NURS 6521 Discussion: Diabetes and Drug Treatments

Diabetes mellitus is a group of metabolic diseases brought on by hyperglycemia from a defect in insulin secretion, insulin action, or both.  The diagnose of DM is determined by glycosylate hemoglobin (HbA1c) levels, fasting blood sugar levels, 2-hour plasma glucose level during oral glucose tolerance testing using 75-g oral glucose load, or a random glucose levels of individual with symptoms (McCance & Huether, pg. 684).  The HbA1c range 6.5% or higher indicates diabetes type 2 and verifies the permanent attachment of glucose to hemoglobin molecules and tells the average plasma glucose exposure over the life of red blood cells 120 days (McCance & Huether, pg. 685).  Type 1/juvenile diabetes is most common with pediatrics.  According to McCance & Huether between 10-13% of children diagnosed with type 1 diabetes have a 1^st degree relative parent or sibling with type 1 diabetes.  The onset for type 1 diabetes is a long period with gradual destruction of beta cells eventually leading insulin deficiency and hyperglycemia and the body does not make insulin.  Type 2 Diabetes affects 9.3% of adults in the US according to McCance & Huether.  DM II is a chronic condition that affects the way the body processes sugar this usually happens during adulthood. 

The body doesn’t make enough insulin to regulate the excessive amounts of sugar circulating in the bloodstream (mayoclinic. et. al).  Gestational diabetes appears during pregnancy and then goes away after delivery of the baby.  Blood sugars are monitored closely during pregnancy.  Diet and insulin are usually used during the pregnancy (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 398).  DM II is usually controlled by losing weight, eating healthy, and exercise.  If diet and exercise aren’t enough then diabetic medications or insulin are usually added (Rosenthal, L. D., & Burchum, J, R. 2021 pg. 402).  Metformin is usually the 1^st drug used for DM II which is an oral tablet used to decrease blood glucose production in the liver and improve the body’s sensitivity to insulin so that the body can use insulin more effectively.  Some people start having vitamin b12 deficiency from the diabetic medication and need to take supplements; other meds are sulfonylureas example glyburide which helps the body excrete insulin but can cause weight gain ((Rosenthal, L. D., & Burchum, J, R. 2021 pg. 399).  Insulin is added if the oral medications are not enough.  Long-term the goal would be to control DM II without medication or insulin.  Lifestyle changes for the better are the key to maintaining this goal.

Reference:

McCance, K. L. & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children(8th ed.). St. Louis, MO: Mosby/Elsevier

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2^nd ed.) St. Louis, MO: Elsevier.

What is Diabetes Mellitus? Retrieved from https://www.mayoclinic.org/symptoms/what is diabetes-/basics/causes/November 24,2020

Sample Answer 2 for NURS 6521 Discussion: Diabetes and Drug Treatments

According to Rosenthal  & Burchum “The primary defect in type 1 diabetes is destruction of pancreatic β cells—the cells responsible for insulin synthesis and release into the bloodstream. Insulin levels are reduced early in the disease and usually fall to zero later” (2021). Juvenile diabetes used to be the name for type 1 diabetes until people realized that you could develop type 1 later in life as well. Type 2 diabetes is caused by an influx of glucose in the bloodstream, damaging pancreatic β cells. When this happens insulin production decreases and insulin resistance can become a problem (2021). Rosenthal & Burchum also state that “Gestational diabetes is defined as diabetes that appears in the pregnant patient during pregnancy and then subsides rapidly after delivery” (2021). This can be caused by several things involving the placenta, changes in hormones, and the fact that there is another human being inside of you (2021).  

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Type 1 diabetes is one of the least common types of diabetes but is still very important to understand. Insulin Aspart or Novolog is a short-acting insulin that can be used for type 1 diabetes. This medication will reach the patient’s system in 10-20 minutes, peak in 1-3 hours, and can last for up to 3-5 hours. This should be used 5-10 minutes before eating. It states that “Short-duration insulins are administered in association with meals to control the postprandial rise in blood glucose. To provide glycemic control between meals and at night, short-acting insulins must be used in conjunction with an intermediate- or long-acting agent in people with type 1 diabetes” (Rosenthal & Burchum, 2021).  

