Diabetes

SGLT-2 inhibitors "flozins" second line agents: Canagliflozin-100mg po daily, max 300mg (only one wit DDis need to increase dose from 100mg to 300 when taken with UGT inducers (Invokana) $340 Dapagliflozin-5mg po daily, max 10mg (breast and bladder cancer associated with this one) (Farxiga) $340 Empagliflozin-i0mg po daily, max 25mg (Jardiance) $340 Ertugliflozin (Steglatro) $300

"invokanna" cangliglozins- was taken off due to amputation dapaflozin: associated with bladder cancer and blood caner risk •Mechanism: DECRrease reabsorption of glucose from the kidney " pull out glucose from the kidneys" decrease renal threshold for glucose. Increases urinary excretion of glucose by blocking glucose reabsorption in the kidney •Efficacy: moderate efficacy •Adverse Effects: genitourinary infections "fourniers gangrenines" lower bp, fractures "falls and fractures", euglycemic DKA(diabetic keto acidosis )-have positive kenos but blood sugar closer to normal so you have this. Urogenital infections (rare urosepsis, Fournier's gangrene), Increased urination, Hypotension (BP meds), Dehydration (AKI), Increased LDL (~5-10 mg/dl), decreased TG, Fractures, falls, decreased BMD, Euglycemic DKA (hold if at risk - strenuous exercise (marathon), severe illness, 3 to 4 days prior to elective surgery; avoid in binge drinkers, extremely low carb ketogenic diets,), Breast/bladder CA (dapa) •BBW/Warnings/Precautions: •Dosing: known Cana, Emma, Napa CI: ALL eGFR <45 ml/min or ESRD .DDIs:All DDI only cana: UGT inducers (rifampin, phenytoin, phenobarbital, ritonavir)- increase dose from 100mg to 300 mg) Inc K+ with ACEi, ARB, K+ sparing diuretics, increase dig levels W/P: Hypotension/falls/decrease BMD Hyperkalemia (Cana) Amputation (Cana) Ketoacidosis Urosepsis & Pyelonephritis Renal impairment: do not use if eGFR: Cana: <45, if 45 - 60 max=100 mg do not use if eGFR: Dapa <45 ml/min (since 2/19) Empa <45 ml/min Ertu consistently < 60 ml/min Adv: No hypoglycemia with monotherapy Weight loss (2.2-3.3%, up to 5 kg) Reduces BP Reduced CV mortality in high risk pts: empa > cana> dapa Reduced HF & CKD progression: empa, cana & dapa Dapa is approved for HFrEF (w/o T2DM) Disadv: Increased urination •Clinical Pearls: ALL CAN NOT BE USED IF CRCL IS LESS THAN 45. GOOD FOR PTS WITH CKD, HF, ASCVD(STORKE OR HEART ATTACK) , ASSOICATED WITH WEIGHT LOSS, may need a higher dose with some meds!! target organ: Kidney Primary blood glucose affected: FBG and PPG monitoring parameters: A1c, SCr/CrCl/eGFR, BP Infections, K (cana), BMD, LDL REWATCH VIDEO BEGIN RAMPING !!!!!!!!

which med is associated with Risk of DKA (found in type 1 patients is associated with )

-SGLT2 inhibitor in insulin (monitor and be aware)

A patient has an elevated A1c despite being on 3 or more non-insulin medications.What next?

-USUALLY ADD INJECTIBLE (INSULIN OR GLI1RA) -USE GL1RA FIRST IF NOT ON INSULIN ALREADY

Insulin levels in someone w/o DM

-Very tight control of their blood sugar -help avoid cardiovascular issues -basal amount of insulin all the time and then you have peaks during times of eating carbohydrates -basal insulin, insulin we are using to memhicm basal energy production (one dose amount and stay int he body ) -pradianla meal time insulin: insulin we are using to cover the meals "peak and leave the body quickly) WE DONT HAVE INSULIN THAT COVER BOTH CURRENTLY

"Meal Time" Insulin (Bolus)

-WILL BE YOUR SHORT ACTING AND THE REST ARE BASAL

Preventing DM

-exercise (150 min per week w/o missing two days in a row) -diet -weight loss -metformin 850mg bid but practice use 500 mg bid or qd use this for pre diabetes to prevent diabetes

Non-pharmacologic Interventions

-exercise: 150min per week not missing more than 2 days -diet: avoid high carb diet 45g-60g of carb per meal -Etoh: 1 or less in women or 2 or less in men (beer=12 oz, wine=4oz, hard liquor= 1oz) -sodium less than 2.3 g per day -smoking cessation -weight loss -bariatric surgery (BMI more than 35 with 1 or more comorbidity or greater than 40) , BMI greater than 30 + cormobdity if not achieve success with tx -immuzations: flu pneuovax (once greater than age to than age 5), hep B series

Do Statins Cause DM?

