Diabetes Mellitus PDF

Endocrine System Diabetes Mellitus Diabetes Mellitus Diabetes mellitus: overview of the disease and its treatment Insulin I: physiology Insulin II: preparations and administration Insulin III: therapeutic use Oral hypoglycemics for type 2 diabetes New injectable drugs for diabetes Diabetic ketoacido...

Endocrine System Diabetes Mellitus Diabetes Mellitus Diabetes mellitus: overview of the disease and its treatment Insulin I: physiology Insulin II: preparations and administration Insulin III: therapeutic use Oral hypoglycemics for type 2 diabetes New injectable drugs for diabetes Diabetic ketoacidosis Glucagon for insulin overdose Diabetes Mellitus: Overview of the Disease and Its Treatment Diabetes mellitus – Greek word for “fountain” – Latin word for “honey” Disorder of carbohydrate metabolism – Deficiency of insulin – Resistance to action of insulin Sustained hyperglycemia, polyuria, polydipsia, ketonuria, and weight loss Types of Diabetes Mellitus Type 1 diabetes – 5% to 10% of all cases – Also called insulin-dependent diabetes mellitus (IDDM) – Or called juvenile-onset diabetes mellitus – Primary defect is destruction of pancreatic beta cells Types of Diabetes Mellitus Type 2 diabetes – Most prevalent form of diabetes – Approximately 19 million Americans have it – Also called non–insulin-dependent diabetes mellitus (NIDDM) – Or called adult-onset diabetes mellitus – Obesity is almost always present – Insulin resistance and impaired insulin secretion Conversion of proinsulin to insulin. Proinsulin is the immediate precursor of the insulin secreted by our pancreas. Enzymes clip off connecting peptide (C-peptide) to release active insulin, composed of two peptide chains (A and B) connected by two disulfide (S-S) bonds. Since C-peptide arises only from endogenous insulin, its presence in blood indicates that at least some pancreatic insulin is being made. Complications of Diabetes Short-term – Hyperglycemia and hypoglycemia Long-term – Macrovascular damage Heart disease Hypertension Stroke Hyperglycemia Altered lipid metabolism Complications of Diabetes Long-term (cont’d) – Microvascular damage Retinopathy Nephropathy Neuropathy Gastroparesis Amputations secondary to infections Erectile dysfunction Diagnosis of Diabetes Excessive plasma glucose is diagnostic of diabetes Patient must be tested on two separate days, and both tests must be positive Three tests – Fasting plasma glucose (FPG) – Casual plasma glucose – Oral glucose tolerance test (OGTT) Hemoglobin A1c, oral glucose tolerance test Prediabetes Impaired fasting plasma glucose between 100 and 125 mg/dL Impaired glucose tolerance test Increased risk for developing type 2 diabetes May reduce risk with diet and exercise and possibly certain oral antidiabetic drugs Overview of Diabetes Treatment Primary goal is to prevent long-term complications Tight control of blood glucose level is important Also important to control blood pressure and blood lipids Type 1 Diabetes Requires comprehensive plan Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement Dietary measures – Total carbohydrates – not the type of carbohydrates – are most important – Glycemic index Type 2 Diabetes Like type 1, requires comprehensive plan Should be screened and treated for: – Hypertension, nephropathy, retinopathy, neuropathy, dyslipidemias Glycemic control with: – Diet and exercise – Drug therapy Monitoring Treatment Self-monitoring of blood glucose (SMBG) Glycosylated hemoglobin: Hgb A1c Insulin I: Physiology Biosynthesis Secretion Metabolic actions Metabolic consequences of insulin deficiency Insulin II: Preparations and Administration Sources of insulin – Recombinant DNA technology – Beef and pork pancreas Seven Types of Insulin Short duration: rapid acting – Insulin lispro (Humalog) – Insulin aspart (NovoLog) – Insulin glulisine (Apidra) Short duration: slower acting – Regular insulin (Humulin R, Novolin R) Intermediate duration – Neutral protamine Hagedorn (NPH) insulin – Insulin detemir (Levemir) Long duration – Insulin glargine Time-effect relationship for different types of insulin following subcutaneous injection. Insulin Concentration – 100 units/mL (U-100) – 500 units/mL (U-500) Mixing insulins – NPH with short-acting insulins – Short-acting insulin drawn first Administration Subcutaneous injection – Syringe and needle – Pen injectors – Jet injectors Inhalation – Exubera – withdrawn 2007 Subcutaneous infusion – Portable insulin pumps – Implantable insulin pumps Intravenous infusion Storage Unopened vials should be stored under refrigeration until needed Should not be frozen Can be used until expiration date if kept in refrigerator After opening, can be kept up to 1 month without significant loss of activity Keep out of direct sunlight and extreme heat Storage Mixtures of insulin in vials are stable for 1 