References 

Rosenthal, L. D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier. 

Sample Answer 3 for NURS 6521 Discussion: Diabetes and Drug Treatments

Diabetes

Diabetes is a chronic disorder caused by impairment in the pancreatic beta cells that produce the hormone insulin. The disease can be hereditary or acquired. There are different types of diabetes, notably, Diabetes Mellitus Type 1 (DM type 1/ juvenile diabetes), Diabetes Mellitus type 2 (DM type 2), gestational diabetes, and diabetes insipidus. 

Diabetes has different risk factors, and they are divided into modifiable and non-modifiable risk factors. Modifiable risk factors are those that one can be controlled to reduce the risk of acquiring diabetes. Examples of modifiable risk factors include obesity, lack of physical activity, smoking, and (Deshpande et al., 2018). Non-modifiable factors are those that humans do not control as they occur naturally. Some examples of non-modifiable risk factors are age (older people are at a higher risk of acquiring the disease), sex (men are more affected than women), heredity, and race (Deshpande et al., 2018).

Differences between DM type 1 (juvenile diabetes), DM type 2, gestational diabetes, and diabetes insipidus

DM type 1 (juvenile diabetes), DM type 2, and gestational diabetes have problems emanating from the pancreas, unlike diabetes insipidus (DI). In DI, there is either a reduced response to antidiuretic hormone (ADH) or decreased release of antidiuretic hormone. The resultant effect is electrolyte imbalance. Moreover, there are two types of DI, notablycentral and nephrogenic diabetes, both have congenital and acquired causes (Chou et al., 2011).

DI is the only type of diabetes marked by the excessive passage of urine as the only feature. However, the most common type of DI is the idiopathic central DI. It is usually linked to defects in the vasopressin precursor synthesis and, hypothalamus malformation, and vasopressin deficiency(Chou et al., 2011). However, acquired forms of DI include ischemia or brain injury, surgery, trauma, sarcoidosis, autoimmune, vascular disease and Langerhans Cell Histiocytosis, metastasis, and structural malformations (Chou et al., 2011). Congenital forms of nephrogenic diabetes DI are linked to mutations in AVPR2 or AQP2 gene (Chou et al., 2011). 90% of nephrogenic genetic diabetes (congenital) is due to the AVPR2 receptor, and they are due to multiple drugs treatments, including lithium, antifungals, antibiotics, and antineoplastic agents. Other causes include renal disease, craniopharyngioma surgery, obstructive uropathy, electrolyte imbalance such as hypercalcemia and hypokalaemia.

DM type 1 or juvenile diabetes is caused by inadequate insulin production from the pancreas. It primarily affects children but can occur later in life. The leading cause of DM type 1 is an autoimmune disorder, where the beta cells undergo self-destruction, producing little or no insulin. Infections, especially viral infections, can also destroy the pancreas and lead to DM type 1. The patient complains of confusion, headache, excessive thirst, hunger and urination, fatigue, among other features. Most DM type 1 gets the hyperosmolar hyperglycaemic state with sugars more than 33mmols per liter. In such cases, the patient needs a lot of fluid to avoid getting into shock.

The best therapy for the patient is usually insulin injection. The patient needs to obtain artificial insulin, which comes in injection. The injection is given subcutaneously twice per day every in one’s lifetime.

The difference with DM type 2 is that in type 2, the insulin is always produced but in an inactive form. Moreover, it can be due to the insensitivity of the cells to insulin being reduced. Therefore, as opposed to type 1 DM, where insulin is given, oral hypoglycaemic agents are provided to sensitize the insulin produced.

Gestational diabetes occurs only during pregnancy. The term refers to an ordinary woman who did not have diabetes but acquired it when pregnant. However, this can lead to complications for the unborn child, such as big for gestational age, and the mother can have diabetes even after delivery.

Diabetes Mellitus type 2

Diabetes mellitus type 2 is the most common diabetes in the world. According to Kesavadev (2016), by 2015, 416 million people aged between 20 and 75 years had DM type 2. The disease usually begins with three cardinal features of polydipsia, polyuria, and polyphagia. Moreover, in the urine analysis, there is typically the presence of glucose in the urine. Most patients do not know that they have diabetes until they get the severe form of the disease (complications). Patients start to present with confusion, deep and increased breathing, and the production of a sweet fruity smell (a sign of ketones). The state is always called diabetic ketoacidosis, and it is at this stage, most of the patients will learn that they have diabetes.

