Endocrine 1 - Diabetes

Rapid Acting Insulin

• Lispro

• Aspart

• Glulisine

Short Acting Insuline

Regular

Intermediate Insulin

NPH

Intermediate-Long Insulin

Determir

Long Acting Insulin

• Glargine

• Degludec

GLP-1 Agonist Suffix

-glutide

SGLT-2 Inhibitors Suffix

-flozin

Metformin name

Binguanide

Sulfonylureas Prefix

• Gly-

• Gli-

Meglitinies Suffix

-linide

Thiazolidinediones Suffix

-glitazones

DPP-4 Inhibitors Suffix

-gliptin

Type 1 Diabetes

Deficiency of insulin

WILL ALWAYS REQUIRE INSULIN!!!!!!

Type 2 Diabetes

Resistant to action of insulin (ORAL meds and in some instances insulin)

• Pt may experience sustained hyperglycemia, polyuria, polydipsia, ketonuria, weight loss

DM1 and DM2 Diagnosis

• Fasting Glucose >126 mg/dL

• Random plasma glucose > 200 mg/dL & symptomatic

• Elevated plasma glucose post oral glucose tasting test (2 hours after 75g oral glucose ingestion of > 200 mg/dL)

• Hemoglobin A1C > 6.5%

• NEED TWO ABNORMAL RESULTS FOR DIAGNOSIS - from same sample or two different samples

What can cause a false reading on A1C?

• G6PD

• HIV

• Sickle cell

Goals of Therapy in DM

• Prevent acute and chronic complications

Acute DM complications

• Hypoglycemia

• DKA

• HHNS

Chronic DM Complications

• Microvascular

• Macrovascular

Microvascular Complications

Small Vessel Diseases!!!

• Retinopathy

• Neuropathy

• Nephropathy

Macrovascular Complications

Major Vessels!!!

• Cardiovascular

• Cerebrovascular

• Peripheral vascular

What reduces microvascular complications?

Glycemic control!!!!

What reduces macrovascular complications?

Cholesterol control!!!

• What medications are best for cholesterol care?

  • Statins

  • Ezetimibe

BP Control

Reduces macro AND micro complications!!!!!

• Beta Blockers: “-lol”

• ACE Inhibitors: “-pril”

• ARBS: “-sartan”

• Calcium Channel Blockers: Amlodipine, Diltiazem, and Verapamil

Prediabetes

• Impaired fasting glucose between 100-125 mg/dL

• Impaired glucose tolerance test

• May reduce risk for developing T2DM

  • May reduce with diet changes + Exercise + Oral antidiabetic drugs!!! (Metformin)

• Many people who meet this criteria never develop diabetes  even if do not take precautions

Diet for Prediabetes

DIET IS CRUCIAL - DO NOT RESORT TO PHARM FIRST!!!!!!!!

T1 DM

Pancreatic beta cell destruction: INSULIN REQUIRED

T1 DM Tx: Basal

Steady amount for the FULL DAY!!!!!!

• Long Acting (Glargine) - Just one dose for the day!!

• Intermediate (if cannot afford Glargine) - NPH x 2 doses in day!!

T1 DM Tx: Bolus

Post prandial (eating) glucose excursions

• Short Acting: Regular

• Rapid Acting: Lispro + Aspart

  • 50% split 3 ways (given PRIOR to each meal) - Do not given until see the tray!!!!!

Fun Fact about Glargine

It CANNOT be mixed with anything

Insulin MOA

Works by increasing peripheral glucose uptake by skeletal muscle and fat

NPH fun fact

Only insulin that is cloudy!!!

For SQ injections:

Rotate sites every few days to prevent lipodystrophy

IV Infusion with Insulin

REGULAR INSULIN ONLY

Use? 

• For DKA pt going into surgery

• Hyperkalemia

How should the appearance of insulin be?

Clear except for NPH

Mixing Insulin

1. Air into the NPH (cloudy)

2. Air into the short acting

3. Pull up the short acting

4. Then pull of the NPH

CLOUDY, CLEAR, CLEAR, CLOUDY

Have accurate insulin syringe size!!!

