Exam 2: DM Flashcards
Def: Basal Insulin
Longer acting insulin that is meant to cover the body’s basal metabolic
insulin requirement (regulating hepatic glucose production); basal
insulin controls blood glucose in the fasting state
Def: Bolus insulin
Short or rapid acting insulin which is meant to reduce glycemic
excursions after meals
Def: Diabetic ketoacidosis
Serious complication related to a deficiency of insulin and increase in
insulin counter-regulatory hormones
Def: Dipeptidyl-peptidase 4
Enzyme that rapidly degrades active incretin hormones after they are
released
Def: Euglycemia
Normal concentration of glucose in the blood. Also called normoglycemia
Def: Fasting
No eating for the past 8 or more hours
Def: Glucose
Major source of energy for the body
Def: Glycogen
The stored form of glucose in the liver and skeletal muscle
Def: Glycogenesis
The synthesis of glycogen from glucose that occurs chiefly in the livery and skeletal muscle
Def: Glycogenolysis
The conversion of glycogen to glucose in the body
Def: Gluconeogenesis
The synthesis of glucose in the body from non-carbohydrates, such as proteins and fats
Def: Hemoglobin A1C
A value that represents the percent of hemoglobin in the blood that is
glycosylated. This percent reflects the glycemic control over the past 2 to 3 months
Def: Hyperosmolar hyperglycemic state
Serious condition characterized by hyperglycemia, hyperosmolarity and dehydration and the absence of ketoacidosis that may occur in type 2 diabetes
Def: Hypoglycemia
Most common acute complication of diabetes; occurs from a relative excess of insulin in the blood and is characterized by below-normal blood glucose levels
Def: Insulin resistance
the inability of peripheral target tissues to respond properly to normal circulating concentrations of insulin
Def: Ketosis
A condition characterized by the abnormal accumulation of ketones in the body tissues and fluid
Def: Lipolysis
Breakdown of fats and lipids to fatty acids (alternative fuel source)
Def: Macrovascular disease
Large blood vessels disease; most commonly affected are the coronary arteries, the large arteries in the brain, and large arteries in the periphery
Def: Microvascular complications
Small blood vessel disease caused by long term exposure to hyperglycemia; most commonly affects the eyes, kidneys, and nerves
Def: Nocturia
Excessive urination at night
Def: Persistent albuminuria
A term that reflects when the kidney is allowing an abnormal amount of protein (> 30 μg/mg) to be filtered through the glomerulous.
Marker used in addition to serum creatinine and GFR to stage chronic
kidney disease
Def: Polydipsia
Excessive thirst
Def: Polyphagia
Excessive hunger
Def: Polyuria
Excessive urination
Abbreviation: A1c
Hemoglobin A1c
Abbreviation: ASCVD
Atherosclerotic cardiovascular disease
Abbreviation: BG
Blood glucose
Abbreviation: BGM
Blood glucose monitoring
Abbreviation: CGM
Continuous glucose monitoring
Abbreviation: CKD
Chronic kidney disease
Abbreviation: CVOT
Cardiovascular outcome trial
Abbreviation: DKA
Diabetic ketoacidosis
Abbreviation: DPP-4
Dipeptidyl-peptidase 4
Abbreviation: FPG
Fasting plasma glucose
Abbreviation: GDM
Gestational diabetes mellitus
Abbreviation: GLP-1
Glucagon-like polypeptide 1
Abbreviation: hHF
Hospitalization for heart failure
Abbreviation: HHS
Hyperosmolar hyperglycemic state
Abbreviation: IFG
Impaired fasting glucose
Abbreviation: IGT
Impaired glucose tolerance
Abbreviation: MACE
Major adverse cardiovascular event
Abbreviation: OGTT
Oral glucose tolerance test
Abbreviation: PPG
Post prandial glucose
Abbreviation: SGLT-2
Sodium-glucose contransporter 2
Abbreviation: T1DM
Type 1 diabees
Abbreviation: T2DM
Type 2 diabetes
Abbreviation: TIR
Time in range
Abbreviation: UACR
Urine albumin to creatinine ratio
3 Hormones that control blood glucose
- Pancreatic hormones
- Counter-regulatory hormones
- Gut-derived hormones
