RED Endocrine 3 and 4 Learning objectives PDF

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Summary

1. Define diabetes mellitus, distinguishing between Type 1 and Type 2 (causes,prevalence, key features). Outline secondary causes of diabetes. Brieflydescribe the processes that lead to the presentation of common signs andsymptoms of diabetes.Diabetes Mellitus is a Chronic metabolic disorder charact...

Description

1. Define diabetes mellitus, distinguishing between Type 1 and Type 2 (causes, prevalence, key features). Outline secondary causes of diabetes. Briefly describe the processes that lead to the presentation of common signs and symptoms of diabetes. Diabetes Mellitus is a Chronic metabolic disorder characterised by hyperglycaemia, caused by and Insulin deficiency (Type 1) or Impaired b-cell function and/ or loss of insulin sensitivity (insulin resistance) (Type 2)

Type 1 causes and prevalence: • •

Autoimmune - progressive destruction of islet b-cells ~0.6% of UK population

Key features of Type 1 DM:

• • • • • • • •

Rapid onset Onset usually < 40 years No complications (secondary) at diagnosis Weight – normal or loss Metabolic acidosis- Nausea and vomiting, breathlessness and abdominal pain Ketoacidosis- acetone breathe Osmotic diuresis- frequently passing urine, dehydration and thrist susceptibility genes & environmental triggers: viruses, toxins

Type 2 causes and prevalence:

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Relative insulin deficiency (impaired b-cell function) AND/ OR insulin resistance ~5.4% of UK population

Key features of Type 2 DM: 

complications (secondary)

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altered mental status

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Onset usually > 40 years

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Gradual onset

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Complications (secondary) present in 25% of patients at time of diagnosis

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Usually overweight

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No ketones in urine

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susceptibility genes & environmental triggers reduced physical activity increased calorie consumption

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usually asymptomatic

secondary causes of DM: 

Endocrine- Cushing’s, acromegaly, phaeochromocytoma

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Pancreatic disease- chronic pancreatitis, surgery, cystic fibrosis, tumour

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Genetic disorders- Down’s syndrome, Prader-Willi, etc

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Drug-induced - steroids, beta-blockers, diuretics

Common signs and symptoms of diabetes : 

Glycosuria- Presence of glucose in the urine . Renal tubule will reabsorb almost all the glucose present in the normal glomerular filtrate but when the plasma glucose is elevated, amount of glucose in the glomerular filtrate exceeds the capacity of the renal tubule to reabsorb it therefore remains in the filtrate.

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Polyuria- Due to osmotic diuresis, there is a high osmolality in the urine due to the presence of glucose leading to reduced water reabsorption

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Thirst- excessive urine production leading to dehydration and increased plasma osmolality ( due to the hyperglycaemia) leads to thirst

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fatigue & malaise- poor glucose utilisation due to lack of insulin action

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blurred vision- high levels of glucose in the lens changes the refractive index

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infections (e.g. candidiasis)- the presence of glucose in the urine is a favourable environment for infections as it is a food and energy source

2. Outline the principal methods of treatment of Type 1 and Type 2 diabetes (including lifestyle recommendations, the major classes of drug and their mode of action). Describe the techniques available for assessing the degree of glycaemic control achieved. Aims of Management

    

Alleviate symptoms (thirst, polyuria, tiredness) Normalise metabolic parameters – glucose, lipids etc. Improve quality of life Educate Prevent long-term/ secondary complications

– microvascular – affects the capillaries- small blood vessles – macrovascular- affects medium to large blood vessels

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Healthy diet - Regular meals - Low fat, sugar and salt intake - High in fibre and low glycaemic index food such as lentils, wholegrain bread, rye, pasta, porridge and bran cereals - Alcohol awareness- max 14 units a week  weight loss if necessary, 5-10% of BW if obese so 30+ as BMI.  Lifestyle - Exercise (improve insulin sensitivity, weight loss) – 30 mins on at least 5 days of the week - Smoking cessation (decrease CV risk) Type 1 DM: - Treat with insulin - Sources of insulin are animal ( bovine ( cows) and porcine ( pigs) ) - Human- get semi synthetic- modified from porcine or get recombinant from E.coli or yeast cells - Injection routes: sc or iv - Sc is more convenient and the usual route whereas Iv offers finer control in serious illness, in ketoacidosis and in surgery ( post op) Type 2 DM: • •

Diet 10-20%, drugs (80-90%, ~ 20% insulin) Drugs include:

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Biguanides metformin - MOA not clear, activate AMP kinase? ↓ gluconeogenesis ↑ glucose utilisation

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Sulphonylureas -glicazide tolbutamide glibenclamide – stimulates insulin secretion via blockage of islet Beta cells ATP sensitive K+ channels. Get depolarisation and more insulin secretion. But get weight gain and hypos

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Prandial glucose regulators- rapid-acting insulin secretagogues (also known as meglitinides) repaglinide nateglinide – same MOA as sulphonylureas

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Thiazolinediones (also known as glitazones) pioglitazone (rosiglitazone) - PPARJagonists “insulin sensitizers” helps the body to use insulin

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Alpha-glucosidase inhibitors -acarbose -Delays digestion & absorption of starch and sucrose by breaking CHO chains to delay the absorption

