Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Optimal diabetes control in adults. Dr H Oosthuizen Management principals 1. 2. 3. 4. 5. Preserve Beta cell function. Early aggressive treatment. Reduce glucose toxicity. Treat to target. Information and education. Three corner stones of therapy. • Diet • Exercise • Medication Additional metabolic targets. • • • • • • • • BP: 130/80 mmHg (with no proteinuria). BP: 125/75 mmHg (with proteiuria). Total cholesterol < 5mmol/L LDL cholesterol < 3mmol/L (diabetes only) < 2.6mmol/L(additional risk factors) HDL cholesterol > 1mmol/L Trigliserides < 1.7mmol/L BMI = 20-24 kg/m2 Waist circumfence = 102 cm (f), 88cm (m). Medication for Type 2 diabetic patient. 6 classes of drugs: 1. Sulphonylurea 2. Biguanide 3. Acarbose 4. Meglitinides 5. Thiazolidinediones 6. Insulin PHARMACOLOGICAL MANAGEMENT. • • SITES OF ACTION OF CURRENT ORAL ANTIDIABETIC AGENTS Liver: glucose production - biguanides - thiazolidinediones Pancreas: insulin secretion - sulphonylureas - meglitinides insulin replacement - insulin PHARMACOLOGICAL MANAGEMENT. SITES OF ACTION OF CURRENT ORAL ANTIDIABETIC AGENTS • Adipose tissue: peripheral glucose uptake and and muscle utilization - thiazolidinediones - biguanides • Intestine: glucose absorption - alpha-glucosidase inhibitors / TZD Biguanides : metformin(glucophage) Mechanism of action • Inhibits hepatic glucose prodution (gluconeogenesis). • Increases the sensitivity of peripheral tissue to insulin. • Increases peripheral glucose uptake. • Decreases glucose absorption from the intestine. • Does not stimulate insulin secretion. Metformin Contra-indications • Impaired renal function. • Impaired hepatic function. • Alcoholism. • Conditions which promote tissue hypoxia: coronary heart disease, cardiac failure, peripheral vascular disease, obstructive airways disease • • • • Pregnancy. Major surgery. Type 1 Diabetes Ketoacidosis Metformin Side effects • Diarrhea • Abdominal discomfort • Nausea • Metallic taste • Anorexia • Lactic acidosis • Impaired intestinal Vit B12 & Folate absorption • Megaloblastic anemia (B12 malabsorption) Metformin ADVANTAGES • Reduces insulin resistance. • High initial response rate. • Long record of relative safety. • No weight gain or modest weight loss. Thiazolidinediones pioglitazone (actos), rosiglitazone (avandia) troglitazone (rezulin) TZD/pioglitazone: Mechanism of action • Primary effects on adipocytes are secodarily transmitted to muscle and liver via other mediators (TNF, leptin and FFA). • TZD induce lipoprotein lipase: trigliseride uptake into fat and circulating FFA. • Reduced insulin resistance at liver and muscle. • Enhances GLUT4 gene expression, thus improved insulin action at target tissue. TZD/pioglitazone: Mechanism of action • Pioglitazone increases glucose uptake in skeletal muscle and adipose tissue – increasing glycolysis + synthesis of glycogen in skeletal muscle. • Increase oxidation and lipogenesis in adipose tissue – increase peripheral glucose sensitivity and utilization. • Reduces gluconeogenesis.(by liver) • Reduce insulin resistance. Thiazolidinediones Contra-indications/precautions • Impaired hepatic function or active liver disease. • Cardiac failure. • Type 1 diabetes. • Diabetic ketoacidosis. • Pregnancy. • Lactation. Thiazolidinediones Side effects • Upper Respiratory Tract infection. • Weight gain. • Anemia - Hb and Hematocrit. • Haemodulation and Oedema. • Plasma volume expansion and cardiac hypertrophy. • Ovulation and possible pregnancy. • Unknown long term safety profile. Thiazolidinediones ADVANTAGES • Corrects a primary pathophysiologic