Endocrine Diabetes Flashcards
Hypoglycemia Whipples Triad
(3)
- Symptoms suggestive of hypoglycemia
- A documented low blood glucose level (<65)
- Need to ro lab error (FSG and plasma glucose both prone to false lows)
- Improvement of symptoms and glucose levels by administration of glucose
hypoglycemia is a constellation of symptoms depending on the patient bc people’s baselines are different - runners have baseline blood sugars of 65
Hypoglycemia Symptoms
Autonomic Symptoms (glucose <65)
- Adreno-Medullary-Neural-Sympathetic = Tr_____, anx_____, pal______
- Neural-Parasympathetic = H_____, sw______, para______
Neuroglycopenic symptoms (glucose <50)
- Glucose <50 = ____Ness, _____ vision, impaired cog_____ (leth_____, conf____)
- Glucose <30 = C____, Seiz______
Autonomic Symptoms (glucose <65)
- Adreno-Medullary-Neural-Sympathetic = Tremors, anxiety, palpitations
- Neural-Parasympathetic = Hunger, sweating, parasthesias
Neuroglycopenic symptoms (glucose <50)
- Glucose <50 = Weakness, Blurred vision, impaired cognition (lethargy, confusion)
- Glucose <30 = Coma, Seizures
long standing diabetics sometimes don’t feel low blood sugar so we really worry about Type 1’s especially - (Hypoglycemia awareness)
Causes of Hypoglycemia
In a Medicated Individual
Drugs
- Ins_____
- Sulf_______ (especially in elderly!)
- Alc_____
- Others
Critical Illness
- Hepatic, renal, or cardiac failure
- S______ (including malaria)
Hormone deficiency
- Cor______
- Gluc_____ and epinephrine (in insulin-deficient diabetes mellitus)
- Severe ____thyroidism
- Adrenal ______
Non___ cell tumor
Drugs
- Insulin
- Sulfonylurea (especially in elderly!)
- Alcohol
- Others
Critical Illness
- Hepatic, renal, or cardiac failure
- Sepsis (including malaria)
Hormone deficiency
- Cortisol
- Glucagon and epinephrine (in insulin-deficient diabetes mellitus)
- Severe hypothyroidism
- Adrenal insufficiency
Nonislet cell tumor
- sulfonylureas are falling out of favor*
- Sulfonylurea + insulin is always a wrong answer - can especially precipitate hypoglycemia especially in elderly*
Causes of Hypoglycemia
Seemingly Well Individual
Endogenous hyperinsulinism
- In_____oma (↑ _-peptide)
- Functional __-cell disorders (nesidioblastosis)
- Noninsulinoma pacreatogenous hypoglycemia
- Post gastric _____ hypoglycemia
Accidental, surreptitious, or malicious hypoglycemia
Artifactual hypoglycemia - poor peripheral ______
Endogenous hyperinsulinism
- Insulinoma (↑ C-peptide)
- Functional B-cell disorders (nesidioblastosis)
- Noninsulinoma pacreatogenous hypoglycemia
- Post gastric bypass hypoglycemia
Accidental, surreptitious, or malicious hypoglycemia
Artifactual hypoglycemia - poor peripheral perfusion
Hypoglycemia- Variability
- Diabetes (1) >>> Diabetes (1), because:
- Deficits in glucagon
- Medication used more likely to precipitate hypoglycemia
- Recurrent hypoglycemia can lead to hypoglycemic _______ (due to impaired counterregulatory system)
- DM1 patients receiving _____ therapy have a threefold increased risk of severe hypoglycemia
- ______ also more prone due to impaired counterregulatory mechanism and impaired appetite
-
DM1 >>> DM2, because:
- Deficits in glucagon
- Medication used more likely to precipitate hypoglycemia
- Recurrent hypoglycemia can lead to hypoglycemic unawareness (due to impaired counterregulatory system)
- DM1 patients receiving intensive therapy have a threefold increased risk of severe hypoglycemia
- Elderly also more prone due to impaired counterregulatory mechanism and impaired appetite
Rule of 15s
(conscious patient)
=
When glucose < 70, start by
- 15G-20G CHO PO (e;g ½ cup orange juice, glucose tablets, hard candy, glucose paste).
- Recheck in 15 min, and repeat treatment if still < 100.
Rule of 15s
(Severe hypoglycemia, unable to take PO)
=
- Give 20-50ml 50% dextrose IV then D5W IV infusion, to maintain blood glucose > 100mg/dl.
- Glucagon 1mg IM as initial therapy, if patients can’t take PO or no IV access.
