Chaper 48: Diabetes Mellitus

Question 1

Diabetes Mellitus: Overview of the Disease and Its Treatment

Answer 1

Disorder of carbohydrate metabolism
Deficiency of insulin
Resistance to action of insulin

Sustained hyperglycemia, polyuria, polydipsia, ketonuria, and weight loss

Ketones and weight loss with type I

Question 2

TIDM

Answer 2

As a rule, type 1 diabetes develops during childhood or adolescence, and symptom onset is relatively abrupt -typically follows viral infection

Can develop during adulthood

Accounts for 5% of all cases of diabetes mellitus

Primary defect is destruction of pancreatic beta cells due to autoimmune process

Trigger for this immune response is not entirely known, but genetic, environmental, and infectious factors likely play a role

Need insulin replacement for life

Question 3

TIIDM

Answer 3

Most prevalent form of diabetes

Accounts for 90% to 95% of all cases of diabetes

Affects approximately 22 million Americans

Insulin resistance and impaired insulin secretion

Insulin resistance

Strong family association

Will not have ketone urea –will produce a little insulin to prevent ketoacidosis.

May need oral meds and insulin sup

typically overweight or obese at time of dx

Question 4

Complications of DM

Answer 4

Short-term
Hyperglycemia
Ketoacidosis -Type I
Hypoglycemia

Long-term Macrovascular damage
Heart disease
Hypertension
Stroke
Hyperglycemia
Altered lipid metabolism

Long-term Microvascular damage
Retinopathy
Nephropathy: Angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)
Sensory and motor neuropathy
Gastroparesis
Amputation secondary to infection
Erectile dysfunction

Question 5

DM and preg

Answer 5

Before insulin: Virtually all babies born to severely diabetic women died during infancy

Factors during pregnancy
Placenta produces hormones that antagonize the actions of insulin
Production of cortisol increases threefold
Glucose can pass freely from the maternal to the fetal circulation (fetal hyperinsulinemia)
See lg infants (over 8lb)

Proper glucose levels are needed in the pregnant patient and in the fetus to prevent teratogenic effects
Want 3 month prior to conception if possible
Screening early preg visits

Fetal death frequently occurs near term

Earlier delivery is desirable

Baby may be hypoglycemic on delivery

Question 6

Gestational DM

Answer 6

Appears in the mother during pregnancy and subsides rapidly after delivery
Managed in much the same manner as any other diabetic pregnancy
Blood glucose should be monitored and controlled with diet and insulin
Diabetic state usually disappears almost immediately after delivery
If diabetic state persists beyond delivery, it is no longer considered gestational and should be rediagnosed and treated accordingly
If pt has GDM, at much higher risk of dm as they age, typically type 2

Question 7

DM dx

Answer 7

Hemoglobin A1c
3m average BG
6.5 or higher dx

Tests based on glucose:

Fasting plasma glucose (FPG) test
Criteria for dx would be over 126
Fast of 8hr

Casual plasma glucose test
Random plasma glucose
> 200 + s/sx of DM

Oral glucose tolerance test (OGTT)
2 hr test post carb load
>200 mg per deciliter considered dx

Question 8

Prediabetes

Answer 8

Impaired fasting plasma glucose between 100 and 125 mg/dL
Impaired glucose tolerance test
Increased risk for developing type 2 diabetes
May reduce risk with diet changes and exercise and possibly with certain oral antidiabetic drugs
Many people who meet criteria for “prediabetes” never develop diabetes, even if they do not take precautions against diabetes
If overweight pt, weight loss can take them out of this category
May give metformin, lifestyle changes for 3m to see if they can move out of this category
Many do not develop DM

Question 9

Overview of DM tx

Answer 9

Primary goal is to prevent long-term complications
Tight control of blood glucose level is important
Controlling blood pressure and blood lipids is also important

Question 10

Type 1 DM tx

Answer 10

Requires a comprehensive plan
Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement

Question 11

TIDM dietary measures

Answer 11

Evidence suggests no ideal percentage of calories that should be ingested from carbohydrate, fat, or protein

Macronutrient distribution for any given individual is based on the person’s current eating patterns, preferences, and goals

Glycemic index

Substituting low-glycemic-load foods for higher-glycemic-load foods may modestly improve glycemic control

Question 12

Physical activity for TIDM

Answer 12

150 min of exercise a week

Question 13

Insulin requirements for TIDM

Answer 13

Lifelong replacement

Question 14

TIDM HTN mgmt

Answer 14

An ACE inhibitor (e.g., lisinopril) or an ARB (e.g., losartan) can reduce the risk of diabetic nephropathy

