Description
CHAPTER ONE
1.0 INTRODUCTION
- BACKGROUND OF STUDY
Diabetes mellitus (DM) has been defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both (Akinmokun et al., 1992). Insulin is a hormone produced in pancreas and enables body cells to absorb glucose that is converted into energy when the body is in need. If the body cell does not absorb the glucose, it will accumulate in the blood causing “hyperglycemia”, chronic hyperglycemia however leads to various potential complication (Pasquali, 2000).
Under normal physiological conditions, plasma glucose concentrations are maintained within a narrow range, despite wide fluctuations in supply and demand, through a tightly regulated and dynamic interaction between tissue sensitivity to insulin (especially in liver) and insulin secretion (DeFronzo and Goodman, 1995). In type 2 diabetes these mechanisms break down, with the consequence that the two main pathological defects in type 2 diabetes are impaired insulin secretion through a dysfunction of the pancreatic β-cell, and impaired insulin action through insulin resistance (Holt, 2004). Type 2 Diabetes mellitus has a greater genetic association than type 1 DM, the pathogenesis of type 2 Diabetes mellitus is characterized by impaired insulin secretion and insulin resistance. Some causes of insulin resistance are:
- Obesity/overweight (especially excess visceral adiposity)
- Excess glucorticoids (cushing’s syndrome or steroid therapy)
- Excess growth hormone (acromegaly)
- Pregnancy, gestational diabetes
- Polycystic ovary disease
- Lipodystrophy (acquired or genetic, associated with lipid accumulation in liver)
- Autoantibodies to the insulin receptor
- Mutations of insulin receptor
- Mutations of the peroxisome proliferators’ activator receptor γ (PPAR γ)
- Mutations that cause genetic obesity (e.g., melanocortin receptor mutations)
- Hemochromatosis (a hereditary disease that causes tissue iron accumulation) (Guyton and Hall, 2006).
The metabolic syndrome (MS), or insulin resistance syndrome accommodates the clustering together of certain cardiovascular risk factors associated with insulin resistance and hyperinsulinemia (Campbell, 2005). It was first identified in 1988 by Gerald Reaven, a Stanford University endocrinologist, in a lecture to the American Diabetes Association. At various times, this syndrome has been called dysmetabolic syndrome, insulin resistance syndrome or syndrome X. Now simply known as metabolic syndrome (Reaven et al., 2005). Metabolic syndrome is associated with a high risk of coronary heart disease and premature mortality (Isomaa et al., 2001). Besides resulting in macrovascular complications, there is growing evidence that metabolic syndrome, like Diabetes mellitus, causes micro vascular complications in patients with type 2 Diabetes mellitus (Knowler et al., 1990). Nearly 70-80% of the population with Diabetes mellitus is diagnosed with metabolic syndrome. Metformin is a biguanide euglycemic agent, has been approved by the food and drug administration for the treatment of type 2 Diabetes mellitus (Drouin et al., 2004). Although metformin is as effective as sulfonylureas, the drug differs in several respects: Metformin reduces insulin resistance without directly affecting insulin secretion, causes weight loss rather than weight gain, and has lactic acidosis rather than hypoglycemia as its most serious side effect (Kaku, 2010). Glibenclamide is a second-generation sulfonylurea drug. It is at least as effective as the first-generation agents and is effective in doses that are considerably less than those needed with first generation sulfonylureas (Charles ,2010). It is a useful medication for patients with type 2 diabetes whose hyperglycemia is not adequately reduced by dietary management and exercise. It can be used as the initial drug in these patients or as the replacement drug for those with primary or secondary failure during therapy with first generation sulfonylureas (Charles, 2010). Side effects are minimal, and the most important is hypoglycemia. Although no difference persists between the treatment groups for total-cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol, the antidiabetic agents seem to lower serum lipids most effectively, which may help prevent coronary events in T2DM patient (Penbe et al., 2003).
The present study was designed to investigate and compare the effects of glibenclamide and metformin on prevalence of metabolic syndrome in type 2 diabetic patients.
1.2 STATEMENT OF PROBLEM
To know if antidiabetic agents glibenclamide and meltformine has any effect on lipid and glycated haemoglobin in type 2 diabetes patients
1.3 AIM OF STUDY
To evaluate the effect of antidiabetic agent glibenclamide and meltformine on lipids and glycated haemoglobin in type 2 diabetes patient attending UITH Ilorin.
1.4 SPECIFIC OBJECTIVE
- To estimate concentration of lipid and glycated haemoglobin in type 2 diabetes patient on antidiabetic agents (glibenclamide and meltformine)
- To examined lipid parameters and glycated haemoglobin in pairs for their correlations for each study group.
- To compare the results obtained between the two groups
1.5 SIGNIFICANCE OF THE STUDY
This study showed the effect of two different antidiabetic agents (glibenclamide and meltformine) on lipid parameters and effect of long term management of type 2 Diabetes mellitus patients.
1.6 RESEARCH HYPOTHESIS
Plasma fasting lipid parameters will show no significant difference in both antidiabetic agents.
Glycated haemoglobin results pattern will show if the patients are adhering to the use of antidiabetic agents.
There will be a correlation between lipids and glycated haemoglobin based on the use of antidiabetic agents.