Def: Pancreas
Glandular organ that secretes digestive enzymes and hormones
Pancreas: Plays a fundamental role in ___ and ____
Digestion and food energy utilization
Def: Exocrine
Digestion break down
Def: Endocrine
Regulates immediate utilization and storage of food energy
Pancreas: Endocrine function: Alpha cells
Secrete glucagon
Effect the breakdown of liver glycogen and increase glucose levels in the blood
Pancreas: Endocrine function: Beta cells
Secrete insulin and amylin
Increase uptake of glucose into cells and facilitate conversion of glucose to glycogen in the liver
Insulin is a(n) ____ hormone
anabolic
Insulin is a key regulatory hormone of ______
glucose disappearance
Insulin secretion is regulated by __ and ___ hormones
Glucose and incretin
Insulin is ___ during absorptive state and ____ during post-absorptive state
Increased and decreased
Insulin effects in liver, muscle, and adipose tissues
Inhibits hepatic glucose production and glucagon secretion
stimulate glycogenesis in liver
stimulates glucose uptake in muscle fat tissue
Amylin co-secreted with insulin in response to ___
nutrient stimuli
Amylin inhibits:
postprandial glucose excursions
- suppresses digestive secretions
- slows gastric emptying
Glucagon is a(n) ___ hormone
catabolic
Glucagon is a key regulatory hormone of ____
glucose appearance
T/F: Glucagon works antagonistically to insulin
True
Glucagon release is inhibited by
Increased glucose levels and presence of fatty acids and ketones
Glucagon release is stimulated by
decreased glucose levels and presence of amino acids
Def: Counter-regulatory hormones
Counteract the storage functions of insulin in regulating blood glucose levels during periods of fasting, exercise, stress, and other situations that either limit glucose intake or deplete glucose stores
4 Counter-regulatory hormones
Glucagon
Epinephrine
Growth hormone
Cortisol
4 Counter-regulatory hormones
Glucagon
Epinephrine
Growth hormone
Cortisol
Counter-regulatory Hormones: What does glucagon do?
Promotes gluconeogenesis and glycogenolysis, increases release of fatty acids from adipose cells
Counter-regulatory Hormones: What does epinephrine do?
Increases the use of fat for energy, promotes glycogenolysis, inhibits insulin release
Counter-regulatory Hormones: What does growth hormones do?
decreases the peripheral use of glucose
Counter-regulatory Hormones: What does cortisol do?
critical during periods of fasting and starvation, increase gluconeogenesis
Function of Gut: Oral ingestion of food stimulates release of ____ from _____
incretin hormones from the small intestine
Function of gut: ____ released from L cells of ileum and colon
GLP-1
Function of gut: ___ released from K cells of duodenum
GIP
2 Intestinal hormones
GIP and GLP-1
Intestinal hormones: GIP: acts at ___
B-cell
Intestinal hormones: GIP: Effects
Enhances glucose-dependent insulin secretion
May act as an insulin sensitizer in adipocytes
GIP has NO effect on glucagon secretion, gastric motility, or satiety
Intestinal hormones: GLP-1: Acts at ___
Alpha and B-cells
Intestinal hormones: GLP-1: Effects
Enhances glucose-dependent insulin secretion
Suppresses glucagon secretion
Slows gastric emptying
Has satiety effect on the brain
Def: Diabetes
Chronic, progressive metabolic disorder characterized by abnormalities in the ability to metabolize carbohydrate, fat, and protein, leading to a hyperglycemic state
Diabetes: How many with diabetes
37.3 million
Diabetes: how many with prediabetes
96 million
Diabetes: National diabetes statistics: How many Americans diagnosed every year
1.4 million
T/F: racial and ethnic minorities continue to develop diabetes at lower rates
False - HIGHER rates
T/F: New diabetes cases higher in non-Hispanic black and people of Hispanic origin
True
T/F: Less people are developing diabetes during their youth
False - MORE
