Diabetes

Diabetes (T2D)

• 100 amputations a week on patients with diabetes
• 3.8m Britons have diabetes
• 600,000 of people don't know they have the disease
• 24,000 diabetic die early each year
• Chronic metabolic disease caused by insulin deficiency - the pancreas does not produce enough insulin to maintain a normal blood glucose level
• OR
• Reduced effectiveness- insulin that is produced does not work correctly suggesting a defect of insulin action at the receptor, this is known as insulin resistance.
• OR
• BOTH

Why we love Insulin

Clinical Features & Screening

• CLINICAL FEATURES
• Characterised by a raised blood glucose concentration
• Presents with acute symptoms and severe multisystem chronic complications
• Age of diagnosis >40 and onset is low
• Increased weight
• The endogenous insulin is present but insuffienct/ inefficient
• SCREENING IN THE COMMUNITY
• NHS health check - aged 40 - 7
• If exhibit symptoms of diabetes
• If have multiple risk factors - overweight, family history, ethnicity

Aetiolgy (Cause)

• RISK FACTORS
• Age - being over 40 (over 25 for south Asian). This may be because people tend to gain weight and exercise less as they get older.
• Genetics- first degree relative with the T2D. Parent with T2D increases risk to 1 in 3.
• Weight- overweight/obese. Abdomen fat increases risk because chemicals are released with can disrupt the body's cardiovascular and metabolic systems. This increases the risk of CVD and stroke.
• Ethnicity - South Asian (x6 more common), Chinese, African-Caribbean and Black African (x3 more common).
• CAUSE
• Impaired insulin secretion from pancreas and insulin resistance.
• There is a strong genetic component involved more than Type I, so there is a probability of inheriting Type II. A missense mutation is the glucagon gene has been shown to be associated with the development of type II.
• Environmental - lifestyle; excessive calorie intake and inadequate calorie expenditure, high sugar diet.

Pathophysiology Overview

• 
• As tissues are not taking up the insulin, the liver continues to produce and secrete glucose → hyperglycemia and glycosuria. Glycosuria occurs because the filtered glucose exceeds the renal threshold → glucose appears in the urine and acts as an osmotic diuretic → frequent urinations and excessive thirst which are the most common symptoms → over time the hyperglycemia damages the blood vessels → macro/microvascualr complications.
• The main cause of morbidity and mortality in diabetes in the poorly controlled hyperglycemia over a period of years. The damage is irreversible.

Pathophysiology

• Macrovascular Complications
• Macroangiopathy - large vessel disease which leads to accelerated atherosclerosis. Increases the risk of:
• IHD ( Angina/MI)
• Stroke
• CVD - 8/10 people with T2D die from CV events.
• Hypertension
• Peripheral vascular disease (PVD) - pain in legs and arms due to poor perfusion, skin ulcers and amputations
• Atherosclerosis also increases susceptibility to infection
• Microvascular Complications
• Microangiopthay - disease of fine capillary damage. This occurs due to protein glycation and small osmotic damage in small blood vessels.
• Retinopathy - can cause blindness, cataracts, glaucoma.
• Nephropathy - result in renal failure
• Neuropathy - damage to nerves
• Sensory: numbness, tingling and neuropathic pain. Autonomic: impotence, GI disturbance, postural hypotension. Damage to sympathetic/parasympathetic nerves may result in loss of normal cardiovascular reflexes.

Complications

• CHRONIC
• 'Diabetic Foot' - caused by PVD, neuropathy, increased susceptibility to infection.
• The peripheral nervous tissue becomes progressively damaged, → pain → eventual numbness in the feet →Can result in amputation.
• ACUTE
• Hyperosmolar Hyperglycemic State (HHS) - due to high glucose → dehydration and high osmolarity. Treated with sliding scale insulin and IV saline.
• Diabetic ketoacidosis - state of uncontrolled catabolism associated with insulin deficiency(usually Type 1). Breakdown of fatty acids → which ↑ ketone bodies → ↓ plasma pH. Treated with sliding scale insulin, IV saline and potassium. (as there will be electrolyte imbalances.
• Hypoglycaemia - symptomatic if glucose <202mmol/L. Treat onsite with 2 teaspoons of sugar/equivalent and hospital IM Glucagon (will ↑ conc. of glucose)

Signs and symptoms

• SYMPTOMS
• Fatigue
• Polydipsia
• Frequent urination - especially at night
• Genital itching or thrush
• Always hungry
• Blurred vision
• Sudden weight loss
• Wounds taking longer to heal

Diagnosis

• Symptoms
• Urine sample - detection of glucose
• HbA1c - gives the average blood glucose levels over the previous 2-3months.
• Glucose Tolerance Test (GTT) - 75g glucose in water. Blood glucose before and 2 hours after the glucose has been given. Fasting plasma glucose ≥7.0mmol/L
• Random plasma glucose ≥ 11.1mmol/L
• Blood pressure
• Blood lipids
• Family history

