Treatment of type ii diabetes by Husna Saqlain

Assistant Professor en PARUL UNIVERSITY
19 de Dec de 2020

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Treatment of type ii diabetes by Husna Saqlain

  2. TYPE-II DIABETES:  Pancreas makes a hormone called insulin. It helps your cells turn glucose, a type of sugar, from the food you eat into energy. Diabetes happens when one or more of the following occurs:  Your pancreas does not make any insulin.  Your pancreas makes very little insulin.  Your body does not respond the way it should to insulin.  Symptoms include: dehydration, frequent urination, blurry vision, fatigue,tingling sensation in your hands or feet.  Diagnosis: Different diagnostic tests include A1c, fasting plasma glucose test and oral glucose tolerance test(OGTT)
  3. TREATMENT OF TYPE-II DIABETES:  NON PHARMACOLOGICAL TREATMENT: Medical nutrition therapy is recommended for all patients. Weight loss: Losing weight can lower your blood sugar levels.Controlling portions and eating healthy foods are simple ways to lose weight. Healthy eating: It is important to center your diet around foods with fewer calories, fewer refined carbohydrates especially sweets, more vegetables and fruits, more foods with fiber. Physical exercise: Aerobic exercise can improve insulin sensitivity and glycemic control and may reduce cardiovascular risk and improve well being.
  4.  Physical activity goals include atleast 150 min/week of moderate (50-70% maximal heart rate) exercise.  Ongoing diabetes education should emphasize self care behaviors including healthy eating, being active, monitoring blood glucose levels, taking medication, reducing risk of complications.  Patients must be involved in decision making and have strong knowledge of the disease and associated complications.  Islet cell and whole pancreas transplantation is ocassionallyused in patients who require immunosuppression for other reasons eg. (Kidney transplants).
  5. PHARMACOLOGICAL THERAPY USING ORAL HYPOGLYCEMIC DRUGS:  Oral hypoglycemic drugs are used only in the treatment of type 2 diabetes which is a disorder involving resistance to secreted insulin. The different classes of oral hypoglycemic drugs include:  BIGUANIDES: Metformin enhances insulin sensitivity of hepatic and peripheral tissues, allowing for increased glucose uptake. It reduces A1c levels by 1.5%- 2%.Metformin reduces plasma triglycerides and low density lipoprotein and also high density lipoprotein cholesterol.  As it does not increase pancreatic insulin release hypoglycemia is uncommon when used alone.  DOSE: Start at 500mg orally twice daily with meals and increase by 500mg weekly as tolerated until reaching glycemic goals or 2500mg/day.
  6.  SIDE EFFECTS: The most common side effects are gastrointestinal, including metallic taste in mouth, mild anorexia, abdominal discomfort and diarrhea. A rare side effect includes lactic acidosis which usually occurs in the presence of predisposing conditions that include renal insufficiency, heart failure, hypoxia, serious acute illness.  PHARMACOKINETICS: Metformin should be taken with meals and should be started at low doses to avoid intestinal effects. These doses then can slowly be increased as necessary to 2550mg/day.  THIAZOLIDINEDIONES (GLITAZONES):  TZD’s bind to the peroxisome proliferator activator receptor-gama located primarily on fat and vascular cells,enhancing insulin sensitivity in muscle liver and fat tissues indirectly. They increase glucose utilization and diminish glucose production. Examples include Pioglitazone and Rosiglitazone. DOSE: Pioglitazone: Initially 15 mg to 30mg orally once daily.
  7.  Rosiglitazone: Initiate with 2 to 4mg orally once daily with maximum dose of 8mg/daily.  SIDE EFFECTS:Fluid retention may occur perhaps because of peripheral vasodilation and improved insulin sensitization in the kidney with increased sodium and water retention. This may result in peripheral edema, heart failure.and weight gain.  PHARMACOKINETICS:These have peak plasma concentrations in humans within 2 hours of administration on an empty stomach. Food delays absorption by 1 or 2 hours. These are highly protein bound and are metabolized in the liver.the half life of pioglitazone is 3 to 7 hourse.  ALPHA-GLUCOSIDASE INHIBITORS:  They inhibit the upper gastrointestinal enzymes that converts dietary starch and other complex carbohydrates into simple sugars which can be absorbed. The result is to slow the absorption of glucose after meals. The net effect is reduction in post prandial glucose (40-50mg/dl).