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GLP1-mimetics incretin mimetics - exenatide liraglutide - Promote insulin release in anticipation of high blood glucose levels after consuming a meal, reduce glucagon secretion, reduce gastric emptying, promote satiety ( feeling of being full) and reduce glucose production (liver)

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DPP-4 inhibitors incretin enhancers (also known as gliptins)- sitagliptin vildagliptin saxagliptin RISK OF HYPO. Promote insulin release, reduce glucagon secretion , reduce gastric emptying, promote satiety and reduce glucose production (liver). Also blocks degradation of incretins

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Sodium-glucose transporter 2 (SGLT-2) inhibitor -dapagliflozin canagliflozin empagliflozin - Inhibit renal glucose reabsorption - reversibly inhibit SGLT-2 in renal PCT to reduce glucose reabsorption and increase urinary glucose excretion  decrease in blood glucose

3. Define hypoglycaemia, how this might develop in a patient with diabetes and state the physical signs and subjective symptoms (autonomic, neuroglycopaenic) associated with a “hypo”.

Acute complication insulin overdose, excessive exercise and inadequate CHO intake Type 1 DM Type 2 DM sulphonylureas (elderly), hepatic or renal disease, some drugs signs and symptoms•

Palpitation, tremors, sweating, anxiety - counter-regulatory activity of SNS • Loss of concentration, slurred speech, behaviour/ mood changes, seizures, loss of consciousness - glucose deficiency in brain(neuroglycopaenia or neuroglucopaenia)

4. State how diabetic ketoacidosis may arise in untreated or poorly-controlled type 1 diabetes. Describe the effects of insulin deficiency on fat, protein and carbohydrate metabolism and fluid balance. Diabetic ketoacidosis occurs when there is hyperglycaemia & metabolic acidosis (ketosis) due to : • Omission or reduction in insulin dose • Illness/ infection • Emotional upset, particularly in adolescence • Menstruation/ pregnancy ketosis • Rare syndromes of insulin resistance In T1DM there is autoimmune destruction of islet b-cells therefore little/ no insulin is produced causing a lack of insulin action. Therefore, hepatic ketogenesis occurs which is normally inhibited by insulin. Ketogenesis is the synthesis of ketone bodies from fatty acid breakdown products (from metabolism of FFA) to form energy as the body is unable to use up glucose. Acidic ketones (acetoacetate, b-hydroxybutyrate) decrease blood pH 2 x acetyl CoA = acetoacetate Beta-hydroxybutyrate & acetone ( acidic molecules causing metabolic acidosis) Ketone bodies increase protein breakdown to release amino acids in the skeletal muscle and there is increased lipolysis to generate fatty acids and glycerol together these waste products allow increased gluconeogenesis to occur in the liver whilst glycogen breakdown is also happening. The increase in glucose leads to osmotic duresis causing polyuria, thirst and dehydration whilst the increased level of ketones causes metabolic acidosis ( N and V, breathlessness and abdominal pain). In worse circumstances the osmotic diuresis can lead to Dehydration,

peripheral circulatory failure, renal failure and low cerebral blood flow. The metabolic acidosis causes CNS depression and diabetic coma hence death occurs in this situation.

5. State the major long-term / secondary complications of diabetes, whether they are categorised as microvascular or macrovascular, and how these complications may be influenced by key factors (such as duration of diabetes, degree of glycaemic control) Long term ( secondary) complications of DM type 1 and 2. Development of complications:  Duration of DM  Glycaemic control- NEED GOOD GLYCAEMIC CONTROL  Other risk factors such as smoking, genetics, alcohol Microvascular: Retinopathy (eye disease) • • • • • • •

Commonest cause of blindness < 65 years 95% of patients after 20 years of diabetes Background (simple) – microaneurysm ( small bulge within the capillaries), haemorrhages, exudates when lipoproteins leak out of the capillaries Pre-proliferative- get regions of ischemia- “Cotton-wool spots” indicate regions of ischaemia (blurring of vision) Proliferative- formation of new blood vessels to feed the blood deficient areasimpairment of vision get floaters or clouding or loss of vision Maculopathy – when the macula is affected with lipid deposits- Central vision deteriorates - blurring, distorting vision Advanced retinopathy- severe loss of vision

Nephropathy (kidney disease)

• • •

1 in 4 patients on dialysis programmes High cardiovascular risk Get a natural progression down these stages

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Early get microalbuminuria Later get proteinuria, ↑ BP, ↓ eGFR Advanced get End-stage renal disease

Neuropathy (nerve damage)

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Loss of sensation – Need foot review to test sensation and check for ulcers and ischaemia

Macrovascuar: Accelerated atherosclerosis In type 1- due to poor glycaemic control In type2- Due to poor glycaemic control, genetice predisposition and metabolic syndrome Metabolic syndrome 

Due to being overweight or obese

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Dyslipidaemia

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Hypertension ( High LDL and HIGH triglycerides)

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Abdominal obesity

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Coagulation abnormalities

• Cardiovascular disease ( ischaemic heart disease) o Leading cause of death in diabetes o MI increases the risk of heart failure and rhythm disturbamces • Cerebral vascular disease (stroke) o FATAL o CONTROL HYPERTENSION • Peripheral vascular disease • Risk of amputation • Risk of ulceration...