impairment: insulin resistance. • Once daily dosing. • Lowers serum triglycerides. • Increases HDL cholesterol. • Can be used in renal insufficiency. Insulin secretagogues • Repaglinide • Nateglinide • Sulphonylureas Sulphonylureas • • • • • • Chlorpropamide (diabinese) Gliclazide (diamicron, glucomed) Glipmepiride (amaryl) Glipizide (minidiab) Glybenclamide (daonil, glyben, glycomin) Tolbutamide (rastinon) Sulphonylureas Contra-indications • Impaired renal and hepatic function. • Pregnancy • Type 1 diabetes • Thyroid and adrenal dysfunction. Sulphonylureas DISADVANTAGES • Hypoglycaemia – may be prolonged or severe. • Weight gain. • Drug interactions, especially 1st generation. • Hyponatraemia with Chlorpropamide. • Cannot use if allergic to SU compounds. • Direct Exocytosis of Beta cells: ? Beta cell life span? Type 2 Hyperglycaemia • 3rd generation sulphonylureas. Amaryl • Once daily. • Insulin release action. • Stimulation of glucose transport. • Stimulation of non-oxidative glucose metabolism in fat and muscle cells Meglitinide analogues • Repaglinide • Nateglinide Nateglinide/Repaglinide • Meglitinide group of drugs • Stimulate insulin secretion from beta cells (glucose dependent) • Minimal excretion via kidneys Repaglinide/Nateglinide mechanism of action • Pharmacologically distinct binding site on potassium channel. • No direct exocytosis of insulin from beta cell. • Beta cell sparing? • Overcome metabolic stress on cells. Repaglinide/Nateglinide ADVANTAGES • Improve primary pathophysiologic impairment: insulin secretion. • Physiologic route of insulin delivery. • Permits flexibility in lifestyle: Dose coupled to meals – no need for snacking-promote weight loss. • High initial response rate. • No lag period before response. • Can be used in various degrees of renal impairment. • Low incidence of severe hypoglycaemic episodes. Alpha-Glucosidase Inhibitors Acarbose (glucobay) Alpha-Glucosidase Inhibitors Mechanism of action • Acts by competitive inhibition of alphaglucosidase enzymes. • Reduces the rate of monosaccharide generation and absorption. • Delays glucose absorption in the intestine. • Modulates peaks in post-prandial glucose. • Taken with meals. Alpha-Glucosidase Inhibitors Acarbose Indications • Obese and non-obese Type 2 patients inadequately controlled by diet and exercise therapy. • May be used in combination with Repaglinide, SU’s, Metformin or Insulin. Alpha-Glucosidase Inhibitors Acarbose Side effects • Dose related absorption. • Flatulence • Abdominal bloating/upset. • Skin reactions. Alpha-Glucosidase Inhibitors Acarbose ADVANTAGES • Good safety profile. • No weight gain. • Dose coupled to meals. • Unique mechanism. Rationale for COMBINATION THERAPY • Improving metabolic effect by combining drugs with different mechanisms of action. • Reducing side effects by sub-maximal dosage. • Starting combination therapy according to metabolic guidelines. • Prescribing drugs according to individual patient need. Management of patients prsenting with very high Blood Glucose levels. • Level higher than~20mmol/L-admission into hospital, depending on symptoms. • If type of diabetes is uncertain - C-peptide test needed. Check for blood/urine ketones. Initiation of insulin may be necessary: • Use supplementation/adjustment scale. • Work insulin dosage out according to Body weight. • Adjust insulin dosage according to blood glucose readings. Insulin adjustment scale Eg. Of patients on basal-bolus regimen Pre-meal reading <3mmol/L 3-5mmol/L 5-7mmol/L 7-10mmol/L 10-13mmol/L 13-17mmol/L 17-22mmol/L Change insulin Decrease 1-3 units Decrease 0-1 units Increase 