Diabetes: Accepted terminology key points
Type 1 and Type 2 diabetes
DO NOT USE: roman numerals, “insulin dependent” “non-insulin dependent” diabetes, “adult-onset” “juvenile-onset” diabetes, diabetic
Diabetes etiologic classification: Type 1 diabetes
Autoimmune B-cell destruction, usually leading to absolute insulin deficiency
Diabetes etiologic classification: Type 2 diabetes
Progressive loss of B-cell insulin secretion frequently on the background of insulin resistance
Diabetes etiologic classification: Gestational diabetes (GDM)
Diabetes that is first diagnosed in the 2nd or 3rd trimester that is not clearly pre-existing type 1 or type 2 diabetes
Diabetes etiologic classification: Other causes
genetic defects
disease of the exocrine pancreas (cystic fibrosis, pancreatitis)
Drug-induced hyperglycemia
Pathophysiology of T1DM: Defect in pancreatic B-cell function»_space;
Pancreatic B-cell fxn»_space; deficiency of insulin/amylin
Pathophysiology of T1DM: Relative increase in ___ and its effects
glucagon; disequilibrium is created with insulin
Pathophysiology of T1DM: Increase in BG fails to ______
suppress production of glucagon
Pathophysiology of T1DM: Effects metabolism of ____
fat, protein, and CHOs
Pathophysiology of T1DM: Protein and fat breakdown occurs because of ____
lack of insulin – results in weight loss
Pathophysiology of T1DM: ____ will result if no treatment
Ketoacidosis
Stages of T1DM: Stage 1
Autoimmune
Normoglycemic
Presymptomatic
Stages of T1DM: Stage 2
Autoimmune
Dysglycemic
Presymptomatic
Stages of T1DM: Stage 3
Autoimmune
Hyperglycemic
Symptomatic
Progression of T1DM: Rate of progression dependent on
Age at first detection of autoantibody (younger > older)
Number of autoantibodies
Autoantibody specificity
Autoantibody titers
Metabolic defects: Muscle
Insulin resistance in muscle (inefficient glucose uptake)
Metabolic defects: Liver
Insulin resistance in liver (increases glucose secretion)
Metabolic defects: Pancreas
Pancreatic B-cell decline (reduced insulin secretion)
Increased activity of alpha-cells in the pancreas (higher blood levels of glucagon increase BG levels)
Metabolic defects: fat cells
Increased free-fatty acid levels in the blood from fat cell breakdown (more insulin resistance, toxic to beta-cells)
Metabolic defects: gut
Loss of incretin function from gut (deficiency/resistance)
Metabolic defects: kidney
Sodium-glucose co-transporter up-regulation in the kidney (results in higher BG levels)
Metabolic defects: brain
Neurotransmitter dysfunction within the brain
Summary of pathophysiological defects in T1DM
Defect in pancreatic B-cell fxn
Absolute insulin deficiency
Summary of Pathophysiological defects in T2DM
Insulin resistance involving muscle, liver, and adipocyte Defects in insulin secretion GLP-1 deficiency and resistance Excess glucagon secretion Reabsorption of glucose by the kideny Defects in signaling to the brain
Def: Acanthosis nigricans
Manifestation of insulin resistance – skin thickening and pigmentation occurring on neck or armpit
GDM: Risk factors
Overweight/obese
Older age (>30)
Family hx of T2DM
GDM: pathophysiology
Insulin resistance
Diminished insulin secretory response (usually normal fasting glucose, PPG high)
GDM: Risks to mother and baby
Macrosomia (large head, complications for vag. birth) Shoulder dystocia (shoulder gets stuck) Preeclampsia C-section Stillbirth
DM: Clinical manifestations of hyperglycemia
Skin infections, genital pruritus, polydipsia, visual changes, polyuria, polyphagia, weight loss, fatigue, paresthesias
Summary: fungal microbiome growth, osmotic diuresis, poor use of food energy, tingling
Does food INCREASE/DECREASE glucose?
Increase
Does exercise INCREASE/DECREASE glucose?
Decrease
Does alcohol INCREASE/DECREASE glucose?
Decrease
Does stress/illness INCREASE/DECREASE glucose?
Increase
Glucocorticoids, Clozapine, Olanzapine INCREASE/DECREASE glucose?
