INSULIN THERAPY. Introduction to Insulin-overview, uses.

Introduction to Insulin-overview, uses.
Brief overview of Diabetes Mellitus-definition, risk factors, diagnosis criteria, complications , use of OHAs.
Types of insulin.
Profile of insulin types.
Insulin optimization and intensification.
Patient education

1. INSULIN THERAPY By Dr Ryan koome.

2. OUTLINE Introduction to Insulin-overview, uses. Brief overview of Diabetes Mellitus-definition, risk factors, diagnosis criteria, complications , use of OHAs. Types of insulin. Profile of insulin types. Insulin optimization and intensification. Patient education.

3. INSULIN Hormone produced by the pancreas. Produced by the beta cells found in the islets of Langerhans. Secretion triggered by high blood glucose Regulation is by hormonal and neural pathways. Somatostatin inhibits release of insulin and glucagon. Glucagon stimulates insulin release Neural is via sympathetic( alpha inhibits via adenylyl cyclase while beta stimulates adenylyl cyclase hence stimulates insulin release. Muscarinic( cholinergic) stimulates insulin release via the IP3/DAG-intracellular calcium .

4. ROLE OF INSULIN Suppressing endogenous glucose production by the liver. Stimulation of peripheral glucose uptake in muscle and adipose tissue. Suppressing fat adipose tissue from breaking down fats(Lipolysis) .

5. FUEL AND KEY ANALOGY Our body ingests carbohydrates. Digestion of carbohydrates starts in mouth via action of salivary amylase. Halted in stomach and continues in the small intestine via action of pancreatic amylase. Brush border enzymes (maltase and sucrase) break disaccharides into monosaccharides which are then absorbed into the blood stream. Glucose needs to be delivered to different body tissues and this is done by a key called insulin. Glucose is the fuel in your fuel tank but needs a key called insulin

6. INDICATIONS OF INSULIN Type 1 and Type 2 Diabetes Mellitus inadequate control on OHAs OHAs contraindicated Gestational Diabetes mellitus impaired glucose tolerance in pregnancy. Metformin is generally recommended but some patients require insulin(NPH or detemir) insulin glargine contraindicated in pregnancy.

7. DEFINITION OF DIABETES MELLITUS Metabolic progressive disorder characterized by repeated episodes of abnormally high blood glucose levels. The chronic hyperglycemia damages body tissues such as the eyes, kidney, nerves, heart and the blood vessels. Diabetes mellitus can be caused by either insulin resistance or impaired insulin secretion. Insulin resistance results in Type 2 Diabetes Mellitus whereas impaired insulin secretion results in Type 1 Diabetes Mellitus. Type 2 Diabetes Mellitus accounts for about 90% of the diabetes cases worldwide .

8. RISK FACTORS FOR TYPE 2 DIABETES MELLITUS Obesity- BMI greater than 25. Age- 40 years or older. Physically inactive Genetics. Abnormal cholesterol level-LDL levels above 100 Have had Gestational DM or given birth to a baby of or greater than 4kg. Hypertensive patients

9. CRITERIA FOR DIAGNOSIS OF DM Symptoms of diabetes plus Random blood glucose greater or equal to 200mg/dl (11.1 mmol/l) Fasting blood glucose level greater or equal to 126 mg/dl (7.0mmol/l) Classical symptoms of diabetes include polyuria, polydipsia and unexplained weight loss

10. ACUTE COMPLICATIONS OF DIABETES MELLITUS Diabetic ketoacidosis-occurs due to untreated type 1 diabetes. Hyperglycemic Hyperosmolar state(HHS)-occurs due to insulin deficiency in older patients with type 2 Diabetes Mellitus. Leads to HONK (Hyperosmolar non- ketotic coma) Hypoglycemia-occurs due to over-treatment with insulin or OHAs.

