Insulin and Diabetes Flashcards by Ashley Ross

Describe the age, onset, primary cause and nature of insulin defect for DM1

Age: childhood or adolescence

Onset: abrupt

Cause: autoimmune destruction of pancreatic B cells

Insulin defect: insulin dependent, lack absolute insulin

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Describe the age, onset, primary cause and nature of insulin defect for DM2

Age: 40+

Onset: Gradual

Cause: insulin resistance in tissue, B cell dysfunction w/ impaired insulin secretion, increased HGP

Insulin defect: non-insulin dependent, low normal or high insulin levels

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Describe the symptoms, proneness to ketosis of DM1

Sx: thin, hyperglycemia, polydipsia, polyuria, nocturia

Proneness to ketosis: PRONE!

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Describe the symptoms, proneness to ketosis of DM2

Sx: 90% obese, asymptomatic

Proneness to ketosis: uncommon

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Describe the tx of DM1

Eucaloric diet
Preprandial rapid-acting insulin
Basal insulin replacement

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Describe the pathogenesis of hyperglycemia with DM2

Beta cell dysfunction: impaired basal and stimulated insulin secretion
Insulin resistance in tissue: increased rate of hepatic glucose production + inefficient peripheral tissue utilization
increased hepatic glucose production

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Describe the tx of DM2

lifestyle interventions
weight reduction
hypocaloric diet
oral agents +/- insulin

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what are acute diabetic complications

10% of diabetes related deaths from ketoacidosis and hypoglycemia

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What are long range complications of diabetes

Microvascular (nephropathy, retinopathy, neuropathy)
Macrovascular (altered LDL, MI, stroke, HTN)
Hyperglycemia w/ suspectibilty to infections
cavities and gum disease

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What stimulates insulin secretion

Elevated plasma glucose
nutrient breakdown products
vagal stimulation
B2 agonists

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Describe the PK of insulin including t1/2 and elimination

t1/2: 3-5min (can be increased by keeping it away from the liver)

Elimination: liver 60%, kidney 40%

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Describe the target cell metabolic effects of insulin

Liver: promotes glucose storage (glycogen) –> inhibits gluconeogenesis and ketogenesis

Muscle: increase AA transport–> protein synthesis and glycogen synthesis

Fat cells: inhibit intracellular lipolysis, increased TG storage and FA synthesis

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Describe the target cell metabolic effects w/o insulin

Decrease glucose transport into muscle–> hyperglycemia
Decrease conversion of glucose to glycogen–> hyperglycemia
Increase protein to glucose via gluconeogensis in liver–> hyperglycemia, muscle wasting
Increase mobilization of peripheral fat–> increase FFA and ketone bodies–> DKA

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Insulin’s actions include:
A.  Increased conversion of amino acids into glucose
B.  Increased gluconeogenesis
C.  Increased glucose transport into cells
D.  Inhibition of lipoprotein lipase
E.  Increased lipogenesis
F.   Stimulation of glycogenolysis

C.  Increased glucose transport into cells

E.  Increased lipogenesis

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A 24-year-old woman with type 1 diabetes wishes to try tight control of her diabetes to improve her long-term prognosis. Which of the following insulin regimens would be most appropriate?
A.  Morning injections of insulin lispro mixed with insulin aspart
B.  Evening injections of regular insulin mixed with insulin glargine
C.  Morning and evening injections of regular insulin supplemented by small amounts of NPH insulin at mealtimes
D.  Morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes
E.  Morning injections of NPH insulin and evening injections of regular insulin

D.  Morning injections of insulin glargine, supplemented by small amounts of insulin lispro at mealtimes

(basal + release around meals)

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What are rapid acting insulins and their DOA and onset

Gluisine
Aspart
Lispro
(inhaled Afrezza ~3 hrs)

DOA:~4 hrs, onset 5-15min

*short and rapid acting are prandial insulins

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What are short acting insulins and their DOA and onset

regular insulin

DOA 5-7 hrs
onset: 30-60min

*short and rapid acting are prandial insulins

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What are intermediate acting insulins and their DOA, onset, and peak

NPH insulin

DOA: 10-20hrs
Onset: 2-4 hrs
Peak: 8-10hrs
**Given BID

*intermediate and long acting are basal insulins

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What are long acting insulins are their administration

Glargine (Lantus)- SC QD *peakless
Detemir (Levemir)- SC BID
Degludec (Tresiba) SC QD

*intermediate and long acting are basal insulins

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What insulin is relatively peakless?

