Diabetes Mellitus Handouts PDF

Diabetes mellitus Dr. Nicole Flemming Learning Objectives 1. Compare and contrast the main pathophysiological basis of Type 1 and Type 2 Diabetes Mellitus (T1DM & T2DM) 2. Explain the acute and chronic complications of diabetes mellitus, including hypoglycaemia, hyperglycaemia, ketoacidosis Glucose...

Diabetes mellitus Dr. Nicole Flemming Learning Objectives 1. Compare and contrast the main pathophysiological basis of Type 1 and Type 2 Diabetes Mellitus (T1DM & T2DM) 2. Explain the acute and chronic complications of diabetes mellitus, including hypoglycaemia, hyperglycaemia, ketoacidosis Glucose transporters glucose reabsorption glucose transporter - insulin stimulated uptake Table sourced from: Hantzidiamantis PJ, Lappin SL. Physiology, Glucose. [Updated 2022 Sep 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK545201/ Glucose transporters promotes uptake deficiency and break down - increase blood glucose SGLT1 is mediating sodium-dependent glucose uptake on apical side active to plasma membrane in skeletal muscle vesicles to cell membrane enters Images sourced from Kumar and Clarke’s Clinical Medicine, 23, 699-741 GLUT-2, SGLT - insulin independent facilitates uptake of glucose against gradient Insulin & glucagon beta cells of islets affect carbohydrate, lipid and protein metabolism NOTE: there are other hormones that affect blood glucose, however these will be covered later in your studies Compare and contrast the main pathophysiological basis of Type 1 and Type 2 Diabetes Mellitus (T1DM & T2DM) Diabetes mellitus overview Diabetes mellitus is a chronic metabolic disorder characterised by elevated blood glucose levels (i.e., hyperglycaemia) Type 1 diabetes mellitus: severe/absolute insulin deficiency Type 2 diabetes mellitus: insulin resistance and/or less severe insulin deficiency autoimmune attack - absolute insulin deficiency relative insulin deficiency Type 1 Diabetes Mellitus Type 1 diabetes is characterised by autoimmune-mediated destruction of insulin producing pancreatic β-cells Accounts for ~10% of diabetes Earlier onset, peak incidence around time of puberty (but can present at any age) Genetic susceptibility, e.g., human leukocyte antigen 1,2 childhood and young adulthood T-cell mediated auto-immune attack on β-cells metabolic abnormality - hyperglycaemia 1,3 Autoantibodies to insulin, to GAD, IA-2, ZnT8 2,4 Environmental triggers, e.g., diet, viruses, drugs, etc 1 Loss of β-cell mass and insulin production Hyperglycaemia à Type 1 diabetes No cure, management with exogenous insulin stress, diet - cow's milk, drugs strong genetic HLA - for MHC II Immune system and self-tolerance in addition to genetic factors, other factors to drive beta cell destruction unknown exact env. triggers early nutrition for risk factors Acute complications: diabetic ketoacidosis, hypoglycaemia Chronic complications: micro- and macrovascular ketone bodies accumulate - life threatening 1) Mikael Knip, Riitta Veijola, Suvi M. Virtanen, Heikki Hyöty, Outi Vaarala, Hans K. Åkerblom; Environmental Triggers and Determinants of Type 1 Diabetes. Diabetes 1 December 2005. 2) Goyal R, Jialal I. Diabetes Mellitus Type 2. [Updated 2022 Jun 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. 3) Taplin CE, Barker JM. Autoantibodies in type 1 diabetes. Autoimmunity. 2008 Feb;41(1):11-8. doi: 10.1080/08916930701619169. PMID: 18176860. 4) Burrack AL, Martinov T, Fife BT. T Cell-Mediated Beta Cell Destruction: Autoimmunity and Alloimmunity in the Context of Type 1 Diabetes. Front Endocrinol (Lausanne). 