11. CHRONIC COMPLICATIONS OF DIABETES MELLITUS MICROVASCULAR Retinopathy and blindness – mostly after 15 years. About 40% of patients with DM develop retinopathy with 2% becoming blind. Erectile dysfunction-up to 75% of male patients develop ED. Nephropathy- about 1/3 of patients with DM develop kidney disease. Neuropathy- tingling and numbing Diabetic foot ulcers- 15 to 40 times likely to require amputation .

12. MACROVASCULAR Stroke Coronary heart disease Peripheral vascular disease

13. DIET AND EXERCISE Obesity and physical inactivity are the two major risk factors for type 2 DM. Improving a diet and engaging in physical activity provides good glycemic control for most patients with DM. Lifestyle modification considered mainstay treatment due to fact it is cost effective and offers the long-term control.

14. CLASS MOA EXAMPLES Sulfonylureas Increase insulin secretion Glibenclamide, gliclazide, glimepiride Meglitinides Increase insulin secretion Repaglinide, nateglinide DPP4-inhibitors Increase insulin secretion Decrease glucose production by decreasing glucagon. sitagliptin., vildagliptin, saxagliptin , linagliptin Biguanides Decrease hepatic glucose production Increase peripheral insulin sensitivity metformin Thiazolidinediones Decrease hepatic glucose production Increase peripheral insulin sensitivity pioglitazone Alpha glucosidase inhibitors Slow down carbohydrate metabolism acarbose SGLT2 inhibitors Increase glucose elimination Dapaglifozin , empaglifozin , Canaglifozin

15. INSULIN

16. TYPES OF INSULIN HUMAN INSULIN short acting. intermediate acting. biphasic(short and intermediate acting. ANALOGUE INSULIN rapid acting long acting biphasic(rapid and intermediate) Ultra long acting

17. ALTERNATE CLASSIFICATION of types Rapid acting- lispro, aspart and glulisine. Short acting- regular insulin. Intermediate acting- neutral protamine Hagedorn or isophane insulin. Long acting- glargine and detemir. Premixed/ Biphasic

18. USE of the types of insulin INSULIN TYPE USE rapid Mealtime replacement short Mealtime replacement intermediate Basal replacement Long Basal replacement Biphasic/ premixed Mealtime and basal replacement

19. PROFILES OF INSULIN TYPES TYPE ONSET OF ACTION PEAK DURATION OF ACTION Rapid acting 10-30 minutes 0.5-3hrs 3-5 hours Short acting 30 min-1 hour 2-4 hrs 4-8 hours intermediate 2-4 hours 4-10 hrs 10-18 hours Long acting Detemir 1-2 hours Glargine 1-1.5hours Detemir 4-6 hours Glargine 5hrs Detemir 5-23 hours Glargine 24 hours Premixed/ biphasic 0.5-1 hours Analogues less than 15 minutes 2-10 hours 10-18 hours

20. LONG-ACTING INSULINS 1. INSULIN GLARGINE

21. 2. INSULIN DETEMIR

22. BASAL INSULIN Background insulin. Keeps blood glucose levels stable during periods of fasting. While asleep the liver will secrete glucose into our bloodstream. basal insulin helps to keep the glucose produced levels under control .

23. Duration of action of insulin types

24. HUMAN INSULIN brands Short acting insulin-actrapid,Humulin, insuman Rapid Intermediate- insulatard Biphasic- Mixtard 30

25. ANALOGUE INSULIN brands Rapid acting- novorapid Long acting- levemir Biphasic- novomix 30

26. INSULIN OPTIMISATION AND INTESIFICATION

27. EARLY INTRODUCTION OF INSULIN Evidence of ongoing catabolism(weight loss) Symptoms of hyperglycemia are present or when fasting blood glucose levels are greater than or equal to 300mg/dl(16.7mmol/L)

28. INTERNATIONAL GUIDELINES ON INITIATION AND INTESIFICATION IN T2DM GUIDELINE INITIATION INTESIFICATION IDF Basal OD Premixed OD/BID Basal plus or Basal bolus Diabetes Australia Basal OD Premixed OD Add GLP-1 agonist( semaglutide ) Basal plus or Basal bolus Premixed bid or tid Canadian Diabetes Basal OD Premixed OD/BID Basal plus or basal bolus Premixed BID NICE Basal OD or BID Premixed OD/BID Basal plus or Basal bolus Premixed BID AACE Basal Add GLP-1 agonist