Glargine (Lantus)

*Peakless =LESS risk of hypoglycemia

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What insulin can you administer IV or infusion pump for managing DKA

Regular insulin

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Compare the absorption of Insulin lispro vs regular insulin

Rapid dissociation of lispro hexamer to monomer following SC injection results in more rapid absorption.

*NOTE: NO difference in onset of action if given by the IV route.

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Which of the following statements is correct regarding insulin glargine?
A.  It is primarily used to control postprandial hyperglycemia
B.  It is considered a “peakless” insulin
C.  The prolonged duration of action is due to slow dissociation from albumin
D.  It is commonly used in a regimen with insulin lispro or insulin aspart
E.  It may be administered intravenously in emergency cases

B.  It is considered a “peakless” insulin

D.  It is commonly used in a regimen with insulin lispro or insulin aspart

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WD is a 40-year-old patient with type 2 diabetes who has a blood glucose of 400 mg/dL today at his office visit. The PA would like to give some insulin to bring the glucose down before he leaves the office. Which of the following would lower the glucose in the quickest manner in WD? 
A.  Insulin aspart 
B.  Insulin glargine 
C.  NPH insulin 
D.  Regular insulin 
E.  Insulin lispro 
F.   Insulin detemir

A.  Insulin aspart

E.  Insulin lispro

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NPH insulin has a delayed onset by combing insulin with ___

promatine

Describe the dosing of insulin in type1 compared to type2

type1: lower dose typically, multiple dose therapy/basal-bolus type 2: higher dose, less urgency for starting aggressive therapy due to less like DKA

What factors can alter blood glucose control?

1. Diet (alcohol, overeating, irregular meals) 2. Physical activity (improve insulin sensitivity) 3. Stress (increase GC levels) 4. Puberty 5. Menstrual cycle (glucose higher premenstrually) 6. Drugs

Drugs that can increase blood glucose

1. GCs | 2. Sympathomimeticss

Drugs that can decrease blood glucose

1. BB | 2. Ethanol

Complications of insulin therapy

1. Hypoglycemia (MC) 2. Impaired CNS fxn 3. Autonomic system hyperactivity 4. weight gain 5. DKA 6. Hyperglycemia 7. Immunologic rxns

Hypoglycemia is more common in who

- older diabetes or diabetics taking long-acting insulins (goes down slowly and don't see the SNS effects/no warning signs) - rapid onset of sx w/ short acting insulins

Signs of hypoglycemia

1. impaired CNS fxn 2. night sweats 3. HA 4. visual disturbance 5. bizarre behavior 6. Increased SNS and PNS (hunger)

``` An unconscious patient wearing a diabetes alert bracelet is admitted to the ED. Blood sugar as measured by a glucometer was found to be very low, and the patient has skin turgor suggestive of dehydration. Before receiving stat lab results which of the following is most likely to be immediately administered? A.  Bicarbonate solution B.  Dextrose solution 5% C.  Hypotonic saline D.  Normal (isotonic saline) E.  Potassium chloride solution ```

B.  Dextrose solution 5%

Why are diabetes who are hypoglycemic also usually dehydrated?

low glucose causes dehydration because ketone bodies are excreted and not absorbed, acts as an osmotic diuretic and fluid is excreted to that way

How do you tx hypoglycemia

1. Glucose (oral) 2. +/- glucagon 3. Dextros 50% IV if severe

How can you distinguish hypoglycemia from DKA

1. DKA is generally gradual onset (hrs-days) 2. acetone/sweet breath from ketone bodies 3. dry 4. flushed skin 5. thirst

``` An unconscious patient wearing a diabetes alert bracelet is admitted to the ED. Blood sugar as measured by a glucometer was found to be very high, and the patient has skin turgor suggestive of dehydration. Before receiving stat lab results and in addition to IV administration of rapid-acting insulin which of the following is most likely to be immediately administered? A.  Bicarbonate solution B.  Dextrose solution 5% C.  Hypotonic saline D.  Normal (isotonic saline) E.  Potassium chloride solution ```

