Trends in Hyperglycemia Control in Type 2 Diabetes through Glycemic Management

Research Article

J Fam Med. 2016; 3(10): 1094.

Trends in Hyperglycemia Control in Type 2 Diabetes through Glycemic Management

Sameer Al-Ghamdi*

Department of Family Medicine, College of Medicine, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia

*Corresponding author: Sameer Al-Ghamdi, Department of Family Medicine, College of Medicine, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia

Received: October 29, 2016; Accepted: November 21, 2016; Published: November 23, 2016


Introduction: This systematic review article revolves around the assessment of the underlying factors and trends associated with the hyperglycemic control among the patients suffering from Diabetes mellitus Type 2.

Method: The review of research articles was performed between Feb. and may 2016 through meta-analysis and 40 out of 842 research papers were included in this study as they were most relevant and authentic. The validity of the research studies for their inclusion in the meta-analysis is performed through Newcastle Ottawa scale.

Result: The review of the research articles provided ample data regarding the benefits of disease-specific educational counseling of the patient suffering from Type 2 Diabetes.

Keywords: Diabetes self-care; Hyperglycemia; Patient education; Type 2 DM


Diabetes mellitus type 2 can be considered as a group of metabolic diseases resulting due to hyperglycemia. This hyperglycemia may be accounted to defects in insulin sensitization and secretion. Type 2 Diabetes mellitus (DM) is suggested to be the leading cause of death among the population in the United States. It is reported that type 2 DM is a direct cause of mortality and has increased the death toll up to 73,000 per year. Moreover, DM type 2 has been suggested to be the underlying cause of 220,000 deaths annually. Type 2 Diabetes is also associated with various co-morbidities among which the most common are kidney failure and blindness observed among the adult population [1].

The American Diabetic association has reported that more than 20 million people have been diagnosed for Diabetes at present, whereas, 6 million of the population remain undiagnosed. The derangement of glucose homeostasis being observed among the population is responsible for the ultimate development of Diabetes. Hence, the multi-factorial analysis of genetic, ethnic and racial heritage and environmental factors contributing to the growing rate of Diabetes mellitus type 2 is needed. It is important to understand the precise interplay associated with all the contributing factors through generation of evidence based on long-term trials. Researchbased evidence regarding Diabetes mellitus will help in the effective prevention and management of Diabetes mellitus [1-9].

In 2012, the American Diabetes Association and the European Association for Diabetes provided a detailed position statement regarding the problem and for the management of hyperglycemia in patients suffering from type 2 DM specifically. This position statement is of dire need to pronounce the growing public health concern associated with the increasing need of managing Diabetes mellitus adequately. Moreover, scarcity of comparative treatment and management alternatives of type 2 DM evokes the need of conducting future longitudinal researches for producing long-term treatment outcomes [1,2,9].

Glycemic Targets for the Management of Type 2 Diabetes

Glucose control is the major target to be achieved during the management of type 2 Diabetes. Reducing hyperglycemia decreases the onset of microvascular complications but its effect on the reduction of cardiovascular complication is uncertain. It is suggested that long-term management of hyperglycemia may reduce the risk of cardiovascular complications. A personalized management approach for balancing the benefits and risks associated with glycemic control is necessary. It is mandatory to find out the age-related effects and the health status of patients who are being exposed to the adverse effects of lipid-lowering medications. The clinicians and other healthcare providers involve in the management of Diabetes have a greater responsibility to address the risk and consequences associated with an adverse event [2,3].

It is estimated that the usual HbA1c goal that is needed to be achieved is 53.0mmol/mol of plasma. Control of glucagon secretion and regulation of Paracrine mechanisms is another mechanism associated with the hyperglycemic control. These secretions help in the generation of positive feedbacks, which is helpful in providing favorable energetic conditions. Human cells are also known to release acetylcholine parallel to glucagon and this neurotransmitter is also helpful in the generation of the feedback loop. Such paracrine mechanisms control the secretion of glucagon from the a-cells that are responsible for releasing inhibitory factors. It should be notified that paracrine control does not depend upon capillary transport in the interstitial spaces and the microcirculation in the Islets of Langerhan is particularly important. Since glucose in the blood is responsible for the stimulation of insulin release, which in turn inhibits glucagon secretion from the a-cell [2,4].

It is further illustrated that inhibition of a-cells is secondary to the stimulation of β-cells and insulin can be considered as the first mediator of a-cells inhibition. Paracrine factors may be released from b-cells via two routes i.e. dependent Ca+2 releases from the secretary vessels or Ca+2 independent releases from b-cells via plasma membrane transporters. Insulin secretion is directly related to the level of glucagon response to hypoglycemia. It is estimated that glucagon release is inhibited to its maximum as the concentration of glucose is raised to 0–7 mM range as it indicates the secretion of Insulin [4,5].

In the Ca+2 process of release, paracrine influence is found on the secretion of glucagon in response to hypoglycemia. GABA is evident to release by activation through both the above mentioned routes. Studies conducted on the islets of Langerhan indicated that amount of glucose in the blood is known to control the GABA release from the cells. This reduction in GABA stimulates the increase of GHB, which in-turn inhibits the secretion of glucagon from the a-cells. Moreover, Somatostatin is also considered to be a potent inhibitor of both insulin and glucagon and was proposed to be regulator of insulin and glucagon release. Thus somatostatin mediates the inhibition feedback mechanism during hyperglycemia.