0-1 units Increase 1-2 units Increase 2-3 units Increase 3-4 units Increase 4-6 units When and how to start insulin treatment in type 2 diabetes. Insulin therapy in Type 2 patients on OAD’s can be started in two ways: 1. Supplemental therapy 2. Substitution therapy Insulin initiationsuplemental therapy • Continue OAA treatment. • Add 02iu/kg NPH at breakfast or at bedtime. • Dose increase by 2-4iu every 3-4 days, if necessary. • If more than 36iu insulin needed to obtain control – stop OAA treatment and continue insulin alone. • Divide dose into 2 daily injections – 2/3 mane, 1/3 nocte-(30/70 premix). Protophane dosage 60kg patient 70kg patient 80kg patient 90kg patient >100 kg patient = = = = = 12u 16u 20u 24u 28u Insulin initiationSubstitution therapy • Stop OAA treatment. • Start 2 injections – 0.2iu/kg NPH or premixed insulin (30/70); 2/3 TDD before breakfast, 1/3 TDD before supper. • Increase dose 2-4iu every 3-4 days if necessary. • If PP BG is too high, prmixed insulin better than NPH. Drug interactions • • • • • • • Substances that may enhance the hypoglycaemic effects of oral medication Monoamine oxidase inhibitors (MOAI’s) Beta blocking agents Angiotensin converting enzyme inhibitors (ACE-inhibitors). Non-steroidal anti-inflammatory agents (NSAIDS) Salicilates Alcohol Octreotide and anabolic steroids Drug interactions • • • • • • Substances that may reduce the hypoglycaemic effects of oral medication. Oral contraceptives Thiazides Corticosteroids Danazol Thyroid hormones Sympathomimetics Drug interactions Beta Blocking Agents • May mask the symptoms of hypoglycaemia. • May mask the body’s response to hypoglycaemia. Alcohol • May intensify and prolong the hypoglycaemic effect of oral hypoglycaemic medication. Drug interactions Agents that may delay the metabolism of certain oral hypoglycaemic agents • Interactions with antifungal agents e.g. ketoconazole. • Interactions with antibacterial agents e.g. erythromycin. Drug interactions Compounds that induce or inhibit the cytochrome-P450 (CYP3A4 or CYP2C9) enzyme system • May either delay or increase the metabolism of certain oral hypoglycaemic agents e.g. 1. Ketoconazole is a CYP3A4 inhibitor 2. Rifampicin is a CYP3A4 inducer Home glucose monitoring. Advantages • Frequent measurements. • Availability. • Treatment adaptable. • Testing at appropriate times. Disadvantages • Inaccuracy due to wrong technique. • Not all readings are reported. • Cost Monitoring via HbA1c Advantages • Laboratory measurement. • Done 3-6 monthly. • Gold standard. Disadvantages • Average reading • Hypoglycaemic episodes not picked up. • Expensive • Different methods in different labs. • False security. Home glucose monitoring. • New trends in diabetes management. • New Glucometers – Optium Plus Accutrend sensor Lifescan Glucometer Elite Freestyle • Computer assisted systems. Type 2 Diabetes • Treat the patient not the glucometer. • Control other risk factors: 1. Obesity – life style modification drug therapy 2. Dislipidaemia 3. Hypertension – drug side effects combination therapy 4. Smoking Conclusion • Elevated postprandial blood glucose = risk factor for Cardiovascular disease and mortality, independent of Fasting blood glucose levels and HbA1C. • Early and aggressive treatment of Type 2 diabetes, to improve glycaemic control, decreases the risk of long term complications. • Insulin treatment initiated when near normalization of BG cannt be achieved with OAA’s alone. Conclusion • Better BG control – reduces/avoids atherosclerosis – BP management. • Education on dislipidemia. • Quality of Life factors affect control and management.