Lecture 5.2 - Diabetes Mellitus.pdf

Diabetes Mellitus - definition: ◦A serious, long-term (or "chronic") condition that occurs when raised levels of blood glucose (hyperglycaemia) occur because the body cannot produce any or enough of the hormone insulin or cannot effectively use the insulin it produces - if left untreat...

Diabetes Mellitus - definition: ◦A serious, long-term (or "chronic") condition that occurs when raised levels of blood glucose (hyperglycaemia) occur because the body cannot produce any or enough of the hormone insulin or cannot effectively use the insulin it produces - if left untreated, can have a significant affect on body organs e.g. eyes, kidneys, brain ◦A group of heterogenous chronic metabolic disorders clinically characterised by hyperglycaemia. Diabetes Mellitus - classification: ◦Type 1 diabetes (5-10%): ‣ Autoimmune pancreatic beta-cell destruction ‣ Absolute insulin deficiency -> beta-cells cannot produce insulin ◦Type 2 diabetes - around 90% of patients: ‣ Progressive loss of beta-cell insulin secretion ‣ Insulin resistance -> body doesn't respond to insulin ◦Gestational diabetes mellitus (GDM): ‣ Diabetes diagnosed 2nd-3rd trimester pregnancy (caused by elevated blood sugar levels; insulin resistance) ‣ No clear overt diabetes prior to gestation ‣ Typically resolved after pregnancy, but some people can go on to have type 2 diabetes ◦Specific types of diabetes due to other causes: ‣ Monogenic diabetes syndromes (e.g. maturity-onset diabetes of the young, MODY) ‣ Diseases of the exocrine pancreas (e.g. cystic fibrosis, pancreatitis) ‣ Drug/chemical-induced diabetes (e.g. with glucocorticoids - work in similar ways to cortisol) Type 1 diabetes (T1DM) - aetiology: ◦Chronic autoimmune destruction of the insulin-producing pancreatic beta cells Model of stages of T1DM: T1DM - autoimmune markers: ◦Autoimmune markers of T1DM include: ‣ Islet cell autoantibodies (ICA) ‣ Autoantibodies to GAD (GAD5; glutamic acid decarboxylase)  ‣ Autoantibodies to insulin, the tyrosine phosphatases IA-2 and IA-2b, and zinc transporter 8 (ZnT8) ◦T1DM is defined by the presence of one or more of these autoimmune markers ‣ Autoantibody tests have their lowest false negative rate at the time of diagnosis. The false negative rate rises after this T1DM - common features: ◦Most common form of diabetes in childhood and adolescence (90% diagnosed under the age of 30 years), but it can occur at any age (even in the 8th/9th decade of life). ◦Majority of people with T1DM are lean, but obesity should not preclude testing for type 1 diabetes. ◦People with T1DM are prone to other autoimmune disorders: ‣ E.g. Hashimoto thyroiditis, Graves' disease, Coeliac disease, Addison disease, Vitiligo, Autoimmune hepatitis, Myasthenia gravis and Pernicious anaemia T1DM - typical presentation: ◦Presenting symptoms (usually presenting with rapid onset - usually weeks) of: ‣ Polyuria (excess urine production) - volume of urine ‣ Polydipsia (increased thirst - drinking a lot of water/fluids due to excess water loss) ◦Weight loss (fat and protein are catabolised by tissues due to lack of insulin) ◦Children and adolescents often present with diabetic ketoacidosis (DKA) as the first manifestation of the disease. T1DM - DKA (diabetic ketoacidosis): ◦Life-threatening acute metabolic complication of diabetes resulting from an absolute or relative insulin deficiency and characterised by: ‣ Hyperglycaemia ‣ Hyperketonaemia ‣ Metabolic acidosis ◦Clinical symptoms: ‣ Polydipsia and polyuria. ‣ Weight loss. ‣ Abdominal pain, nausea and/or vomiting. ‣ Shortness of breath - CO2 is acidic, and the body breathes out more to get rid of the CO2 ‣ Lethargy, drowsiness and/or confusion - means patient needs to be treated rapidly -> medical emergency ◦Clinical signs: ‣ Fruity smell of acetone on the breath ‣ Tachypnoea - shortness of breath ‣ Tachycardia ‣ Dehydration ‣ Shock (tachycardia, hypotension, drowsiness, reduced urine output). Effects of insulin deficiency:  ◦Diabetes is often described as ‘starvation in the midst of plenty’. There is plenty of glucose circulating in the blood but the lack of insulin prevents it getting into the cells that need it. DKA - pathophysiology: Hyperglycaemia - osmotic diuresis: ◦When serum glucose concentrations exceed the renal reabsorption