AACE/ACE Consensus Statement American Association of Clinical Endocrinologists and American College of Endocrinology

Transcription

1 AACE/ACE Consensus Statement 2017 American Association of Clinical Endocrinologists and American College of Endocrinology Jeff Worrell, Lt Col, USAF (retired) CRNA MSN

2 Why am I here? Metabolic Syndrome Hyperglycemia Hypertension Hyperlipidemia/triglycerides Increased abdominal fat

3 1. Explain extent of diabetes in American population 2. Differentiate type 1 and type 2 diabetes 3. Describe mechanism of action of insulin 4. Describe tight control of blood glucose 5. List glucose concentrations in common IV solutions 6. Discuss measures to compound and administer insulin drip 7. Describe mechanism of action of wide variety of medications used to control type 2 diabetes Envision future of exceptional glycemic control

4 oprevalence: In 2012, 29.1 million Americans, or 9.3% of the population, had diabetes. o Approximately 1.25 million American children and adults have type 1 diabetes.

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6 Surgical procedures may result in a number of metabolic perturbations that can alter normal glucose homeostasis. The resulting hyperglycemia due to abnormal glucose balance is a risk factor for: Postoperative sepsis Endothelial dysfunction Cerebral ischemia Autonomic dysfunction Impaired wound healing

7 Unmanaged hypoglycemia may result in a number of neurological complications including: Somnolence Unconsciousness Seizures and depending on the duration Irreversible neurological insult Death

8 The trauma associated with surgery results in increased production of stress hormones Increases in cortisol and catecholamine levels related to surgery have been well documented metabolic changes outlined above that occur during surgery cause a marked catabolic state. Changes in normal metabolic patterns due to surgery trigger gluconeogenesis, glycogenolysis, proteolysis, lipolysis, and ketogenesis ultimately resulting in hyperglycemia and ketosis

9 Type 1 diabetes is usually diagnosed in children and young adults, and was previously known as juvenile diabetes. Only 5% of people with diabetes have this form of the disease In type 1 diabetes, the body does not produce insulin

10 Type 2 diabetes is the most common form of diabetes Your body does not use insulin properly. This is called insulin resistance At first, the pancreas makes extra insulin to make up for it. But, over time your pancreas isn t able to keep up and can t make enough insulin to keep your blood glucose levels normal

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13 Skin Complications Eye Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) High Blood Pressure (Hypertension)Heart Disease Stroke Hyperglycemic Nonketotic Syndrome (HHNS) Gastroparesis

14 Tight Diabetes Control What Does Tight Control Mean? Tight control means getting as close to a normal (nondiabetic) blood glucose level as you safely can. Ideally, levels between 70 and 130 mg/dl before meals Less than 180 two hours after starting a meal With a glycosolated hemoglobin (A1C) level less than 6.5 percent

15 Diabetes Control and Complications Trial (DCCT) Researchers followed 1,441 people with type 1 diabetes for several years. Half of the people continued standard diabetes treatment Thee other half followed an intensive-control program. - See more at:

16 The results? Diabetic eye disease started in only one-quarter as many people. Kidney disease started in only half as many people. Nerve disease started in only one-third as many people. Tight control is most worthwhile for healthy people who can expect to live at least 10 more years. Not recommended for children or elderly

17 Moderate Versus Tight Glycemic Control Glycemic goals within the hospital setting have changed in the last 14 years. The initial target of mg/dl ( mmol/l) was based on a 42% relative reduction in intensive care unit mortality in critically ill surgical patients. However, a meta-analysis of over 26 studies, including the largest, Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation (NICE-SUGAR), showed increased rates of severe hypoglycemia and mortality in tightly versus moderately controlled cohorts.

18 Normoglycemia in Intensive Care Evaluation Survival Using Glucose Algorithm Regulation (NICE-SUGAR) evidence established new standards: Initiate insulin therapy for persistent hyperglycemia greater than 180 mg/dl (10.0 mmol/l). Once insulin therapy is initiated, a glucose target of mg/dl ( mmol/l) is recommended for most critically ill patients. More stringent goals, such as mg/dl ( mmol/l) may be appropriate for select patients, such as cardiac surgery patients, and patients with acute ischemic cardiac or neurological events provided the targets can be achieved without significant hypoglycemia.