2017 Dec 5;8:343. Type 2 Diabetes Mellitus becomes resistant to insulin Type 2 diabetes is characterised by peripheral resistance to endogenous insulin with associated β-cell dysfunction 1 Accounts for ~85-90% of diabetes 1 Later onset, most commonly seen in persons over 45 years 1 Risk factors (e.g., age, obesity, sedentary lifestyle, dyslipidaemia, hypertension, diet, some medications) 2,3 Genetic component likely, but incompletely understood 2 1,2 Insulin resistance à tissue is less responsive to receptor insulinactivation disrupted Increased insulin production à required to stimulate insulin signalling and achieve normal blood glucose 1,2 Overtime relative insulin insufficiency develops due to progressive decline in β-cell function and mass 1,2 Hyperglycaemia à Type 2 diabetes, typically some residual insulin production Treatment with lifestyle intervention (physical activity, diet, weight loss), glucose lowering medications, exogenous lose capacity to produce insulin more often in younger age groups genetic component as well not respond to insulin effectively visceral fat - lead to inflammation and insulin resistance compensate for resistance insulin may be needed 1,2 may need exogenous insulin Acute complication: hyperosmolar hyperglycaemic state Chronic complications: micro- and macrovascular provoke decline and loss increase GLUT-4 expression can improve T2DM Change lifestyle Move vesicles to surface and have GLUT-4 expressed 1) Goyal R, Jialal I. Diabetes Mellitus Type 2. [Updated 2022 Jun 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. 2) Ali O. Genetics of type 2 diabetes. World J Diabetes. 2013 Aug 15;4(4):114-23. doi: 10.4239/wjd.v4.i4.114. PMID: 23961321; PMCID: PMC3746083. 3) Haile K, Timerga A. Dyslipidemia and Its Associated Risk Factors Among Adult Type-2 Diabetic Patients at Jimma University Medical Center, Jimma, Southwest Ethiopia. Diabetes Metab Syndr Obes. 2020 Nov 26;13:4589-4597. doi: 10.2147/DMSO.S283171. PMID: 33273834; PMCID: PMC7705268. General signs and symptoms Some of the signs and symptoms for type 1 and type 2 diabetes include Increased thirst (i.e., polydipsia) Increased urination (i.e., polyuria) Increased hunger (i.e., polyphagia) Unexplained weight loss Presence of ketones in the urine (typically T1DM) Fatigue, tired, weak Feeling irritable or mood changes Blurry vision Delayed wound healing Recurrent/frequent infections (e.g., gum, skin and vaginal infections) type 1 - symptoms can be sudden and life threatening type 2 - opposite DiagnosEc and monitoring tests There are different tests that can be used to diagnose and/or monitor diabetes 1 Fasting blood glucose (≥ 7 mmol/L) Random blood glucose Oral glucose tolerance test (OGTT) sweet drink and test post-prandial 2 hr (≥ 11.1 mmol/L) Glycated haemoglobin A1c (HbA1c) (≥ 6.5%) Urine glucose test Autoantibodies no fast (≥ 11.1 mmol/L) abnormally high glucose levels in urine can use dipstick 1) Goyal R, Jialal I. Diabetes Mellitus Type 2. [Updated 2022 Jun 19]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023. * Values taken from: Kumar and Clarke’s Clinical Medicine, 23, 699-741; Michels et al. (2014). Type 1 Diabetes. https://doi.org/10.1016/S0140-6736(13)60591-7 indicate diabetes, 7 to 11.0 - impaired Explain the acute and chronic complications of diabetes mellitus, including hypoglycaemia, hyperglycaemia, ketoacidosis most often with type 2 diabetes elevated osmolarity Hyperosmolar hyperglycaemic state higher demand body uses some blood glucose polyphasia “Growing evidence indicates that disruption of glucose sensing in selective CNS areas, such as the hypothalamus, is closely interlinked with the pathogenesis of obesity and type 2 diabetes mellitus. However, the underlying intracellular mechanisms of glucose sensing in the hypothalamus remain elusive.” liberate stored energy Point of difference from DKA increase uptake volume loss to... HHS is characterised by hyperglycaemia and hyperosmolarity, but typically no ketoacidosis. less than 1% glucose excreted in urine if exceeds 10-12 mmol/L exceed capacity of transporters to reabsorb glucose neural damage from losing water SGLT2 - hypoglycaemia, perpetuate hyperglycaemia upregulated in proximal tubules and sodium reabsorption reduce downstream NaCl at macula densa Diabetic hyperfiltration before reduced GFR restore balance RAAS Elevated to contribute to diabetes decrease in renal perfusion, renal failure due to pre-renal cause DiabeEc hypoglycaemia too much insulin missed meal unplanned exercise below 4 mmol/L more with type 1 Treatment guidelines MILD 1. Check BGL, if