1. Diabetes Mellitus Aaqid Akram MBChB (2013) Clinical Education Fellow

2. Objectives What is Diabetes? Prevalence + Risk Factors Presentation Diagnosis Management Complications

3. What is diabetes? Deficiency/diminished effectiveness of endogenous insulin Hyperglycaemia Deranged metabolism Complications relating to vessels. Type 1: body’s failure to produce sufficient insulin Type 2: resistance to insulin Gestational/Secondary (pancreatic/endocrine/drug/genetic)

4. Type 1 Diabetes Mellitus (T1DM) 15% of total DM population Genetic predisposition Autoimmune process Gradual destruction of beta cells of pancreas Autoantibodies may be detected by 6 months old Higher incidence in Scandinavian people (Caucasian, North Europe) Insulin Rx Susceptible to DKA

5. Type 2 Diabetes Mellitus (T2DM) Appx 85% Usually older (>30yo) Excess body weight/physical inactivity South Asian/African Impaired insulin secretion/Insulin resistance

6. Prevalence + Risk Factors 3,000,000 diagnosed/850,000 undiagnosed Increasing incidence in all age groups Obesity (Central) Physical activity Ethnicity Hx gestational DM Impaired glucose tolerance/fasting glucose PCOS FHx Low fibre/high glycaemic index diet Drug therapy Metabolic syndrome

7. Presentation Polyuria Polydipsia/Dehydration Lethargy Boils Pruritis vulvae Infections Subacute until complications Weight loss

8. Diagnosis Symptoms + raised fasting glucose (>7mmol/L) X2 raised random glucose (>11mmol/L) at least two weeks apart. Oral glucose tolerance test (OGTT) 75grams anhydrous glucose >11mmol/L after 2 hours HbA1c >48 mmol/mol

9. HbA1c - Diagnosis Glycated Hb 3 months Diagnosis in Adults only Children Suspected T1DM Symptoms <2 months High diabetes risk + acutely unwell Drugs causing rapid glucose rise Acute pancreatic damage Pregnancy Erythropoiesis Haemoglobinopathies Glycation Red cell destruction Chronic opiate use

10. Management Education Diet + Lifestyle Optimise glucose control (Medicine/Insulin) Reduce risk factors for complications CVS risk factors essential Monitoring + early intervention for complications CV disease Foot problems Eye problems Kidney problems Neuropathy

11. Management - T1DM Acutely unwell (DKA) – A+E Further Investigations: HbA1c/U+E/TFT/Cholesterol/Islet Cell Ab/C peptide/Coeliac disease Lifestyle advice: Diet Regular physical activity Smoking ID bracelet Carry Insulin

12. Insulin Therapy Patient preference: Twice daily injections: needing assistance/dislike of needles Multiple injections: well motivated/good understanding/active lifestyles Preferred device Self monitoring of blood glucose Action plan for inter-current illness/hypoglycaemic episode DAFNE Train relative/partner in glucagon administration

13. Insulin Short Acting: Rapid acting analogues: insulin aspart/lispro/glulisine 30mins/1hour/4 hours Soluble: Conventional 30mins/2 hours/8 hours Intermediate Acting: Isophane (NPH) Can be mixed with solubleinsulin (ready mixed) 3 hours/6 hours/20 hours

14. Insulin Long acting analogues: Genetically modified Glargine/detemir 2hours/plateau/24 hours Endogenous basal insulin secretion Biphasic: Mix of short + intermediate

15. Insulin Regimens Once Daily Only suitable for T2DM Intermediate/long at bedtime On oral hypoglycaemic agents Twice Daily Biphasic Pre breakfast/Pre evening meal Three meals a day Nocturnal hypo/fasting hyper Basal Bolus Intermediate/long acting Night time Rapid/short acting at meal times Flexibility Insulin Pump Fast acting Continuous (CSII) basal rate Pre meal boluses

16. Management – T2DM Acutely Unwell (HHS) – A+E Further Investigations: HbA1c/U+E/TFT/Cholesterol Lifestyle advice: Diet (high fibre / low glycaemic index) Regular physical activity Smoking DESMOND Depression screening Medical management Referral to specialist services Dietician Retinal Screening Service Foot Protection Team Diabetes Specialist (Nurse/Doctor) Renal Physicians Neurologists Vascular Surgery

17. Metformin + Insulin + sulphonylureaSulphonylurea + DPP-4/TDZSulphonylurea + exanatideTDZ + Insulin Metformin + Sulphonylurea [Normally] Rapid acting insulin secretagogue [Erratic lifestyle] DPP-4 / TDZ [risk of hypoglycaemia] Metformin (Biguanide) Lifestyle DietExercise

18. Benefits vs Risks DrugBenefits/IndicationsRisks Biguanide Reduce macrovascular complications Fewer hypoglycaemic events Does not cause weight gain GI side effects Nephrotoxic SulphonylureaMay be used as first line if CI to biguanide Hypoglycaemia Weight gain GI side effects Rapid acting insulin secretagoguesRapid onset of actionHypoglycaemia Thiazolidinediones May be used as monotherapy if CI to biguanides and sulphonylureas Unsuitable in Heart failure Risk of bladder cancer Increased risk of fractures Risk of liver failure AcarboseOnly used if other oral meds CIGI Side effects Dipeptidylpeptidase-4 inhibitors Usually third line May be used second line if risk of hypoglycaemia Hypersensitivity reactions Glucagon like peptide 1 mimetics Help if insulin therapy disliked (HGV/PCV licence) May cause significant weight loss GI side effects Pancreatitis Interaction with warfarin

19. Further Medical Management – T1DM Treat hypertension as required Calculate CVS risk factors Statins: hyperlipidaemia or high CVS RF Aspirin : >50 or high CVS RF Influenza Vaccine Pneumococcal Vaccine

20. Intercurrent Illness Sick Day Supply Box Increase frequency of blood glucose monitoring Treat underlying cause Maintain CHO intake Fluid Intake – glass every hour (3L in 24 hours) Dehydration – stop metformin DO NOT STOP INSULIN + stick test ketonuria up to x2 a day CBG<13 = continue as normal CBG 13-22 = increase by 2 units each injection CBG >22 = increase by 4 units each injection

21. Complications – Diabetic Nephropathy

22. Complications – Diabetic Retinopathy

23. Complications – Diabetic Neuropathy

24. Complications – Diabetic Foot