Increase
T1DM: Screening: 2 most common
Islet cell autoantibodies (ICA)
Glutamic acid decarboxylase autoantibodies (GAD65)
T2DM: Screening: Recommendations
- any age with overweight with 1 or more risk factors
- Patients with prediabetes test yearly
- women diagnosed with GDM test every 3 years
- All pts after age 35
- Normal results –> test minimum every 3 years
- people with HIV
T2DM: Screening and Tests
- Fasting plasma glucose (FPG) - no eating at least 8 hrs
- Casual plasma glucose
- 2hr plasma glucose during oral glucose tolerance test (OGTT) – usually for pregnant women for GDM, inconvenient for pt (75g glucose dissolved in water); diagnoses more pts than A1C and FPG
- Hemoglobin A1C - predictive for complications with DM , reflects average glycemia over 3 months (RBC lifespan ~120 days)
T2DM: Screening and Tests: Advantages of A1C over FPG and OGTT
Greater convenience (fasting not required) Less day to day variations during stress/illness
T2DM: Cons of A1c
Inaccurately reflects glycemia in conditions that alter RBC turnover
- sickle cell disease
- pregnancy
- G6PD
- ESRD
- Recent blood loss/transfusion
- Hemodialysis
Diagnosis for T1DM
Presence of 2 or more autoimmune markers
Plasma glucose rather than A1C is used to diagnosed
C-peptide matches insulin levels –> low levels of C-peptide = T1DM
Diagnosis: T2DM: Prediabetes
A1c: 5.7-6.4%
FPG: 100-125 mg/dL - impaired fasting glucose (IFP)
OGTT: 140-199 mg/dL - impaired glucose tolerance (IGT)
Diagnosis: T2DM: Diabetes
A1c: ≥6.5%
FPG: ≥ 126 mg/dL
OGTT: ≥200mg/dL
Random glucose: ≥200mg/dL plus classic symptoms of hyperglycemia or hyperglycemic crisis
*requires 2 abnormal tests from same sample or 2 separate test samples for diagnosis
DM: Goals of therapy
Attain optimal glycemic control
Reduce onset/progression of complications
Aggressively address CV risk factors
Improve QOL
Glycemic goals for T1DM and T2DM
A1c <7%
FG 80-130
Peak PPG <180 (measured 1-2 hours after the beginning of the meal)
Children/Adolescent gylcemic goals
A1c <7.5%
FG 90-130
Bedtime/overnight 90-130
Pregnant women gylcemic goals concepts
Test for undiagnosed DM at first prenatal visit if at risk
Test for GDM at 24-48 weeks of gestation with 75g OGTT
Stricter glycemic goals than non-pregnant women
Majority develop T2DM later on
Hospitalized patients gylcemic goals
Target glucose range 140-180 mg/dL (keep stable)
Use insulin if persistent hyperglycemia >180
Older adults glycemic goals: Healthy
A1c <7-7.5
FG 80-130
Bedtime: 80-180
Older adults glycemic goals: Complex/intermediate
A1c: 8%
FG: 90-150
Bedtime glucose: 100-180
Older adults glycemic goals: Very complex/poor health
A1c: <8.5%
FG: 100-180
Bedtime glucose: 110-200
Why are A1c targets >8.5% not recommended?
Risk from glycosuria, dehydration, hyperosmolar hyperglycemic state (HHS), poor wound healing, etc.
A1c goals should be individualized based on
Duration of diabetes
Life expectance (age is just #, life expectancy tells you more)
Comorbidities
Known CVD or advanced microvascular complications
Risk of hypoglycemia
Individual patient considerations (motivation, adherence, caregiver?)