All patient’s at risk for hypoglycemia should be given an Rx for glucagon (I give to all my Type 1 Patients for emergencies)
Diabetes Transition of Care
Acute (2)
Subacute (1)
Chronic (2)
(1) = ______ deficiency of insulin leading to state of starvation
(1) = ______ insulin deficiency and profound dehydration
Diabetic Ketoacidosis (DKA) = Significant deficiency of insulin leading to state of starvation
Hyperglycemic Hyperosmolar State (HHS) = Relative insulin deficiency and profound dehydration
Causes of DKA
- ______ - (40%) – impaired insulin secretion or insulin resistance (DKA frequent presentation of COVID PNA)
- Inadequate insulin treatment or non_______ (25%).
- _____ -onset diabetes (15%)
- ________ diseases (MI, stroke) – increase in counterregulatory hormones
- Acute St_____
- Insulin pump f______
- Infection - (40%) – impaired insulin secretion or insulin resistance (DKA frequent presentation of COVID PNA)
- Inadequate insulin treatment or noncompliance (25%).
- New-onset diabetes (15%)
- Cardiovascular diseases (MI, stroke) – increase in counterregulatory hormones
- Acute Stress
- Insulin pump failure
DKA Patho
DKA Management
Hyperglycemic Hyperosmolar State (HHS)
- ~33% new onset diabetics present with HHS
- Non-ad______ or in______ to receive medical therapy
- In______
- Often, a preceding ______ results in several days of increasing de_______.
- ~33% new onset diabetics present with HHS
- Non-adherence or inability to receive medical therapy
- Infection
- Often, a preceding illness results in several days of increasing dehydration.
Hyperglycemic Hyperosmolar State Key Features
- Hyperglycemia Hyperosmolar State (HHS) is a metabolic derangement that occurs principally in patients with T__DM.
- Severe _______ and n_______ deficits.
- Characterized by hyperglycemia, _____osmolarity, _____ketosis
- (BUT ketosis ≠ Type 1).
-
HHS and DKA can overlap!
- “Ketosis Prone”
- SGLT2
- Infection (lots of DKA in COVID-19)
- Hyperglycemia Hyperosmolar State (HHS) is a metabolic derangement that occurs principally in patients with T2DM.
- Severe dehydration and neurologic deficits.
- Characterized by hyperglycemia, hyperosmolarity, minimal ketosis
- (BUT ketosis ≠ Type 1).
-
HHS and DKA can overlap!
- “Ketosis Prone”
- SGLT2
- Infection (lots of DKA in COVID-19)
HHS Patho
HHS Management
Treating Diabetes in the Acute/Subacute Setting
- Most anti-diabetic oral agents _____ while hospitalized
- Until more data is available Type 1 and Type 2 Diabetes are often treated similarly though are different diseases.
- Several unavoidable problems:
- Diabetic meal? (“consistent carb”)
- Unpredictable procedures
- Patient “refusal” of insulin
- Change in patient appetite
- Steroids
- Dialysis
- Infections
- Outside meals…
- Most anti-diabetic oral agents stopped while hospitalized
- Until more data is available Type 1 and Type 2 Diabetes are often treated similarly though are different diseases.
- Several unavoidable problems:
- Diabetic meal? (“consistent carb”)
- Unpredictable procedures
- Patient “refusal” of insulin
- Change in patient appetite
- Steroids
- Dialysis
- Infections
- Outside meals…
Treating Diabetes in the Subacute Setting
Should we use sliding scales?
- Sliding scales are an antiquated and dangerous way to manage sugar control in any setting:
- By definition, giving insulin based upon pre-meal glucose is reacting to high sugars that have been present since the previous meal
Basal-Bolus Insulin
How much insulin a day should Type 1 DM, and organ failure patients receive (CHF, ESRD, liver failure)?
How much insulin a day should stable type 2 DM patients get?
Basal Insulin ___-____% of TDD
How much percentage of the total daily dose of insulin should be bolus insulin (the insulin we give in addition to basal insulin for meals)?
0.2-0.3 units/kg/day in Type 1/End organ failure
0.5 units/kg/day in stable medical patients with Type 2 DM
Basal Insulin 40-50% of TDD
Bolus Insulin should be 50-60% of TDD
Diabetes Management
Target glucose for majority of patients =
- Basal Insulin without bolus may be preferred in many patients. DPP4s are safe in the hospital and may be added in many for post-prandial control
- Basal plus bolus (with meal) insulin is essential for patients with Type __ Diabetes and a diabetes specialist should always be consulted to comanage
- If they have insulin pump sometimes best for patient to manage glucose
- Never ____ basal insulin in a Type 1 Diabetic even if not eating!!
- B____/_______ insulin remains standard of care for most diabetics whether they have Type 1 or Type 2 Diabetes.