Drug management and dietary recommendations

DM type 2 is managed through oral hypoglycaemic agents. There are different medications, but the commonly used drug is metformin, and it can be used singly or combined with other drugs such as glibenclamide. Metformin is a biguanide, and it comes in two different sizes, of 850 and 500 milligrams(Pourmatroud, 2019). Glibenclamide weighs only 5mg(Furman, 2017). They are taken twice a day, early in the morning and evening before bedtime. However, a physician prescribed the drugs after assessing the patient and understanding the need to provide the drug over another. The drug is administered orally and is stored in a cool and dry place.

Diet is essential when managing diabetes, and patients need to know the diet they need to prevent complications. A diet richin whole grains is the best instead of refined foods. The main reason is that they have a lot of calories, and they increase the risk of obesity. Also, fat content to be consumed should be in small amounts to prevent the body from getting cardiovascular diseases such as atherosclerosis and arteriosclerosis (Pozzilli & Fallucca, 2015). The main reason is that people with diabetes have a high chance of getting high blood pressure. Therefore, regulating the amount of fats will help prevent the aforementioned diseases and coronary artery disease (CAD) (Pozzilli & Fallucca, 2015).

Fruits and vitamins are good as they reduce the chances of getting high blood pressure, a common risk factor in diabetic patients. Ensuring that one consumes one or two fruits per day helps boost the patient’s immune. It is good to have a balanced diet to live healthily.

Short term and long-term effects of diabetes and on drug treatment

Short-term effects include nausea and vomiting, deep breathing and acidosis, ketone production, among other products. They tend to occur suddenly and can be resolved faster. Long-term effects of diabetes include neuropathy, nephropathy, retinopathy, and micro-angiopathy (Retnakaran & Zinman, 2019). Diabetic foot is another common complication, and it can lead to amputation of the limb if there is poor control of diabetes.

Nephropathy can lead to renal failure, retinopathy can lead to partial or complete blindness, and neuropathy can lead to numbness. Therefore, it is usually essential to ensure that the diabetic patient is cared for effectively to prevent short-term and long-term effects. Taking medications can also impact the patient, such as nausea and vomiting. Sometimes coughing can be evident, but the benefits outweigh the medication’s mild to zero side effects (Retnakaran & Zinman, 2019). The medication helps keep the patient’s sugar levels at the desired rate, and therefore, patients should ensure they take their medications regularly.

References

Chou, Y., Wang, T., & Chou, L. (2011). Diabetes insipidus and traumatic brain injury. Diabetes Insipidus. https://doi.org/10.5772/22309

Deshpande, A. D., Harris-Hayes, M., & Schootman, M. (2018). Epidemiology of diabetes and diabetes-related complications. Physical Therapy, 88(11), 1254-1264. https://doi.org/10.2522/ptj.20180020

Furman, B. (2017). Glibenclamide ☆. Reference Module in Biomedical Sciences. https://doi.org/10.1016/b978-0-12-801238-3.97414-2

Kesavadev, J. (2016). Insulin pumps in type 2 diabetes mellitus. Diabetology: Type 2 Diabetes Mellitus, 120-120. https://doi.org/10.5005/jp/books/12165_10

Pourmatroud, E. (2019). Metformin in health issues and reproductive system. Metformin [Working Title]. https://doi.org/10.5772/intechopen.90465

Pozzilli, P., & Fallucca, F. (2015). Diet and diabetes: A cornerstone for therapy. Diabetes/Metabolism Research and Reviews, 30(S1), 1-3. https://doi.org/10.1002/dmrr.2512

Retnakaran, R., & Zinman, B. (2019). Short-term intensified insulin treatment in type 2 diabetes: Long-term effects on β-cell function. Diabetes, Obesity and Metabolism, 14, 161-166. https://doi.org/10.1111/j.1463-1326.2019.01658.x