29. CONT.. INITIATION Start with basal insulin 10IU/ day or 0.1-0.2 units/kg/day. TITRATION Titrate basal insulin dose by 2 units per day until you achieve glycemic target of FBG(3.9-7.2 mmol/L) If FBG is greater than 10mmol/L increase dose by 4 units every 3 days. INTESIFICATION Add prandial insulin at main meal to get your basal plus. Add prandial insulin before each meal to get your basal bolus . Begin with 4 units

30. THE 5 M’s Match Motivate Method Monitor Modify

31. Match insulin to patient Attitudes, wishes and needs of the patient. Consider what the patient desires and also how the physician has assessed and viewed the patient. Consider frequency (does the patient not desire to take insulin often, consider once daily basal injection). Glucophenotype (which insulin is problematic either fasting or postprandial). Risk of hypoglycemia.

32. MOTIVATE PATIENT TO ACCEPT INSULIN Welcome with warmth Ask and asses complaints. Tell the truth while counseling. Explain with empathy need for insulin Reassure and ensure return

33. METHOD FOR INJECTION Use of wrong technique can create unwanted complications. Clearly demonstrate injection technique during the clinical visit. How often to change the syringes.

34. Choosing injection site 3 principal injection sites Abdomen Thighs- both front and back Upper arms Encourage rotation

35. INSULIN TECNIQUE Ensure clean injection site and hands. Abdomen, upper thighs or upper arms. 4mm pen needles and 6mm syringe needles. Encourage self inspection of injection sites and check for lipohypertrophy. Inspect and palpate injection sites at least once a year if lipohypertrophy is detected. Do not reuse needles or share insulin pens, cartridges or vials. Safe disposal of needles.

36. MONITOR Inform patient to monitor therapy Individualize monitoring technique to the patient. Insulin regime-if basal monitoring should be top notch. Risk of hypoglycemia-higher risk, monitor better. Glycemic target Ability of the patient to act on data

37. Types of monitoring Glucose monitoring Lab based Self monitoring Hb AIC-below 7% Continuous glucose monitoring system Patient reported outcomes Quality of life

38. MODIFY Regular reevaluation Dose titration Revise regime, choice of preparation or delivery device at intervals .

39. INDICATIONS FOR MODIFICATION MODIFICATION INDICATION Dose titration Mild deviation from glycemic target Newly started regime Change of preparation e.g Long to ultra long Mild deviation from glycemic target Patient unwilling to increase dose frequency Glycemic variability Change of injection frequency e.g Basal plus 1 to basal plus 2 Gross deviation from glycemic target Isolated post prandial hyperglycemia Change of regime Basal to premix Gross deviation from glycemic target Post prandial hyperglycemia

40. CASE STUDY A 56-year-old woman presents to her medical practitioner at KUTRRH with symptoms of fatigue, increased thirst, frequent urination, labored breathing and has noticed considerable weight loss. She does not get regular medical care and is unaware of any medical problems. Her family history is significant for obesity and diabetes with high blood pressure in both parents and several siblings. She is not treated with any medications. Five of her six children had a birthweight of over 9 pounds. Physical examination reveals a BMI (body mass index) of 34, blood pressure of 150/90 mm Hg, and evidence of mild peripheral neuropathy. Laboratory tests reveal a fasting blood glucose of 18mmol/l a fasting lipid panel reveals total cholesterol 264 mg/dL, triglycerides 17 mg/dL, high-density lipoproteins 43 mg/dL, and low-density lipoproteins 170 mg/dL. What kind of diabetes does this woman have and support with risk factors and criteria for diagnosis? State one additional lab test you would use to confirm diagnosis. State any complications of diabetes the lady has. Design a stepwise treatment regiment for this patient? As a pharmacist give at least two patient education you think is relevant to this patient while taking the regimen

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