ADA Recommendations
Weight loss 5-10% (7% target)
Exercise: 150min/week at least
Treat other CVD
Monitor yearly
Metformin is not better than placebo for pts >60, metformin = LTC in obese pts, metformin+ LTC decrease 50% risk in women with h/o GDM
TLC
Weight loss: 7% with better food choices, less calories, more activity
Children 60min/day x3/week
Adults: at least 150min/week (no more than 2 consecutive days without exercise)
Decrease calories to increase insulin sensitivity CHO counting (15g/serving, 3-4/meal, 1-2/snack)
25g/day fiber and whole grain
Sodium<2.3g/day
Drug therapy: T2DM suggestions: Start with ___ and then consider addition of agents after ____
Metformin and after 3 months
When to use insulin for T2DM
evidence of weight loss
A1c ≥10%
BG ≥300
Very symptomatic
Biguanide: Metformin: MOA
Inhibit hepatic glucose production
Increase insulin sensitivity of hepatic and muscle tissues
Biguanide: Metformin: Contraindications
Known hypersensitivity Medical surgeries (restart 2 days later if good renal fxn is established Alcohol abuse (3x LFT) Renal disease (risk of lactic acidosis) (eGFR <45 ok to continue but don't initiate, <30 d/c) Iodinated contrast media with eGFR <60, hepatic disease, alcoholism, Hf, if receiving contract intra-arterially
Biguanide: Metformin: Adverse effects
GI: diarrhea, cramping, bloating (start at lower dose and titrate up to max dose or until therapeutic. Decrease dose and increase slowly)
Vit B12 deficiency (monitor 2-3 years, espp if develop neuropathic sx )
Lactic acidosis - d/c in acute medical situations
GLP-1 RA: MOA
Increase glucose-dependent insulin secretion
Decrease PP glucagon secretion
Increase satiety
Decrease gastric emptying time
GLP 1 RA: Dosing for exenatide (Byretta) and BG target
BID, post meal BG
GLP 1 RA: Dosing for exenatide XR (Bdureon) and BG target
QWeekly, mixed BG
GLP 1 RA: Dosing for liraglutide (Victoza) and BG target
QD, mixed BG
GLP 1 RA: Dosing for dulaglutide (Trulicity) and BG target
QWeekly, mixed BG
GLP 1 RA: Dosing for semaglutide (Ozempic) and BG target
Qweekly, mixed BG
GLP 1 RA: Which medications recommend to inject within 3 days of missed dose?
Exenatide XR (Bydureon) and dulglutide (Trulicity)
GLP 1 RA: Which medications recommend to inject within 5 days of missed dose?
Semaglutide (Ozempic)
GLP 1 RA: Exenatide XR (Bydureon): Effect in ___ and dosing/titration
Effect in 2 weeks
No titration: 2mg SC once weekly
GLP 1 RA: Exenatide XR (Bydureon): Caution with renal fxn
Use with caution if eGFR 30-50ml/min
dont use if <30ml/min
GLP 1 RA: dulaglutide (Trulicity): Effect in ___ and dosing/titration
Effect in 1 week, 0.75mg sc once weekly and titrate up at 4 week intervals (1.5, 3, 4.5mg)
GLP 1 RA: semaglutide (Ozempic): Dosing/titration
0.25mg SC once weekly and then titrate 0.5, 1mg at 4 week intervals
GLP 1 RA: liraglutide (Victoza): Effect in ____ and dose/titration
Effect in 1 week
- 6mg daily for week 1
- 2mg daily for week 2
- 8mg daily thereafter
GLP 1 RA: Order of greatest to least weight loss
Sema
Lira
Dula
Exena
GLP 1 RA: Adverse effects
GI: N/V/D
Pancreatitis symptoms: severe abdominal pain, often radiating to the back // a/w N/V, fever
Sema: risk of DM retinopathy complications
Exenatide XR: small nodules/lumps at injection site, itchy, may be transient
GLP 1 RA: Contraindications
Thyroid C-cell tumors (personal/family hx of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2)
Hx Pancreatitis or TG >500
Hx Gallbladder disease
Hx gastroparesis or severe GI disorder
Alcoholism (serious disease can lead to pancreatitis)
SGLT2i: MOA
Inhibits SGLT2 in proximal tubule (decrease glucose reabsorption)
SLGT2i: Caution with eGFR
eGFR <45 not effective (if filtering doesn’t work well, not much glucose to reabsorb)
Dapa: <45 –> AVOID for T2DM (All other indications eGFR <25 avoid starting)
Empa: <30 –> AVOID (HF patients with eGFR <20: not defined)
SLGT2i: Adverse effects
Polyuria (diuretic effect) – take in AM, caution in elderly and pt using diuretics (dehydration)
Genital fungal infections (esp women)
UTI
Cana: DKA? amputations (2x risk once on black box, later removed)?
