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Diabetes and Endocrine revision cases Dr Marie Freel Senior Lecturer in Endocrinology Friday 5 th October 2012

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Presentation on theme: "Diabetes and Endocrine revision cases Dr Marie Freel Senior Lecturer in Endocrinology Friday 5 th October 2012"— Presentation transcript:

1 Diabetes and Endocrine revision cases Dr Marie Freel Senior Lecturer in Endocrinology Friday 5 th October 2012

2 Lecture plan Diabetes –Management of type 1 and type 2 Diabetes –Diabetic complications –Management of medical emergencies resulting from Diabetes Endocrinology –Adrenal disorders –Thyroid disorders

3 Case 1 19 year old medical student –Polyuria/polydipsia –Weight loss Blood glucose (random) –16 mmol/L Questions: Is diagnosis secure? Long term treatment strategy?

4 Algorithm for diagnosis of diabetes- WHO Classical symptoms plus one of: Random plasma glucose  11.1mmol/L Fasting plasma glucose  7.0 mmol/L 2 hour post OGTT plasma glucose  11.1mmol/L HbA1c >6.5% (48 mmol/mol) since 2011 If no symptoms, need 2 abnormal plasma samples

5 Management of type 1 diabetes Always requires insulin! Type of insulin depends on individual (eg. age/intelligence/lifestyle/motivation) Measure control using glycosylated haemoglobin (HbA1c) Close correlation with microvascular complications Units changed from % to mmol/mol in 2011 Aim for <58.5 mmol/mol (<7.5%)

6 Complications of diabetes Microvascular –Retinopathy –Nephropathy –Neuropathy Macrovascular –Ischaemic heart disease –Cerebrovascular disease –Peripheral vascular disease ADDRESS OTHER RISK FACTORS GOOD GLYCAEMIC CONTROL

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8 Diabetic retinopathy Increased risk with long duration and poor control In child with age onset of 11y, average time to retinopathy is 9y and 14y to established changes

9 Diabetic retinopathy Fundus after retinal laser photocoagulation for proliferative retinopathy Can reduce visual fields by up to 50% and fall below DVLA standards for driving

10 Microvascular complications of diabetes Nephropathy (26% after 10y, 51% after 20y) –commonest cause of renal failure in UK –Microalbuminuria ( mg/24h) first sign –Can progress to proteinuria (>300 mg/24h), indicates irreversible renal damage –ACEi is treatment of choice Neuropathy –Peripheral neuropathy –Autonomic neuropathy –Mononeuritis multiplex –Annual assessment of vibration and light touch

11 Preparations of insulin: Human insulins –Soluble, short acting eg. actrapid –Intermediate acting eg. insulatard Analogue insulins –Recombinant DNA technology –Flexible –Short acting: novorapid, humalog –Long acting: glargine, detemir Mixes –Short (30%) + Intermediate insulin(70%) –eg. Novomix 30, Humalog Mix 25

12 The Holy Grail

13 Insulin regimes Twice daily mixed insulins –2/3 dose in morning, 1/3 in evening –Only 2 injections –But inflexible, need regular meals/snacks Multiple daily injections –requires long acting basal insulin (once or twice daily) –Bolus injections of short acting insulin with meals –More flexible –But >4 injections/day

14 CSII Use of a pump providing continual sc administration of soluble insulin More convenient for some Requires motivation and understanding of CHO counting Expensive: »Poor control »Recurrent hypoglycaemia

15 Case 2 56 y man Overweight (BMI 36) Newly diagnosed Type 2 Diabetes (HbA1c 8.9%) BP 156/92 mm/Hg What advice would you give him? What medications (if any) would you start?

16 Newly diagnosed Type 2 diabetes Lifestyle advice Screen for micro and macrovascular complications Consider: statin/antihypertensive/aspirin Pharmacological management of diabetes?

17 Metformin Acts by inhibiting gluconeogenesis in the liver and enhance peripheral glucose uptake No direct effects on beta cell function Reduction in HbA1c of 1-2% Treatment of choice in obese type 2 DM

18 Metformin – side effects and contraindications Lactic Acidosis : –metformin reduces excretion of lactate –Especially in renal (excreted unchanged by kidneys),hepatic or cardiac failure Renal failure with radiological contrast GI upset – can be reduced with dose titration

19 Sulphonylureas Insulin secretagogues –Stimulate beta cell to secrete insulin –Increase basal and post-prandial insulin secretion Need some residual beta cell function No effect on insulin sensitivity

20 Sulphonylureas Gliclazide is most commonly used Hypoglycaemia (elderly, renal failure) Weight gain

21 Case 2 (continued) Despite therapy with maximal dose metformin and gliclazide, glycaemic control continues to deteriorate What do you do now?

