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ALL YOU NEED TO KNOW ABOUT Diabetes - Type 1 and 2 Elena Boby and Nidhi Rege Reviewed by DrRajiv Ark Remindertotutors: please change the description, summary and learning objectives onMedAll Keep thisslide on here untilyou’ve done it(as areminder) Here’s whatwedo: ■ Weekly tutorialsopento all! 18:00 every Thursday ■ Focussed oncore presentationsand teaching diagnostictechniquefrom a If you’re new here… clinical perspective Welcome to ■ Raccuracyby doctorsto ensure Teaching ■ We’ll keepyouupdatedabout our Things! upcoming events viaemail and groupchats! TYPE 1 DIABETES Elena BobyBefore we begin,how confidentare you on the topic of diabetes ?What we’ll be covering 1.Pathophysiology 2.Features 3.Investigations 4.Management 5.Complications Pathophysiology Anautoimmunecondition wherethe insulin producing cellsof theislets of langerhans in the pancreas aredestroyed by theimmune system What isthe role of insulin in thebody? A)Convert glucose into glucagon forstorage in theadiposetissue B) Convert glucose into glycogen for storage in the adipose tissue C)Convert glucose into glycogen for storage in the muscle and liver D)Convert glucose into ketone bodies as a reserve energy resource What is the roleof insulin in the body? A)Convert glucose into glucagon forstorage in theadiposetissue - glucagonis the hormonethat turns glycogen back into glucosewhen energyis needed A)Convert glucose into glycogen for storage in the adipose tissue - glycogen is storedin theliver andmusclenot adipose tissue A)Convertglucoseintoglycogen for storagein themuscle and liver A)Convert glucose into ketone bodies as a reserve energy resource Sodestruction ofinsulin producingcells->less insulinavailable toconvertglucoseintoglycogen ->moreglucose remains in the blood A 7-year-old girl is brought to the GP by her mother because of a 2-week history of increasing thirst and frequent urination. Her mother reports that she has also been more tired than usual and has lost weight despite having a good appetite. On examination, the child appears pale and tired, and her weight is below the 25th percentile for her age. There is no fever, rash, or abdominal tenderness What clues from the question point towards T1DM as the main differential?Features 1. Polydipsia - excessive drinking in an attempt to dilute the high blood sugar levels 1. Polyuria - high levels ofglucose spilling into urine draws wateralongwith it (due to osmotic diuresis) 1. enteringthe cells forrespiration so insteadthe body breaks down fat andom muscle forenergy 1. Fatigue - due to the inabilityro use glucose effectively 1. Recent onsetInvestigations Which 2 investigations would confirma diagnosis of type 1 diabetes A)Low c-peptide levels A)Anti-glutamic decarboxylase antibodies A)Fasting glucose over 7mmol/L A)Fasting glucose >= 7mmol/L A) random glucose >= 11.1 Which investigations would confirm a diagnosis of type 1 diabetes? A) Low c-peptidelevels - this +autoantibodies is the investigation of choice if there is doubt between T1or T2 but it does not confirm the diagnosis A) Anti-glutamic decarboxylase antibodies - again, does not cell autoantibodies are othercommon onesdies andislet A) Fasting glucoseover 6 mmol/L A) Fastingglucose>=7 mmol/L A) Randomglucose >= 11.1 NOTE:IN ANASYMPTOMATIC PATIENT THISNEEDSDOBE DEMONSTRATEDTWICE Fasting Glucose Oral Glucose Tolerance Test Random Glucose (OGTT - alternative to fasting glucose) Preparation Overnight fast Overnight fast + glucose No preparation needed challenge Procedure Quick (single blood Longer (2+ hours, multiple Quick (single blood sample) Duration sample) samples) Information Baseline glucose level Response to glucose load over Glucose level at any time Provided time Use Cases Screening for diabetes Confirmatory or gestational Diagnosis in symptomatic diabetes patients Interpretation Normal: < 5.6 mmol/L (< Normal: < 7.8 mmol/L (< 140 Normal: < 7.8 mmol/L (< 100 mg/dL) mg/dL, 2-hour) 140 mg/dL) Diabetes: ≥ 7.0 mmol/L (≥ Diabetes: ≥ 11.1 mmol/L (≥ 200 Diabetes: ≥ 11.1 mmol/L (≥ 126 mg/dL) mg/dL, 2-hour) 200 mg/dL)Whichof these scenarioswould need to be tested further (c-peptidelevel+ insulinautoantibodies) AKA which ones are inducible between T1 and T2? 