-lead to a gradual not noticeable change with statins •Key findings ▫The risk of developing diabetes is limited to patients who are already at high risk. ▫The minor increase in blood glucose with statins may be enough to push at-risk patients across the diagnostic threshold."pravastatin may increase and lovastatin may decrease chances of developing diabetes "

Prandial insulin

-novolog, lisper, solostar, afezza, aspart

Insulin Pump Therapy

-quck acting insulin

What factors that will influence your choice of initial therapy?

-renal function -route of administration -wt loss of wt gain -cost -Adrs/CI -A1c lowering % -other disease states

MR is a 13 year old girl newly diagnosed with T1DM. She weighs 85 lbs.

1st calculate physiologic insulin need: 0.5 units/kg 85ibs/2.2kg=38 kg x 0.5 units= 19units 50% of the 19 units will be the basal and 50% will also be the bolus so lets say we have 18 unites of Total daily dose than 9 unit would be Lantus sub in the morning and Humalog 3 units sub q pre meals TID (THIS IS THE GENERAL STARTING POINT FOR INITIAL REGIMEN)

Symptoms of hyperglycemia

3 P's •Polyuria •Polydipsia "increase thirst" •Polyphagia "increase hunger" •Difficulty Concentrating •Lethargy •Headache •Blurry Vision"can occur in high or low blood sugar" .wt loss in type 1 DM

How does T1DM present differently from T2DM?

3ps are the same (POlypoly) type 1 can have keto in the urine or blood and antibodies damage them so they re not producing insulin

TR is a 68 year old man admitted to the hospital. He is taking Humalog Mix 75 (N=12 hr during long acting/25 (rapid acting unit) 26 units before breakfast and 12 units before dinnerYour hospital does not carry Humalog Mix 75/25 and you need to convert the patient to Novologand insulin NPH.

75% (26)=19.5 and 25% (26)= 6.5 for safety reasons we will generally round down give 19 units of the insulin ph in the morning and 6 units of the Novolog before breakfast

Why is tighter A1c control not always better?

ACCORD Stopped early due to increased harm 10,250 type 2 DM (for 10 years, avgA1C 8.2%, avgage 62), high risk for CVD A1c target <6% vs. 7-7.9% More deaths (5% vs. 4%) in the intensive-treatment group NNH=100 ADVANCE 11,140 type 2 DM > 55 yr with CVD RF A1c <6.5% vs. >6.5% No difference in CVD events and mortality VADT 1791 poorly controlled type 2 DM veterans, high risk for CVD A1c <7% or 8-9% No difference in composite of CVD events

Third line agents per ADA

Alpha-glucosidase inhibitors •Mechanism: PREVENT breakdown of carbs •Efficacy: moderate (good for high carbs in diet used in Japan ) •Adverse Effects: gas bloating diarrhea (GI issues) •Other info ▫Dosing frequency: TID, pre-meal ▫Treatment of hypoglycemia: glucose/dextrose(monosaccarhide do not require to be broken down to be absorbed), fruit, juice (delay in the benefit of getting the sugar back up)

TYPE 2 WE ARE RELYING ON THE BODY JUST GIVING A LITTLE BIT OF HELP SO CAN ADD

BASAL (10 UNITS DAILY OF LONG OR ULTRA LONG ACTING INSULIN 0 -BEST TO ADMIN AT BEDTIME OR THE SAME TIME EVERYDAY ROUGHLY OR A TIME THAT THEY CAN REMBER . INSLUIN TREXIMBA LAST IN THE BODY FOR 48 HOOURS BUT INJECT EVERY 24HR IF YOU FORGT UR DOSE CAN INJECT AT DIFF TIMES OF THE DAY IF IT WAS 8 HRS AWAY. INSULIN LEVIMERE NOT LONG ACTING REQURE BID DOSIG -HIGH INSUINI NEEDS AND RESISTANCE IS SAVED FOR HIGHER COONCENTRATION

Individuals at risk for T2DM

BMI >25 (>23 in Asian Americans) plus one of the following: •1st degree relative with DM (parents, children, sibling ) •African American, Latino, Native American, Asian American or Pacific Islander •Physical inactivity •Women with h/o GDM •Women with PCOS (insulin resistance) •Metabolic syndrome (encompass insulin resistance, low HDL, high triglycerides, hypertension, central obesity) •Prediabetes

What to keep when insulin is added?

Basal insulin added •Keep or add metformin, SGLT2 inhibitor, GLP-1 agonist (both of those help with weight loss) •Stop or reduce dose of TZD, SFU (or any med that cause weight gain) -once controlled we stop and see what it do made gradually the increase and decreases over sudden visits Full basal bolus insulin •Keep or add metformin, SGLT2 inhibitor, GLP-1 agonist ▫Risk of DKA with SGLT2 inhibitor in insulin insufficiency(monitor and be aware that it could happen) •Stop other oral medications, especially SFU (defiantly stop this because it acts on the pancreas make the pancreas kick out more insulin)

Day 2 Questions?