month at room temperature and 3 months under refrigeration Mixtures in prefilled syringes should be stored in refrigerator for up to 1 week and should be stored vertically – needle pointing up Insulin III: Therapeutic Use Indications – Principal – diabetes mellitus – Required by all type 1 and some type 2 patients – IV insulin for DKA – Hyperkalemia – can promote uptake of potassium – Aids in the diagnosis of GH deficiency Insulin Therapy of Diabetes Tight glucose control: benefits/drawbacks Dosage Dosing schedules – Conventional therapy – Intensive conventional therapy – Continuous subQ infusion Achieving tight glucose control Complications of Insulin Treatment Hypoglycemia Lipodystrophies Allergic reactions Hypokalemia Drug interactions – Hypoglycemic agents – Hyperglycemic agents – Beta adrenergic blocking agents Oral Hypoglycemics Biguanides – Metformin (Glucophage) Sulfonylureas – Tolbutamide (Orinase) Thiazolidinediones (glitazones) – Rosiglitazone (Avandia) – Pioglitazone (Actos) Glinides (meglitinides) – Repaglinide (Prandin) – Nateglinide (Starlix) Oral Hypoglycemics Alpha-glucosidase inhibitors – Acarbose (Precose) – Miglitol (Glyset) – Muraglitazar (Pargluva) Gliptins Combination products Biguanides: Metformin Trade names: Glucophage, Glucophage XR, Fortamet, Glumetza, Riomet MOA – Inhibits glucose production in liver – Reduces glucose absorption slightly in gut – Sensitizes insulin receptors in target tissues Biguanides: Metformin May be used as monotherapy or with a sulfonylurea, a glitazone, or exenatide More effective in combination Well suited for patients who skip meals Prevention of type 2 diabetes Gestational diabetes PCOS Biguanides: Metformin Side effects – Decreased appetite, nausea, diarrhea – Decreases absorption of B12 and folic acid – Patients lose average of 7-8 pounds Toxicity – lactic acidosis – Alcohol, cimetidine (Tagamet), and iodinated radiocontrast media may intensify acidosis Sulfonylureas First oral hypoglycemics Promote insulin release Major side effect is hypoglycemia First-generation controversy – Cardiovascular toxicity Second-generation agents – Much more potent than first-generation drugs – Significant drug-drug interactions less common Sulfonylureas Drug interactions Alcohol NSAIDs Sulfonamides Cimetidine Beta-adrenergic blocking agents Glinides Repaglinide and nateglinide Same mechanism as that of sulfonylureas Adverse effect: hypoglycemia Drug interaction: gemfibrozil (Lopid) Thiazolidinediones (Glitazones) Rosiglitazone (Avandia) and pioglitazone (Actos) – Reduce glucose levels by decreasing insulin resistance – Not related chemically or functionally to sulfonylureas, biguanides, or alphaglucosidase inhibitors Rosiglitazone Only minor side effects – Renal retention of fluid – Raises levels of plasma lipids Drug interactions – Insulin also promotes fluid retention, hence the combination poses increased risk for heart failure – Gemfibrozil (Lopid) can raise plasma levels of rosiglitazone Pioglitazone (Actos) Newest glitazone No hepatoxicity Adverse effects – generally mild – URI, headache, sinusitis, myalgia – Promotes water gain Drug interaction – Gemfibrozil (Lopid) Alpha-Glucosidase Inhibitors Acarbose and miglitol Act in intestine to delay absorption of carbohydrates Do not depend on the presence of insulin Monotherapy or combination Alpha-Glucosidase Inhibitors Adverse effects – Flatulence, cramps, distention, borborygmus, and diarrhea (fermentation of carbohydrates) – Long-term high dose may cause liver dysfunction – Monitor every 3 months – Should avoid concurrent use with metformin due to GI effects Sitagliptin (Januvia) Enhances the actions of incretin hormones Stimulates glucose dependent release of insulin Suppresses postprandial release of glucagon Monotherapy or combination Generally well tolerated URI, headache, inflammation throat/nasal Colesevelam (Welchol) Bile-acid sequestrant – used to lower plasma cholesterol Can also help lower blood glucose FDA-approved for type 2 treatment in 2008 Many diabetic patients have high cholesterol Combination Products Metformin/Glyburide Metformin/Glipizide Metformin/Rosiglitazone Metformin/Pioglitazone Metformin/Repaglinide Metformin/Sitagliptin Pioglitazone/Glimepiride Rosiglitazone/Glimepiride New Injectable Drugs for Diabetes Pramlintide (Symlin) – Supplement to mealtime insulin (type 1 or type 2) – Adverse effect: hypoglycemia Exenatide (Byetta) – Adjunctive therapy to improve glycemic control in patients with type 2 diabetes – Adverse effects Hypoglycemia Gastrointestinal effects Glucagon for Insulin Overdose Preferred treatment is IV glucose – Immediately raises blood glucose level Glucagon can be used if IV glucose is not available – Delayed elevation of blood glucose – Will not work in starvation Promotes glycogen breakdown and the malnourished have little glycogen left