1. A 14 yearold presents with weightloss, lethargy. Ketones and glucose found in the urine 1. a 32 -year-oldobese man presents with polyuria. A random glucose is 12.5mmol/L 1. polyuria and polydipsia.Ketones are present in the urine. 1. a 58-year-oldobese man presents with polyuria. A random serum glucose is 12.0 mmol/L1. A 14 yearold presents with weightloss, lethargy. Ketones and glucose found in the urine - T1DM, no furtherinvestigation needed 1. A32 -year-old obesemanpresentswithpolyuria. A random glucose is12.5mmol/L- intermediate age for T1or T2. Not clear cut sodo C-peptide + autoantibodies 1. A61-year-old woman (bodymassindex23 kg/m²) presentswith polyuriaand polydipsia. Ketonesarepresent inthe urine - atypical agefor T1DM but otherfeaturesconsistent, so doC-peptide + autoantibodies 1. A 58-year-oldobese man presents with polyuria. A random serum glucose is 12.0 mmol/L - T2DM, no need for further investigationManagement ofT1DM - monitoring 1.HbA1c measured every 3-6 months, aiming for a targetof 48 mmol or lower 1.Self monitoring of blood glucose everyrecommendedat least 4x a day Targets: - 5-7 mmol/L on waking - 4-7 mmol/L before mealsManagement ofT1DM - Insulin Basal bolus regime - what does this mean? Lantus NOTE: insulinis (long Novorapid acting) needed to manage (short acting) T1DM but diet plays ahugerole This is the This is the in effective maintenance additional management too dose of injection taken - complexcarbs, insulin, dependingon increasing dietary regardless of the sugar activities or content of the fibreand small meals during meal,exercise regular mealsare the day during the day, all part of this illness etcSickday rules DONOT STOPTAKING INSULIN -illness oftenincreases blood glucoselevels and can lead toDKA 1. Monitor more frequently(every2-4 hrs) 1. the doctororcommunity nurse when starting the insulin)d - this will be discussed with 1. Stay hydrated 1. Maintain carbohydrate intake toprevent hypoglycemia 1. Keepa hypoglycemia kiton hand 1. Check for urine ketonesif bloodglucose ispersistently highA24-year-old womanpresentstotheED witha2-day Laboratoryinvestigations history of nausea, vomiting,abdominal pain,andincreasing reveal thefollowing: fatigue.She reportsincreased thirst andfrequent urination over thepast week.She hasnosignificant medical history ● Blood glucose:22 mmol/L but mentionslosing someweight unintentionally over the (396 mg/dL) ● Arterial blood gas:pH past month.O/E, HRis110,BPis 90/60mmHg, and RR is 28 with afruity odor onher breath 7.25,HCO₃⁻14 mmol/L ● Serumketones:positive ● Urineanalysis:glucose What is the mostlikely diagnosis andketones present A. Hyperosmolar Hyperglycemic State (HHS) B. Acute Pancreatitis C. Diabetic Ketoacidosis (DKA) D. Lactic Acidosis E. GastroenteritisA. Hyperosmolar Hyperglycemic State (HHS) - typically more common in T2DM and unlikely due to the presence of acidosis and ketosis B. Acute Pancreatitis- Abdominal pain is common, but there is no lipase/amylase data or history suggesting pancreatitis. C. Diabetic Ketoacidosis (DKA) D. Lactic Acidosis - ketones would not be present E. Gastroenteritis - Symptoms like nausea and vomiting could mimic DKA but would not explain hyperglycemia, metabolic acidosis, or ketosi.Complications of T1DM - DKA A 24-year-old woman presents to Features of DKA the ED with a 2-day history