DAY2 END OF LECTURE

WEIGHT NEUTRAL MEDS :

DDP (GLIPTINS), METFORMIN (SOMEWHAT WEIGHT LOSS)

NPH IS GENERALLY NOT USED

DUE TO .....PEAK (CAUSE PEAK WHICH IS HYPPGLYCEMIA)

New strategy: In high risk individuals, use DM medications that prevent ASCVD or progression to

ESRD

Dawn phenomenon when FBS are high

Early morning glucose elevation produced by the release of growth hormone, which decreases peripheral uptake of glucose resulting in elevated morning glucose levels. Admin of insulin at a later time in day will coordinate insulin peak with the hormone release. •High FBS and normal to high BS in the middle of the night •Morning hormones released lead to a spike in BS in the morning

ADA diagnostic criteria for DM "FPG check on 2 occasion or A1c check on 2 occasion they qualify?"

Fasting Plasma Glucose (FPG): greater than or equal to 126 mg/dl 2h-OGTT (75 g glucose load): greater than or equal to 200mg/dl A1c: greater than or equal to 6.5% Random Plasma Glucose + signs and symptoms of hyperglycemia: greater than or equal to 200 mg/ dl

Continuous Glucose Monitor

Flash CGM (e.g.FreeStyle Libre)=more affordiable, lead to significantly approved control) •BS reading when reader is waved over sensor •Sensor in upper arm •Arrow indicates trends in BS (increasing, decreasing) •Cost $70 for device + $1300/yr for sensors •Free smart phone app for iPhone 7 or later, Android OS 5.0 or higher (Libre) •Alarm if within 20 ft of device (Libre 2) -20 ft of device will continue to read and Traditional CGM (e.g. Dexcom G6) •Continuous readings •Attached to abdomen •Alarms for low and high BS •Cost $800 for device + $1300/yr for sensors -if you have a smart phone with the app do not need to purchase the device (not on exam)

Glycemic goals ADA

HbA!C: less than 7% or less than 7.5% for pediatric patients FBG: 80-130mg/dl 2hr PPG less than 180 mg/dl (1-2hr) important to know just in case we need a change in therapy

Efficacy

High Efficacy (~ 1.5% A1c lowering) •Biguanides (Metformin) •Sulfonylureas •Longer acting GLP-1 agonists (exenatide ER, semaglutide, dulaglutide & liraglutide) •Thiazolidinediones Highest Efficacy •Insulin

what is the period shortly following diagnostic of type 1 DM that reduce insulin need ( so bs should be low) and aid blood glucose control in the pancreas

Honeymoon Phase or period

IF PT CAN SELF TITRATE

IF FBG IS AT GOAL CAN SELF TITRATE BUT IF CAN NOT HAVE TO SEE MORE FREQUENTLY -SLOW TITRATION HELP IF PT HAVE A HIGH GLYCEMIA FOR A LONG TIME (WHEN BODY GO CLOSE TO NORMAL THEY BODY REACT AS IF HYPORGLYCEMIA BECAUSE ITS USE TO BEING SO HIGH)

Diabetes mellitus

Impaired insulin secretion (type 1) and/or insulin resistance (type 2) leading to elevated blood sugars

Calculating 10-year ASCVD risk

Includes •Age, sex, race •BP •Tot chol, HDL, LDL •h/o DM •Smoking history •If on BP meds, statin or ASA New strategy: In high risk individuals, use DM medications that prevent ASCVD or progression to ESRD

Initiation of Insulin in Type 2 DM

Key Points -Initiate 10 units or (0.1-0.2 units/kg) daily of long or ultra-long acting insulin -Increase by 2 units every 3-7 days until FBG at goal w/out hypoglycemia

If basal insulin + non-insulin meds not enough

Key points -If not on oral meds that decrease wt, consider adding those meds before prandial insulin - Prandial insulin •4 units or 10% of basal dose before largest meal •If A1c is close to goal (<8%), decrease TDD by the number of units added as prandial insulin • •Subsequent options - adding more prandial doses or twice daily pre-mixed insulin •

INSULIN BASAL IS

LONG ACTING OR ULTRA LONG ACTING (HIGH INSULIN NEEED LOTS OF RESISTANCE ) STOPED HERE DIDNT FINISH ALL OF DAY 2!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!!! -help promote endogenous insulin (help against insulin resistance )

ADA Algorithm for Tx of Type 2 DM: 2020

LOOK AT

Pramlinitide

MOA: unknown •Approved for type 2 diabetes and 1 diabetes noramally added on .Mechanism: slows gastric emptying , amylin analog •Efficacy: moderate •Adverse Effects: nausea dose: injectable TID BBW: FOR sever hypoglycemia (causes severe hypoglycemia clinical perils: expensive

Diabetes complications

Macrovascular •ASCVD: heart disease and or stroke/ cardiovascular disease but mainly heart disease and or stroke • Microvascular •Retinopathy: transmit the image to your brain •Neuropathy: periphheral neuropathy start in the finger tips and nose progress to numbness •Nephropathy:

