Chaper 48: Diabetes Mellitus Flashcards
Diabetes Mellitus: Overview of the Disease and Its Treatment
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
TIDM
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
TIIDM
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
Complications of DM
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
DM and preg
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
Gestational DM
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
DM dx
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
Prediabetes
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
Overview of DM tx
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
Type 1 DM tx
Requires a comprehensive plan
Integrated program of diet, self-monitoring of blood glucose, exercise, and insulin replacement
TIDM dietary measures
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
Physical activity for TIDM
150 min of exercise a week
Insulin requirements for TIDM
Lifelong replacement
TIDM HTN mgmt
An ACE inhibitor (e.g., lisinopril) or an ARB (e.g., losartan) can reduce the risk of diabetic nephropathy
TIDM dyslipidemia
Statins ex. Atrovastain
Type 2 DM tx
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
When tight glycemic control is inapppropriate
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)
Monitoring DM tx
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
Monitoring DM tx: HgA1C
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
Metabolic consequences of insulin deficiency
Catabolic mode
Increased glycogenolysis
Increased gluconeogenesis
Reduced glucose utilization
Insulin preps
“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
Short duration: rapid acting insulin
Insulin lispro [Humalog]
Insulin aspart [NovoLog]
Insulin glulisine [Apidra]
Looking at onset of 15min
Short duration: slower acting insulin
Regular insulin [Humulin R, Novolin R]
Onset: 30 min
intermediate duration insulin
Neutral protamine Hagedorn (NPH) insulin
Onset: 1-3hr
Needs to be taken BID
Long duration insulin
Insulin glargine (Lantus)
Insulin detemir (Levemir)
Taken once/twice a day at same time each day
No peak
Insulin lispro (humalong)
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
Insulin glulisine [Apidra]
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
Regular insulin [Humulin R, Novolin R]
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
NPH insulin [Humulin N, Novolin N]
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
Insulin glargine [Lantus]
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
Insulin detemir [Levemir]
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
Insulin Appearance
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
Insulin [ ]
100 units/mL (U-100)
500 units/mL (U-500)
Mixing insulin
NPH with short-acting insulins
Short-acting insulin drawn first
Insulin admin
Subcutaneous injection
Syringe and needle
Pen injectors
Jet injectors
Subcutaneous infusion
Portable insulin pumps
Implantable insulin pumps
Intravenous infusion
Inhalation
Not used as much
Insulin storage
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
Insulin therapeutic use
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
Insulin dosing schedule
Three dosing schedules:
Twice daily premixed insulin regimen
Intensive basal/bolus strategy
Continuous subcutaneous insulin
Insulin pump
Achieving Optimal Glucose Control
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
Complications of insulin tx -hypoglycemia
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
Other compl of insulin tx
Lipohypertrophy
Allergic reactions
Hypokalemia
Insulin drug interactions
Hypoglycemic agents
Hyperglycemic agents
Beta-adrenergic blocking agents
Harder for pt to recognize hypoglycemia
Oral hypoglycemics
Biguanides
Metformin [Glucophage]
Sulfonylureas
Thiazolidinediones (also known as glitazones)
Rosiglitazone [Avandia]
Pioglitazone [Actos]
Meglitinides (also known as glinides)
Repaglinide [Prandin]
Nateglinide [Starlix]
Metformin [Glucophage]
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
Sulfonylureas
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
Meglitinides (glinides)
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
Thiazolidinediones (glitazones)
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]
Pioglitazone [Actos]
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
Alpha-glucosidase inhibitors
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
DPP-4 inhibitors (also called gliptins)
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]
Sodium-glucose cotransporter 2 (SGLT-2) inhibitors
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
Other drugs for DM tx
Colesevelam [Welchol]
Bromocriptine
Noninsulin Injectable Drugs
Pramlintide -Amylin mimetic
incretin mimetics
GLP-1 receptor agonists (also called incretin mimetics)
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)
Amylin mimetics
Pramlintide [Symlin]
Reduces postprandial levels of glucose by delaying gastric emptying and suppressing glucagon secretion
Adverse effects: Hypoglycemia and nausea, injection site reactions
Acute Complications of Poor Glycemic Control
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
Diabetic Ketoacidosis
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
Hyperosmolar Hyperglycemic State (HHS)
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
Glucagon for Treatment of Severe Hypoglycemia
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