Question 15

TIDM dyslipidemia

Answer 15

Statins ex. Atrovastain

Question 16

Type 2 DM tx

Answer 16

Similar to type 1, requires comprehensive plan
Patient should be screened and treated for:
Hypertension, nephropathy, retinopathy, neuropathy, dyslipidemias

Glycemic control with:
Modified diet and physical activity
Drug therapy

Question 17

When tight glycemic control is inapppropriate

Answer 17

Long-standing type 2 diabetes
Advanced microvascular or macrovascular complications
Extensive comorbid conditions
History of severe hypoglycemia
Limited life expectancy

May allow older adults to have higher hgA1c bc we don’t want them to develop hypoglycaemia ( worry about dizziness -> falls, fx)

Question 18

Monitoring DM tx

Answer 18

Self-monitoring of blood glucose (SMBG)
Common target values for blood glucose
70 to 130 mg/dL before meals
100 to 140 mg/dL at bedtime
Needs to be individualized to pt
May let kids/YA run a higher BG bc of physical activity. Do not want them to be hypoglycaemic

Question 19

Monitoring DM tx: HgA1C

Answer 19

Also called glycosylated hemoglobin or glycated hemoglobin
Provides an index of average glucose levels over the prior 2 to 3 months
A1c goal of below 7% is good for most patients
Goal below 8% may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, or advanced microvascular or macrovascular complications

Question 20

Metabolic consequences of insulin deficiency

Answer 20

Catabolic mode
Increased glycogenolysis
Increased gluconeogenesis
Reduced glucose utilization

Question 21

Insulin preps

Answer 21

“High alert” agents

Recombinant DNA technology
Human insulin: Identical to insulin produced by the human pancreas
Human insulin analogs: Modified forms of human insulin that have the same pharmacologic actions as human insulin but different time courses

Question 22

Short duration: rapid acting insulin

Answer 22

Insulin lispro [Humalog]
Insulin aspart [NovoLog]
Insulin glulisine [Apidra]
Looking at onset of 15min

Question 23

Short duration: slower acting insulin

Answer 23

Regular insulin [Humulin R, Novolin R]
Onset: 30 min

Question 24

intermediate duration insulin

Answer 24

Neutral protamine Hagedorn (NPH) insulin
Onset: 1-3hr
Needs to be taken BID

Question 25

Long duration insulin

Answer 25

Insulin glargine (Lantus) Insulin detemir (Levemir) Taken once/twice a day at same time each day No peak

Question 26

Insulin lispro (humalong)

Answer 26

Analog of human insulin Rapid onset (10 to 20 min) Short duration (3 to 5 hr) Administered immediately before eating or even after eating Rapid-acting analog of regular insulin Onset: 15 to 30 minutes after subcutaneous (subQ) injection Duration: 3 to 6 hours Usual route is subQ via injection or use of an insulin pump Acts faster than regular insulin but has a shorter duration of action Should be injected 5 to 10 minutes before meals

Question 27

Insulin glulisine [Apidra]

Answer 27

Synthetic analog of natural human insulin Rapid onset (10 to 15 min) Short duration (3 to 5 hr) Should be administered close to the time of eating

Question 28

Regular insulin [Humulin R, Novolin R]

Answer 28

Unmodified human insulin Four approved routes: SubQ injection, subQ infusion, intramuscular (IM) injection (used rarely), and oral inhalation (approved but not currently used) Effects begin in 30 to 60 minutes Peak in 1 to 5 hours Duration up to 10 hours Clear solution U-100 (100 units/mL) U-500 (500 units/mL) Not used very often

Question 29

​NPH insulin [Humulin N, Novolin N]

Answer 29

Drug is injected twice or three times daily to provide glycemic control between meals and during the night Usually 2x/day NPH insulin is the only one suitable for mixing with short-acting insulins Allergic reactions are possible NPH insulins are cloudy suspensions that must be agitated before administration NPH insulins are administered by subQ injection only NPH, neutrall protamine Hagedorn. 70/30 combo -70 NPH, 30 regular

Question 30

Insulin glargine [Lantus]

Answer 30

Modified human insulin Prolonged duration of action (up to 24 hr) Once-daily subQ dosing to treat adults and children with type 1 diabetes and adults with type 2 diabetes Clear solution

Question 31

Insulin detemir [Levemir]

Answer 31

Human insulin analog Slow onset and dose-dependent duration of action Used to provide basal glycemic control Clear, colorless solution Dosing: Once or twice daily by subQ injection Do not mix with other insulins Must not be given IV