Target glucose 140-180 for majority of patients
- Basal Insulin without bolus may be preferred in many patients. DPP4s are safe in the hospital and may be added in many for post-prandial control
- Basal plus bolus (with meal) insulin is essential for patients with Type __ Diabetes and a diabetes specialist should always be consulted to comanage
- If they have insulin pump sometimes best for patient to manage glucose
- Never stop basal insulin in a Type 1 Diabetic even if not eating!!*
- Basal/Bolus insulin remains standard of care for most diabetics whether they have Type 1 or Type 2 Diabetes.
Diabetes and COVID
Is a higher A1C associated with increased mortality when hospitalized for covid?
Does diabetes increase risk for mortality when hospitalized for covid?
Mortality rate is close to 50% higher in those with covid-19 presenting with ___
Hyperglycemia is now further compounded/complicated by positive outcome data on high dose ______ and mortality
Pre-hospitalization A1c – unclear tight glycemic control changes outcomes, A1c NOT associated with mortality, Tight glycemic control in hospital may be beneficial however no data is available to show that tight glycemic control during hospitalization changes outcomes
Compared to pt without diabetes, individuals with diabetes showed higher levels of IL-6, ferritin, hsCRP and ddimer upon admission, overall mortality 33.1%
Mortality rate is close to 50% higher in those with covid-19 presenting with DKA
Hyperglycemia is now further compounded/complicated by positive outcome data on high dose dexamethasone and mortality
Types of Diabetes
- Type 1 diabetes =
- Type 2 diabetes =
- _______ Diabetes Mellitus (GDM)
- Other specific types of diabetes due to other causes:
- ____genic diabetes syndromes (>20 types)
- Diseases of the exocrine pancreas, e.g., cystic ____ , chronic p_______
- D____- or chemical-induced diabetes
- In_______ disease (ie hemochromatosis)
- Type 1 diabetes = β-cell destruction
- Type 2 diabetes = Progressive insulin secretory defect
- Gestational Diabetes Mellitus (GDM)
- Other specific types of diabetes due to other causes:
- Monogenic diabetes syndromes (>20 types)
- Diseases of the exocrine pancreas, e.g., cystic fibrosis, chronic pancreatitis
- Drug- or chemical-induced diabetes
- Infiltrative disease (ie hemochromatosis)
Old Paradigms
- Type 1 Diabetes use to be thought of as
- Age?
- Insulin?
- Onset
- Type 2 Diabetes use to be thought of as
- Age?
- Insulin?
- Onset?
- Type 1 Diabetes use to be thought of as
- Young <20
- Insulin dependent
- Abrupt
- Type 2 Diabetes use to be thought of as
- Older >60
- May not need insulin
- Insidious Onset
New Paradigms
What has changed? Why?
Obesity higher in what populations? what income? What education levels?
- We are now seeing older patients with type 1 and younger patients with type 2 because more obesity over the past 20 years = More diabetes*
- Obesity higher in Hispanic/Black ethnicity, Obesity higher in lower income, Obesity higher in those with lower levels of education*
Metabolic Syndrome and Diabetes
=
- 87% of patients with diabetes have metabolic syndrome
- Obesity and diabetes should not be thought of as two separate diseases - they largely overl
Normal Regulation of Glucose
Hyperglycemia Patho
Diabetes Patho
Overtime what happens what builds up in the body? leading to?
Eventually overtime, there is a buildup of inflammatory factors that leads to cardiovascular disease
Natural History of Type 2 Diabetes
What happens with B cells?
What happens with the body’s response to insulin?
Beta Cell Dysfunction
Insulin Resistance
What needs to happen before a patient with type 2 diabetes even presents with hyperglycemia?
Many things happen before a patient even presents with hyperglycemia → diabetes does NOT start with hyperglycemia → there are many variables which is why we have many tools/medications to use when treating diabetes
Managing Diabetes
FDA Approved Obesity Drugs
(4)
Orlistat
Liraglutide/Semiglutide
Phentermine-topiramate
Bupropion-naltrexone
- orlistat bascially inhibits fat absorption and you end up with fatty stools - not great long term
- With all of these meds - they can’t be suddenly stopped
- given for a 1 year and weight is lossed then they are stopped bc not approved by insurance for chronic therapy and they gain all the weight back
- ozempic (semiglutide) - new and looking pretty good - not shown in chart
Bariatric Surgery and Weight Loss
Overall difference between control and bariatric surgery?
Which type of bariatric surgery has highest long term percentage weight loss?