D.  Normal (isotonic saline)

tx of DKA

1. Normal saline IV 2. regular insulin (iv boluse then low dose infusion) 3. +/- K and PO4 replacement

Diabetic ketoacidosis rare in Type 2 diabetics BUT dehydration in untreated, poorly controlled individuals can lead to potential life-threatening ___ coma

non-ketotic hyperosmolar

What Immunologic reactions can be seen with insulin therapy

1. Insulin allergy (rare w/ human insulin) 2. Insulin resistance 3. Lipodystrophy (SC atrophy at injection site or hypertrophy)

What are targets for DM2

1. pancreas 2. Liver 3. GI tract 4. muscle 5. fat 6. kidney

Which of the following statements is characteristic of metformin? A.  Metformin is inappropriate for initial management of type 2 diabetes B.  Metformin decreases hepatic glucose production C.  Metformin undergoes significant metabolism by the CYP450 system D.  Metformin should not be combined with sulfonylureas or insulin E.  Most common adverse effects are gastrointestinal in nature

B.  Metformin decreases hepatic glucose production E.  Most common adverse effects are gastrointestinal in nature

Actions of Metformin

1. decrease HPG in liver/gluconeogensis 2. increase glucose uptake into muscle 2. slow glucose absorption 3. Decrease VLDL synthesis 4. Decrease platelet aggregation 5. increase fibrinolysis

Benefits of Metformin

1. decrease A1c by 1-1.5% 2. No hypoglycemia 3. no wt. gain

Describe the PK of metformin including absorption and elimination

1. orally absorbed | 2. excreted unchanged by kidneys

Adverse reactions of Metformin

1. GI effects (N/V, bloating, diarrhea) 2. Lactic acidosis 3. CI renal impairment EGFR = 30ml/min and CHF

``` A 54-year-old obese patient with type 2 diabetes has a history of alcoholism. In this patient, metformin should be avoided or used with extreme caution because the combination of ethanol and metformin increases the risk of which of the following? A.  An antabuse-like reaction B.  Excessive weight gain C.  Hypoglycemia D.  Lactic acidosis E.  Serious hepatotoxicity ```

D.  Lactic acidosis

``` Which of the following agents promotes the release of endogenous insulin? A.  Acarbose B.  Canagliflozin C.  Glipizide D.  Metformin E.  Pioglitazone ```

C.  Glipizide (Sulfonylurea- acts on pancreas)

Examples of sulfonylureas

1. Glipizide | 2. Glyburide

MOA of Sulfonylureas (glipidzide)

1. increased insulin release in response to glucose via depolarization of blocking K channels (before B cells lose fxn) * blocks ATP-sensitive Kchannel--> depolarization--> Ca entry--> increase insulin release

How do thiazide diuretics affect glucose levels

Open K channels--> hyperpolarize cell--> decrease insulin release--> hyperglycemia **Opposite action of Sulfonylureas

Adverse effects of Sulfonylureas

1. Hypoglycemia-- esp. w/ glyburide (do NOT use in elderly) 2. Weight gain (due to increase in insulin) 3. GI 4. require hepatic-renal dysfunction dose reductions

Describe the PK of Sulfonylureas including adminstration and elimination

administration: PO QD elimination: metabolized by liver then renally excreted

What is the MOA of thiazolidinediones

1. increase target sensitivity to insulin (liver, fat cells, and muscle) via increase gene transcription (PPAR-gamma) * slow onset of effect (6-14 weeks to maximum effect)

The PPAR-γ receptor that is activated by thiazolidinediones (pioglitazone) increases tissue sensitivity to insulin by which of the following mechanisms? A.  Activating adenylyl cyclase and increasing the intracellular concentration of cAMP B.  Inactivating a cellular inhibitor of the GLUT2 glucose transporter C.  Inhibiting acid glucosidase, a key enzyme in glycogen breakdown pathways D.  Regulating transcription of genes involved in glucose utilization E.  Stimulating the activity of a tyrosine kinase that phosphorylates the insulin receptor

D.  Regulating transcription of genes involved in glucose utilization

Describe the PK of thiazolidinediones including absorption, administration, and elimination