TYPE 1 MUST COVER PREDINDAL AND BASAL

NEEDS

Thiazolidinediones second line agents; Rosiglitazone-increases LDL (Avandia) $115 Pioglitazone-15mg po qd, max 45mg (Actos) <$20 Delayed onset -takes 8-12 weeks (faster w/ insulin/ SU - 4 weeks)

Names; pioglitazone (actos) •Mechanism: DECREASE insuline resistance (muscle) •Efficacy: high • •Adverse Effects: weight gain, rare bladder cancer AVOID IN PTS WITH HF ,atypical fractures: rare. Edema, Weight gain, Heart failure, Hgb/HCT decreased by 2-4% (dilutional?), Increased LFTs, Bone fractures, Macular edema Bladder CA? (Pio) - controversial - higher risk for bladder ca in general men, smokers, geriatric pts. Longer duration (>10 yrs) & higher dose also may increase risk •BBW/Warnings/Precautions: AVOID IN PT'S WITH HF, HISTORY OF BLADDER CANCER,smoking and age increase risk DDIs: Effects increased by strong 2C8 inhibitors (gemfibrozil, pregabalin) CI: Class III or IV HF BBW: Exacerbation of HF W/P: • Fractures: upper arm, hand and foot • Hepatic impairment-do not initiate if ALT >2.5x ULN, d/c if increase >3xULN • ? Ischemic heart disease (Rosi) Resumption of ovulation in PCOS •Dosing: known Pioglitazone dosing Primary target organs: Muscle and Fat tissue Primary glucose affected: FPG monitoring parameters: A1c, FBG, LFTs, eye exams, s/s HF, weight Adv: No hypoglycemia Improves HDL Lowers TG (Pio) Disadv: Weight gain Increases LDL (Rosi) •Clinical Pearls:delyaed onset 4 weeks and up to 8-12 weeks, inexpensive END OF SECOND LINE

medications that affect BS Increase mostly

Niacin Corticosteroids: prednisone B-Blockers -increase insulin resistance Thiazide diuretics-monitor adjust accordingly Protease Inhibitors Atypical Antipsychotics Ethanol: "decrease" do not drink alcohol in the fast state can be dangerous Calcineurin Inhibitors: transplatioon Fluoroquinolones "increase or decrease" Phenytoin

Moderate Intensity Statin Doses

Rosuvastatin (Crestor) 5-10 mg daily+ Atorvastatin (Lipitor) 10-20 mg daily+ Simvastatin (Zocor) 20-40 mg daily+ Pitavastatin 2-4 mg daily Lovastatin 40 mg daily Pravastatin 40-80 mg daily Fluvastatin 40 mg bid Fluvastatin XL 80 mg daily

WEIGHT LOSS

SGLT4(FLOZINS), GLIP1RA(TIDES)

WEIGHT GAIN MEDS

SULFONYLUREAS, THIAZOLIDINEDIONES

FBS are high Somogyi effect

Somogyi effect: •High FBS and low BS in the middle of the night •Liver overshoots when trying to address low BS -need to give them less insulin in this case -will adjust the Lantus and decrease the Lantus

Second line agents: SULFONYLUREAS: Glyburide-2.5mg po daily, max 10mg BID (Diabeta, Glynase, Micronase) Glipizide-5mg PO daily, effective max 10mg BID, max 20mg BID (Glucotrol, Glucotrol XL) Glimepiride-1mg daily, max 8mg daily (Amaryl) <$10

Sulfonylureas Glyburide, Glipizide (10mg BID) •Mechanism: increase insulin release w/o regards to meals from the pancreas •Efficacy: high efficacy, .ADE: Hypoglycemia, Rash, Photosensitivity, Weight gain .DDIs: Avoid use with bosentan (glyburide only). May increase effect of alcohol CI's: CI: Concomitant use of glyburide with bosentan W/P: • Hypoglycemia • Sulfonamide allergy -low likelihood of x-reactivity • Caution in hepatic/renal dysfunction Avoid glyburide & glimepiride in geriatrics, BEERS list •Warnings/Precautions: hypoglycemia, beers over 65 avoid glyburide and others glipizide is the best, weight gain (increase insulin in the body eat extra the glucose is converted into fat), photosensitivity -cheap, do not use with meglitinides (3rd line) Adv/disadv: Adv: • Inexpensive Disadv: • Hypoglycemia (especially with renal dysfunction • Weight gain • Lose efficacy over time Primary Blood Glucose Affected and monitoring parameters: target organ: pancreas , FPG effected most monitoring: -FPG, A1c -SMBG if hypoglycemia suspecte

Honeymoon phase of diabetes

The Honeymoon Phase (or Honeymoon Period) amongst people with type 1 diabetes refers to the period of time shortly following diabetes diagnosis when the pancreas is still able to produce a significant enough amount of insulin to reduce insulin needs and aid blood glucose control. -temporaily you need to decrease the insulin dose and then go back up the body is just doing what it is suppose to temporarily

