Evidence-Based Pharmacology Diabetes Mellitus

The words “diabetes mellitus” (DM), therefore, refer to the output of copious amounts of sweet-tasting urine, a key presentation of this renowned metabolic disease. DM is an endocrine disorder precipitated by either partial or total loss of insulin activity. Insulin is an anabolic hormone produced by beta cells of the pancreas, which causes reduction in the glucose levels in blood. It further promotes synthesis and storage of carbohydrates, fats, and proteins. DM is a metabolic syndrome, and as such, it is a growth disturbance. Commonly, the disease does not occur alone. Instead, it exists concomitantly with other ailments including obesity, renal failure, hypertension, and hyperlipidemia. The four main pathophysiological changes that typify diabetes embrace hyperglycemia, wasting, production of sorbitol, and non-enzymatic glycosylation of body proteins.

Due to the large amounts of sugars, the reabsorption of glucose from renal tubules becomes challenging; thus, it is excreted in urine. Glucose is water-soluble like an osmotic diuretic that makes the patient produce very large amounts of urine. Hence, such polyuria precipitates dehydration and triggers excessive thirst (polydipsia). In the partial or total absence of insulin, the entry of glucose into cells is curtailed. Therefore, compensatory processes, in particular gluconeogenesis, are initiated to produce glucose from proteins and fats; this presents clinically as a loss in body weight or wasting. The reduction of glucose produces sorbitol, which deposits in the eye lens leading to the development of cataracts. Additionally, sorbitol accumulates on the intima of small blood vessels forming a plaque that limits blood supply to tissues. The complications associated with these events include peripheral neuropathy, nephropathy, and retinopathy. The non-enzymatic coupling of glucose to body proteins results in the formation of glycosylated hemoglobin (HbA1C). Besides, this protein is an important parameter in the diagnosis and clinical assessment of glycemic control. Consequently, particular management approaches, both pharmacological and non-pharmacological, can be used on patients with the condition. Therefore, it is essential for clinicians to devise comprehensive follow-up plans for such patients to monitor the effectiveness of therapy and to detect or prevent any possible complications.

Type 2 Diabetes Mellitus

The condition also known as noninsulin-dependent, or adult onset diabetes is the most prevalent type of diabetes (Olokoba, Obateru, & Olokoba, 2012). With this kind of DM, the body either does not produce adequate amounts of insulin, or it is resistant to the effects of the hormone leading to poor maintenance of glucose levels. As such, the insulin levels may be decreased or elevated within the reference ranges. Unlike other types of DM, this condition is of a relatively slow onset. Despite the prevailing assumption that type 2 DM is a reserve for the adult population aged over forty, the disease is increasingly affecting children and has been described as maturity-onset diabetes of the young (MODY). It primarily strike obese kids, and its prevalence is on the rise due to the current changes in lifestyle.

A combination of factors induces type 2 diabetes. Numerous studies have proven that various bits of genes influence the body’s production of insulin. The condition is strongly genetic, and the research has shown that for homozygote twins, there is about a 70% chance that both individuals would have diabetes should they be susceptible (Kumar & Modi, 2014). Obesity, especially abdominal one, also make a person prone to suffering from type 2 DM. In fact, many diabetes patients are overweight. Being a metabolic syndrome, type 2 DM can additionally be caused by other disorders. The excessive production of glucose by the liver and poor intercellular communication leads to the development of diabetes. Hence, such miscommunications, particularly those involving the synthesis and the use of insulin or glucose, could trigger a cascade of reactions that would ultimately induce diabetes. Moreover, dysfunctional beta cells that produce faulty insulin or insufficient insulin are implicated in the poor glycemic control that typifies type 2 DM.

In the instance of this kind of diabetes, infection and stress can initiate the manifestation of a hyperosmolar hyperglycemic state (HHS). The latter could further result in a complication commonly referred to as hyperosmotic non-ketotic coma (HOC). Since DM is the chronic disease, certain criteria guide the diagnosis of type 2 diabetes.

Diagnosis of Type 2 DM

The diagnosis of diabetes mellitus type 2 depends on the clinical signs and symptoms of the sick as well as the findings of various laboratory tests. However, not all patients exhibit classical symptoms of polyuria, polydipsia, and polyphagia. The following laboratory tests are conducted in the diagnosis of diabetes:

1. Random blood sugar (RBS)

As the name suggests, a sample of blood is taken at a random time. Levels of blood glucose are denoted in millimoles per liter or milligrams per deciliter. Notwithstanding one’s last meal, a random blood sugar level of 11.1 mmol/L or 200 mg/dL points to diabetes, particularly when combined with any of the characteristic signs of diabetes such as extreme thirst and frequent urination (Mayo Clinic Staff, 2014).