of - Acuteonset nausea, vomiting and abdominal - History suggestive and frequent urination over therst of T1DM past week. She has no significant - Abdominal pain medical history but mentions losing - Vomiting some weight unintentionally over - Kussmaul’s sign the past month. O/E, HR is 110, BP - Acetone smelling is 90/60 mmHg, and RR is 28 with breath a fruity odor on her breath and - Labs: Acidosis and deep hyperventilation ketones A-E assessment always comes first Normalsaline https://canadiem.org/tiny-tips- diabetic-ketoa/idosisTreatment ofDKA Acutely unwell patient - A-Eassessmentalwaysdonefirst! The fixed rateinsulinhas to be prescribed separately The insulin dosesbetweenhyperkalemia treatment andDKA treatment aredifferent- always look upin theBNF to avoid getting mixed up! Type 2 Diabetes - Diagnosis and Management Nidhi RegeHow do you feel about thistopic? 1 - Know nothing 2 - Know bitsand bobs 3 - Kind ofconfident 4 - Very confident 5 - I can teach thismyself !What is it? Sometimesreferred to as‘non insulindependent’ Diabetes Diabetes Mellituscaused by : - insulin secretion - insulin resistancePathophysiologyHow may someone with Type 2 DM present? Acute Subacute features (over months or Features years) Polyuria polyURIA Polydipsia Complications and Risk Asymptomatic Weight loss polyDIPSIA Fatigue Factors Blurry vision Weight loss Candida infections Recurrent UTIsWhat are the Risk Factors? Risk factors Credits: Emirates Diabetes SocietyDiagnostic Criteria? for someone with asymptomaticdisease 1. FastingGlucose>=11.1 mmol/L or Random Plasma Glucose>=7 mmol/Lor HbA1c>48mmol/L ontwo separateoccasions 1. FastingGlucose>=11.1mol/L orRandom PlasmaGlucose >=7 mmol/L orHbA1c>48mmol/L ononeoccasion 1. FastingGlucose>=7 mmol/Lor Random PlasmaGlucose >=11.1 mmol/L or HbA1c>48mmol/L ontwo separate occasions 1. FastingGlucose>=7 mmol/Lor Random PlasmaGlucose >=11.1 mmol/L or HbA1c>48mmol/L ononeoccasionDiagnostic Criteria? for someone with asymptomaticdisease 1. FastingGlucose>=11.1 mmol/L or Random Plasma Glucose>=7 mmol/Lor HbA1c>48mmol/L ontwo separateoccasions 1. FastingGlucose>=11.1mol/L orRandom PlasmaGlucose >=7 mmol/L orHbA1c>48mmol/L ononeoccasion 1. Fasting Glucose>=7mmol/Lor RandomPlasma Glucose>=11.1mmol/L orHbA1c>48mmol/L ontwo separateoccasions 1. FastingGlucose>=7 mmol/Lor Random PlasmaGlucose >=11.1 mmol/L or HbA1c>48mmol/L ononeoccasionJust to recap …. Diagnostic Criteria Symptomatic: Asymptomatic: One of: One of: >=11.1 mmol/L random plasma >=11.1 mmol/L random plasma glucose glucose OR OR >=7 mmol/L fasting plasma glucose >=7 mmol/L fasting plasma glucose OR OR >=48 mmol/mol HbA1C >=48 mmol/mol HbA1C on one occasion on at leasttwo occasionsHow are these tests done? Oral Glucose ToleranceTest 1.Patientwill fastforat least 8hours, nothing butstill water allowed 2.First Blood test - tellsyoufasting plasma glucose 3.Consume 75g of glucose, usually a sugary drink 4.Moreblood teststaken - usually 2 hoursafterglucoseconsumed Randomplasma glucose 1. Glucosemeasured at any point of day WhataboutHbA1c?HbA1c Contraindications for using HbA1c ● children and young people less ● Long-term marker of glycaemic than 18 years of age. control (over 3 months) ● Pregnant women or women who are 2 months postpartum. ● HOWEVER HbA1C< 48 mmol/L ● People with symptoms of diabetes for less than 2 months. does not ruleout diabetes → ● People at high diabetes risk who are acutely ill. Less sensitivethanother blood ● People taking medication that may glucose measurements, so cause hyperglycaemia (for example long-term corticosteroid should berepeated treatment). ● People with acute pancreatic ● Used to monitor diabetic control damage, including pancreatic surgery. and responseto medication ● People with end-stage renal disease (ESRD)Initial Treatment ● Lifestylemodifications ● Drug treatment to reduce blood glucose ● Assess HbA1c, cardiovascular risk and kidney function Aims of Lifestyle Management ● Encourage high fibre, low glycaemic index sources of carbohydrates ● Include low-fat dairy products and oily fish ● Avoid intake of foods containing saturated fats and trans fatty acids ● Avoid sugary foods ● Discourage the use of foods marketed specifically at people with diabetes ● Initial target weight loss in an overweight person is 5-10% What is the target HbA1c for diabetes controlled on lifestyle changes? 1.36 mmol/L 2.48 mmol/L 3.53 mmol/L 4.64mmol/l What is the target HbA1c for diabetes controlled on lifestyle changes? 1.36 mmol/L 2.48mmol/L 3.53 mmol/L 4.64mmol/l What is the target HbA1c for diabetes controlled on lifestyle changes? 1.36 mmol/L 2.48mmol/L 3.53 mmol/L 4.64mmol/l This is alsmodification + metforminen people are on lifestyleWhat class is metformin? 1.Biguanide 2.SGLT-2 inhibitor 3.Gliptins 4.DPP-4 inhibitorWhat class is metformin? 1.Biguanide 2.SGLT-2 inhibitor 3.Gliptins 4.DPP-4 inhibitor Increased insulin sensitivity + Decreased hepatic Metformin gluconeogenesis Take once daily with Adverse effects breakfast Contraindications ● Gastrointestinal upset - dose titrated up slowly OR ● eGFR<30 (modified release can also be used if standard ml/min release not tolerated) Take twice daily with ● Ketoacidosis ● Lactic acidosis if tissue hypoxia, renal failure, or or after a meal at the ● Low BMI severe liver disease - STOP DURING AKI OR same time each day INTERCURRENT ILLNESS If you miss a Generalanaestheticor U&Es tested procedureusing iodine- Weight dose → Take before starting containingX-ray contrast as soon as you → Then loss media: Stopmetforminon remember annually day andfor2 daysafterJane comes in with confirmed Type 2 Diabetes and has significant cardiovascular disease. What additional drug class should you prescribe alongside Metformin? 1.Another Biguanide 2.SGLT-2 inhibitor 3.DPP-4 inhibitor 4.SulfonylureaJane comes in with confirmed Type 2 Diabetes and has significant cardiovascular disease. What additional drug class should you prescribe alongside Metformin? 1.Another Biguanide 2.SGLT-2 inhibitor 3.DPP-4 inhibitor 4.SulfonylureaSGLT2 inhibitors Inhibition of glucose reabsorption in kidney Adverseeffects ● UTI Weight ● Fournier’s Dapagliflozin, SGLT2 = - loss gangrene etc. gliflozin ● EuglycaemicDKA Do you start it before,at the same time or after metformin?Doyoustarta SGLT-2before, atthe same time orafter metformin? 1.Before 2.At the same time 3.AfterDoyoustarta SGLT-2inhibitor before, atthe same time oraftermetformin? Wait until metformin testablishedandeen 1.Before tolerability has been confirmed! 2.At the same time 3.AfterWhat are the indications forSGLT2inhibitors? - ChronicHeartFailure - Established AtheroscleroticCVD - Coronary Heart Disease - AcuteCoronary Syndrome - PreviousMI - AQ-Riskof……. - Stableangina - PreviousCoronary or other 1. 5% Revascularisation - Cerebrovascular Disease(eg 2. 20% 3. 10% ischaemicstrokeor TIA) 4. 25% - Peripheral Arterial DiseaseWhat are the indications forSGLT2inhibitors? - ChronicHeartFailure - Established AtheroscleroticCVD - Coronary Heart Disease - AcuteCoronary Syndrome - PreviousMI - AQ-Riskof……. - Stableangina - PreviousCoronary or other 1. 5% Revascularisation - Cerebrovascular Disease(eg 2. 20% 3. 10% ischaemicstrokeor TIA) 4. 25% - Peripheral Arterial DiseaseCredits to PassMedicineAnna, is already on Metformin titratedto the highest dose,but her glycaemic control is poor. What is the HbA1c threshold to add another drug? 1. 48 mmol/L 2. 58 mmol/L 3.53mmol/L 4.62 mmol/LAnna, is already on Metformin titratedto the highest dose,but her glycaemic control is poor. What is the HbA1c threshold to add another drug? 1. 