Treatment of T2DM Summary

Which medication should be used in all patients if tolerated and not contraindicated? -Metformin Which six classes are considered 1st & 2nd line? -GLIP-1, GLIP-1 RA, SULFONYREAS, Thiazidones(TZD), SGLIT2, DDP4L, BIGUANIDES After a medication for T2DM is initiated, how long does it take for blood sugars to respond to the medication? TYPICALLY 2 WEEKS UNLESS ITS A TZD

A1c Reflects blood glucose in the previous 3 months Normal A1c 4 - 5.6%

called hemoglobin A1C measure how much glucose attach to hemoglobins(last 2-3 m) in percent -check every 2months -estimated average blood glucose -higher A1c higher chance of developing diabetes's complication (Marcovascular complication) -measure diabetes and prediabetes

DPP-4 inhibitors also second line agents Sitagliptin-100mg po daily, also the max (Januvia) $330 Saxagliptin (avoid in HF pt's) (Onglyza) $325 Linagliptin-5mg po daily, also the max (no renal adjustment needed for this one) (Tradjenta) $330 Alogliptin (avoid in HF pt's) (Nesina) $310

citagliptins etc .Mechanism: prevents breakdown of endogenous GLP-1 "hypoglycemia not an issue with this med so well tolerated" -Inhibits DPP4, resulting in prolonged endogenous GLP-1 levels, resulting in increased insulin secretion, decreased glucagon secretion •Efficacy: moderate efficacy •Adverse Effects: WELL TOLERATED. rare joint pain and rare bulls pemphigoid: history of pancreatitis try other other options (avoid GLP-1 or DPP-4 unless you have to but just a caution). Uncommon: Increased URI/ nasopharyngitis •Warnings: weight neutural (do not cause weight gain), similar MOA so don't use with GLP-1 so don't use together. ALOGLIPTIN/ SAXAGLIPTIN can worsen HF DONT USE in HF PT'S. MORE EXPENSIVE .W/P: • Renal impairment dose reduction needed if eGFRl<50 for sita, saxa, and alo (none with lina) • Pancreatitis • Alo - rare reports of liver failure • Saxa - Decreased lymphocytes, rarely requires d/c Heart failure (Saxa/Alo)-may increase risk of developing/worsen existing HF, use with caution if patient has HF DDIs: Increased by strong 3A4 inhibitors (saxa, lina)May increase effects of ACEi/Digoxin. Don't use w/ GLP-1 agonists (both incretin based MOA) Adv/disadv: Adv: • No hypoglycemia as monotherapy • Weight neutral • Generally well tolerated Disadv: • Minimal efficacy High cost •Dosing: sitagliptin (dose: ) and Linagliptin (dose: ) primary target organ: Pancreas .Primary blood glucose affected: PPG .monitoring parameters: PPG, A1c, renal function •Clinical Pearls: MORE EXPENSIVE

Prandial: Insulins can be divided into two categories based on function: basal (long-acting insulin) and prandial (rapid-acting or "mealtime" insulin). Basal insulin is designed to be injected once or twice daily to provide a constant level of insulin action throughout the.

day

•The 2nd line Non-Insulin Drug classes ▫Names (brand & generic of individual products) ▫Mechanism ▫Relative efficacy (% reduction in A1c) ▫Contraindications/warnings ▫Starting/maximum dosing for specified medications ▫Common/worrisome ADRs ▫Which DM medication classes should not be used together ▫Dosing ▫Which medications (brand & generic names) are recommended 3rd line according to ADA algorithm & selected information related to these meds highlighted in class ▫Recommend what would be BEST based on patient specific information •How to start and titrate insulin in a patient with type 2 DM on oral therapy •Which medications to continue or discontinue after insulin is initiated •Insulin generic names and brand names

day 2 need to know

DOA is depended on the

dose

metformin cause

gi upset most people build tolerance can't use it if egfr less than 30

What kind of diet should be followed?

help you limit those most

stoped at the glycemical goal chart

here

What is the primary treatment for T1DM?

insulin

siliqua and xultophy

insulin glargine / insulin degudec/ lixsenatide and liraglutide "no peaks basal"

Basal/bolus vs. Mixed

larger number =longer acting insulin short= rapid acting or shorter insulin

day 3

lecture focus on insulin

Example of a sliding scale will give rapid acting insulin

less than 150 of blood glucose give 6 units -151-200 give8 units -201-250 give 10 units -252-300 give 12 units -301-350 give 14 units

basal insulin is

long acting and ultra long acting insulin (use once or twice expected to continue for a while)

which oral hypoglycemic diabetic med is associated with weight loss:

metformin(really neutral but some loss), SGLT2 inhibitor, GLP-1 agonist

insulinis a hormone made by pancreatic beta cells is a key that allows glucose into

muscle cells. -insuline enter fat cell(if not utilize store fat) or live (block gluconogenisis)

How will post-prandial BS differ? FBS = 200. (180 to 30) Injects Humalog 6 units. Has 2 slices of toast (40 g CHO) and black coffee for breakfast. FBS = 200. Injects Humalog 6 units. Has 2 slices of toast (40 g CHO) and black coffee for breakfast.

