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 ORReduced 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

69d09d3a-ec84-40e7-be65-243e58bdfdd9 (image/jpg)

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.

0a4e7e42-8137-4dd1-8b74-12d954bdc9f8 (image/png)

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 ComplicationsMicroangiopthay - 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

a295cd2a-9043-42e3-abd5-cab365d2b9f7 (image/png)

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 SulfonylureaFirst 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 insulinMetformin + DPP-4 Inhibitor + sulfonylurea or Metformin + Pioglitazone + Sulfonylurea + Insulin

Drug Treatment

02506369-b58d-470a-ba74-679a69b2067c (image/png)

Caption: : Drug treatment if diabetes is not controlled by diet alone for 3 months

Insulin sensitizers - bigunaide, glitazonesInsulin 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 secretionPOST-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

09b5e664-e6ff-4c4e-9864-01303c6ab875 (image/png)

Pharmacoeconomics

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

Clinical Monitoring

8d0c72aa-50d2-4610-99a0-a87fd8f9434c (image/png)

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%).

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.  

NICE Guidelines (2009 & 2015)

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

3c020db1-0ebf-4de3-a819-4482612cafda (image/png)

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 

Caption: : If use insulin or medication to manage diabetes - entitled to free prescription with a medical exemption certificate - FP92A

Signposting - Diabetes UK

Integrated Care Approach

Integrated Care Approach

9799233c-7b94-48bf-968a-f52bede708e0 (image/png)