48 mmol/L 2.58mmol/L 3.53mmol/L 4.62 mmol/LAnna, is already on Metformin titratedto the highest dose,but her glycaemic control is poor. What is the HbA1c threshold to add another drug? 1. 48 mmol/L Bonus Question: 2.58mmol/L 1. 48 mmol/Low target HbA1c? 2. 50mmol/L 3.53mmol/L 3. 53mmol/L 4.62 mmol/L 4. 62mmol/LAnna, is already on Metformin titratedto the highest dose,but her glycaemic control is poor. What is the HbA1c threshold to add another drug? 1. 48 mmol/L Bonus Question: 2.58mmol/L 1. 48 mmol/LnowtargetHbA1c? 2. 50mmol/L 3.53mmol/L 3. 53mmol/L 4.62 mmol/L 4. 62mmol/LWhat drug can you add?Sulfonylureas Stimulate insulin secretion by beta cells Adverse effects ● Hypoglycaemia Gliclazide, Weight ● Weightgain glimepiride gain ● Hyponatraemia Pioglitazone PPARgamma receptor activation → Adipogenesis and fatty acid uptake Adverse effects Weight ● Weightgain Only gain Contraindications thiazolidinedione ● HEART ● Fluid retention available(rhymes Eating all FAILURE ● Liver impairment withthedrugs ● Increased fracture and the bladder cancer risk ending -zone) “pies”DPP-4 inhibitors Increased incretin through inhibition of breakdown→ Glucagon inhibition Adverse effects ● Increased Sitagliptin, DPP → “Dip” pancreatitis risk allogliptin,etc. the “-gliptins”Dual Therapy Combinations ● metformin + DPP-4 inhibitor ● metformin + pioglitazone ● metformin + sulfonylurea ● metformin + SGLT-2 inhibitor (if NICE criteria met)Triple Therapy Combinations -if HbA1c exceeds 53mmol/L ● metformin + DPP-4 inhibitor + sulfonylurea ● metformin + pioglitazone + sulfonylurea ● metformin + (pioglitazone or sulfonylurea or DPP-4 inhibitor) + SGLT-2 if certain NICE criteria are met ● insulin-based treatmentGLP-1 mimetics - swap out of the current drugs first! Incretin effect → Inhibition of glucagonand increase in insulin release Exenatide Exenatide: SC injection 60 minutes Adverseeffects Liraglutide before morning and ● Nausea and Semaglutide evening meals vomiting ● Linked to severe Liraglutide: SC pancreatitis in some Weight loss patients injection once daily 1 hour before mealDiabetes : A numbers game Fasting Plasma Glucose 7 mmol/L Random Plasma Glucose 11.1 mmol/L HbA1c target for lifestyle treatment +/- metformin >48 mmol/L HbA1c threshold for dual or triple therapy 58 mmol/L HbA1c target when on dual or triple therapy 53 mmol/LBen has come in with a HbA1c of 63 mmol/L. His past medical history includes congestive cardiac failure. What drug is contraindicated? 1.Metformin 2.Dapagliflozin 3.Gliclazide 4.PioglitazoneBen has come in with a HbA1c of 63 mmol/L. His past medical history includes congestive cardiac failure. What drug is contraindicated? 1.Metformin 2.Dapagliflozin 3.Gliclazide 4.PioglitazoneCharlie known to the Diabetes Clinic has come in with a painful ulcer on his scrotum. What drug could have caused this? 1. Sitagliptin 2. Canagliflozin 3.Metformin 4.PioglitazoneCharlie known to the Diabetes Clinic has come in with a painful ulcer on his scrotum. What drug could have caused this? 1. Sitagliptin 2.Canagliflozin 3.Metformin 4.Pioglitazone Session Summary What we covered What we didn’t cover - Presentation - Complications - Risk Factors - HHS (Acute - Investigations and Presentation of T2DM) Diagnosis - Lifestyle Management - Medical Management Complications Macrovascular Microvascular CORONARYARTERY DISEASE DIABETIC RETINOPATHY CEREBROVASCULAR DISEASE DIABETIC NEPHROPATHY PERIPHERALARTERIALDISEASE DIABETIC NEUROPATHYResources I found useful - NICE CKS and Guidelines - Kumar and Clark’s - Oxford Handbook of Clinical Medicine - Geeky Medics and OSCEstop for counselling - Keep on doing SBAs so you don’t forget numbers! THANKS FOR WATCHING! Tutor1: ElenaBoby Tutor2: Nidhi Rege Pleasefill outthe feedback form on Medall and see you next week!