DOUBLE CHECK UNITS ALWAYS

Complications of Insulin Tx

• Hypoglycemia

• Lipohypertrophy

• Allergic rxn

• Hypokalemia

• Diabetes insipidus (polyuria)

Insulin Storage

• Unopened vials should be stored in the fridge until needed NEVER FROZEN

  • Used until expiration date IF KEPT IN FRIDGE AND NOT OPENED (3 months

• After opening, can be kept outside of fridge FOR UP TO 1 MONTH without significant loss of activity (DATE THE VIALLLLLLL)

• Stable 1 month room temp

• Keep out of direct sunlight and extreme heat)

• If have prefilled syringes, needle needs to be UPRIGHT in fridge

Assessing Therapy & Dosage Adjustment

• Know you goal fasting and post-prandial blood sugars

• Identify where in the day problems occur for the pt

• Determine which insulin can affect problem areas

• Adjust medication

HTN in T1 DM

ACE-I (-pril) & ARB (-sartan)

• Can reduce the risk of diabetic nephropathy in those with increased albumin to creatinine ratio

Dyslipidemia in T1 DM

STATIN

• Self monitoring of BG: Check 6-7x/day

• Dexcom = 24/7 monitoring!!

• Total number of carbs, not the type, is MOST important!!!!

Beta Blockers in T1 DM

Blocks signs of hypoglycemia so BE CAREFUL!!!!

• Tremor/tachy

• Monitor

  • Sweating

  • Hunger

  • Irritability

T2 DM

Insulin Resistance + Decreased pancreatic insulin output

• Most of their meds are ORAL

• Should be screened and treated for: 

  • Retinopathy

  • Nephropahty

  • HTN

  • Neuropathy

  • Dyslipidemias

• Glycemic control + Modified diet + Exercise + Drug Therapy

Monitoring Tx for T2 DM

• Remember with T1 monitor BG before and after meals (up to 6x/day)

• With T2, once or twice a week or every other week!!!

70-130 mg/dL before meals

100-140 mg/dL at bedtime

Hemoglobin A1C

Provides an index of average glucose levels over the past 2-3 months

• < 7% is good for most patients

T2 DM Tx

• Metformin is initial DOC

• GLP-1 agonist (-tide) & SGLT-2 inhibitors (-flozin) are first line drugs as well d/t weight loss and glucose control!!

Early Tx of Insulin Therapy

• 10+ A!C (> 7 is good) This is like 240 BG

• Glucose > 300-350 mg/dL

• S/S of hyperglycemia

• Positive for urine ketones (proteins!!)

USE 3-4 PO MEDS PRIOR TO INSULIN UNLESS DM POORLY CONTROLLED

Insulin Effects

• High efficacy

• Weight gain

• Hypoglycemia

Binguanides: Meformin MOA

• Inhibits glucose production in the LIVER

• Reduces glucose absorption

• Sensitizes insulin receptors in target tissues

Metformin Benefits

• Good A1C reduction

• Cheap

• High Efficacy

• SOME WEIGHT LOSS

• Some possible lipid benefits

• Possible CV benefit (obese pt)

Metformin Side Effect Profile

• Gastrointestinal: N/V/D; Cramps

• Lactic Acidosis: Pt with reduced renal function (Hold if GFR < 30)

  • Dose reduction if < 45 mL/min

• VITAMIN B12 DEFICIENCY!!!! - TEST PERIODICALLY ESPECIALLY IN ANEMIA AND NEUROPATHIES

  • Give B12!!

Metformin In-patient issues

• Hold for 48 hours when using IV contrast dye (acute renal failure)

• Check creatinine before starting again

SGLT-2 Inhibitors (-flozin)

• Intermediate efficacy

• No hypoglycemia

• Weight loss

• ASCVD/CHF benefits

• High cost

• Oral

SGLT-2 I Black Box

BLACK BOX FOR RISK OF AMPUTATION

SGLT-2 I Risks/SE

• Bone fractures

• DKA risk

• GU infections (UTI)

• Risk of volume repletion (hypotension)

• Increase LDL cholesterol

• Risk for Fournier’s gangrene

GLP1 Receptor Agonist (-Tide)

• High efficacy

• Best efficacy for weight loss (decreased appetite)

• HIGH cost

• SQ 

• CVD risk reduction with liraglutide + semaglutide

GLP1 Receptor Agonist Black Box

BLACK BOX FOR THYROID CANCER + MEDULLARY THYROID CARCINOMA CONTRAINDICATION

GLP1 Receptor Agonist SE

• GI Common: N/V/D

• Injection site rxns

• Acute pancreatitis risk - MONITOR AMYLASE LEVELS

DPP-4 Inhibitors (-Gliptin)