Question 32

Insulin Appearance

Answer 32

Except for NPH insulins, all insulins made in the United States are formulated as clear, colorless solutions NPH insulin is a cloudy suspension Patients should inspect their insulin before using it and should discard the vial if the insulin looks abnormal

Question 33

Insulin [ ]

Answer 33

100 units/mL (U-100) 500 units/mL (U-500)

Question 34

Mixing insulin

Answer 34

NPH with short-acting insulins Short-acting insulin drawn first

Question 35

Insulin admin

Answer 35

Subcutaneous injection Syringe and needle Pen injectors Jet injectors Subcutaneous infusion Portable insulin pumps Implantable insulin pumps Intravenous infusion Inhalation Not used as much

Question 36

Insulin storage

Answer 36

Unopened vials should be stored under refrigeration until needed Insulin should not be frozen Insulin can be used until the expiration date if kept in the refrigerator After opening, insulin can be kept up to 1 month without significant loss of activity Insulin should be kept out of direct sunlight and extreme heat Mixtures of insulin in vials are stable for 1 month at room temperature and for 3 months under refrigeration Mixtures in prefilled syringes should be stored in a refrigerator for at least 1 week; they should be stored vertically with the needle pointing up Roll before admin

Question 37

Insulin therapeutic use

Answer 37

Principal: Diabetes mellitus Required by all patients with T1DM and by many patients with T2DM Most insulin sold is used by people with type 2 diabetes, largely because T2DM accounts for 90% to 95% of all cases of diabetes IV insulin for diabetic ketoacidosis Gestational diabetes Hyperkalemia: Can promote uptake of potassium Aids in the diagnosis of growth hormone (GH) deficiency

Question 38

Insulin dosing schedule

Answer 38

Three dosing schedules: Twice daily premixed insulin regimen Intensive basal/bolus strategy Continuous subcutaneous insulin Insulin pump

Question 39

Achieving Optimal Glucose Control

Answer 39

Careful attention to all elements of the treatment program (diet, exercise, insulin replacement therapy) A defined glycemic target Self-monitoring of blood glucose according to the patient’s individualized management plan A high degree of patient motivation Extensive patient education The responsibility for managing diabetes rests with the patient

Question 40

Complications of insulin tx -hypoglycemia

Answer 40

Hypoglycemia Blood glucose below 70 mg/dL Rapid treatment mandatory Conscious patients: Fast-acting oral sugar (e.g., glucose tablets, orange juice, sugar cubes, nondiet soda) If swallowing reflex or gag reflex is suppressed: Nothing should be given by mouth IV glucose or parenteral glucagon is the preferred treatment Chocolate slows absorption of glucose

Question 41

Other compl of insulin tx

Answer 41

Lipohypertrophy Allergic reactions Hypokalemia

Question 42

Insulin drug interactions

Answer 42

Hypoglycemic agents Hyperglycemic agents Beta-adrenergic blocking agents Harder for pt to recognize hypoglycemia

Question 43

Oral hypoglycemics

Answer 43

Biguanides Metformin [Glucophage] Sulfonylureas Thiazolidinediones (also known as glitazones) Rosiglitazone [Avandia] Pioglitazone [Actos] Meglitinides (also known as glinides) Repaglinide [Prandin] Nateglinide [Starlix]

Question 44

Metformin [Glucophage]

Answer 44

Drug of choice for initial therapy in most patients with type 2 diabetes Most common side effects: Gastrointestinal (GI) disturbances Lactic acidosis, a potentially fatal complication, is rare Uses: Prevention of type 2 diabetes Gestational diabetes Polycystic ovary syndrome (PCOS) If pt is not tolerating metformin after 2-3 weeks, can try metformin ER Metformin ER may have large copay or not be covered at all

Question 45

Sulfonylureas

Answer 45

First oral antidiabetics available Promote insulin release Can be used only for type 2 diabetes Major side effects: Hypoglycemia, weight gain First generation Not used much at all Second generation Glymepirides, glyphosis, glyberides Cardiotoxicity If pt is allergic to sulfa AB should not be taking this

Question 46

Meglitinides (glinides)

Answer 46

Repaglinide [Prandin] Generally well tolerated Adverse effect: Hypoglycemia, weight gain Drug interactions: Gemfibrozil [Lopid] Nateglinide [Starlix] Pharmacology nearly identical to that of repaglinide Promote insulin secretion by pancreas

Question 47

Thiazolidinediones (glitazones)

Answer 47

Reduce glucose levels primarily by decreasing insulin resistance Only indication is type 2 diabetes, mainly as an add-on to metformin Rosiglitazone [Avandia]: Restricted use Pioglitazone [Actos]

Question 48

Pioglitazone [Actos]

