Comparative effectiveness of antidiabetic drugs glibenclamide versus glibenclamide plus metformin on serum glucose concentration and serum c-peptide concentration in Iraqi diabetic type 2 patients

Diabetes type2 is characterized by hyperglyc emia, this hyperglycemia result from dysfunction of beta – cells to secret adequate insu lin that maintain serum glucose concentration. Cpeptide is an peptide with 31 ami no acid this peptide play an important function in the synthesis of insulin, and ow used as reliable indicator for insulin secretion in diabetes mellitus type 2. We s tudied the effects of antidiabetic drug glibenclamide versus glibenclamide plus metformin o n serum glucose concentration and serum cpeptide concentration in comparison with c ontrol group. 84 patients enrolled in this study and divided into 3 groups, in the first group patients treated with glibenclamide. In the second group patients treated with glibenclamide plus metformin. While the third group normal patients represent as control group. Then we estimated the postprandial serum glucose concentration and serum cpeptide concentration for each patient in all groups. Data collected and statisti cally analyzed. We find that there is significant increase in serum glucose concentration in glibenclamide group and glibenclamide plus metformin when compared with con tr l group; also there is Kufa Med.Journal 2011.VOL.14.No.1 147 significant decrease in serum cpeptide concentrat ion in glibenclamide group and glibenclamide plus metformin group when compared wi th control group. These results strongly indicate that, there is a failure in effec ts of antidiabetic drugs used by Iraqi patients and there is dysfunction of beta –cells of pancreas to normalized serum glucose concentration. Introduction According to the world health organization ,at leas t 171 millions people suffer from diabetes ,or 2.8%of the population , its incidence is increasing rapidly and it is estimated that by 2030 this number will almost double(1). Als o the prevalence of diabetes increased sharply with age until 75 in both sexes, and the prevalence of type 2 mellitus is generally higher in developed countries it is in creasing most rapidly in developing countries (2). Type 2 diabetes is characterized by hyperglycemia resulting from insulin resistance in the setting of inadequate betacell compensation (3). And the causes of type 2diabetes involve both genetic susceptibility and environmental factors, although the genetic component may be greater than in type 1 (4). In type 2 diabetes delayed insulin secretion result in higher peak glucose concentration particularly when suppression of glucagon is impaired whereas insulin resistance prolong the duration of hyperglycemia (5). The diagnostic criteria for diab etes mellitus recommended by the world health organization in 2000 are either ; Fast plasma glucose =or >126 mg /100ml or Postprand ial plasma glucose =or >200 mg /ml (6). Also many investigators have used cpeptide level as biomarker of beta –cell function (7). Cpeptide is an active peptide with molecular weight 3600 containing 31 amino acid ,cpeptide has an essential function in the s ynthesis of insulin and cpeptide is the more reliable indicator of insulin secretion than i nsulin itself (8). And it became a most useful independent indicator of insulin biosynthes is (9). The antidiabetic drugs used are glibenclamide and metformin, the glibenclamide used in the treatment of type 2 diabetes, the drug works by inhibit ATP-sensitive K + channel in pancreatic beta –cells this causes membrane depolarization which causes vo ltage dependent Ca++ channel s to open which cause an increase in intra cellular Ca++ in the beta –cell which stimulate insulin release (10). While metformin exert its eff ect primarily by decreasing hepatic glucose out put and has a comparatively minor effec t in increase insulin sensitivity (11). 1. Patients and methods Patients: 84 patients were participated in this study of b th sex and from different ages groups ,are selected randomly from diabetic center in Mar jan hospital in Hilla city . these patients are classified in three groups ; Group 1; included 28 patients with diabetes type 2, treated with glibenclamide antidiabetic drug only. Group 2; included 31 patients with diabetes type 2, treated with glibenclamide plus metformin antidiabetic drugs. Group 3; included 24 normal and healthy patients, c onsider as control group Data about sex, age, type of drugs treated, and dur ation of disease are collected. Kufa Med.Journal 2011.VOL.14.No.1 148 2. Biochemical analysis Serum glucose concentration: We estimated the postprandial serum glucose concent ration according to the Trinder reaction (enzymatic colorimetric method), the gluco se is oxidized to d-gluconate by the glucose oxidase with formation of hydrogen peroxide , in the presence of peroxidase a mixture of phenol and 4aminoantipyrin is oxidized by hydrogen peroxide to form a red quinoneimine dye proportional to the concentration of glucose in the sample (12, 13). Serum cpeptide concentration: Also we estimated the serum cpeptide according to enzyme –linked immunosorbent assay (ELISA),based on the principle of competitive binding , endogenous c –peptide of a patient sample competes with a cpeptide –horser adish peroxidase conjugate for binding to the coated antibody ,after incubation th e unbound conjugate is washed off ,the amount of bound peroxidase conjugate is invers ely proportional to the concentration of cpeptide in the sample ,after ad dition of the substrate solution, the intensity of color developed is inversely proportio nal to the concentration of cpeptide in patient sample (14). 3. Statistical analysis: The data was analyzed by method analysis of varianc e (ANOVA) by utilizing SPSS program, to determine the significance level of dif ference in serum glucose concentration and serum cpeptide concentration in all three groups. Results In comparison glibenclamide group and glibenclamide plus metformine group, the serum glucose concentration increase significantly than control group p<0.001, table 1. While there is no significantly difference between glibenclamide group and glibenclamide plus metformin group according to ser um glucose concentration p>0.05, table 1. While in comparison the glibenclamide group and gli benclamide plus metformin group the serum c-peptide concentration is significantly decrease than control group p<0.05 (glibenclamide versus control) , and p<0.01 (gliben clamide plus metformin versus control), table 2.While there is no significant dif ferences between glibenclamide group and glibenclamide plus metformin group related to s erum c-peptide p>0.05 ,table 2. Also in this study the distribution of patients acc ording to age, showing that the most patients age between 40 years to 69 years old figur e 1. In figure 2 showing the distribution of patients ac cording to sex, in this study the males more than females, also the figure 3 showing the du ration of diabetes disease . Table 1; serum glucose concentration (mg/100ml) in different groups, data expressed as mean ± SD Glibenclamide plus metformin group Glibenclamide group Control group 244.16±91.06 217.22±88.46 96.68 ±27.48 Control group *** *** Glibenclamide group n.s Kufa Med.Journal 2011.VOL.14.No.1 149 Glibenclamide plus metformin group *** p<0.001 significant n.s = non significant Table 2; serum cpeptide concentration (ng/ml) in different groups, data expressed as mean ± SD Glibenclamide plus metformin group Glibenclamide group Control group 2.96±1.94 3.24±1.91 4.61±2.55