Diabetes Mellitus type 1 and 2 (Learning outcome 1)

Type 1 Diabetes Pathophysiology There is insulin deficiency from autoimmune destruction of pancreatic Beta cells. Patients require insulin for survival and are prone to Ketoacidosis and also weight loss. Epidemiology Usually of a juvenile onset but can occur at any stage. 0.4% of British population Onset typically<40yrs. Usually normal weight or slim. Onset dramatic. Family history less common Presence of ketones

Type 2 diabetes Pathophysiology Less insulin secretion and an increase in insulin resistance. It is associated with obesity, lack of exercise and alcohol excess. Typically progresses from impaired glucose tolerance or impaired fasting glucose. Epidemiology 4% of UK population. Onset > 40. There is genetic predisposition and associated with obesity. Greater prevalence in Asians and in the elderly Symptoms Osmotic symptoms Polyuria Polydipsia Blurred vision Tiredness Screening Caucasian>40 years age or Ethnic minority> (25yrs) and One or more of First degree relative with diabetes BMI>25 Waist> 31.5 inches (female) 35 inches Asian (male)/37incheswhite/black (male) Hypertension/previous MI or CVA Overweight female with PCOS Infection Candiasis Thrush Weight loss

History of glucose disturbance (IGT/IFG) Female with previous gestational DM Severe mental problems Diagnosis of Dm Symptoms of Hypewrglycaemia + Raised venous glucose ONCE Raised venous glucose twice OGTT If random >11.1 and if fasting >7. OGTT 11.1

States leading up to Diabetes Impaired Glucose Tolerance OGTT> 7.8 but <11.1

Impaired Fasting Glucose Fasting glucose > 6.1 but < 7

Treatment Insulin and non-insulin medication (Learning outcome 3) Anti-diabetic drugs General They should only be prescribed if the patient fails to respond to diet and exercise for 3 months. If drugs do not work then insulin can be added. If it is added to the hypoglycaemic it is normally given at bedtime as a long acting Insulin. If it replaces oral regimen then it may be given as twice dialy biphasic/isophane insulin. Insulin is associated with long term weight gain and hypoglycaemia, so in the short term it may give better control but in the long term it should be seen as the last step and weight gain will worsen the problem. Biguanides Metformin Metformin exerts its affect by decreasing gluconeogenesis and by increasing the peripheral utilisation of glucose. Only works in the presence of insulin so it is early/first line Start metformin treatment in a person who is overweight whose blood glucose is inadequately controlled by lifestyle interventions (nutrition and exercise) alone.

Continue with metformin if blood glucose control remains or and another oral glucose-lowering medication (usually a sulfonylurea) is added. Step up metformin therapy gradually over weeks to minimise risk of gastro-intestinal (GI) side effects. Review the dose of metformin if the serum creatinine exceeds 130 micromol/litre or the estimated glomerular filtration rate (eGFR) is below 45 ml/minute/1.73-m Stop the metformin if the serum creatinine exceeds 150 micromol/litre or the eGFR is below 30 ml/minute/1.73-m Insulin secretagogues (Sulfonyureas)Glicazide/long term is glibenclamide Sulfonylureas augment insulin secretion so work when beta cell function is present. Major problem is hypo episodes. Consider a sulfonylurea as an option for first-line glucose-lowering therapy if: the person is not overweight the person does not tolerate metformin (or it is contraindicated) a rapid response to therapy is required because of hyperglycaemic symptoms.

Add a sulfonylurea as second-line therapy when blood glucose control remains or becomes inadequate (see 1.3.1) with metformin. Continue with a sulfonylurea if blood glucose control remains or becomes inadequate (see 1.3.1) and another oral glucose-lowering medication is added

Thiazolidinediones (glitazones) They transcribe insulin sensitive genes and reduce peripheral insulkin resisatnce leading to reduction of blood glucose sugars. If glucose concentrations are not adequately controlled (to HbA1c < 7.5% or other higher level agreed with the individual), consider, adding a thiazolidinedione to: the combination of metformin and a sulfonylurea if human insulin is likely to be unacceptable or ineffective because of employment, social or recreational. a sulfonylurea if metformin is not tolerated metformin as an alternative to a sulfonylurea where the persons job or other issues make the risk of hypoglycaemia with sulfonylureas particularly significant. Warn a person prescribed a thiazolidinedione about the possibility of significant oedema and advise on the action to take if it develops. Do not commence or continue a thiazolidinedione in people who have evidence of heart failure, or who are at higher risk of fracture