  8.  DOSE:ACARBOSE and MIGLITOL are the two common drugs. Initiate therapy with very low dose (25 mg orally with one meal a day) and increase very gradually (over several months) to maximum 50mg three times daily or 100mg three times daily for patients above 60kg.  SIDE EFFECTS: The most common side effects are flatulence, bloating, abdominal discomfort, and diarrhea which can be minimized by slow dosage titration.  PHARMACOKINETICS: These drugs exert their effects topically by inhibition of the carbohydrate digesting enzymes at the surface of the intestinal mucosa. The drugs should be taken with the first bite of the meal so the drug is present to inihibit enzyme activity.  SHORT ACTING INSULIN SECRETAGOGUES (MEGLITINIDES OR GLINIDES): Glinides stimulate insulin secretion from pancreatic beta cells by binding a site adjacent to the sulphonylurea receptor. They require the presence of glucose to stimulate insulin secretion. As glucose levels decrease to normal, stimulated insulin secretion diminishes.
  9.  DOSE: REPAGLINIDE: Start with0.5 to 2mg orally with maximum 4mg per meal. NATEGLINIDE: Start with 120mg orally three times daily before each meal.  SIDE EFFECTS: The main side effect is low blood sugar (hypoglycemia) and weight gain.  PHARMACOKINETICS: These drugs should be administered before each meal(upto 30 minutes prior). If a meal is skipped, the medication should also be skipped.It is useful in patients with renal insufficiency and those with erratic meal schedules.  SULPHONYLUREAS: Sulphonylureas enhance insulin secretion by binding to the sulphonylurea receptor on pancreatic beta cells. All sulphonylureas are equally effective in lowering blood glucose when administered in equipotent doses. These are usually used as a second line option. These are often avoided in favor of DPP-4 inhibitors or SLGT-2 inhibitors.  DOSE: The starting dose of sulphonylureas is 1-2 mg once daily. It can be
  10. Increased to a maximum of 8mg once daily.  SIDE EFFECTS: The most common side effect is hypoglycemia. Other side effects include weight gain, risk for cardiovascular events.  PHARMACOKINETICS: They are absorbed rapidly and are highly protein bound and are metabolized by the liver.  SODIUM GLUCOSE CO TRANSPORTER-2 (SGLT-2) INHIBITORS: Inhibition of SGLT-2 lowers the renal tubular threshold for glucose reabsorption and glucosuria occurs at lower plasma glucose concentrations. In clinical care practice, SGLT-2 inhibitors are considered to be second or third line therapy. Older patients with stage 4 or 5 chronic kidney disease are not optimal treatment candidates. DOSE: CANAGLIFLOZIN: Initial dose is 100mg orally once daily, taken before the first meal of the day. DAPAGLIFLOZIN: Start at 5mg daily orally once daily in the morning with or without food. The dose maybe increased to 10mg once daily in patients requiring
  11. additional glycemic control.  SIDE EFFECTS: Genitourinary tract infections, especially yeast infections which occur more commonly in women.  PHARMACOKINETICS: Rapid oral absorption, long elimination half life allowing once daily administration an extensive hepatic metabolism mainly via glucuronidation to inactive metabolites and a low renal elimination as a parent drug.