22 Thiazolidinediones Pioglitazone is only one still licensed Can be used as monotherapy or in combination with other agents (more commonly)

23 Thiazolidinediones – mechanism of action Increase insulin sensitivity in peripheral organs Act on nuclear receptors in adipocytes – peroxisome proliferator activated-receptor-gamma (PPAR-γ) Activation of PPAR-γ = increased transcription of insulin sensitive genes Leads to improved insulin sensitivity in skeletal muscle and reduced hepatic glucose production Possible CV benefit

24 Thiazolidinediones – side effects and contraindications Weight gain/oedema Contraindicated in cardiac failure Deranged LFTs (occasionally ) Increased fracture risk

25 Novel treatments in Type 2 DM- The Incretins

26 food ingestion increase insulin secretion suppress glucagon secretion slow gastric emptying promote satiety Glucagon like peptide-1 (GLP-1) DPP-4 Breakdown The Incretin Effect

27 New agents in Type 2 DM Gut derived incretin peptides (GIP, GLP-1) potentiate glucose-dependent insulin secretion 2 drug classes recently developed to prolong action of GLP-1: GLP-1 receptor analogue (exenatide, liraglutide) DPP-IV inhibitor to prevent degradation of GLP-1 (sitagliptin)

28 GLP-1 agonists: Exenatide/Liraglutide Licensed as adjunct therapy in patients with poorly controlled type 2 DM Administered by subcutaneous injections Advantages: weight loss, insulin avoidance Disadvantages: cost, injections, GI side effects, ? risk of pancreatitis

29 DPP IV inhibitors:Sitagliptin/Vildagliptin Adjunct treatment (with metformin or glitazone) Oral agent taken once or twice daily Well tolerated, weight neutral

30 Antihyperglycemic therapy in type 2 diabetes: general recommendations. Inzucchi S E et al. Dia Care 2012;35: Copyright © 2011 American Diabetes Association, Inc.

31 Case presentation 3: 22 year old female, poorly controlled type 1 DM ‘generally unwell’, vomiting and abdominal pain Home BMs >20

32 Case presentation: On examination: » Dry & drowsy BP 95/60 RR 28 »Urine: glucose +++ ketones +++ »BM 30 ABG (air): H+ 74 pO 2 14 pCO HCO 3 7 UE: Na 142 K4.9 Cl 95 Ur 11 Cr 84 Glucose 29

33 Diabetic Ketoacidosis (DKA): Definition Metabolic acidosis (H + >45) Increased anion gap Bicarbonate <15mmol/l Hyperglycaemia >13.9 mmol/l Ketosis (++)

34 DKA: Epidemiology Annual incidence (European) 1-5% of patients with type 1 diabetes Can occur in type 2 diabetes More common in young and in females Mortality declining (usually due to underlying illness than DKA itself)

35 DKA Causes –Infection19-56% –reduction in insulin doses15-41% –First presentation of diabetes10-22% –MI / CVA3-6% –Surgery –Pancreatitis –Steroid therapy

36 DKA-pathogenesis Combination of insulin deficiency and  counter-regulatory hormones: Hyperglycaemia »  gluconeogenesis/glycogenolysis Acidosis/Ketosis »  lipolysis Fluid and electrolyte losses »Osmotic diuresis »Loss of Na/K/Mg

37 DKA-Management Initial investigations: ABCs BM/urine ketones Bloods – include venous HCO3 ABG Infection screen CXR/ECG

38 DKA - Treatment Correct acidosis/hyperglycaemia/fluid & electrolyte disturbances IV insulin: »Soluble human insulin (1U/ml) »Initial bolus in severe cases ( if K allows) »IV sliding scale

39 DKA Care pathway- 0-4 hours Check blood glucose hourly (BM)Check blood glucose hourly (BM) Reduce infusion to 3 units/hour once BM<14Reduce infusion to 3 units/hour once BM<14 Once BM <14, commence 10% dextrose infusion to maintain BM 9-14 mmol/lOnce BM <14, commence 10% dextrose infusion to maintain BM 9-14 mmol/l