Gliptins GLP-1 enhancers (Liraglutide and Exenatide) Bind to and activate the GLP-1 receptor so increase insulin secretion/supress glucagon and slow gastric emptying. Promote weight loss. Consider exenatide as an option only if all the following apply for the individual: a body mass index over 35.0 kg/m in those of European descent specific problems of a psychological, biochemical or physical nature arising from high body weight inadequate blood glucose control (HbA1c 7.5%) with conventional oral agents after a trial of metformin and sulfonylurea other high-cost medication, such as a thiazolidinedione or insulin injection therapy, would otherwise be started. Continue exenatide therapy only if a beneficial metabolic response (at least 1.0 percentage point HbA1c reduction in 6 months and a weight loss of at least 5% at 1 year) occurs and is maintained. Liraglutide is mpre potent then exenatide however it is excreted by the kidney so be careful in CKD. Caustion using exenatide when egfr 30-50. However stop liraglutide at 60.

Insulin regimes If using basal/pre mixed insulin then combine with metformin and/or sulphonylurea howerver review if there are frequent hypoglyacaemias Insulin alone When no other measures have led to adequate control Hba1c<7.5. structured education Dose titration to target continuing telephone support dietary understanding frequent self-monitoring management of hypoglycaemia

Management of acute changes in plasma glucose control support from an appropriately trained and experienced healthcare professional. Start off with isophane insulin with a peak of 4-12hours. It is cheap and favoured by NICE. Start offtaking it at bed time or twice daily. Alternative long acting insulin glargine if they lead a busy life and cannot bare hypos. Or need a carer. Consider bi daily pre mix analogues when Hba1c is > 9 and Monitor all twice daily for need of post prandial insulin.

Patient education(Learning outcomes 6) Offer structured education to every person and/or their carer at and around the time of diagnosis, with annual reinforcement and review. Inform people and their carers that structured education is an integral part of diabetes care. Select a patient-education programme that meets the criteria laid down by the Department of Health and Diabetes UK Patient Education Working Group. Treatment should always be based on a patient centred approach with education and diet as the first steps. Offer structured education to every person and/or their carer at and around Provide individualised and ongoing nutritional advice from a healthcare professional with specific expertise and competencies in nutrition. When setting a target glycated haemoglobin (HbA1c): involve the person in decisions about their individual HbA1c target level, which may be above that of 6.5% set for people with type 2 diabetes in general encourage the person to maintain their individual target unless the inform a person with a higher HbA1c that any reduction in HbA1c towards the agreed target is advantageous to future health Measure the individuals HbA1c levels at: 26-monthly intervals (tailored to individual needs) until the blood glucose level is stable on unchanging therapy; use a measurement made at an interval of less than 3 months as a indicator of direction of change, rather than as a new steady state 6-monthly intervals once the blood glucose level and blood glucose-lowering therapy are stable Offer self-monitoring of plasma glucose to a person newly diagnosed with type 2 diabetes only as an integral part of his or her self-management education Discuss its purpose and agree how it should be interpreted and acted upon. Dietary advice Emphasise advice on healthy balanced eating that is applicable to the general population when providing advice to people with type 2 diabetes. Encourage high-fibre, low-glycaemic-index sources of carbohydrate in the diet, such as fruit, vegetables, wholegrains and pulses; include low-fat dairy products and oily fish; and control the intake of foods containing saturated and trans fatty acids). Integrate dietary advice with a personalised diabetes management plan, including other aspects of lifestyle modification, such as increasing physical activity and losing weight. Target, for people who are overweight, an initial body weight loss of 510%, while remembering that lesser degrees of weight loss may still be of benefit and that larger degrees of weight loss in the longer term will have advantageous metabolic impact. Individualise recommendations for carbohydrate and alcohol

intake, and meal patterns. Reducing the risk of hypoglycaemia should be a particular aim for a person using insulin or an insulin secretagogue. Advise individuals that limited substitution of sucrose-containing foods for other carbohydrate in the meal plan is allowable, but that care should be taken to avoid excess energy intake.