need rapid acting insulin that get up Fromm 200 to 100 and need some insulin that cover for the meal so 2 hr after you eat don't want your blood sugar to be higher fbs=120 and 40g of cHO the answer with the bagel is right

prandial insuline is

rapid acting insulin "meal time insulin"

Basal/bolus vs. Mixed

rapid/long=peak mix =70% in and 30% novolong the peak with the N will cover that noon time meal 4 injection will cover for all the meal may end up with hypoglycemia or hyperglycemia with regular meal times

Mediterranean Diet

recommended -use a pyramid starting with vegetables,etc

SMBG-what is the role in T2DM?SMBG-what is the role in T1DM?

type 2 diabetes: self monitoring is on ly helpful if pt understand what the numbers mean and can make changes . can be used to adjust dosage as well. only the ones on oral meds need to question and ask type 1 diabetes on intense insulin treatment . need to check 4X a day

3Ps (polyuria, polydipsia,polyphagia)

urination, thirst, and appetite are associated with type 1 and type 2 DM

Type 1 diabetes mellitus (T1DM)

•5-10% of individuals with DM •Autoimmune •No insulin production •Young age •Weight loss and ketones present at diagnosis -age less than 20 (normally 12-13) "can't use the food that is digested for energy which leads to ketones and weight loss: primary treatment will be on insulin

Type 2 diabetes mellitus (T2DM)

•90% of individuals with DM •Insulin resistance (high than normal insulin production) •Often obese •Adult onset -usually will not see ketones " since insulin is still leading to fat breakdown so no need for ketones don't see it with type 2"

Factors to consider

•A1c lowering needed •Contraindications and ADRs •Wt loss needed? •Hypoglycemia risk •Cost •h/o of ASCVD, HF or CKD •Route of administration: oral or sub q

Epidemiology of DM

•Affects 30.3 million people in the U.S. •9.4% of U.S. population overall, 25.2% of age > 65 •Leading cause of kidney failure, nontraumaticlower-limb amputation and new cases of blindness in adults • •7th leading cause of death in 2015

Aspirin 81 mg daily?

•All patients with ASCVD Primary prevention : no ASCVD event Consider in •> age 50 and < 70 with ASCVD risk factors •Need to consider risk of bleeding -not for use if older than 70 must fall within the above criteria

Converting insulin doses

•Between rapid acting insulins 1:1 •Between basal insulins 1:1 Except ▫when converting from Toujeo (insulin glargine U-300) - use 80% of the Toujeo dose ▫When converting from NPH bid to insulin glargine, insulin detemir, or insulin degludec- use 80% of the total daily dose (not on exam)

Initiation of Insulin Monotherapy

•Calculate total daily dose •Select specific insulin products ▫Pump vs. SC injections •Calculate basal and bolus doses •Adjust as needed based on BG readings ▫Rule of 550 (some use 500 (450 for reginsulin)) ▫Rule of 1650 (some use 1700 or 1800 (1500 for NPH insulin)) ▫"Sliding scale"

Gestational Diabetes (GDM)

•Hormonal changes lead to elevated BS during pregnancy •Often BS normalize after delivery •BS must be controlled to prevent adverse maternal and fetal outcomes •40% of patients with GDM develop DM later in life

Pre-Diabetes Diagnostic Criteria

•Impaired Fasting Glucose •check first thing in the morning between 100-125 pis pre diabetes) •Impaired Glucose Tolerance • 2 hours after meals between 140-199 (pre diabetes) •A1c: 5.7%-6.4% is pre diabetes

Day 3 Need to Knows

•Initiation of Insulin in Type 1 DM ▫Calculate total daily dose ▫Select specific insulin products Pump vs. SC injections Basal bolus vs Mixed insulins ▫Calculate basal and bolus doses ▫Adjust as needed based on BG readings ▫Calculate correction doses Rule of 550 Rule of 1650 •Adverse effects & Patient education

Individualizing A1c Goal

•Lower A1c Goals ( <6.5%, MORE aggressive) -younger and no complications • •Higher A1c Goals (<8%, LESS aggressive) •elderly , have cormobidites, health issues, mental health issues when they experience hypoglycemia can not respond well. Pt at high fall risk etc • •Children (<18 years) with Type 1: A!C goal is less than 7.5% -may not recognize hypoglycemia and may not bee able to treat it

Some other types of DM

•Maturity onset diabetes of youth (MODY) • •Cystic fibrosis related diabetes •Latent autoimmune diabetes in adults (not on exam)