2. Fasting blood sugar (FBS)

A blood sample is taken after a patient has fasted overnight for about eight to twelve hours. The values below 5.6 mmol/L (100 mg/dL) are normal (Mayo Clinic Staff, 2014). If an individual’s blood glucose levels range from 5.6 to 6.9 mmol/L (100 to 125 mg/dL), he or she is considered to be in a prediabetic state. However, blood sugar levels, which are equal to or more than 7mmol/L (126 mg/dL) recorded on two different occasions are indicative of diabetes (Mayo Clinic Staff, 2014).

3. Oral glucose tolerance test (OGTT)

In this test, the subject is required to fast overnight after which the FBS level is determined. Afterward, the patient is made to drink a sugary liquid with 75 g of glucose. Blood sugar levels are then measured intermittently for the subsequent two hours. Blood glucose levels below 7.8 mmol/L (140 mg/dL) are healthy (Mayo Clinic Staff, 2014). The results between 7.8 mmol/L and 11.0 mmol/L (140 and 199 mg/dL) indicate prediabetes state (Mayo Clinic Staff, 2014). However, the levels that are equal to or more than 11.1 mmol/L (200 mg/dL) two hours after the glucose load may imply diabetes.

4. Intravenous glucose tolerance test (IVGTT)

The IVGTT is useful in the determination of blood glucose levels following an intravenous introduction of a 50% glucose solution into the subject’s bloodstream. Therefore, this test is not only relevant to the diagnosis of diabetes but also to the assessment of other metabolic disorders and cancer. IVGTT has better sensitivity compared to OGTT, as glucose samples bypass the digestive system. Though rarely used, this test enables individuals with difficulties of ingesting glucose to have their blood sugar levels measured (Hahn, Ljunggren, Larsen, & Nystr?m, 2011).

5. Glycated hemoglobin (HbA1C) test

The test is used to establish the average amount of glucose in the blood for the last 2 to 3 months. An HbA1C level of 6.5% or above on two different instances is indicative of diabetes (Mayo Clinic Staff, 2014). Any results falling in the range of 5.7% to 6.4% show a high risk of developing the condition. Normal HbA1C levels should be less than 5.7%.

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Assumptions and Missing Information

Two significant assumptions and misnomers underlie the clinical methods for the management of type 2 diabetes. Eventually there will be a notable increase in the number of individuals who undergo lifelong therapies. The first grave supposition is that type 2 DM is an irreversible, progressive condition the diagnosis of which is based on the levels of blood glucose more than only one threshold among the three tests. One such threshold is founded on the observation that an FBS value of 7.0 mmol/L relates to the beginning of the rise of retinopathy. However, this diagnostic characterization does not establish the constant relation that exists between blood sugar and the possibility of complications or the influence of other aspects including the period of dysglycemia, genetics, age, etiology, and comorbidity. For instance, a 55-year-old overweight male with high blood pressure and an FBS level of 14 mmol/L does not have the same prognosis as a healthy 76-year-old female subject with an FBS value of 7.0 mmol/L.

Another assumption is that treatment with glucose-lowering agents is of benefit to all persons diagnosed with type 2 DM and that these advantages are not appreciable only until a particular glucose target is reached. The most recent recommendations provide for greater goals regarding individuals with comorbidities and a limited life expectancy; thus, precise glycemic control and the glycosylated hemoglobin (HbA1C) value of 7% or lower would be ideal for most patients. It is evident that the preeminence of this method is modest and the additional benefits of therapy depend on the reference line glucose levels. It is imperative to encourage physicians to attain the recommended HbA1C values when managing their patients, as the people whose glycated hemoglobin values remain unchanged or above the stipulated target could undergo the psychological challenge of being viewed as treatment failures or encounter the unwanted therapeutic outcomes.

Approaches to Management of Type 2 DM

There is no definitive cure for type 2 diabetes. However, there are some ways in which the condition can be managed to afford the patient comfort and wellness besides keeping an individual’s glucose levels close to normalcy as well as preventing or delaying complications. The management of diabetes can be non-pharmacological or pharmacological.

