBJECTIVES: The study aimed to assess glycemic control in a Jordanian population with type 2 diabetes and to explore the sociodemographic, clinical and medication-related factors as well as the anthropometric indexes and laboratory values associated with and possibly contributing to unsatisfactory glycemic control. METHODS: We included 237 patients previously diagnosed as having type 2 diabetes. Data were collected through direct interviews. Sociodemographic and clinical details were collected using a questionnaire designed for the purpose of the study, anthropometric measurements were obtained at the time of the interviews, and laboratory data were extracted from the medical records of King Abdullah University Hospital. RESULTS: Of the participants, 60.8% were found to have unsatisfactory glycemic control (glycated hemoglobin levels ≥7%). Unsatisfactory glycemic control was associated with younger ages at diabetes diagnosis, higher mean weights and higher prevalences of diabetic neuropathy. No relationships were found among glycemic control and body mass index, waist circumference or central obesity. Patients with adequate control were more likely to have health insurance and to have hypothyroidism as a comorbidity. Insulin use and medication plans containing insulin were associated with unsatisfactory control. Patients with unsatisfactory control had higher mean levels of low-density lipoproteins and triglycerides and lower mean levels of high-density lipoproteins. Moreover, elevated triglycerides (≥150 mg/dL) and dyslipidemia were associated with unsatisfactory glycemic control. CONCLUSIONS: More than half of the participants had unsatisfactory glycemic control, highlighting the need for a change in the approach and strategies used for patients with diabetes in Jordan. Factors associated with glycemic control that were found in this study should be further studied and used in the prevention and management of diabetes.

Analgesic properties of a dexmedetomidine infusion after uvulopalatopharyngoplasty in patients with obstructive sleep apnea.

BACKGROUND: Dexmedetomidine is an alpha(2) -adrenergic agonist with sedative and analgesic properties. This study aimed to investigate if the use of a continuous dexmedetomidine infusion with i.v. morphine patient-controlled analgesia (PCA) could improve postoperative analgesia while reducing opioid consumption and opioid-related side effects. METHODS: In this prospective randomized, double-blinded, controlled study, 39 patients with obstructive sleep apnea syndrome undergoing uvulopalatopharyngoplasty were assigned to two groups. Group D (dexmedetomidine group) received a loading dose of dexmedetomidine 1 µg.kg(-1) i.v., 30 minutes before the anticipated end of surgery, followed by infusion at 0.6 µg.kg(-1) h(-1) for 24 hours. Group P (placebo group) received a bolus and infusion of placebo. In both groups, postoperative pain was initially controlled by i.v. morphine titration and then PCA with morphine. Cumulative PCA morphine consumption, pain intensities, sedation scores, cardiovascular and respiratory variables and opioid-related adverse effects were recorded for 48 hours after operation. RESULTS: Compared with placebo group, patients in the dexmedetomidine group required 52.7% less PCA morphine during the first 24 hours postoperatively, with significantly better visual analogue scale scores, less incidence of respiratory obstruction (5 vs. 12 patients, respectively; P = .037) and longer time to first analgesic request (21 (11) vs. 9 (4) minutes; P = .002). Fewer patients in group D experienced nausea and vomiting than those in group P (7 vs. 24 patients, respectively; P < .05). CONCLUSION: Continuous dexmedetomidine infusion may be a useful analgesic adjuvant for patients susceptible to opioid-induced respiratory depression.

Intramuscular ketamine for prevention of postanesthesia shivering in children.

OBJECTIVE: To compare the effects of intramuscular ketamine with pethidine and placebo on post operative shivering in children undergoing tonsillectomy. METHODS: A prospective randomized double-blind study was conducted at King Abdulaziz Naval Base Hospital, Jubail, Kingdom of Saudi Arabia, from November 2006 to October 2007. One hundred and twenty children (American Society of Anesthesiologists Grade 1, aged 5-12 years) were enrolled. Children were randomly allocated to receive ketamine 1 mg/kg (group K, n=40), or pethidine 0.5 mg/kg (group P, n=40), or normal saline (group S, n=40) intramuscularly just after induction of general anesthesia. Hemodynamic parameters, oxygen saturation and tympanic temperature were measured and recorded before induction of anesthesia and at regular intervals thereafter. An investigator blinded to the treatment group, graded postoperative shivering using a 5 point scale. RESULTS: The number of patients shivering on arrival to the recovery room and at 10 and 20 minutes after operation were significantly less in groups K (1,1,1) than in group S (19,12,17). No patient that received pethidine shivered. The time to first analgesic requirement in group S was shorter than groups K and P (p=0.001). CONCLUSION: The study indicates that the use of a prophylactic low dose ketamine was found to be effective in preventing post anesthesia shivering in children undergoing tonsillectomy. Ketamine may have at least theoretical advantages over pethidine as regard respiratory depression, nausea, and vomiting.