GLP-1 RA "tides" second line agents: Exenatide-5 mcg SubQ BID 60 min pre-meal, meals > 6 hrs apart (Max 10 mcg SC BID) (Byetta) $610 Exenatide XR-2 mg SubQ once weekly (Max 2 mg) (Bydureon, Bydureon BCISE autoinjector)"suspension that must be mixed d by the pt" Avoid if CrCL <30, may increase level of warfin $580 Liraglutide-0.6 mg SubQ daily x 1 week, then 1.2 mg SubQ(nausea most associated with this one) (Victoza) $500 combo w/ insulin degludec available Dulaglutide-0.75 mg SubQ once weekly (1.5 mg, 3 mg & 4.5 mg dose increments) expires in 14 dAYS (Max 4.5 mg) (Trulicity) $625 Lixisenatide-10 mcg once daily x 14 days, then 20 mcg SubQ once daily. Give 60 min pre-first meal. (Max 20 mcg)expires at 14 days . avoid if eGFR is less than 15 (Adlyxin) $600 combo w/ insulin glargine available Semaglutide-0.25 mg SubQ q wk x 4wks, then 0.5 mg,q wk (max of 1 mg) (Ozempic inj) (Rybelsus oral) $800 Wt loss: sema > lira> dula > exena > lixi Prime only with 1st dose for multi-dose pens PO: Titrate every 30 days as needed 3 mg, 7 mg and 14 mg PO daily (Max 14 mg). 30 min before eating, drinking & meds w/ < 4 oz water.

•Mechanism: INCREASE insulin secretion relative to meals , they are long-acting, decrease glucagon secretion, increase satisfy, delayed gastric emptying. GLP-1 analog -increased glucose dependent insulin secretion, decreased glucagon secretion, increased B cell growth, slowed GI emptying, increased satiety • •Efficacy: high efficacy • •Adverse Effects: N/V, AKI all associated with dehydration and vomiting so don't continue if having these type of symptoms and drink to replenish "hydrangate: -Hypoglycemia (if combined w/ SU/insulin) -Nausea (most with liraglutide, usually transient after few weeks). Counsel to eat slowly and stop when full or N/V may worsen. -Acute pancreatitis •BBW/Warnings/Precautions: "not in excenatide, lixi medications" but all the other ones medullary thyroid cancer seen in rats, worsen digestion so not good for diabetic gastro....) BBW: BBW: Risk of thyroid Tcell or medullary cancer in rats (except exena IR, lixi) CI: hx or family hx of medullary thyroid cancers and multiple endocrine neoplasia syndrome type 2 (MEN2) DDis: Exenatide may increase levels of warfarin (increase INR) Don't use with DPP-4 inhibitors (both incretin based MOA) W/P: • Pancreatitis • Weight loss • Hypersensitivity • May cause renal insufficiency (dehydration from severe nausea) • Avoid in severe renal impairment (exena CrCl<30, lixi eGFR < 15) • •Dosing:tiation 0.1 for week then go up to 0.6? re watch this video part. known initial dose, max dose, xentide is the only one that require dose adjustment, lix(don't need to know) Primary blood glucose affected: PPG •Primary target organs: Pancreas, GI tract, Liver monitoring parameters: PPG, A1c All expire at room temp at 28 days, except dulaglutide and lixisenatide at 14 days Adv: No hypoglycemia if monotherapy Weight loss (1-2.5 kg) decrease CVD mortality (lira > dula > sema inj) May decrease progression to ESRD Disadv: Injectable, exenatide ER is a suspension that must be mixed by patients •Clinical Pearls: one must be completely mix since it is a suspension have nodules and may be painful-byduron, polyphagia, help lower blood sugar, decrease ASCVD RISK, eventide crcl less than 30 and lixisenatide (crcl less than 15), injectable have cardiovascular benefit

Colesevelam

•Mechanism: bind to bile acids for cholesterol other methods unknown •Efficacy: low efficacy •Other info ▫DDIs: binding interactions ▫CIs: TG greater than 500 is contraindicated?

Bromocriptine

•Mechanism: unknown •Efficacy: low •Adverse Effects/BBW: low bp, nausea •Other info ▫Dosing frequency & route ▫Patient population

Meglitinides

•Mechanism:INCREASE insulin secretion very SHORT ACTING-glucose dependent •Efficacy: moderate efficacy •Adverse Effects: hypoglycemia (less than SFUS), INCREASE weight gain •Other info ▫Other class with similar MOA ▫Dosing frequency: known repoglinide : pre meals, skip if miss meal (only taking when they eat prior to )if don't eat cause a spike in A1c ▫Patient population

Metformin (Glucophage) FIRST LINE for type 2 diabetes Biguanides Metformin-500 mg or 850 mg PO daily x 3-7 days (for GI tolerability), then 500 mg or 850 mg PO BID. Max:1000 mg PO BID or 850 mg PO TID ER 500 mg PO daily with evening meal, inc by 500 mg weekly to 2000 mg PO daily (can split BID) Recommended dosing by eGFR: 30-45, do not initiate, caution if pt is already on (most limit to 1000 mg) <30, do not use (Glucophage, Glucophage XR, Riomet) <$20 -if take off and on willl not develop tolerance for the dm