Sample Answer 4 for NURS 6521 Discussion: Diabetes and Drug Treatments

The four categories of diabetes mellitus are type 1, type 2, gestational, and other specified types. Type 1 diabetes results from the destruction of pancreatic beta cells and requires daily dosing with insulin. This is caused by an autoimmune or idiopathic response. Type 2 is the most common form of diabetes and accounts for 90-95% of all diagnosed cases (Rosenthal & Burchum, 2021). Type 2 usually results from insulin resistance and inappropriate insulin secretion. At one point type 1 diabetes was termed juvenile- onset as it was thought to occur solely in young children. Type 1 is now known to develop in adulthood as well and type 2 is becoming more common in children. Although both type 1 and type 2 carry signs and symptoms, they differ in etiology, prevalence, treatments, and outcomes (Rosenthal & Burchum, 2021). In gestational diabetes, insulin requirements physiologically increase during pregnancy. The increase in insulin demand is due to increased maternal caloric intake, maternal weight gain, presence of the placental hormones such as placental growth hormone, and placental lactogen, as well as increased prolactin and growth hormone production (Lende & Rijhsinghani, 2020). As pregnancy advances, the pancreatic beta cell mass increases to keep up with the demand for increased insulin. Failure of the beta cell expansion with a relative inadequate rise in insulin secretion leads to gestational diabetes ( McMcance & Heuther, 2019).

Insulin is the preferred treatment for control of hyperglycemia in patients with gestational diabetes. Insulin is a large molecule and does not cross the placenta. In patients unable to take insulin, oral hypoglycemic agents can be considered. Metformin is preferred over glyburide due to the risk of possible fetal hypoglycemia associated with maternal administration of glyburide. Typically, the dose of oral medications is once or twice a day. Metformin and glyburide have been shown to cross the placenta and into the fetus. Oral medications have not been adequately studied for possible long-term effects on neonatal outcomes, and therefore they are not recommended as the first choice in treatment for persistent hyperglycemia in gestational diabetic patients (Lende & Rijhsinghani, 2020).

One complication of insulin treatment is hypoglycemia unawareness. Hypoglycemia occurs when insulin levels exceed insulin needs. The more a patient experiences hypoglycemia, they begin to have diminished symptoms over time (Rosenthal & Burchum, 2021).  Frequent blood glucose monitoring minimizes the risk for this complication. When therapy is successful, both hyperglycemia and hyperglycemia are minimized and the patient is actively involved in their own therapy. To reach optimal glucose control, dosage must be closely matched with insulin needs (Rosenthal & Burchum, 2021).

References

Lende, M., & Rijhsinghani, A. (2020). Gestational Diabetes: Overview with Emphasis on Medical Management. International Journal of Environmental Research and Public Health, 17(24). https://doi-org.ezp.waldenulibrary.org/10.3390/ijerph17249573

McCance, K. L., & Huether, S. E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8th ed.). Elsevier Health Sciences.

Rosenthal, L., & Burchum, J. (2021). Lehne’s Pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.). Elsevier Health Sciences.

Sample Answer 5 for NURS 6521 Discussion: Diabetes and Drug Treatments

In this week’s discussion, we are to reflect on differences between types of diabetes. Then, we are to select one type of diabetes to focus on and consider one type of drug used to treat the type of diabetes we selected including proper preparation and administration of this drug.  Then we are to reflect on dietary considerations related to treatment.  Finally, we are to think about the short-term and long-term impact of the diabetes selected, including effects of drug treatments.  Type I diabetes (or juvenile diabetes) is the most common pediatric disease and is usually diagnosed from infancy to the late 30’s (McCance & Huether, 2019). There are two types:  Autoimmune and Nonautoimmune.  In this type of diabetes, a beta cells in the pancreas are destroyed.  Symptoms for diagnosis are polydipsia,  polyuria, polyphagia, weight loss, and hyperglycemia, and intermittent DKA.  The patient is insulin dependent.

Type II diabetes usually affects those people over 40.  Insulin resistance and obesity is associated with type II diabetes.  The pancreas cannot use the insulin produced properly, and there is a reduction in beta cell mass and function (McCance & Huether, 2019).  The cells become resistant to insulin, making an excess of insulin than is necessary to keep blood glucose levels within a normal range.  The symptoms are obesity, dyslipidemia, and hypertension.  The patient experiences polyuria and polydipsia.  There are also recurrent infections, genital pruritus, visual changes, paresthesia, fatigue, and acanthosis nigricans.   The patient is not usually insulin dependent, but may require insulin.