Non-pharmacological Methods

1. Healthy eating

Despite the common perception, no particular diet is recommended for diabetes. Nevertheless, it is imperative to center a patient’s diet on low-fat, high-fiber food such as whole grains, vegetables, and fruits (Asif, 2014). A person with diabetes should also limit the intake of animal products, confectionaries, and processes sugars (refined carbohydrates). Foods with low glycemic indices could be helpful as they contribute to more stable blood glucose levels. In general, these foods are high in fiber. Guidelines recommend that patients ought to consult dieticians to assist them to design a meal schedule that matches their personal health goals, lifestyles, and food preferences. Furthermore, the dietician can educate patients on monitoring their sugar intake and inform them about the amounts of carbohydrates they should take with snacks and meals to establish a strict glycemic control (Asif, 2014).

2. Physical activity

Like everyone else, patients with type 2 diabetes require regular aerobic exercise but only with the doctor’s consent. It is essential that the sick choose activities from which they derive pleasure including biking, swimming, walking, or going for hikes. Therefore, these kinds of physical activities should be integrated into the daily itinerary of a patient. Individuals should take not less than thirty minutes of aerobic exercise more than four days a week (Asif, 2014). Strength training and stretching activities are useful too but the latter should be undertaken gradually especially by the people who have been inactive for a while. In most cases, a combination of exercises helps to gain a more efficient glycemic control compared to the adoption of a single type of activity. Experts, therefore, recommend an exercise program that comprises both aerobic exercises and resistance training. The justification for physical activity in type 2 diabetes is that it reduces blood glucose and contributed to maintenance of a healthy weight. However, individuals should receive an oral hypoglycemic therapy. Besides, such patients are required to take a snack before exercising to avoid episodes of hypoglycemia.

3. Blood sugar monitoring

A patient’s need to measure and record his or her blood glucose level is contingent on the treatment plan. Keen monitoring is the most appropriate way to guarantee the stability of blood glucose levels and its maintenance within the target range. Blood sugar levels could occasionally be unpredictable. However, with the help of a medical team, the sick can learn how glucose levels vary under the influence of alcohol, exercise, food, medication, and different illnesses. Pharmacists who dispense glucometers and glucoketometers could also explain to the patients how the devices function and how the latter should be used correctly.

4. Bariatric surgery

Type 2 diabetes patients with a BMI above thirty-five are the candidates for the weight-loss surgery. A majority of diabetic people have their blood sugar levels normalized after successful completion of the procedure. The operations that bypass a section of the small bowels are known to have a greater effect on sugar levels than any other weight-loss surgeries. Nevertheless, bariatric surgeries are costly and risky. Besides, they require far-reaching lifestyle modifications and could cause long-term complications such as osteoporosis and nutritional deficiencies.

5. Stress management

The diagnosis of type 2 diabetes mellitus poses a challenge of stress to the patient. As such, an relevant management approach should be holistic enough to incorporate methods to help the individual maintain a healthy lifestyle and a positive attitude. Appropriate counseling is an integral part of the management plan both at the time of diagnosis and all through the patient’s life. Additionally, those afflicted by the disease should be taught coping skills while their families and close friends should be encouraged to provide optimal support.

6. Moreover, alternative therapies, namely acupuncture and biofeedback, offer relief to the patients with type 2 diabetes, as they allay the pain stemming from diabetic neuropathy.

Pharmacological Methods

Some type 2 diabetes patients can attain their target blood glucose levels with exercises and diet alone. However, many others also require insulin therapy or diabetes medications. The choice of pharmacological agents depends on several factors such as the patient’s sugar levels and any other health complications he or she might have. In some cases, a combination of drugs from different classes could be used to control blood sugar in a multiplicity of dimensions. The pharmacological methods available for the management of type 2 DM include oral hypoglycemic agents, insulin therapy, herbal medicines, and other supplements.