Monitor for volume depletion and hypotension
SU/Glinide: MOA
Increase insulin secretion (bind to B cells)
SU: dosing
Once daily or BID to minimize hypoglycemia
Take with food
Glyburide (Diabeta) - 20mg max dose (metabolized in liver to activate)
Glipizide (Glucotrol) - 40mg (or 20mg ER) [If CrCl <50 take 50% of dose]
Glinide: Repaglinide dose
Start at 0.5-1mg po TID, 15min before meal
Skip med if you skip meal
Increase dose every week as needed
Max dose 16mg/day
SU/Glinides: Generally achieve ____ efficacy at 1/2 max dose
80%
SU/Glinide: Beneficial for
Thin body type (less insulin resistance, more likely to have secretory defect that causes hyperglycemia) Newly diagnosed (beta cell fxn more preserved) Less significant hyperglycemia
SU/Glinide: Effect in ____
DAYS
SU/Glinide: Adverse Effects
HYPOglycemia
Weight gain
GI distress
Allergic skin rxn (but diff sulfa moiety)
Secondary failure: efficacy adequate at first and then diminishes over (beta cell decline) – failure rate 5-10%/yr
SU/Glinide: Ramadan or fasting pt counseling
If A1C is higher, reduce dose to 50%
If A1C is good, omit dose
DPP-4i: MOA
Inhibit DPP4 (inhibits breakdown of GLP-1 and GIP – increase effect of endogenous incretin hormones)
Facilitates glucose-dependent insulin secretion
decrease PP glucagon secretion
DPP-4i: Don’t use with which other class of DM medications?
GLP-1 RA
DPP-4i: Sitagliptin (Januvia) dosing
100mg PO QD
Adjust dose for renal insufficiency (no need for hepatic)
DPP-4i: Linagliptin (Trudjenta): Dosing
5mg daily
No dose adj for renal and hepatic insufficiency
DPP-4i: Good to use for
Frail, elderly pts that may not need significant decrease in A1C or have hypoglycemic risk, AE of other agents, or unable to use injectable
DPP-4i: Adverse effects
WELL TOLERATED
Risk of pancreatitis (rare)
Saxagliptin related to hospitalizations for HF
TZD: MOA
Activates PPAR-gamma (peroxisome-proliferator activated receptor)
Decrease insulin resistance (improve target cell insulin response) and increase uptake of glucose
TZD: Effect in _____
2-3 weeks due to need for G-protein turnover
May take 3-4 months to see full effect
TZD: Pioglitazone (Actos): Dosing
15-30mg PO daily and then titration every 3-4 weeks to max of 45mg/day
No dose adj needed for renal or hepatic insufficiency (not recommended for renal insufficiency due to fluid retention)
TZD: Adverse effects
Fluid retention and edema Weight gain Fracture risk (decrease bone mass and increase fracture risk in women: upper arm, hand, foot but NOT spine/hip) Macular edema (eye) BLACKBOX: HF Induces ovulation -- risk of pregnancy
TZD: Contraindications
NYHA class 3 or 4 HF Use with caution in pts with edema or class 1 or 2 HF Active liver disease (ALT >2.5x ULN at start of therapy and D/C LFTs >3x ULN)
Insulin: RAA and Short acting: How many minutes before meal
RAA: 15 min
Short acting: 30min
Insulin: Intermediate-acting: Duration
10-16hr (usually BID)
Insulin: Long-acting: Duration
U-100 glargine/detemir: 24 hrs
U-300 glargine: 34hrs
degludec: 42hrs
Which insulins are cloudy?