Gestational diabetes occurs during pregnancy.  There is insulin resistance and inadequate insulin secretion.  It is most likely to occur in women who are obese, 25-years-old, have a family history of diabetes, have a history of gestational diabetes, or are of Native American, Asian, or black (these ethnic groups have a higher incidence rate of gestational diabetes (McCance & Huether).

For this discussion I am focusing on type II diabetes mellitus.  Those with this type of diabetes have a mortality rate twice that of the general population.  Complications from this type of diabetes are myocardial infarction, stroke, nephropathy, retinopathy, and peripheral arterial disease and neuropathy resulting in amputation (Laursen et. al., 2017).  One of the drugs used to treat this type of diabetes is in a class of drugs called biguanide named Metformin.  This drug decreases glucose production by the liver, reduces glucose absorption in the gut, and sensitizes insulin receptors in fat and skeletal muscle.  Metformin is slowly absorbed from the small intestine, and is excreted unchanged by the kidneys.  If there is renal impairment, it can produce toxic levels (Rosenthal  & Burchum, 2021).  It can be used alone, or with insulin.  Importantly,  it can be used for patients who skip meals because it does not lower blood glucose.  It can be taken during pregnancy.

Common side effects are decreased appetite, nausea, and diarrhea.  Metformin decreases absorption of vitamin B12 and folic acid, thus causing vitamin B and folic acid deficiencies.  It does not cause weight gain.  It is important to eat healthy meals while taking Metformin, and not skip meals.  Metformin can cause lactic acidosis.   Initial dosing is immediate release 850-1000 mg daily or extended release 500 mg nightly.

References

Laursen, D., Christenssen, K., Christensen, U., & Frolich, A. (2017). Assessment of short and long-term outcomes of diabetes patient education using the health education impact questionnare (HeiQ). BMC Research Notes 10(213).  https://doi10.1186/s13104-017-2536-6

McCance, L.L. & Huether, S.E. (2019). Pathophysiology: The biologic basis for disease in adults and children (8^th ed.). St. Louis, MO: Mosby/Elsevier.

Rosenthal, L.D., & Burchum, J. R. (2021). Lehne’s pharmacotherapeutics for advanced practice nurses and physician assistants (2nd ed.) St. Louis, MO: Elsevier.

Sample Answer 6 for NURS 6521 Discussion: Diabetes and Drug Treatments

The World Health Organization defines diabetes as a chronic disease that occurs either when the pancreas does not produce enough insulin or when the body cannot effectively use the insulin it produces (American Diabetes Association, 2022 ). Insulin is a hormone that regulates blood glucose. The number of people being diagnosed with diabetes continues to raise as the Centers for Disease Control report released in 2018 showed that 7.3 million Americans, or 11.3% of the population. There are several types of diabetes with the most common including type 1 diabetes, type 2 diabetes, juvenile, and gestational diabetes. These types differ from each other significantly hence this makes it easy for physicians to make correct diagnoses.

Type 1 diabetes

Type 1 diabetes is a chronic illness characterized by the body’s inability to produce insulin due to the autoimmune destruction of the beta cells in your pancreas that produce insulin. The damage is permanent. According to the ICD-10, Type 1 diabetes diagnostic criteria include unexplained weight loss, excessive production of urine, experiencing excess thirst, increased appetite, tiredness, and blurry vision as well as mood changes. If the condition is left untreated, it can lead to heart damage, kidney damage, eye damage, foot damage, nerve damage, and oral infections. According to American Diabetes Association, the American diagnostic criteria for type 1 diabetes includes a 2-hour plasma glucose level ≥200 mg/dL (11.1 mmol/L) or during a 75 oral glucose tolerance test (OGTT).