Absorption/administration: oral QD or BID Elimination: hepatic CYP450 metabolism

Adverse effects of Thiazolideiones

1. Fluid retention edema 2. exacerbation of HF *anithyperglycemia so LOW risk of hypoglycemia

Thiazolideiones should be avoided in who

1. active liver dz 2. mod-sever CHF 3. CV risk

Examples of thiazolideiones

Pigolitazone

Incretin mimetics preferred over DDP-4 inhibitors because

better reductions in postpradial glucose and weight

MOA of GLP-1 Agonists

GLP-1 receptor agonist - increase insulin in response to high BG and inhibition of glucagon release after meals - slow gastric emptying- reduce food intake

Examples of incretin enhancers

MIMETICS: GLP-1 agonist: Exenatide DDP-4 Inhibitors: Sitagliptin (Junuvia)

Adverse reactions of incretins mimetics

1. Hypoglycemia when used with SUs 2. HA 3. N/V/D--GI 4. Pancreatitis 5. DDI: delay absorption of oral meds

Describe the PK of incretin mimetics including administration and elimination

administration: SC BID w/ meal Elimination: renal--> avoid in pts w/ severe renal dz

MOA of DDP-4 inhibitors

enhance the actions of endogenous incretins by blocking their degradation

Describe the PK of DPP-4 inhibitors including administration and elimination

Administration: PO QD w/ or w/o food Elimination: renal -- need dose adjustments with renal dz

Adverse effects of DPP-4 inhibitors

1. Nasopharyngitis 2. URI 3. Ha **NOT associated w/ wt. gain

MOA of SGLT-2 inhibitors

-inhibits PCT transporter reabsorption of glucose and therefore more is renally excreted

Benefits of SGLT-2 inhibitors

1. wt. loss | 2. slight BP reduction

Adverse effects of SGLT-2 inhibitors

1. Dehydration/hypovolemia 2. Mycotic UTIs 3. hypotension 4. expensive 5. renal dysfunction in elderly if taking loop diuretic

Describe the PK of SGLT-2 inhibitors including administration and eliminatoin

1. PO QD 2. fecal-renal elimination via glucuronidation Canaglifozin (40% fecal, 30% renal)

Examples of SGLT-2 Inhibitors

"-gliflozin" class - Canaglifozin - Dapagloifozin

Do not use Canaglifozin if GFR is

less than 45

Examples of alpha-glucosidase inhibitors

Acarbose (Precose)

MOA of alpha-glucosidase inhibitors

inhibition of alpha-glucosidase break down of complex starches which reduces postprandial glucose levels--> digestion of starches delayed from supper SI to distal SI *decrease intestinal glucose absorption

Describe the PK of alpha-glucosidase inhibitors including administration and elimination

adminstration: orally, (low F) metabolized by gut

Adverse effects of alpha-glucosidase inhibitors

1. GI effects (gas, cramps, diarrhea) 2. abdominal distention 3. Hepatotoxicity-- caution w/ liver dz 4. don't work that well (but less SE) *GI effects due to unabsorbed carbohydrates undergoing fermentation

``` A 55-year-old menopausal woman was recently diagnosed with type 2 diabetes based on her fasting blood glucose levels. Her HbA1c levels average >7% so that diet exercise, and a single drug (monotherapy) may be sufficient to regulate her fasting glucose levels. Which of the following should be prescribed? A.  Acarbose B.  Dapagliflozin C.  Insulin lispro D.  Metformin E.  Glyburide F.   Glipizide ```

D.  Metformin

``` Which of the following drugs is most likely to cause hypoglycemia when used as monotherapy in the treatment of type 2 diabetes? A.  Acarbose B.  Canagliflozin C.  Glyburide D.  Insulin lispro E.  Metformin F.   Rosiglitazon ```

D.  Insulin lispro

Which of the following antidiabetic agents is INCORRECTLY paired with its primary mechanism of action? A.  Sitagliptin --> prolongs activity of glucagon-like peptide-1 B.  Glipizide--> stimulates insulin release C.  Exenatide--> increases glucose-dependent insulin release D.  Pioglitazone --> decreases hepatic glucose production E.  Canagliflozin --> increases urinary excretion of glucose

D.  Pioglitazone --> decreases hepatic glucose production

``` The target of drug therapy for type 2 diabetes is generally an A1C of less than: A.  6.8% B.  7.0% C.  7.2% D.  7.4% ```

B.  7.0%

``` Metformin: A.  Reduces A1C by 1-1.5% B.  May decrease both microvascular and macrovascular complications of diabetes C.  Does not cause weight gain D.  All of the above ```