CHAPTER FIVE
5.0 DISCUSSION
The study shows discrepant results about the influence of metformin on lipid profile (10). Some studies, in agreement with ours, reported reduction only in TC levels (Grant, 1996; Ginsberg et al., 1999), while others reported reduction of TC and TG with an increase of HDL-C (Robinson et al., 1998; Yki-Jarvinen et al., 1999). Still other studies showed no changes in lipid profile (Groop et al., 1998; Rains et al., 1998). Another investigation showed an association of metformin with an improvement in the lipid profile even in non-diabetic patients (DeFronzo and Goodman, 1995). New studies are needed to clarify this issue, since TG and HDL-C are very important parameters for the evaluation of metabolic syndrome. A possible reason for these discrepant results may be that the clinical studies cited above analyzed data from independent samples. In our study, this problem was avoided by paired data analysis, in which each patient was his own control, thereby increasing the power of the statistical analysis.
A recent meta-analysis (Wulffele, 2004) covering 41 studies on the effects of metformin on BP and lipid profile showed that only TC reduction was significant. This study was in agreement with these findings and show that this fact was independent of BMI and WC reduction. Since the TG reduction found in the present study underwent interference from BMI and WC (intervening variables), we cannot conclude that metformin had a direct and isolated effect on TG levels.
The glycated haemoglobin level in control which do not take any type of anti-diabetic drugs has been statistically significant elevated as compared with those with type 2 diabetes i.e. (with metformin therapy) and (with metformin plus glibenclamide therapy). This result was in agreement with Krishna et al. (2015) who have demonstrated that anti- diabetic drugs such as metformin and glibenclamide produced a significant decrease in glycated haemoglobin levels compared to pre-treatment values (Krisha et al., 2015). On the other hand, there was no significant difference between those with metformin therapy and those with metformin plus glibenclamide therapy. This result is agreeing with Marwan (2013) who have demonstrated that there were no significant differences in those with metformin plus glibenclamide therapy between metformin treated group and those treated by a combination therapy of metformin plus glibenclamide (Al- Naama et al., 2010).
This results in agreement with Reyadh (2012) who found that use of metformin/glibenclamide combination or metformin alone in the treatment of T2DM maintained cholesterol levels closer to normal levels and in combination therapy serum TC level was lower than metformin used alone (Reyadh et al., 2012). Triglyceride results was found not to be significantly elevated (p<0.05) in those with metformin therapy when compared with control group this result was not in agreement with Attalah (2007) who found increase level of serum triglycerides in diabetic patients, which could be due to the increase of hepatic triglyceride synthesis (Attalah, 2007). Subjects with metformin therapy and those with metformin plus glibenclamide therapy showed no significant differences when compared to the control group. These results were in agreement with Kassim (2011) who found that metformin and glibenclamide therapies produces a non-significant favorable effect on serum triglyceride (Kassim, 2011). Type 2 diabetes is characterized by low HDL cholesterol (HDL-C) and HDL dysfunction (Al-Amery et al., 2013). The precise cause of the low HDL-C in type 2 diabetes is not known but may be the consequence of insulin resistance, augmented very low density lipoprotein production and increased activities of cholesteryl ester transfer protein and hepatic lipase (Fadini et al., 2014). Cagatay et al. (2011) found that using metformin as a mono therapy or combination with glibenclamide in type 2 diabetics produce no significant effect on HDL-C (Barter, 2011). The results of serum low density lipoprotein for diabetic patients with metformin therapy was found to be significantly different (p≤0.05) when compared with control group. Singh and Kumar (2011) found that the level of LDL significantly higher in type 2 diabetics (Cagatay et al., 2009). Increased elimination of lipids and apolipoproteins from VLDL particles results in the increased production of intermediate density lipoprotein (IDL) and LDL (Singh and Kumar, 2011). Dailey et al. (2002) found that combination therapy of metformin and glibenclamide shows a favorable effect on LDL-C levels and closer to that of nondiabetic subjects (Dailey et al., 2002). Petrovic et al. (2010) study revealed a significant elevation in VLDL-C when compared diabetic patients with controls. This may be due to insulin resistance has striking effects on lipoprotein size and subclass particle concentrations for VLDL and that lead to increased hepatic secretion of VLDL-C in type 2 diabetic patients (Petrovic et al., 2010), while Reyadh et al. (2012) who found a no significant difference between metformin and metformin plus glibenclamide treated groups compared with control group (Rosenbaum and Leibel, 2014; Ibrahim et al., 2015; Mohammed et al., 2016).
5.1 CONCLUSION
According to this study, 70.0% of diabetic patients presented significantly elevated LDL. Elevated LDL-C, elevated TCHOL, elevated TRG, and reduced HDL-C levels were noted in 28.37%, 36.37%, 39.01%, and 30.12% of the patients, respectively. The combination of elevated TG and reduced HDL-C were the most prevalent of the combined lipid abnormalities. Moreover, there are statistically significant differences in the levels of HDL-C, TCHOL, TG, and glucose between subjects and controls. In contrast, no differences were observed in levels of GHbA1c and FBS among patients using single or combination of oral hypoglycemia agents.
5.2 RECOMMENDATION
It is highly recommended that individual with type 2 diabetic should check their fasting blood glucose and glycated hemoglobin regularly since these are the major parameters that differentiate between diabetic and normal individual, Checking fasting glucose and glycated hemoglobin regularly would indicate the level of glucose . For individual controls with high BMI should check their glucose regularly since obesity is one predisposing property to type 2 diabetes.