Type 2 diabetes

Type 2 diabetes starts out as insulin resistance. This means your body cannot use insulin efficiently, which causes your pancreas to produce more insulin until it cannot keep up with demand. Insulin production then decreases, which causes high blood sugar. The body is impaired in how it regulates insulin and in the long term, there is a higher presence of sugar in the bloodstream. The symptoms of type 2 diabetes are increased thirst, frequent urination, increased hunger, fatigue, blurred vision, slow-healing sores, unexplained weight loss, numbness or tingling in the hands, and areas of darkened skin, usually in the armpits and neck. If not treated it can lead to kidney damage, eye damage, hearing impairment, sleep apnea, and dementia (DeFronzo et al., 2015). Type 1 diabetes is characterized by the inability of the body to produce enough insulin, the type 2 diabetes is characterized by the inability of the body to utilize insulin hence having high sugar in the blood.

Gestational diabetes

This type of diabetes occurs during pregnancy when insulin-blocking hormones are produced. Gestational diabetes occurs only in people who have preexisting diabetes or have family members who have been diagnosed with the condition. It affects how cells utilize insulin leading to high levels of blood sugar. Pregnancy influences the body significantly and these changes cause your body’s cells to use insulin less effectively, a condition called insulin resistance. Insulin resistance increases your body’s need for insulin. Gestational diabetes can go unnoticed as it has limited symptoms only frequent urination and increased thirst. Lack of early intervention can lead to stillbirth, obesity, early term, excessive birth weight, and difficulties breathing.

 These three types of diabetes differ significantly in that while type 1 diabetes is characterized by the inability of the body to produce enough insulin, type 2 diabetes is characterized by the inability of the body to utilize insulin hence having high sugar in the blood. The gestational occurs only in pregnant women unlike the other which can occur in anybody.

 Selected: Type 2 diabetes treatment

Metformin is the most common type of drug administered to people with type 2 diabetes. The drug works by lowering the glucose level in the liver and improves the body’s sensitivity to insulin so that the body uses insulin more effectively (Foretz et al., 2019). This drug can come comes as a tablet, liquid, and an extended-release tablet which is prepared by obtaining a solution of metformin hydrochloride in water. The tablet is taken with a glass of water before meals. those taking the solution, have to prepare it by adding the extended tablet, they prepare it by measuring the oral liquid with a marked spoon oral syringe, or medicine cup and adding water to make a solution. The liquid is usually taken with meals one or two times a day and the regular tablet is usually taken with meals two or three times a day. The extended-release tablet is usually taken once daily with the evening meal. To help you remember to take metformin, take it around the same time(s) every day. The drug is taken orally.

People diagnosed with type 2 diabetes and prescribed metformin, have to consider some diet patterns. When taking metformin, avoid alcohol since it affects the drug’s effectiveness. Avoid too many refined carbs, especially white bread, white rice, white pasta, candy, soda, desserts, and snacks like chips or crackers (Ley et al., 2014). There are some foods that a patient taking metformin can consider and they include healthy fats, fiber, lean proteins, vegetables, and complex carbs such as brown rice, whole-grain oats, and whole-grain

Short-term and Long effects of type 2 diabetes and metformin

The short-term effects of diabetes type 2 involve developing the complications of hypoglycemia which are low blood sugar and this is linked to some medications such as insulin or a sulfonylurea drug. Other complications involve hyperglycemia which is having too much glucose in the body. Besides, the long-term effects of diabetes include increased risk of developing heart disease, stroke, high blood pressure, narrowing of blood vessels (atherosclerosis), and nerve damage (neuropathy) in limbs.

Taking metformin for a long time can cause vitamin b12 deficiency, lactic acidosis, lower back pain, decreased appetite, difficulty sleeping, and diarrhea.

References

American Diabetes Association. (2022). Statistics About Diabetes. https://diabetes.org/about-us/statistics/about-diabetes

DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., … & Weiss, R. (2015). Type 2 diabetes mellitus. Nature reviews Disease primers, 1(1), 1-22.

Foretz, M., Guigas, B., & Viollet, B. (2019). Understanding the glucoregulatory mechanisms of metformin in type 2 diabetes mellitus. Nature Reviews Endocrinology, 15(10), 569-589.

Ley, S. H., Hamdy, O., Mohan, V., & Hu, F. B. (2014). Prevention and management of type 2 diabetes: dietary components and nutritional strategies. The Lancet, 383(9933), 1999-2007.