Glycemic control and prevention of secondary complications are the most important goals of using pharmacologic treatment of diabetes mellitus (DM). The inadequate responses to oral hypoglycemic agents may be attributed to inadequate postreceptor events even when insulin levels are quite sufficient, and associated with oxidative stress induced by long-term hyperglycemia. The administration of antioxidants such as melatonin and zinc may improve tissue responses to insulin and increase the efficacy of drugs, e.g. metformin, which act through this pathway. This project was designed to evaluate the effects of melatonin and zinc on the lipid profile and renal function in type 2 DM patients poorly controlled with metformin. A placebo-controlled, double-blind clinical trial was performed in which 46 type 2 diabetic patients were selected and allocated into three groups. These groups were treated with single daily oral doses of both 10 mg of melatonin and 50 mg of zinc acetate alone: 10 mg of melatonin and 50 mg of zinc acetate in addition to the regularly used metformin or placebo, given at bedtime for 90 days. Fasting lipid profiles and microalbuminuria (MAU) were measured before initiating the treatments (zero time) and after 30 and 90 days of treatment. Daily administration of melatonin and zinc improved the impaired lipid profile and decreased the level of MAU; the addition of this treatment regimen in combination with metformin improved the tissue responses to this oral hypoglycemic agent. In conclusion, the combination of melatonin and zinc acetate, when used alone or in combination with metformin, improves DM-related complications such as the impaired lipid profile and MAU in type 2 DM patients.

Despite the extensive clinical experience with the use of metformin worldwide, no formal doseranging study has been conducted because the current dosing strategy of metformin was determined empirically, rather than by an understanding of its dose-response relationship in patients with type 2 diabetes. The present study was designed to evaluate the correlation between serum metformin levels and glycemic control, insulin resistance and leptin levels in females newly diagnosed with type 2 diabetes. Sixty type 2 diabetic females were recruited for the study and were allocated into 3 groups; each receiving metformin 1000, 1500 and 2000 mg/day respectively for 3 months. Blood samples withdrawn from each patient at zero time and after 3 months is used to evaluate serum levels of HbA1c, glucose, leptin and insulin, in addition, the measurement of serum level of metformin in blood after 3 months by HPLC. The results demonstrated that all the treated groups with different doses of metformin showed significant improve in all parameters; the use of increased metformin doses was only correlated with plasma leptin levels in the highest dose. In conclusion, serum metformin levels are not good predictors for correlating improvement in clinical and biochemical parameters with increasing the dose in newly diagnosed non-insulin resistant females with type 2 diabetes.

The present study was designed to evaluate the relationship between serum leptin levels and the hormones related to fertility in Iraqi females with polycystic ovary syndrome (PCOS) and marital status. This study was conducted during the period from July to December 2007. Twenty-four women (12 married and 12 unmarried) with PCOS and not maintained on any type of therapy were included in the study. Twelve healthy and normal ovulatory women with an age range matched with that of PCOS women were included. After an overnight fasting, blood samples were drawn from all women at random days. While in those with regular menstrual cycles, blood samples were obtained during the follicular phase of the cycle, except for samples utilized for the assay of progesterone that performed in the day 21 of the cycle (luteal phase). After preparation of serum, the levels of leptin, luteinizing hormone (LH), follicle-stimulation hormone (FSH), progesterone, testosterone and prolactin were analyzed. Both groups of PCOS patients showed significantly lower levels of serum leptin, while prolactin, LH and FSH and testosterone were significantly elevated compared to controls. No significant differences were reported among PCOS patients with different marital status. In conclusion, impaired plasma leptin levels in PCOS women were associated with impaired endocrinological parameters related to fertility.

Long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) mostly associated with renal and hepatic adverse effects, and the adjunct use of compounds with potent protective effects, like silymarin, may be one of the choices to avoid these effects. This project was designed to evaluate the protective effect of silymarin against the suspected renal and hepatic injury induced with long term use of NSAIDs; 220 patients with osteoarthritis were randomized into 5 groups and treated with either silymarin 300mg/day alone, piroxicam 20mg/day alone, meloxicam 15mg/day alone or the combination of each of them with silymarin for 8 weeks. The renal and hepatic functions were evaluated before starting treatment and after 8 weeks including assessment of serum levels of urea, creatinine and the activities of the hepatic enzymes alkaline phosphatase (ALP), glutamic-oxalic acid transaminase (GOT) and glutamic-pyruvic acid transaminase (GPT). The results indicated that using NSAIDs alone produced elevation in the markers of renal and hepatic damage that can be successfully prevented or reversed when silymarin adjunctly used with them. In conclusion, silymarin when co-administered with the NSAIDs (piroxicam or meloxicam) decreases their renal and hepatic toxicities in OA patients. Key words: Silymarin; Piroxicam, Meloxicam; Nephroprotection; Hepatoprotection

Insulin receptor substrate-1 is the first and key substrate of the insulin receptor, act as a multisite docking protein for various effector molecules. It is encoded by the IRS-1 gene, which is found on chromosome 2q36.3 in humans. Insulin receptor substrate is an effective insulin signaling agent that plays a key role in preserving the cell’s basic function, any polymorphism in the IRS genes acts as a competitive insulin receptor inhibitor. A total of 150 healthy men as control and 200 diabetic patients participated in this study; it is across-sectional study, patients were chosen while seeking medical care in the outpatient clinic. This study investigates the association of IRS-1 rs2943641 to the pathogenesis of type 2diabetes mellitus in Iraqi males. This study was conducted to study the association of SNP rs2943641[TT(minor allele type), TC(heterozygous alleles type) and CC(major allele type)] to the pathogenesis of type 2diabetes mellitus according to the logistic regression method which demonstrates that there is a significant association between TC and CC allele groups to the pathogenesis of T2DM. In conclusion, genetic polymorphism of IRS-1 rs2943641 is associated with the pathogenesis of T2DM in Iraqi male.