During the process of glycolysis, pyruvate is metabolized causing an increase in the cytoplasmic ATP/ ADP ratio, which closes the ATPdependent K+ channels leading to depolarization. This depolarization opens the Ca+2 channels causing a rise in the Ca+2 channels and is the main trigger of insulin release. The glucokinase activity plays a role similar to b-cells and may act as sensors for metabolic glucose [5].

The above mentioned mechanism demonstrates the heterogeneity of the metabolic conditions associated with the occurrence of Type 2 Diabetes mellitus. It should be noted that the pancreatic b-cells synthesizes and stores insulin at a regular basis, irrespective of the glucose levels in the blood. Insulin remains stored in the vacuoles and is released when it is triggered by an elevation of the blood glucose levels. An increase in the glucagon from the a-cells is mediated by a decrease in the insulin levels due to drop in the blood glucose. Glucagon stimulation promotes the conversion of glycogen to glucose for maintaining the normal blood glucose levels. The production of glucose to during the period of fasting requires rapid gluconeogenesis and glycogenolysis [4,5].

Three key defects in the process of glucose metabolism may result in the emergence of hyperglycemia causing the condition of Type 2 Diabetes mellitus. These defective processes include increased hepatic glucose production, diminished insulin secretion and impaired action of insulin. Hence, insulin resistance due to any of these defects resulted into higher levels of glucose in the blood. Insulin resistance can be defined as the delayed responses to Insulin receptors and this problem is generally post-receptor. This means that there is a problem in the response mechanism to Insulin release rather than its timely production, which leads to Type 2 Diabetes mellitus [5].

Insulin Signaling Mechanism

It is important to understand the insulin signaling mechanism in response to glucose plasma levels. Human Insulin receptors are heterodimer in nature and composed of two extracellular a-subunits along with two b-subunits, which are located into transmembranes. The ligand-binding domain is located into a-cells and is responsible for the regulation of the intracellular tyrosine kinase activity of b-subunits. The insulin receptor gene in mammals consisted of 22 axons that are responsible for the generation of isoforms by alternative splicing of axon-11; the isoforms (IRa) contains axon-11, whereas the b-isoform (IRb) omits axon-11. This IRb is responsible for binding to insulin on the receptor site and dominate the tissues that are insulin sensitive including adult liver muscle and adipose tissues. On the other hand, IRa binds to insulin growth factors in other tissues such as fetal tissues, hematopoietic cells and central nervous system. The growth factors and Insulin resides in the plasma membranes in the form of inactive covalent dimers, which increases the flexibility of the activation loop to allow ATP and causes active conformation by phosphorylation [6].

These activated insulin receptors further caused phosphorylation of the tyrosine residues in the cellular substrates. The phosphorylation of tyrosine sites provides a signaling cascade in which SH2 domains are binded to the effector proteins such as phosphoinositide 3-kinase, tyrosine kinase and phosphatase SHP2. The classic insulin cascade causes ensues the production of PI by phosphatidylinositol 3-kinase. phospholipid phosphatases and Protein phosphatases modulates the strength of insulin signals and dysregulation of these heterologous signaling mechanisms can causes glucose intolerance, hyperinsulinemia, insulin resistance and dysregulation of lipid metabolism. Translocation of the glucose transporters in the plasma membranes aids the transportation of glucose into the skeletal muscles and facilitates the diffusion of glucose in normoglycemic conditions [7].

Pathophysiology of T2DM

Skeletal muscle accounts for 75% of the glucose uptake that is regulated by insulin stimulation and defects in the skeletal muscle tissue plays a major role in the glucose homeostasis. It is reported that tyrosine phosphorylation by insulin receptor is found to be reduced in non-obese patients who have been suffering from type 2 diabetes mellitus. However, the peripheral insulin resistance is partly compensated by IRS1-independent pathway which helps in the transduction of insulin signals. It is shown through researchbased evidence that type 2 diabetic patients have impaired insulinstimulated tyrosine phosphorylation of IRS1 in skeletal muscles [7,8].

Mechanisms of Insulin Resistance

Dysregulation of Insulin receptors is a common feature that is identified during the anomaly of insulin resistance. The mechanisms for dysregulation might include tumor necrosis factors TNFamediating the down regulation of mRNA transcription. These signaling abnormalities resulted into an impaired glucose transport characterized by a decrease in the fat oxidation capacity of the body, which resulted into Type 2 Diabetes subjects. T2DM is characterized by an impaired flexibility towards body metabolism. It involves the inability of fatty acids to switch towards glucose oxidation in response to insulin. Therefore, a reduced fat oxidative capacity of the body causes insulin resistance in the skeletal muscles [7,9] (Figure 1).

Citation:Al-Ghamdi S. Trends in Hyperglycemia Control in Type 2 Diabetes through Glycemic Management. J Fam Med. 2016; 3(10): 1094. ISSN: 2380-0658