第十五章. Diabetes Mellitus

Diabetes-1/9 第十五章 Diabetes Mellitus 陳曉蓮醫師

2/9 - Diabetes 羅東博愛醫院 Management of Diabetes mellitus A. DEFINITION OF DIABETES MELLITUS Diabetes Mellitus is characterized by chronic hyperglycemia with disturbances of carbohydrate, fat, and protein metabolism resulting from defects in insulin secretion, insulin action, or both. B. Etiologic Classification of Disorders of Glycemia Type 1 (ß-cell destruction, usually leading to absolute insulin deficiency) Autoimmune B. Idiopathic Type 2 (may range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with or without insulin resistance) Gestational diabetes Other specific types of diabetes C. Diagnostic Criteria (Non-Pregnant Adults) Casual plasma glucose > 200 mg/dl and symptoms of diabetes (polyuria, polydipsia, ketoacidosis, or unexplained weight loss) OR Fasting plasma glucose (FPG) > 126 mg/dl OR Results of a 2-hour 75-g Oral Glucose Tolerance Test (OGTT) > 200 mg/dl D. Diagnostic Criteria for Diabetes Mellitus and related stages of glycemia Test Category Fasting Plasma Glucose Two-hour Plasma Glucose Normal <100 (mg/dl) <140 (mg/dl) IFG 100-125(mg/dl) --- (impaired fasting glucose) IGT --- 140-199 (mg/dl) (impaired glucose tolerance with 75-g oral glucose tolerance test) Diabetes* >126 (mg/dl) >200 (mg/dl)

Diabetes-3/9 E. Treatment of Diabetes Mellitus Patient History Age, body weight, family history, durations of symptoms and results of blood glucose and HbA1c Physical Examination Routine examination Special attention a. Height, weight, body mass index (BMI), blood pressure, b. Examination of peripheral pulses palpating dorsalis pedis, posterior tibial, popliteal, femoral arteries c. Neurologic examination vibration, position sense Laboratory Studies Glucose, acid-base status, electrolytes, ketones HbA1c, total cholesterol, triglycerides, high-density cholesterol, and low-density cholesterol, Urinalysis, Microalbuminuria, F. Goals of Glycemic Control for People with Diabetes Biochemical Index. Normal Goal Initiation of Action Suggested Average Fasting Plasma Glucose (mg/dl) or Preprandial < 100 90 130 < 80, > 140 Average Postprandial 2 hours (mg/dl) < 140 < 160 > 180 Average Bedtime Glucose (mg/dl) < 120 110 150 < 110, > 160 A1C (%) sustained < 6% < 7% ** > 7% * Laboratory methods measure plasma glucose. Most glucose monitors approved for home use calibrate whole blood glucose readings to plasma values. Plasma glucose values are 10-15% higher than whole blood glucose values. It is important for people with diabetes to know whether their meters and strips record whole blood or plasma results. ** The true goal of care is to bring A1C as close as possible to the non-diabetic range. A goal of < 7% is chosen as a practical level for most patients on medications that cause hypoglycemia to avoid the risk of that complication.

4/9 - Diabetes 羅東博愛醫院 G. Initial Treatment Strategy Medical nutrition therapy (MNT), physical activity, blood glucose monitoring and patient education are the cornerstones of diabetes management for all patients. Pharmacological management should be used in combination with MNT and physical activity. Current weight status and lifestyle should be considered when choosing initial pharmacological therapy. Initial Presentation (Based on presentation of the items listed within each box) Mild Moderate Severe Mild or no symptoms AND Negative ketones AND No acute concurrent illness Start MNT and Physical Activity 6-8weeks target not met FPG > 200* OR Random > 300* AND Does not meet criteria for mild or severe Start oral Antihyperglycemic Therapy Marked hyperglycemia OR Significant weight loss OR Severe/significant symptoms OR 2+ or greater ketonuria OR DKA, hyperosmolar state OR Severe intercurrent illness or surgery Start Insulin immediately * If diet history reveals markedly excessive carbohydrate intake, one may consider initial trial of MNT and physical activity before initiating oral agent therapy even though glucose levels are above the thresholds listed. * Some patients with type 2 diabetes initially stabilized on insulin may be considered for transition to oral agent therapy. H. SELECTING ANTIHYPERGLYCEMIC THERAPY* Consider Metformin Obesity present Renal/liver function normal Contraindicated: a. Creatinine > 1.4 (women)