Answer 48

Reduces insulin resistance and may also decrease glucose production Indication: Adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes Adverse effects: Generally well tolerated; most common reactions are upper respiratory tract infection, headache, sinusitis, and myalgia

Question 49

Alpha-glucosidase inhibitors

Answer 49

Act in the intestine to delay the absorption of carbohydrates Indication: Type 2 diabetes Acarbose [Precose] Adverse effects: Frequently causes flatulence, cramps, abdominal distention, borborygmus, diarrhea, and liver dysfunction Miglitol [Glyset] Especially effective among Latinos and African Americans Adverse effects: Flatulence, abdominal discomfort, and other GI effects Has not been associated with liver dysfunction

Question 50

DPP-4 inhibitors (also called gliptins)

Answer 50

Promote glycemic control by enhancing the actions of incretin hormones Stimulate glucose-dependent release of insulin Suppress postprandial release of glucagon Decrease hepatic glucose production Sitagliptin [Januvia] DPP-4 , dipeptidyl peptidase-4. SE: pancreatitis, hypersensitivity rxn Don’t prescribe to someone with hx of pancreatitis Saxagliptin [Onglyza] Most common adverse effects: Upper respiratory infection, urinary tract infection, and headache Linagliptin [Tradjenta] Alogliptin [Nesina]

Question 51

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors

Answer 51

Block reabsorption of filtered glucose in the kidney, leading to Indication: Type 2 diabetes mellitus Dapagliflozin [Farxiga] Canagliflozin [Invokana] Side effects: Genital fungal infections in female patients, urinary tract infections, increased urination, weight loss Fungal infections, Etc cause people to d/c drug

Question 52

Other drugs for DM tx

Answer 52

Colesevelam [Welchol] Bromocriptine

Question 53

Noninsulin Injectable Drugs

Answer 53

Pramlintide -Amylin mimetic incretin mimetics

Question 54

GLP-1 receptor agonists (also called incretin mimetics)

Answer 54

Slow gastric emptying, stimulate glucose-dependent release of insulin, inhibit postprandial release of glucagon, and suppress appetite Exenatide [Byetta] Adverse effects: Hypoglycemia and gastrointestinal effects, including pancreatitis Liraglutide [Victoza] May cause medullary thyroid carcinoma (MTC)

Question 55

Amylin mimetics

Answer 55

Pramlintide [Symlin] Reduces postprandial levels of glucose by delaying gastric emptying and suppressing glucagon secretion Adverse effects: Hypoglycemia and nausea, injection site reactions

Question 56

Acute Complications of Poor Glycemic Control

Answer 56

Diabetic ketoacidosis (DKA) Type 1 Hyperosmolar hyperglycemic state (HHS) Type 2 Cardinal features of both conditions: Hyperglycemic crisis and associated loss of fluid and electrolytes Both conditions can be life-threatening Differences Hyperglycemia is more severe in HHS Ketoacidosis characteristic of DKA, absent in HHS Treatment of the two disorders is similar

Question 57

Diabetic Ketoacidosis

Answer 57

Severe manifestation of insulin deficiency Symptoms evolve quickly within hours or days Most common complication in pediatric patients and the leading cause of death Characteristics Hyperglycemia Ketoacids Hemoconcentration Acidosis Coma Altered glucose metabolism Hyperglycemia Water loss Hemoconcentration Altered fat metabolism Treatment Insulin replacement Bicarbonate for acidosis Water and sodium replacement Potassium replacement Normalization of glucose levels Production of ketoacids

Question 58

Hyperosmolar Hyperglycemic State (HHS)

Answer 58

Also called hyperglycemic hyperosmolar nonketotic syndrome (HHNS) Large amount of glucose excreted in urine Results in dehydration and loss of blood volume Increases blood concentrations of electrolytes and nonelectrolytes (particularly glucose); also increases hematocrit Blood “thickens” and becomes sluggish Little or no change in ketoacid levels Little or no change in blood pH No sweet or acetone-like smell to urine or breath Occurs most frequently with type 2 diabetes with acute infection, acute illness, or some other stress Can evolve slowly Metabolic changes begin a month or two before signs and symptoms become apparent If left untreated, can lead to coma, seizures, and death Management Correct hyperglycemia and dehydration with IV insulin, fluids, and electrolytes More common in older adults

Question 59

Glucagon for Treatment of Severe Hypoglycemia

Answer 59

Preferred treatment is IV glucose Immediately raises blood glucose level Glucagon can be used if IV glucose is not available Delayed elevation of blood glucose Cannot correct hypoglycemia resulting from starvation Promotes glycogen breakdown, and the malnourished have little glycogen left