19 Insulin is composed of two peptide chains referred to as the A chain and B chain. A and B chains are linked together by two disulfide bonds, and an additional disulfide is formed within the A chain. In most species, the A chain consists of 21 amino acids and the B chain of 30 amino acids.

20 Long acting insulin glargine Lantus onset 1 hour Duration 24 hr Toujeo onset 6 hours Duration hr Reduce dose by 20-50% day before surgery Intermediate insulin NPH Insulin suspensions onset 30 minutes Duration max 24 hours Reduce dose by 20-50% of night time dose Short acting regular Humulin Onset 15 minutes --- Duration 2-4 hours No regular insulin at home, administered on sliding scale after assessing BG Inhaled Insulin Hold

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23 100 Units of Regular Insulin in 100CC NS flush line 10 ml Follow local protocols:

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25 D5W 5 GM Dextrose per 100 ml Osmolarity 252 D10W 10 GM Dextrose per 100 ml Osmolarity 505 D25W 25 GM Dextrose per 100 ml Osmolarity 1389 D50W 50 Gm Dextrose per 100 ml Osmolarity 2500 Normal Plasma osmolarity Caloric calculation

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27 Pharmacologic therapy of type 2 diabetes has changed DRAMATICALLY over the past 10 years New Drug classes New Drugs New combinations for better glycemic control Diet control, weight loss and exercise are still hallmarks of nonpharmacologic therapy.

28 1. Biguanides 2. Sulfonylureas 3. Meglitinides 4. Thiazolidinediones 5. GLP1-Agonists 6. DPP-4 Inhibitors 7. SGLT-2 Inhibitiors 8. Alpha-glucosidease inhibitors 9. Bile Acid Sequestrants

29 Metformin (Glucophage) is a biguanide. Considered first choice for oral therapy Annals of Internal Medicine 7 June 2016 Biguanides lower blood glucose levels primarily by decreasing the amount of glucose produced by the liver (hepatic gluconeogenesis). Metformin also helps to lower blood glucose levels by making muscle tissue more sensitive to insulin so glucose can be absorbed.

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31 Metformin reduces pyruvate dehydrogenase activity and mitochondrial transport of reducing agents Enhances anaerobic metabolism. This shift to anaerobic metabolism, in the presence of reduced insulin, increases production of precursors for the Krebs cycle. Consequently, there is a decreased ability to channel those precursors into aerobic metabolism, which, in turn, results in increased metabolism of pyruvate to lactate and increases net lactic acid production. Fortunately this is rare: recommended to hold metformin preop

32 Sulfonylureas stimulate the beta cells of the pancreas to release more insulin. Bind to and close ATP-sensitive K+ (KATP) channels on the cell membrane of pancreatic beta cells This depolarizes the cell by preventing potassium from exiting. This depolarization opens voltage-gated Ca2+ channels. The rise in intracellular calcium leads to increased fusion of insulin granulae with the cell membrane, and therefore increased secretion of (pro)insulin

33 Sulfonylurea drugs have been in use since the 1950s. Chlorpropamide (Diabinese) is the only first-generation sulfonylurea still in use today. The second generation sulfonylureas are used in smaller doses than the firstgeneration drugs. There are three second-generation drugs: glipizide (Glucotrol and Glucotrol XL), glyburide (Micronase, Glynase, and Diabeta), and glimepiride

34 Can reduce HbA1c by 1-2% - decreases morbidity 10% Normal ranges for hemoglobin A1c in people without diabetes is about 4% to 5.9%. People with diabetes with INADEQUETE GLUCOSE CONTROL have hemoglobin A1c levels above 6.5%. Hemoglobin A1c is a protein on the surface of red blood cells that glucose molecules stick to, usually for the life of the red blood cell (about three months). The higher the level of glucose in the blood, the higher the level of hemoglobin A1c is detectable on red blood cells. Hemoglobin A1c levels correlate with average levels of glucose in the blood over an approximately three-month time period. Sulfonylureas can reduce blood glucose concentrations by 20%