Compared with control, better overall weight loss
Gastric bypass best overall weight loss compared to other bariatric surgeries
Type 2 DM Pharmacotherapy History
- ______ were mainstay for a long time
- Biguanide = ______ then approved in the 90’s
- In 2015, order of which medications to choose from was not clear → we started with _____ and then it came down to c____ and tol______ when adding other medications
- Sulfonylureas were mainstay for a long time
- Biguanide = metformin then approved in the 90’s
- In 2015, order of which medications to choose from was not clear → we started with metformin and then it came down to cost and tolerability when adding other medications
Diabetes Medications
Diabetes Medications and Effect on Weight
Which Diabetes medications cause weight gain? (3)
Which Diabetes medications are best at causing weight loss? (2)
- Insulin, Sulfonylureas, and Meglitinides (glinides) CAUSE WEIGHT GAIN*
- GLP-1 analogues and SGLT inhibitors BEST AT CAUSING WEIGHT LOSS*
Potential CVD Benefits of Metformin
- MI ______ 39% c/w conventional rx
- All cause mortality ______ 36%
- Metformin is better than _____ at decreasing MI risk
- MI reduced 39% c/w conventional rx
- All cause mortality reduced 36%
- Metformin is better than sulfonylureas at decreasing MI risk
Thiazolidinedione Pros
Pleiotropic effects
- Decreases _____ glucose production
- Decreases liver _____
- Decreases NASH =
- Increases _____ uptake
- Decreases Ath_______
Potent = brings down A1C by __%
Pleiotropic effects
- Decreases hepatic glucose production
- Decreases liver steatosis
- Decreases NASH = Non-alcoholic steatohepatitis
- Increases glucose uptake
- Decreases Atherosclerosis
Potent = brings down A1C by 2%
2022 Type 2 Diabetes Guidelines
- First line therapy =
- If ASCVD high risk =
- If HF+ =
- If CKD+ =
- First line therapy = Metformin
- If ASCVD high risk = SGLT-2i or GLP-1 RA
- If HF+ = SGLT-2
- If CKD+ =SGLT-2 or GLP-1 RA
2022 Type 2 Diabetes Guidelines
- Minimize Hyperglycemia =
- Promote Weight Loss =
- Consider Cost and Access =
- Minimize Hyperglycemia =
- No/low inherent risk of hypoglycemia with DPP-4, GLP-1, SGLT2, TZD
- Careful to choose sulfonylureas or basal insulin with lower risk of hypoglycemia
- Promote Weight Loss =GLP-1 RA or SGLT-2i
- Consider Cost and Access = Sulfonylureas, TZD, certain insulins
Treatment Goals Vary
- High risk of hypoglycemia?
- Newly diagnosed vs. long standing?
- Long life expectancy?
- No comorbidities?
- No vascular complications?
- What type of patient personality should you be more stringent with A1C target?
- What type of resources and support system can you be more stringent with the A1C target?
- High risk of hypoglycemia = less stringent
- Newly diagnosed = more stringent
- Long life expectancy = more stringent
- No comorbidities = more stringent
- No vascular complications = more stringent
- What type of patient personality should you be more stringent with A1C target = highly motivated, excellent self-care capabilities
- What type of resources and support system can you be more stringent with the A1C target = readily available social support
- Ie. treat a young athlete with diabetes to an A1C of 6
- But an elderly patient with lots of hypoglycemia risk do not want such a low A1C
Type 1 Diabetes Chronic Management
Incidence of type 1 DM
- Incidence of T1DM has been __creasing worldwide by 2-5%
- ~ 1 in 300 people in the US has Type 1 DM by age 18.
- T1DM accounts for __-__% of all Diabetes
Inheritance of Type 1 Diabetes* =
- Incidence of T1DM has been increasing worldwide by 2-5%
- ~ 1 in 300 people in the US has Type 1 DM by age 18.
- T1DM accounts for 5-10% of all Diabetes.
Inheritance of Type 1 Diabetes* = Low genetic component in type 1 compared to type 2
Type 1 Diabetes Patho
Match each description with each stage of Type 1 Diabetes
- What stage do you feel symptomatic?
- When are you still normoglycemic?
- Rule of Thumb: “easy to treat” type 1 patients still?
- Term for type of diabetics that have lost all beta cell activity (as well as alpha cell/glucagon?
- Stage 3
- Stage 1
- “Easy to treat” diabetics still make insulin
- “Brittle diabetics” have lost all beta cell activity and alpha cell/glucagon
Insulin Regimen in Type 1 Diabetes
Should mimic what pattern?
Mimics Normal Diurnal Insulin Pattern
Basal insulin + Prandial Bolus Insulin doses with meals
Diabetes Technology (lots out there)
What tech is a “closed loop”
Continuous glucose monitoring with insulin pump is a “closed loop” (Dexcom G6, Freestyle Libre, Freestyle Libre 2)
- inPen - Bluetooth connected pen, insulin delivery recorded on smart phone
- FDA approved insulin pumps (Medtronic 670g “closed loop”, Omnipod, T-slim control IQ automatically can give corrections and Basal IQ predicts and reduces low) - out of pocket cost ~10k, iLet “bionic pancreas” delivers glucagon and insulin not approved yet