NPH, premix analogs/NPH-regular
Insulin: Premix analogs/NPH-regular: Name all of them and dosing frequency
Humalog 75/25 + 50/50 - 15min before meal BID Novolog 70/30 - 15 min before meal BID Ryzodeg 70/30 - QD or BID with any meal Humulin 70/30 - 30min before eating BID Novolin 70/30 - 30min before eating BID
Insulin: T1DM: Dosing
Starting: 0.5U/kg/day (50% basal, 50% bolus (divided into 3 meals)
OR
Carb matching: 1U=15g/CHO + additional 1U/50 over glucose goal
Insulin: T2DM: Reasons to start/add insulin early
A1C >10% Glucose ≥300 Symptoms of hyperglycemia Ongoing catabolism (weight loss) CI for GLP-1RA or unacceptable sx of GLP-1RA
Insulin: T2DM: Basal dosing
Starting dose: 10U/day or 0.1-0.2U/kg/day for obese pts - same time every day
Increase 2-4 U (10-15%) x1-2/week until fasting target is met
Insulin: T2DM: Basa: Overbasalization signs and what to do
Basal insulin dose >0.5/kg/day
High bedtime to morning (BeAM) or post to pre prandial glucose diff (>50mg/dL)
Hypoglycemia
High glycemic variability
Intensify therapy with GLP1 RA or add prandial insulin
Insulin: T2DM: Prandial dosing
Starting dose: 4U (or 0.1U/kg or 10% of basal dose) – 15 min before meal (biggest meal)
Monitor PPG and increase 1-2 U 1-2x/weekly until target
D/C SU and DPP-4i, continue other oral meds
If A1C <8%, decrease basal dosing by # of prandial U
If A1C not controlled, do full basal/bolus therapy or premix
Insulin: T2DM: Pre-mixed insulin regimen
Usually BID – inject 15min before meals
Increase 1-2U x1-2/weekly until target
D/C SU or DPP-4i
If A1C not controlled or hypoglycemia, change regimen
Complications: general A1C testing
every 6 months if treatment is going well, 3 months if it is not
What are some limitations to A1C
Doesn’t show variability or hypoglycemia
BGM recommendations
4-10x/day esp for basal/bolus regiments
For GDM 4-10x/day until controlled 1-2 days
CGM: How long can you wear and what are the goals
14 day wear
>70% in range
<30% above range
<5% below range
Complications: Hypoglycemia: diagnosis
BG <70mg/dL
Level 1 MILD <70
Level 2 MOD <54
Level 3 SEVERE
Complications: Hypoglycemia: Symptoms
Trembling, palpitations, dry mouth, sweating, hunger, anxiety, cognitive impairments, confusion, behavior change, headaches/seizures, slurred speech, weakness, loss of consciousness
- *if occurs during sleep: nightmares, night sweats, headache
- *BB can mask sx of hypoglycemia except sweating
Complications: Hypoglycemia: Consequences
Rebound hyperglycemia (dangerous bc doctor may continue to increase therapy)
Greater risk of dementia
Prolonged QT interval – dysrhythmias, sudden death
Barrier to glycemic control/adherence bc of fears
Complications: Hypoglycemia: Risk factors
Fasting, delayed/missed meals Exercise Drug/alcohol Unawareness of hypoglycemia Use of insulin or SU/glinides Older age/frail Cognitive impairment
Complications: Hypoglycemia: Management
15g glucose - wait 15min - repeat if needed
If severe: give glucagon (IV, IM, SC, intranasal)
What are some equivalents to 15g of glucose?
3-5pieces of hard candy
3-4 pieces of glucose tabs
4oz of juice/soda
1 tbsp of honey/corn syrup/jelly
Complications: DKA: 3 Main ideas
Ketosis
Hyperglycemia
Metabolic acidosis
Complications: DKA: Pathophysiology
No insulin > glucose from food cannot be processed > increase counter-reg H > increase glucose production > increase BG
Body need fuel > lipolysis > ketone byproduct > ketoacidosis
Glucose and ketones peed out > bring more water with it > dehydration
OVERAL: Metabolic acidosis
Complications: DKA: Predisposing factors
Physical/emotional stress
Insulin deficiency
Complications: DKA: Symptoms
Fatigue, headache, polyuria, polydipsia, weight loss, abdominal pain/tenderness, N/V, fruity/acetone breath, Kassmaul respirations, dry mouth, hypotension, tachycardia, mild hypothermia
Complications: DKA: Labs
Glucose > 250mg/dL
Low arterial pH <7.3
Low bicarb <18mEq/L
Ketonemia and moderate ketonuria
Complications: DKA: Complications
Cerebral edema (esp in children)
Respiratory distress syndrome
Thromboembolism
Rhabdomyolysis
Complications: HHS: 3 Main ideas
Hyperglycemia
Hyperosmolality
Dehydration
Complications: HHS: Pathophysiology
Little insulin > not enough cell energy > increase counter-reg hormones > increase glucose production > increase BG
Glucose peed out > osmotic diuresis (brings water) > dehydration and electrolyte abnormalities > hyperosmolality
Complications: HHS: Predisposing factors
Pancreatitis, severe infection/illness MI CHO diets (tube feedings, TPN) Dialysis medications antagonizing insulin
Complications: HHS: Symptoms
Weakness, polyuria, polydipsia, neurological signs, dehydration, seizures, coma
Complications: HHS: Labs
Glucose >600 mg/dL
Plasma osmolality >320 mOsm/kg
Complications: HHS: Complications
Thromboembolism
Rhabdomyolysis
Complications: HHS: Treatment: Add ____ when blood glucose decreases to ____
Dextrose when BG decreases to 250-300mg/dL
Landmark trials for T1DM
DCCT
Landmark trials for T2DM
UKPDS, ACCORD, ADVANCe, VADT
T/F: intensive glycemic controls prevent macrovascular complications
FALSE - they prevent MICROvascular complications – Macrovascular complications come from BP/lipid/antiplatelet control
Which landmark trial says that intensive glycemic control can increase mortality?