35 Meglitinides are drugs that also stimulate the beta cells to release insulin. Repaglinide (Prandin) and nateglinide (Starlix) are meglitinides. They bind to an ATP-dependent K + (K ATP ) channel on the cell membrane of pancreatic beta cells in a similar manner to sulfonylureas Shorter acting than sulfonylureas FDA approved as monotherapy or in combination with metformin or thiazolidinediones

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37 Specifically, TZDs act by activating PPARs (peroxisome proliferatoractivated receptors), a group of nuclear receptors, with greatest specificity for PPARγ(PPAR-gamma, PPARG). They are thus the PPARG agonists subset of PPAR agonists. Also important in fat redistribution and fatty acid metabolism Improve target cell response to insulin WITHOUT increasing insulin secretion from pancreas. Insulin sensitizers

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39 Glitazones : Rosiglitazone (Avandia) and pioglitazone (ACTOS) are in a group of drugs called thiazolidine-diones. Insulin Sensitizer These drugs help insulin work better in the muscle and fat and also reduce glucose production in the liver. Avandia suggested increase risk of MI only available on restricted access program Actos may slightly increase risk of bladder cancer

40 Byetta, Trulicity Glucagon-like peptide-1 (GLP-1) is a hormone that is encoded in the proglucagon gene. It is mainly produced in enteroendocrine L cells of the gut and is secreted into the blood stream when food containing fat, protein and/or glucose enters the duodenum. GLP-1 receptor activation also increases insulin synthesis, and beta cell proliferation.

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42 A new class of medications called DPP-4 inhibitors help improve A1C without causing hypoglycemia. They work by preventing the breakdown of a naturally occurring compound in the body, GLP-1: Glucagon Like Peptide. GLP-1 reduces blood glucose levels in the body, but is broken down very quickly so it does not work well if ingested must be injected (SQ). By interfering in the process that breaks down GLP-1, DPP-4 inhibitors allow it to remain active in the body longer, lowering blood glucose levels only when they are elevated. DPP-4 inhibitors do not tend to cause weight gain and tend to have a neutral or positive effect on cholesterol levels

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44 Glucose in the bloodstream passes through the kidneys, where it can either be excreted or reabsorbed. Sodium-glucose transporter 2 (SGLT2) works in the kidney to reabsorb glucose, and a new class of medication, SGLT2 inhibitors, block this action, causing excess glucose to be eliminated in the urine. Canagliflozin (Invokana) and dapagliflozin (Farxiga) are SGLT2 inhibitors that have recently been approved (2015) by the FDA to treat type 2 diabetes

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46 Acarbose (Precose) and miglitol (Glyset) are alpha-glucosidase inhibitors. These drugs help the body to lower blood glucose levels by blocking the breakdown of starches, such as bread, potatoes, and pasta in the intestine. They also slow the breakdown of some sugars, such as table sugar. Their action slows the rise in blood glucose levels after a meal

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48 The bile acid sequestrant (BAS) colesevelam (Welchol) is a cholesterollowering medication that also reduces blood glucose levels in patients with diabetes. BASs help remove cholesterol from the body, particularly LDL cholesterol, which is often elevated in people with diabetes. The medications reduce LDL cholesterol by binding with bile acids in the digestive system the body in turn uses cholesterol to replace the bile acids, which lowers cholesterol levels. The mechanism by which this medication lowers glucose levels is not well understood

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50 Is a potential cure for diabetes on the horizon? Stimulate non-beta cells in pancreas to produce insulin in response to increased blood glucose Gene transfer: A virus is used as a vector to introduce genes into the pancreas The other cells seems to live without interference from the bodies autoimmune system. Cindy s story.