D.  All of the above

``` GLP-1 receptor agonists (-tides): A.  Reduce A1C by 0.5% B.  Cause more gain than insulin C.  Have been shown to increase the risk of myocardial infarction D.  Must be injected ```

D.  Must be injected

``` DPP-4 inhibitors (-gliptins): A.  Are taken orally B.  Do not cause weight gain C.  Produce small reductions in A1C D.  All of the above ```

D.  All of the above

``` Which of the following can cause hypovolemia, dehydration and cause acute renal injury? A.  Sulfonylureas B.  DPP-4 inhibitors C.  SGLT2 inhibitors D.  GLP1 receptor agonists ```

C.  SGLT2 inhibitors

68-year-old woman with a BMI of 36, systolic hypertension, and type 2 diabetes has not achieved an A1C < 8% on maximum doses of metformin and exenatide. You are considering whether to start her on insulin or an SGLT2 inhibitor. Factors that you might consider could include which of the following? A.  SGLT2 inhibitors cause weight loss B.  SGLT2 inhibitors reduce systolic blood pressure C.  Empagliflozin has been found to reduce the risk of cardiovascular events D.  All of the above

D.  All of the above

``` Compared to NPH insulin, the main advantage of the recombinant insulin analogs glargine, detemir, and degludec is that they: A.  Do not cause weight gain B.  Cause less nocturnal hypoglycemia C.  Have a more rapid peak effect D.  All of the above ```

B.  Cause less nocturnal hypoglycemia

``` A 58-year-old man with type 2 diabetes had a myocardial infarction 12 years ago and is concerned about the effect of diabetes treatment on his heart disease. You could tell him that a number of the drugs used to treat diabetes have been associated with a lower risk of cardiovascular disease. These include: A.  Metformin B.  Liraglutide C.  Empagliflozin D.  All of the above ```

D.  All of the above

The inhaled form of insulin (Afrezza®): A.  Has an earlier maximal effect than injected insulin lispro B.  Has a longer duration of action than injected insulin lispro C.  Does not cause hypoglycemia D.  All of the above

A.  Has an earlier maximal effect than injected insulin lispro

``` Describe what diabetes med target the following tissues: Liver Fat Muscle Pancreas Intestines Kidney ```

1. Liver- Metformin (decrease HGP) 2. Fat- Thiazolidinediones (increase glucose uptake) 3. Muscle- Thiazolidinediones (increase glucose uptake) 4. Pancreas- insulin and sulfonyureas 5. Intestines- incretins mimetics/GLP-4 inhibitors and DPP-4 inhibitors 6. Kidney- SGLT-2 inhibitors

For Metformin describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: LOW 2. Wt effect: neural 3. Main SE: GI/ lactic acidosis

For Sulfonyurleas describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: YES-mod 2. Wt effect: GAIN 3. Main SE: hypoglycemia, wt gain

For Thiazolidinedione describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: ANTI- (Low) 2. Wt effect: GAIN 3. Main SE: edema, HF, fx

For DDP-4 inhibitor describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: low 2. Wt effect: NEUTRAL 3. Main SE: rare

For SGLT-2 inhibitor describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: low 2. Wt effect: LOSS 3. Main SE: UTI, dehydration

For GLP-1 agonist describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

1. Hypoglycemia risk: low 2. Wt effect: LOSS 3. Main SE: GI, pancreatitis

For insulin describe the: 1. Hypoglycemia risk: 2. Wt effect: 3. Main SE:

For Metformin describe the: 1. Hypoglycemia risk: HIGH 2. Wt effect: GAIN 3. Main SE: hypoglycemia

What diabetes med cause weight gain and weight loss

Gain: 1. Sulfonylurea 2. Thiazolidinedione 3. Insulin Loss: 1. SGLT-2 inhibitor 2. GLP-1 agonist 3. Metformin (or neutral) DPP-4 inhibitors (neutral) Meglitinides (neutral)

Examples of insulin secretagogues

1. sulfonylureas (glipizide) | 2. meglitinides (Repaglinide)

Adverse effect of Meglitinides

1. Bloating/gas 2. abdominal cramps 3. diarrhea *wt neutral

benefits of meglitinides over sulfonylureas for choice of insulin secretagogues

1. more dosing flexibility | 2. less hypoglycemia