1. Oral hypoglycemic agents

There are seven classes of drugs in this category. However, an additional two are currently undergoing clinical trials for the management of type 2 diabetes. Thus, these groups involve:

a) Biguanides:

The class incorporates drugs such as metformin, phenformin, and buformin. Nonetheless, phenformin was discontinued, as it precipitates life-threatening lactic acidosis. Metformin is the most widely used diabetes medication applied for type 2 DM since it is euglycemic, and it causes weight loss, decreases the levels of serum lipids, and consequently minimizes the risks of cardiovascular complications (Olokoba, Obateru, & Olokoba, 2012). Additionally, it undergoes no metabolism due to few drug-drug interactions and causes a slight reduction in blood pressure. Furthermore, the drug improves body’s sensitivity to insulin and is useful for patients who cannot secrete insulin because of pancreatic malfunction. The side effects of biguanides include GIT disturbances, weight loss, metallic taste in mouth, and lactic acidosis (especially for those with lung and heart disease or alcoholics). It also inhibits the absorption of folic acid, some amino acids, and vitamin B12.

b) Sulfonylureas:

These drugs are the second to metformin and are used extensively in the management of type 2 diabetes as they help in the secretion of more insulin. The class is divided into three generations and encompasses certain drugs, in particular tolbutamide, glibenclamide, and gliclazide, each belongs to the first, the second and the third generation respectively. However, the utilization of the first-generation agents is declining due to their low potency and numerous side effects. Tolbutamide has a short duration of action and consequent unlikelihood of causing hypoglycemic reactions. Therefore, it is the drug of choice in the treatment of patients with impaired renal function. Their side effects include GIT disturbances, hypersensitivity reactions (they contain sulfur), disulfiram-like effects, weight gain, severe hypoglycemia, and mild diuresis (Olokoba, Obateru, & Olokoba, 2012).

c) Meglitinides and D-phenylalanine:

This class contains drugs such as repaglinide and nateglinide. Although the latter are insulin secretagogues but they are bound on sites different from the sulfonylurea receptor. They are taken fifteen minutes before meals to manage postprandial hyperglycemia. The drugs are also useful for persons with sulfonylurea intolerance and those with reduced kidney function, as they do not require renal excretion. The side effects comprise hypoglycemia, GI disturbances, arthralgia, dizziness, and flu-like symptoms (Olokoba, Obateru, & Olokoba, 2012). Besides, these agents are contraindicated in pregnant women since they can cross the placenta to precipitate hypoglycemia in the fetus.

d) Alpha-glucosidase inhibitors:

The examples of drugs in this class are miglitol and acarbose. They reduce the GIT absorption of glucose by blocking the activity of alpha-glucosidases. Additionally, miglitol inhibits isomaltase and beta-glucosidases. Nevertheless, these agents are not extensively used because they have low hypoglycemic efficacy and cause severe flatulence (Olokoba, Obateru, & Olokoba, 2012). They are taken with food to prevent postprandial hyperglycemia and are aimed at the prevention of diabetes in susceptible individuals.

e) Glizatones/Thiazolidinediones:

This class includes drugs like pioglitazone, rosiglitazone, and troglitazone. They are, however, associated with bladder cancer, bone fractures in women, and hepatotoxicity respectively. The agents are euglycemic, which reduce serum lipid levels, reverse insulin resistance, and can progressively abolish the need for insulin therapy in a type 2 diabetes patient. They act at the gene level and have a lower efficacy compared to metformin. Due to the numerous threats associated with their use, they are not et first-choice treatment option. The agents are contraindicated in pregnant women, patients with CHF, and individuals with hepatic malfunction. When combined with insulin, they increase the risk of edema. Furthermore, they are known to decrease the efficacy of oral contraceptives.

f) Incretinomimetics:

This class embraces dipeptidyl peptidase IV (DPP-IV) inhibitors, amylin analogs, and glucagon-like peptide 1 (GLP-1) receptor agonists. GLP-1 agonists incorporate exenatide and liraglutide. They are the third-line agents in the management of type 2 DM, which are administered to patients who are unresponsive to metformin, sulfonylureas, and glitazones. The drugs that are euglycemic promote regeneration of beta cells, cause weight loss by reducing one’s appetite. The only amylin analogue in clinical utility is pramlintide. It is primarily used in the management of postprandial hyperglycemia. DPP-IV inhibitors such as sitagliptin and vildagliptin are the first line drugs in the treatment of diabetes when combined with metformin. In addition, the fixed dose formulations of these two agents are available. Thus, such a combination is beneficial as DPP-IV inhibitors slow the progression of diabetes.

g) Sodium-glucose co-transporter-2 (SGLT-2) inhibitors:

This class comprises drugs such as dapagliflozin and canagliflozin. They prevent the renal reabsorption of glucose. The euglycemic drugs and reduce blood pressure due to their diuretic effect. They are applied in the management of obesity in type 2 DM besides being employed in glycemic control. However, they cause high incidences of urogenital infections.