Diabetes-5/9 b. Creatinine > 1.5 (men) c. IV contrast d. CHF e. Dehydration f. Alcohol excess g. > 80 years ago (unless creatinine clearance is normal) Consider Thiazolidinediones (TZDs) Obese, signs of insulin resistance Liver function normal; need to follow LFT monitoring schedule** Can be used in renal impairment but may increase fluid retention Full effect of initiation or titration of therapy may take 2-4 months to be seen Contraindicated: a. Class III or IV CHF b. LET > 2.5 times upper limit of normal c. FDA Requirements for LFT monitoring: 1. For pioglitazone (Actos) and rosiglitazone (Avandia) 2. If initial ALT is 2.5 times > normal, do not start this Rx. 3. If ALT is 2.5 times > normal during treatment, check weekly. If rise persists or becomes 3 times > normal, discontinue Rx. 4. For Actos, monitor ALT periodically thereafter according to clinical judgement. 5. For Avandia, monitor ALT every 2 months for the first 12 months and then periodically thereafter. Consider Insulin Secretagogue (sulfonylurea or short-acting secretagogue) Non-obese/mild obesity Repaglinide or nateglinide are useful for patients with postprandial hyperglycemia or hypoglycemia on sulfonylurea Contraindicated: Sulfonylureas in severe liver or renal disease Consider α-glucosidase Inhibitor Milder presentation Use if postprandial hyperglycemia is the predominant hyperglycemic pattern. No GI symptoms Contraindicated:

6/9 - Diabetes 羅東博愛醫院 a. Chronic intestinal disorders b. Acarbose in cirrhosis c. Acarbose and miglitol in renal impairment(creatinine > 2.0) I. Combination Therapy with Oral Agents and Oral Agents with Insulin Fasting Plasma Glucose > 140 OR Postprandial Glucose > 180 OR A1C ³ 7.0% Add Drug of Another Class Acceptable Choices for Combination Therapy a. Insulin secretagogue and metformin (metformin and glyburide, metformin and glipizide available in fixed combinations) b. Sulfonylurea and α-glucosidase inhibitor c. Thiazolidinediones and sulfonylurea d. Thiazolidinediones and metformin (metformin and rosiglitazone available in fixed combination) e. Thiazolidinediones and repaglinide A combination of two drugs of different classes may be used as initial pharmacotherapy when there is marked hyperglycemia or when MNT and physical activity alone have not resulted in an A1C of < 8.0%.

Diabetes-7/9 Combination Therapy with Oral Agents with Insulin Fasting Plasma Glucose > 140 OR 2 Postprandial Plasma Glucose > 180 OR A1C ³ 7.0% Add Third Oral Medication OR Add Insulin Add Third Oral Antihyperglycemic Agent of Different Class (No proven benefit of adding two different insulin secretagogues in combination) Add Insulin (*) (**) Several options available: Intermediate acting insulin q hs (e.g. NPH or lente) Long-acting or basal insulin (e.g. glargine once daily at any time or ultralente pre-supper or hs) Pre-supper insulin mixture (e.g. 75/25 lispro, 70/30 insulin, or 70/30 aspart) Suggested starting dose: 0.1-0.2u/kg ideal body weight Titrate/adjust insulin dosage until glucose goals met If target glucose not met, consider: Changing to multidose therapy using combination of rapid or very rapid acting, intermediate, or long -acting insulin Pre-meal rapid or very rapid-acting insulin (e.g. aspart, lispro, or regular) added to hs intermediate or long-acting/basal insulin Adding oral medication to reduce insulin resistance or improve glycemic control if already on insulin (Metformin, TZDs, sulfonylureas, and α-glucosidase inhibitors are approved for use in combination with insulin) Refer to endocrinologist if goals not met * May need to taper and discontinue some or all oral agents as insulin is initiated and adjusted, particularly if using rapid-acting and basal insulins. **Pre- and postprandial blood glucose should be checked. Frequency may vary 1-4 times/day depending on individual patient and status of glycemic control.

8/9 - Diabetes 羅東博愛醫院 J. Oral Agents Available Biguanides TZDs (Thiazolidinediones) pioglitazone(actos) rosiglitazone(avandia) α-glucosidase Inhibitors acarbose (Precose) miglitol (Glyset) Insulin Secretagogues Sulfonylureas a. glimepiride (Amaryl) b. glipizide (Glucotrol) c. glyburide(glibenclamide) D-phenylalanine Derivatives nateglinide (Starlix) Meglitinides repaglinide- (Prandin) K. INSULIN CHART* Insulin Type Insulin Type Product Onset Peak Duration Very Rapid Acting Insulin aspart analog NovoLog 10 30 minutes 0.5 3 hours 3 5 hours Insulin lispro analog Humalog Rapid Acting Regular insulin Humulin R 30 minutes 1 5 hours 8 hours Novolin R Intermediate Acting NPH insulin Humulin N 1 4 hours 4-12 hours 14 26 hours Long Acting Insulin glargine Lantus 2-3 hours No peak Up to 30 hours Ultralente insulin 3-4 hours 8-10 hours Up to 20 hours

Diabetes-9/9 Premixed Combinations Insulin Type Product 50% NPH; 50% Regular Humulin 50/50 70% NPH; 30% Regular Humulin 70/30 70% NPH; 30% Regular Novolin 70/30 75% lispro protamine suspension, 25% lispro Humalog Mix 75/25 70% aspart protamine suspension, 30% aspart NovoLog Mix 70/30 The onset, peak and duration of any insulin type depend on many factors. Patients may experience variations in timing and/or intensity of insulin activity due to dose, site of injection, temperature, level of physical activity, in addition to other factors.