National Service Framework (NSF)

• The NSF for Diabetes sets quality standards for diabetes care. The standards aim to improve care for people with diabetes. There are 12 standards.
• Standard 4:
• Improve blood glucose control - drug choice/monitoring
• Control hypertension - reduce CVD/retinopathy/nephropathy
• Reduce raised cholesterol levels - give statin + aspirin (secondary prevention)
• Encourage smoking cessation - NRT

Treatment Options

• Diet Alone
• Diet + oral antidiabetic drugs
• Diet + oral antidiabetic drugs + Insulin
• AIMS
• Avoid hypo and hyper
• Maintain normal body weight
• Reduce risk of CVD
• Overall health through good nutrition

Diet

• STRATEGIES
• Refer to dietician
• Aim for realist BMI
• portion and proportion control
• Eat smaller, more frequent meals
• Vary content
• Adjust for any unusual activity
• DIET
• Carbohydrate - 50-60% calories. Low glycaemic index foods such as fibre (slow absorption of sugar), complex carbohydrates (polysaccharides) - pasta, potatoes, rice. Small amount of sugar allowed.
• Fat - low fat diet. <35% energy from fat. More polyunsaturated fats and low cholesterol.
• 5 Portions of fruit and veg
• Reduce salt intake
• Alcohol - ok in moderation. BUT blood glucose will ↑ and then ↓↓. Best with food and count the calories.

Insulin

• Porcine, Bovine, Human sequence insulin, recombinant human insulin
• Route - SC, IM, IV
• T2D - when other methods have failed to achieve good control.
• Temporarily in the presence of intercurrent illness or peri-operatively
• Insulin Pump - The insulin is houses inside the pump in a cartridge called a reservoir. The insulin travels into your body through a flexible tube that ends with a cannula inserted just under the skin.
• Dosage - tailor to the individual depending on motivation, comprehension, lifestyle and pattern of eating and activity.
• Aim- to keep blood glucose 4-10mmol/L and HbA1c <7.5%
• Patients can self-monitor and fine tune dose themselves.
• AE's - weigh gain, hypo, resistance, allergy, lipoatrophy/lipohypertrophy at injection site - rotate injection site.
• Rapid acting -Lispro (Humalog), Asparte (Novarapid) - works within in 15 mins. peaks 30-90misn and can last 4 hours.
• Short- acting - regular insulin. works within 30 mins. peaks 2-4hours and last 4-8 hours
• Intermediate -Isophane/NPH, Humulin I. usually taken with short acting. work within 1 hour, peak up to 7 hours, and lasts 18-24 hour.
• Long acting- Ultralente, Glargine (Lantus), Determir (Levermir) . works within 6-14 hours, peaks at 10-16hrs and last 20-24hrs.

Insulin Counselling

• Insulin absorption - to be aware of the factors influencing insulin absorption which can have an effect on blood glucose control
• Injection site - to ensure that the appropriate sites are used for injecting insulin
• Injection technique - to ensure that insulin is injected correctly
• Injection site rotation - to prevent lipohypertrophy
• Timing of injection - to optimize glycemic control
• Self-injecting - support parents and young children using self-injecting insulin

Insulin Regimen

Drug Treatment -

• Initial drug treatment-
• Treatment with a single non‑insulin blood glucose lowering therapy (monotherapy)
• Metformin OR if contra - DPP-4 Inhibitor or Pioglitazone or Sulfonylurea
• First intensification of drug treatment -
• Treatment with 2 non‑insulin blood glucose lowering therapies in combination (dual therapy)
• Metformin + DPP-Inhibitor/Pioglitazone/Sulfonylurea OR if contra - DPP-4 + Pioglitazone/Sulfonylurea or Pioglitazone + Sulfonylurea
• Second intensification of drug treatment -
• Treatment with either 3 non‑insulin blood glucose lowering therapies in combination (triple therapy) or any treatment combination containing insulin
• Metformin + DPP-4 Inhibitor + sulfonylurea or Metformin + Pioglitazone + Sulfonylurea
• + Insulin

Drug Treatment

• 
• Pie de imagen: Drug treatment if diabetes is not controlled by diet alone for 3 months
• Insulin sensitizers - bigunaide, glitazones
• Insulin secretogogues - sulphonylureas, meglitinides, DPP-4 inhibitors (gliptins)
• GI glucose absorption inhibitor - acarbose