Learning object 11 Diabetes as a risk factor in cardiovascular disease

Cardiovascular risk estimation Consider a person to be at high premature cardiovascular risk for his or her age unless he or she: is not overweight, tailoring this with an assessment of bodyweight-associated risk according to ethnic group is normotensive (< 140/80 mmHg in the absence of antihypertensive therapy) does not have microalbuminuria does not smoke does not have a high-risk lipid profile has no history of cardiovascular disease and has no family history of cardiovascular disease.

Blood pressure therapy Measure blood pressure at least annually in a person without previously diagnosed hypertension or renal disease. Offer and reinforce preventive lifestyle advice. Add medications if lifestyle advice does not reduce blood pressure to below 140/80 mmHg (below 130/80 mmHg if there is kidney, eye or cerebrovascular damage) First-line blood-pressure-lowering therapy should be a once-daily (ACE) inhibitor. First-line blood-pressure-lowering therapy for a person of African-Caribbean descent should be an ACE inhibitor plus either a diuretic or a generic calcium-channel antagonist A calcium-channel blocker should be the first-line blood-pressure lowering therapy for a woman becoming pregnant.

Management of blood lipid levels For a person who is 40 years old or over: initiate therapy with generic simvastatin (to 40 mg) or a statin if the cardiovascular risk from non-hyperglycaemia-related factors is low, assess cardiovascular risk initiate simvastatin therapy (to 40 mg), or a statin of similar efficacy and cost, if the cardiovascular risk exceeds 20% over 10 years For a person who is under 40 years old, consider initiating generic simvastatin therapy (to 40 mg)

Increase the dose of simvastatin, in anyone initiated on simvastatin in line with the above recommendations, to 80 mg daily unless total cholesterol level is below 4.0 mmol/litre

Learning objective 2 emergencies Hypoglycaemia Definition Biochemical: Glucose value <3.00mmol/l Clinically: whipples triad: low plasma glucose, symptoms associated with low glucose and resolution of symptoms when hypo corrected. Symptoms Autonomic: sweat, tremor, palpitation Neuroglycopenic: Drowsiness, confusion, slurring Causes: Strict control/unawareness/exercise/hot weather Management

Diabetic ketoacidosis Glucose is produced from breaking down glycogen and converting lactate,glycerol and amino acids to glucose(gluconeogenesis) If there is insulin deficiency, Glycogenolysis and gkuconeogensis raise glucose in blood continuously. LEADS TO OSMOTIC DIURESIS AND DEHYDRATION Proteolysis and lipolysis occur to produce glucose and ketones Ketogenesis occurs causing METABOLIC ACIDOSIS AND KETONURIA.

Definition Hyperglycaemia(>15)/ Metabolic acidosis/Ketonuria Symptoms Thirst/weight loss/nausea/vomiting/abdo pain/headache/confusion/coma Signs Hypotensive/low volume dehydrated tachycardic pulse/kussmaul breathing/pear drop breath Investigations
Blood glucose (>15 mmol/L) Urinalysis U&Es (dehydration)-low sodium, if it is high then secere dehydration ABG (severe metabolic acidosis) Cardiac monitor (t wave changes from hypokalaemia)

Step wise approach

Check glucose if it is greater than 20 need to give 4-8 units insulin IV.Bloods taken. Start insulin pump at 6n/hour, Expect drop of 5mmol/l/hr. If not increase dose. If Glucose drops below 10 then pump drops to 3 units and contniue until food by mouth and subcut injections. then stop

Glycaemic control

Fluid replacement

1L of 0.9% saline. then 1l /hr>1l/2hr>1l>4hr. and use 5% dextrose when blood sugar < 10mmol/l

Dont add to first bag monitor urine output and only when >30ml/h If <3 then give 40mmol check U&Es hourly.

Potassium