  12.  PHARMACOLOGICAL TREATMENT USING INSULIN: Insulin: All available insulins are manufactured using recombinant DNA technology and are highly purified. The most commonly used concentration is 100 units/ml. Insulin is usually injected into the fatty tissue just under the skin. This is also called as subcutaneous tissue. TYPES OF INSULIN: FAST ACTING INSULIN:  Is absorbed quickly from your fat tissue(subcutaneous) into the bloodstream.  Is used to control the blood sugar during meals and snacks and to correct high blood sugars.  Example: Rapid acting insulin analogs (Insulin Aspart, Insulin Lyspro) Regular Human Insulin
  13.  INTERMEDIATE ACTING INSULIN:  Is absorbed more slowly and lasts longer.  Is used to control the blood sugar overnight, while fasting and between meals. Examples include NPH Human Insulin Pre Mixed Insulin.  LONG ACTING INSULIN:  Is absorbed slowly has a minimal peak effect and a stable plateau effect that lasts most of the day.  Is used to control the blood sugar overnight, while fasting and between meals. Examples include Insulin Glargine, Insulin Detemir.
  14. COMPLICATIONS OF DIABETES:  Diabetes increases your risk for many serious health problems.  People with diabetes have an increased risk of developing a number of serious health problems. Consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidneys, nerves and teeth. In addition, people with diabetes also have a higher risk of developing infections. In almost all high-income countries, diabetes is a leading cause of cardiovascular disease, blindness, kidney failure, and lower limb amputation.  Maintaining blood glucose levels, blood pressure, and cholesterol at or close to normal can help delay or prevent diabetes complications. Therefore people with diabetes need regular monitoring.
  15.  Cardiovascular disease: affects the heart and blood vessels and may cause fatal complications such as coronary artery disease (leading to heart attack) and stroke. Cardiovascular disease is the most common cause of death in people with diabetes. High blood pressure, high cholesterol, high blood glucose and other risk factors contribute to increasing the risk of cardiovascular complications.  Kidney disease (diabetic nephropathy): caused by damage to small blood vessels in the kidneys leading to the kidneys becoming less efficient or to fail altogether. Kidney disease is much more common in people with diabetes than in those without diabetes. Maintaining near normal levels of blood glucose and blood pressure can greatly reduce the risk of kidney disease.  Eye disease (diabetic retinopathy): most people with diabetes will develop some form of eye disease (retinopathy) causing reduced vision or blindness. Consistently high levels of blood glucose, together with high blood pressure and high cholesterol, are the main causes of retinopathy. It can be managed through regular eye checks and keeping glucose and lipid levels at or close to normal.
  16.  Nerve disease (diabetic neuropathy): diabetes can cause damage to the nerves throughout the body when blood glucose and blood pressure are too high. This can lead to problems with digestion, erectile dysfunction, and many other functions. Among the most commonly affected areas are the extremities, in particular the feet. Nerve damage in these areas is called peripheral neuropathy, and can lead to pain, tingling, and loss of feeling. Loss of feeling is particularly important because it can allow injuries to go unnoticed, leading to serious infections and possible amputations.  Pregnancy complications: Women with any type of diabetes during pregnancy risk a number of complications if they do not carefully monitor and manage their condition. To prevent possible organ damage to the fetus, women with type 1 diabetes or type 2 diabetes should achieve target glucose levels before conception. All women with diabetes during pregnancy, type 1, type 2 or gestational should strive for target blood glucose levels throughout to minimize complications.
  17. NOVEL DRUGS FOR DIABETES: Class Brand (Company) Year Launched DPP-4 inhibitors Onglyza (AstraZeneca) 2009 Nesina (Takeda) 2013 Tradjenta (Boehringer Ingelheim) 2011 GLP-1R agonists Adlyxin (Sanofi) 2016 Byetta (AstraZeneca) 2005 Bydureon (AstraZeneca) 2012 Januvia (Merck) 2006 Lyxumia (Sanofi) 2015 Tanzeum (GlaxoSmithKline) 2014 Trulicity (Eli Lilly) 2014 Victoza (Novo Nordisk) 2010 Insulin analogues Afrezza (MannKind) 2015 Apidra (Sanofi) 2006 Humalog (Eli Lilly) 1996 Humalog 200 (Eli Lilly) 2015