Pharmacology and Pharmacokinetics

• BIGUANIDE (METFORMIN)
• ↓ gluconeogenesis
• ↑ peripheral utilisation of glucose
• First line treatment in obese patients as it does not increase appetite
• AE's- anorexia, N&V&D
• SULPHONYLUREAS
• ↑ Insulin secretion
• For patients who metformin is contra
• Common AE- hype
• long acting - glibenclamide - greater risk of hypo
• short acting - gliclazide, tolbutamide
• ALPHA- GLUCOSIDASE INHIBITORS (ACARBOSE)
• Inhibits intestinal glucosidase, impairing carb digestion and glucose absorption
• Small but significant effect in lowering blood glucose
• AE- GI effects; flatulence, bloating and D.
• THIAZOLIDINEDIONES (PIOGLITAZONE)
• Enhance insulin receptor sensitivity → ↓ peripheral insulin resistance
• Used alone or in combo
• Small increase risk of bladder cancer
• GLIPTINS (DPP-4 INHIBITORS)
• Inhibit DPP-4 → ↓ glucagon secretion and ↑ insulin secretion
• POST-PRANDIAL REGULATORS
• Stimulate insulin release
• Rapid onset and short duration
• Administered shortly before each meal
• Repaglinide - mono or combo with metformin
• Nateglinide - ONLY with metformin
• ↑ ketone bodies → ↓

Pharmaceutics

Pharmacoeconomics

• 10% of the NHS budget is spent of the disease
• £17b will be cost to NHS by 2025

Clinical Monitoring

Control of Hypertension

• Not all drugs are appropriate
• B-Blockers should generally be avoided - mask some symptoms of hypo
• Diuretics used with caution - Hypokalemia can impair insulin release and worsen glucose tolerance
• ACEI- usually drug of choice. Especially in presence of proteinuria and in presence of HF.

NICE Guidelines (2009 & 2015)

• RECOMMENDATIONS
• Individualized care - tailored to the individual taking into account their personal preferences, comorbidities, risks from polypharmacy, and their ability to benefit from long‑term interventions because of reduced life expectancy.
• Patient education - structured education programme meets all patient needs, eg. linguistics, culture
• Dietary advice - Individualize, Integrate and emphasize
• Blood pressure management - check annually, lifestyle advice. Repeat blood pressure measurements within:
• 1 month if blood pressure is higher than 150/90 mmHg
• 2 months if blood pressure is higher than 140/80 mmHg
• 2 months if blood pressure is higher than 130/80 mmHg and there is kidney, eye or cerebrovascular damage.
• Antiplatelet therapy - Do not offer antiplatelet therapy (aspirin or clopidogrel) for adults with type 2 diabetes without cardiovascular disease
• Blood glucose management - HbA1c measurements and targeting measure very 6 months if stable. Managed either by lifestyle and diet, or by lifestyle and diet combined with a single drug not associated with hypoglycaemia, support the person to aim for an HbA1c level of 48 mmol/mol (6.5%). For adults on a drug associated with hypoglycaemia, support the person to aim for an HbA1c level of 53 mmol/mol (7.0%).

NICE Guidelines (2009 & 2015)

• 7. Managing complications
• Gastroparesis - antiemetic not helpful but maybe erythromycin and metocloprimaide alternated.
• Neuropathy - treat neuropathic pain
• Erectile dysfunction
• Diabetic foot problems
• Eye Disease: Retinopathy - regular eye tests. Can be managed with laser treatment. Need good glucose and BP control. Refer to optometrist or ophthalmic optician. Free eye tests for diabetics.
• Kidney Disease: Nephropathy - minimize by good glucose and BP control. Characterised by microalbuminaemia. Worsens to proteinuria. ACEI slows progression.

PVD & Neuropathy

• Diabetic Foot care
• Provide advice on good basic foot care, avoid narrow fitting, tight shoes
• Keep toenails well trimmed, cut straight across
• Seek attention of chiropodist/podiatrist if appropriate
• Warn of danger signs - pins and needles
• Get cuts, burns on feet treated
• Watch for fungal infections

Driving

• Need to inform DVLA if on insulin injections not on oral medication
• If on oral medication advise patient to avoid delaying or missing meals and snacks
• If had 2 or more episodes of hypo in last 12 months inform DVLA
• Take breaks on long journeys
• Always keep hypo treatments to hand in the car
• Consider timing of meals and snacks
• Be aware of hypo signs and stop driving
• Declare diabetes when applying for motor insurance.

Medicine's Management & Optimisation

• 
• MEDICINES OPTIMISATION
• Ensure all appropriate drugs prescribed
• Best choice of anti-diabetic agent
• Correct dosage regime
• Compliance with regime
• Complications optimally managed
• Education - eg - hypo, seeking help
• Insulin - how to use, storage, test strips, monitors, diary
• Pie de imagen: If use insulin or medication to manage diabetes - entitled to free prescription with a medical exemption certificate - FP92A

Integrated Care Approach

• Signposting - Diabetes UK
•