• Intermediate Efficacy

• High Cost

• Neutral Weight Change

• Potential risk of CHF - Saxagliptin

• Oral

DPP-4 Inhibitors (-Gliptin) MOA

Sitagliptin

• Enhances the actions of incretin hormones

• Stimulates glucose dependent release of insulin

• Suppresses postprandial release of glucagon

• Generally well tolerated

DPP-4 Inhibitors (-Gliptin) SE

• Potential risk of acute pancreatitis

• Joint pain

Thiazolidenidiones (-Glitazone) MOA

Reduces glucose levels by decreasing insulin resistance

Thiazolidenidiones (-Glitazone)

• High efficacy

• Weight GAIN

• Low cost

Thiazolidenidiones Black Box

BLACK BOX FOR CHF!!!!! - FLUID RETENTION

Thiazolidenidiones AE

• Increased fracture risk: Not good with osteopenia/osteoporosis

  • Bladder cancer

  • Hepatotoxic: Monitor LFTs

Thiazolidenidiones DI

Do not give with

• Gemfibrozil (for high cholesterol)

• Do NOT give with insulin!!!

BOTH PROMOTE FLUID RETENTION

Rosiglitazone (Avandia)

Minor SE:

• Renal retention of fluid

• Raises levels of plasma lipids

DI:

• Insulin also promotes fluid retention!!! - Combo - Increased risk for HF

• Gemfibrozil (Lopid) - raise levels of rosiglitazone

Pioglitazone (Actos)

Newest glitazone!!!

• Hepatotoxicitt: Monitor LFTs

AE: Mild

• URI, HA, sinusitis, myalgia

• Promotes water gain

Drug interaction:

• Gemfibrozil

Sulfonylureas (Gli- ; Gly-)

• High efficacy

• Can cause hypoglycemia

• Can cause weight GAIN

• Neutarl ASCVD/CHF effect

• Low Cost

• Oral

• Neutral in kidney disease

Sulfonylureas (Gli- ; Gly-) FDA Special Warning

Increased risk of cardiovascular mortality based on studies of older generations

Meglitinides

Not used as often - Rapid Sulfonlyurea

• Repaglinide (Prandin) & Nateglinide (Starlix) - Work quick! Take with food!

• Same MOA of sulfonylureas

• AE: Hypoglycemia

Meglitinide Benefits

• Better focus on post-prandial BG than sulfonylureas

• Can use if renal impairment exists

Meglitinide Risks

• Weight gain

• Cost

• Hypoglycemia

• Mealtime dosing

DKA

T1 DM

• RAPID onset

• Significantly increased blood glucose, ketoacidosis, dehydration

DKA S/S

• Thirst

• Abdominal pain

• Mental status change

• Fruity breath

• Tachycardia

• LOW Na+

• HIGH K+

• Ketones in urine

DKA Tx

• Check K+ BEFORE giving insulin

  • Hold if K+ baseline is < 3.3)

• Find and FIX underlying cause

• NOT ABOUT NORMALIZING GLUCOSE

• Fluid replacement!!!! - IV Na+ % depends on serum Na)

• IV insulin: 0.1 unit/kg bolus, 0.1 unit/kg/drip (double drip if minimal response)

• Once we meet glucose, pH and bicarb goal: Convert IV drip to SQ insulin

HHNS

T2 DM

• LARGE amount of GLUCOSE excreted in urine

• Dehydration and loss of blood volume!!!!

• No fruity breath

• GRADUAL ONSET - metabolic changes begin a month or 2 before s/s appear

• Blood thickens (becomes sluggish)

• If untreated, can lead to coma, seizures, death

HHNS Tx

• Correct HYPERGLYCEMIA and DEHYDRATION with

  • IV insulin

  • Fluids

  • Electrolyes

• SLOWLY titrate down

Hypoglycemia

• Preferred Tx is IV GLUCOSE (immediately raises blood glucose level)

• Glucagon can be used if IV glucose is not available

  • Will NOT work in starvation (MUST have glucose)

  • Delayed elevation of blood glucose

Diabetic Nephropathy Prevention

Normal creatinine < 30 and increased urinary secretion

• ACE-I or ARBs Tx of choice!!!

CVD Prevention

BP management WITHOUT increased urine albumin

• ACE/ARB or thiazide or amlodipine (dCCB)

BP mgmt  WITH increased urine albumin

• ACE/ARB first line

Lipid Management

• DM + Overt CVD = High dose STATIN

• DM + age 40-75: Moderate dose STATIN

Antiplatelet

• ASA

• Clopidogrel is alternative with ASA allergy

Disease Prevention with DM: Drug Regimen

• Metformin

• BP (ACEI)

• Lipids (STATIN)

• Antiplatelet (ASA)