Other agents are currently undergoing clinical trials and investigations for the management of type 2 diabetes. The examples include rimonabant, an endocannabinoid receptor blocker, and adiponectin, a cytokine that increases tissue sensitivity to insulin.

2. Insulin therapy

Insulin can be used occasionally for the treatment of type 2 diabetes. Currently, the hormone is commonly prescribed due to its benefits unlike in the past when it was considered an option of the last resort. Insulin is administered subcutaneously, and various combinations of the hormone can be prescribed depending on individual’s needs. Usually, type 2 diabetes patients commence insulin therapy with a single long-acting shot at night.

3. Other medications

Apart from the diabetes drugs described above, low-dose aspirin, cholesterol-lowering, and blood pressure medications can be prescribed as a measure to prevent heart and vascular complications.

4. Alternative medicine

Many substances have been proven to be useful in the management of type 2 diabetes. However, they should be taken along with the prescription medicines after consulting an authoritative source of drug information such as a pharmacist. Therefore, this would help in impeding harmful drug-drug interactions or adverse effects (Birdee & Yeh, 2010). Some of the substances that contribute to better glycemic control include ginseng, omega-3 fatty acids, garlic, cinnamon, alpha-lipoic acid, aloe vera, and polyphenols among others.

Follow-up

Holistic type 2 diabetes care necessitates a long-term candid doctor-patient relationship, appropriate involvement of consultants as required, consistent control and monitoring of blood pressure, glucose, aspirin/statin use, and tobacco consumption. Most patients need to be assessed every three to four months while some may need to make more visits to the healthcare provider. In addition to follow-up on adherence to medication and the recommended lifestyle modifications, intermittent monitoring is essential for the identification and resolution of a potential complication. Consequently, the patient should have an eye examination every twelve to twenty-four months, an annual GFR and serum creatinine. Further clinicians should yearly assess the patient for microalbuminuria and conduct liver function tests as well. HbA1C levels should be checked every three months until the results are below 7% (American Diabetes Association, 2014). Afterwards, they can be assessed biannually. However, for patients whose treatment has been altered or those who fail to meet the treatment goals, quarterly assessments are recommended. Thyroid function tests could also be conducted if necessary. In addition, it is important to evaluate the fasting lipid profile at least once a year for a healthy individual and more often in cases where the patient has not reached the treatment objectives. Moreover, it is imperative to conduct foot examinations every year to check for symptoms of peripheral neuropathy (diabetic foot), and the patients showing related symptoms are advised to undergo ECG tests.

Reflection

The American Diabetes Association (2014) gives clear guidelines on the canons of medical care in case of diabetes. The article is an authoritative data resource to both patients and practitioners with regard to the recommended methods of managing diabetes and it encompasses the appropriate follow-up measures that should be taken. The American Diabetes Association is a renowned organization and the credible information provider on diabetes. The journal articles used in this paper have been authored by the experts with a good background in medicine and related disciplines. They introduced facts about type 2 diabetes including various available approaches to its diagnosis and management. For instance, Olokoba, Obateru, & Olokoba (2012) review the current trends in the treatment of diabetes while Birdee & Yeh (2010) explore the alternative and complementary therapies for diabetes that are at modern disposal. Therefore. tese articles may be qualified as credible since they are in line with the contemporary clinical methods in the management of type 2 DM.

Conclusion

In summary, type 2 diabetes mellitus is a common metabolic disorder typified by hyperglycemia, polyuria, polydipsia, and polyphagia. Though previously deemed as a reserve for the adult population, current lifestyles and increasing cases of obesity have led to the development of the disease among the young. Hence, clear guidelines on the diagnosis of the ailment were elaborated, and they are based on the results of specific tests as well as the perceivable signs and symptoms. Similarly, several treatment options are available, which range from non-pharmacological to pharmacological methods. Even though diabetes is incurable, tight glycemic control can be achieved through physical activity, proper diet, adherence to the prescribed drugs, and well-advised incorporation of complementary therapy such as herbs and acupuncture. Type 2 diabetes could result in many complications. Therefore, it is necessary to follow up and monitor patients closely by conducting periodic tests in order to assess the effectiveness of drugs and to prevent the development of additional problems.