capacity, glucose is lost in the urine (glycosuria), leading to osmotic diuresis with loss of water and electrolytes. Type 2 diabetes (T2DM) - aetiology: ◦Imbalance between increasing insulin resistance and relative insulin deficiency T2DM - risk factors: ◦↑ Body weight and visceral adiposity (central obesity) -> trigger a cascade of inflammatory response ◦Sedentary lifestyle ◦Ethnicity (e.g. Asian, African and Afro-Caribbean ) ◦T2DM family history (particularly with first degree relatives and with earlier age of onset) ◦History of gestational diabetes ◦Unhealthy diet ◦Drug treatments (e.g. statins, corticosteroids, diuretics, beta-blockers) ◦Polycystic ovary syndrome -> can get insulin resistance from this ◦Metabolic syndrome  Metabolic syndrome: ◦Metabolic syndrome represents a clustering of metabolic diseases which lead to cardiovascular disease. ‣ Obesity (high BMI) ‣ Insulin resistance ‣ Dyslipidaemia ‣ Hypertension ◦People with metabolic syndrome have a 5-fold greater risk of developing T2DM T2DM - Common features: ◦Predominant form of diabetes worldwide (90%-95% cases globally) ◦More prevalent in older adults (≥65 years), but prevalence increasing in young adults and children due to increasing obesity prevalence in these age groups ◦T2DM prevalence closely follows the prevalence of obesity (diabesity epidemic). ◦Patients with T2DM are usually obese (but NOT always) ◦The clinical presentation is heterogeneous, with a wide range in age at onset, severity of hyperglycaemia, degree of obesity and severity of other associated metabolic abnormalities. T2DM - typical presentation: ◦ T2DM frequently goes undiagnosed for many years because hyperglycaemia develops gradually and, at early stages, is often not severe enough for the patient to notice the classic triad of diabetes symptoms (polyuria, polydipsia and weight loss). ◦T2DM patients are more likely to present with a variety of symptoms such as: ‣ Lack of energy ‣ Persistent infections (e.g. thrush infections of the genitalia or feet infections) ‣ Slow healing of minor skin damage ‣ Visual problems T2DM - hyperglycaemic hyperosmolar state (HHS): ◦Life-threatening metabolic complication of diabetes -> medical emergency ◦T2DM patients seldom develop spontaneous DKA, as they retain sufficient beta- cell function and insulin secretion to prevent DKA for many years. ◦T2DM patients (particularly elderly) may present with HHS: ‣ Severe hyperglycaemia (usually associated with stressful events) ‣ Hypovolaemia (osmotic diuresis and dehydration) ‣ Hyperosmolality (when the patient passes lots of urine) ‣ NON-significant ketonaemia or acidosis DKA vs HHS:  Diabetes criteria for diabetes and pre-diabetes: Diagnosis - key points: ◦Without symptoms of hyperglycaemia diagnosis should NOT be based on a single glucose measurement. ◦At least one additional blood glucose test with a value in the diabetic range is essential. ◦Diabetes diagnosis should NEVER be made on the basis of glucose in the urine (glycosuria) or a stick reading of a finger-prick blood glucose alone. ◦A diagnosis of diabetes has legal and medical implications for the patient (e.g. for driving license), so it is essential to be sure. ◦Differential diagnosis: Type 1 diabetes is defined by the presence of one or more of the related autoimmune markers Prediabetes: ◦Prediabetes is the term used for individuals whose glucose levels do not meet the criteria for diabetes, BUT are too high to be considered normal. ◦Patients with prediabetes are characterised by the presence of impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). ◦Prediabetes increases risk for diabetes and cardiovascular disease. ◦Prediabetes, as T2DM, is associated with the metabolic syndrome. Assessment of glycaemic control: ◦Glycated haemoglobin (HbA1c) measurement - once every 3 months ◦Blood glucose monitoring (BGM) - fingerprick done 3-4 times a day ◦Continuous glucose monitoring (CGM) Glycated haemoglobin: ◦Glycated haemoglobin (HbA1c) is used for longer-term monitoring of diabetes, as well as for screening and diagnosis of prediabetes and diabetes. ◦HbA1c is produced due to the reaction of glucose in the blood with the terminal valine of the haemoglobin molecule. ◦HbA1c reflects the average blood glucose levels over the past 2-3 months: ‣ Goal for many non-pregnant adults is