ACCORD
What is considered ASCVD?
ACS MI Angina Coronary revascularization stroke Transient ischemic attack (TIA) Peripheral arterial disease (PAD)
Rates of HF hospitalizations ____ with DM
x2
What are some CV risk factors?
HLD, HTN, smoking, obesity, CKD, albuminuria, FHx of premature coronary disease (men <55 or women <65)
Chronic complications: Prevention: BP control
Goal: <130/80 Lifestyle interventions Meds: ACEI/ARB, Thiazides, DHP-CCB - if UACR >30 then 1st line is ACE/ARB **ACEI/ARB contraindicated for pregnancy
Monitor BP every visit and at home
Monitor SCR, eGFr, and K annually
Chronic complications: Prevention: Lipid Control
Get lipid profile at diabetes diagnosis and then 5 years thereafter <40yo
Primary prevention 40-75yo: moderate statin
Secondary prevention: any age: high statin
Monitor at initiation, 4-12weeks later and then annually
**statins contraindicated in pregnancy
What are high intensity statins?
Atorvastatin 40-80
Rosuvastatin 20-40
Chronic complications: Prevention: Antiplatelet control
Effective in reducing CV morbidity/mortality in high risk pts with previous MI/stroke (controversial for primary prevention due to bleeding risk)
Secondary prevention: low dose aspirin OR clopidogrel 75mg/day if ASA allergy
ASA in pt <21 yo contraindicated due to Reye’s syndrome
Microvascular complications: DKD and screening
CKD due to DM
T1DM: annually after 5 yrs after diagnosis
T2DM: annually starting diagnosis
Albuminuria via UACR - normal <30 - mod 30-300 - severe >300 eGFR <60ml/min is abnormal **use UACR and eGFR to stage CKD
Microvascular complications: DKD: risk factors
HTN, poor glycemic control, HLD, smoking
Microvascular complications: DKD: treatment
ACEI/ARB for HTN with albuminuria
SGLT2 regardless of glycemic control (or nonsteroidal mineralocorticoid RA finerenone)
GLP1RA suggested for CV risk reduction and slow CKD progression
T/F: DM is leading cause of ESRD
True
Microvascular complications: Diabetic retinopathy
Strongly related to duration of DM and level of glycemic control
Risk factors: Hyperglycemia, nephropathy, HTN, dyslipidemia
Microvascular complications: Diabetic retinopathy: prevent
HTN, DM, HLD
Microvascular complications: Diabetic retinopathy: Screening
Dilated and comprehensive eye exam
T1DM: annually 5 yrs after diagnosis
T2DM: annually starting at diagnosis
Microvascular complications: Diabetic peripheral neuropathy (DPN)
associated with diminished perception of vibration, pain, and temperature in lower extremities (loss of feeling, touch, and position sense, paresthesias, numbness, or pain)
Cannot be reversed (prevent with glycemic control)
Microvascular complications: Diabetic peripheral neuropathy (DPN): Screening
Diabetic neuropathy and sensory function (pinprick, temp, vibration, pressure)
T1DM: annually after 5 yrs of diagnosis
T2DM: annually starting at diagnosis
Microvascular complications: Diabetic peripheral neuropathy (DPN): Treatment
Optimize glycemic control and foot self-care education and smoking cessation
Pregabalin and duloxetine and gabapentin (off-label)
**cannot reverse
Which interventions are done at every visit
BP and smoking cessation
Which interventions are done every 3 months
A1C
Which interventions are done yearly?
Dilated eye exam, comprehensive foot exam, UACR, SCr, eGFR, lipid panel
Which immunizations are recommended
Influenza yearly
Pneumococcal PPSV23 at diagnosis
Hep B at diagnosis (19-59 yo)