•Mechanism:• Decreases hepatic glucose production • Decreases insulin resistance primarily in the liver •Efficacy: High efficacy •CI:CI: eGFR < 30 .BBW:Lactic Acidosis; d/c if predisposed to hypoxemia .W/P: HF exacerbation, Hepatic Impairment, Renal Impairment Avoid excessive EtOH Contrast dye-d/c prior if h/o liver dx, alcoholism, HF or intra-arterial dye admin. Hold for 48h-confirm renal function returned to baseline before restarting Resumption of ovulation in PCOS .ADE: Diarrhea ( up to 30%, 5 - 10% can't tolerate despite slow titration), N/V, Flatulence, Vit B12 def (7%), Lactic Acidosis (RARE but SEVERE-effect the lungs try to make up for it) •Dosing .adv/disadv: Adv:: 1st line because - · No hypoglycemia · weight neutral/loss · likely decreases CVD events · prevents DM (pre-diabetes) · inexpensive Disadv: B12 deficiency .primary blood glucose affected:FPG Monitoring parameters: FBG, A1c ,SCr Hgb/HctB12 esp. if anemic or new or worsening peripheral neuropathy Primary target organ: liver, muscle

When to consider initiating insulin in a newly diagnosed patient with T2DM

•Ongoing weight loss: MEANS INSULINE INSUFFICENCICYE , NOT ENOUGH INSULIN TO MAINTAIN YOUR WEIGHT OR WHAT YOU ARE EATING •A1c > 10%: IF DOING EVERUTHING TO TAKE CARE OF THEIR SELF THEN OK TO INITIATE INSULIN BUT MOST NOT SO LIFE STYLE CHANGES IS BEST AND METFORMIN ALONE IS GOOD COMBO

Mixing insulin

•Only regular with NPH can be mixed in same syringe ahead of time • Rapid acting insulin can be mixed with Insulin NPH/Humulin N and Novolin N (intermediate acting=once to twice a day) in the same syringe and injected immediately for stability reason Mix Clear before cloudy(NPH must roll it so don't get bubble so pull out the insulin want to pull out the clear fist before you pull out the cloudy so ur not contaminating )

What IF

•Over 1% A1c lowering is needed? -Metformin(WT NEUTRUAL), sulfonylurea, glp1-ra, thiaziadonines, INSULIN? •Wt loss needed?-SGLT2 INHIBITORS (ORAL), GLP1-RAs •No insurance coverage? -Metformin, sulfonylureas, insulin regular and NPH •h/o of ASCVD-sgllt2, glip1 ra •h/o CKD (CrCl > 45): decrease product of ckd and hf: SGLT2 INHIBITORS, CANA DAP, ERE2 DO NOT HAVE DATA •Person is afraid of needles? Benfit outway the risk, insulin,glp-r1a, •h/o bladder cancer: avoid TZD and DABAFLIZOIN

What if....

•Pregnant/Lactating?: ONLY USE INSULIN IS THE SAFIEST, •Renal insufficiency (SCr 1.8 mg/dL, eGFR 25 ml/min)?: not use metformin, ALL GLIPTIN HAVE DOSE ADJUSTMENT , •Cirrhosis?-AVOID METFORMIN AND TZD (DUE TO DAMAGE TO THE LIVER) •Chronic NYHA Class 3 HF? GOOD SGLT2 (ALL EXEPT ERTHRO), AVOID-TZD, ACTOS, ZAPTAGLIPTIN AND ALLO •13 years old?: TYPE 1-ONLY USE INSULIN, TYPE2: METFORMIN, MAYBE VICTOZA AND LIRAGLUTIDE •85 years old? And fall risk is a concern?: AVOID SULFLYNEUROS (GLIPIZIDE IS GOOD) .HTN AND MAY LEAD TO FALL RISK: ONE THAT CAUSE DEHYDRAGTION SGLT2 INHIBITORS •h/o thyroid cancer: ALWAYS ASK WITH. GLIP1RAS •h/o pancreatitis: USE WITH CAUTION WITH GLIP1 AND DPP4 INHIBITORS

Preventing DM complications

•Renal (UAER = UACR): elevate ULR (urine) if greater than 30mg/g and have elevated bp then pt should be on a ACE or ARBs •Eye care • •Foot care: prevent amputation •A1c: most effective at preventing the progression of microvascular disease (ADA less than 7%) •BP goal: 2 diffrent guidlines ADA-less than 140/90 unless 10 year ASCVD risk that is greater than 15%, then bp goal is less than 130/80. ACC/AHA also recommends 130/80 •Cholesterol: all pt's between the age 40-75 should be on a moderate intensity statin

Patients without health insurance

•U-100 insulin syringes are available without a prescription in most states •Regular insulin and NPH insulin vials are available over the counter -walmart brand have the cheapest 25$

GLP-1 agonist + basal insulin

•Xultophy(PREFERRED) - liraglutide/insulin degludec - (dosed by units of insulin) 16 units SC daily, titrate by 2 units every 3-4 days prn •Soliqua - lixisenatide/insulin glargine • if on < 30 units insulin or on lixisenatide: 15 units SC once daily • If on 30 -60 units of insulin then start at 30 units SC once daily •titrate by 2 to 4 units every 7 days as needed