40 DKA Care pathway- 4 hours- discharge

41 DKA-treatment Average deficit in DKA is 10% of body weight in litres IV 0.9% sodium chloride one litre immediately in A&E Aim to replace fluid deficit over 24 –48 hours 1 litre 0.9%NaCl over one hour 1 litre 0.9% NaCl over 2 hours 1 litre 0.9% NaCl over 4 hours

42 DKA - Treatment IV Potassium: – serum K may be normal or increased but total body K low and will fall with insulin –add KCl after 1L, aim for 4-5 mmol/L plasma KKCl (mmol/L) > <3.540

43 DKA- Treatment IV Bicarbonate: –controversial, probably no (if pH >7) –can worsen hypokalaemia and cause intracellular acidosis NG tube Urinary catheter Antibiotics LMW heparin

44 DKA - aftercare Regular monitoring: –UE/ glucose every 1-2h – regular ABG usually unnecessary –Resolution: glu 18, pH>7.3 Convert back to sc insulin: –24 h after resolution of ketosis –Eating & drinking –STOP SLIDING SCALE MINS AFTER GIVING SC INSULIN

45 DKA- Prevention Contact diabetes team Reinforce sick day rules: »Never stop insulin, may need to increase dose even if food intake poor »If unable to take solids take liquid CHO eg. lucozade »Monitor for ketones and increase frequency of BM monitoring

46 Case 5 21 year old female ‘unwell’ for few months Weight loss Amenorrhoea Acutely unwell over past 48 hours with vomiting and diarrhoea On examination: Dark skin Dehydrated Hypotensive  Na  K

47 Adrenal insufficiency Inadequate adrenocortical function Primary insufficiency –Addison’s disease –Congenital Adrenal Hyperplasia (CAH) –Adrenal TB/malignancy Secondary insufficiency –Due to lack of ACTH stimulation –Iatrogenic (excess exogenous steroid) –Pituitary/hypothalamic disorders

48 Addison’s Disease Commonest cause of primary adrenal insufficiency cases/million per year Autoimmune destruction of adrenal cortex –>90% destroyed before symptomatic –Autoantibodies positive in 70% Associated with other autoimmune diseases –Type 1 DM, autoimmune thyroid disease, pernicious anaemia

49 Clinical Features of Addison’s Disease Anorexia, weight loss Fatigue/lethargy Dizziness and low BP Abdominal pain, vomiting, diarrhoea Skin pigmentation

50 Diagnosis of adrenal insufficiency ‘Suspicious biochemistry’  Na,  K hypoglycaemia SHORT SYNACTHEN TEST Measure plasma cortisol before and 30 minutes after iv ACTH injection Normal: baseline >250nmol/L, post ACTH >480 ACTH levels Should be  (causes skin pigmentation)

51 Negative feedback loop + +

52 Diagnosis of adrenal insufficiency ‘Suspicious biochemistry’  Na,  K hypoglycaemia SHORT SYNACTHEN TEST Measure plasma cortisol before and 30 minutes after iv ACTH injection Normal: baseline >250nmol/L, post ACTH >480 ACTH levels Should be  (causes skin pigmentation) Renin/aldosterone levels   renin  aldosterone Adrenal autoantibodies

53 Management of adrenal insufficiency Do not delay treatment to confirm diagnosis Hydrocortisone as cortisol replacement If unwell, give intravenously first Usually 15-30mg daily in divided doses Try to mimic diurnal rhythm Fludrocortisone as aldosterone replacement Careful monitoring of BP and K Need education ‘sick day rules’ Cannot stop suddenly Need to wear identification

54 Alert to long term steroid treatment

55 Outcome of case 5 Early morning cortisol 75nmol/L, increasing to 150nmol/L after synacthen Plasma ACTH significantly elevated Adrenal antibodies positive On hydrocortisone 30mg daily and fludrocortisone Better: Weight increased Periods restarted Skin lighter

56 Iatrogenic Adrenal suppression Long term steroid treatment suppresses ACTH production (negative feedback to anterior pituitary) Atrophy of adrenal cortex Implications: Unable to respond to stress (illness/surgery) Need extra doses of steroid when ill/surgical procedure Cannot stop suddenly Gradual withdrawal of steroid therapy if >4-6 weeks


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