Diabetes mellitus Flashcards
Diabetes mellitus
is a group of metabolic diseases characterized by hyperglycemia due to defects in insulin secretion or action
Diabetes mellitus is often accompanied by hypertension and hypercholesterolemia
increasing the risk of complications
Type 1 diabetes
accounts for less than 10% of cases and results from autoimmune destruction of pancreatic beta cells
Type 1 diabetes requires exogenous insulin
to control blood glucose and prevent diabetic ketoacidosis
The honeymoon phase in type 1 diabetes
is a transient period of reduced insulin requirement early in the disease
Type 2 diabetes
accounts for more than 90% of cases and is initially characterized by insulin resistance
Type 2 diabetes risk factors
include older age
Ketosis in type 2 diabetes
is usually prevented by sufficient insulin secretion but can occur during severe stress
Other specific types of diabetes
include MODY
Gestational diabetes mellitus
is abnormal glucose tolerance first detected during pregnancy
Women with pre-existing diabetes before pregnancy
are not classified as having gestational diabetes
After delivery in gestational diabetes
glucose tolerance usually returns to normal but increases the risk of type 2 diabetes
The A1C diagnostic threshold for diabetes
is 6.5% or higher
Classic diabetes symptoms with random plasma glucose of 200 mg/dL or more
confirm a diabetes diagnosis
Fasting plasma glucose of 126 mg/dL or higher
is diagnostic for diabetes
Two-hour plasma glucose of 200 mg/dL or more during an OGTT
confirms diabetes diagnosis
Prediabetes fasting glucose range
is 100-125 mg/dL
Prediabetes A1C range
is 5.7-6.4%
Prediabetes 2-hour OGTT range
is 140-199 mg/dL
Normal glucose tolerance fasting glucose
is below 100 mg/dL
Normal glucose tolerance A1C
is below 5.7%
Management of diabetes involves three steps
glycemic control
Diabetes treatment goals include A1C
below 7.0%
Preprandial plasma glucose goal
is 90-130 mg/dL
Peak postprandial glucose goal
is below 180 mg/dL
LDL cholesterol goal in diabetes
is below 100 mg/dL
HDL cholesterol goal in diabetes
is above 40 mg/dL
Triglycerides goal in diabetes
is below 150 mg/dL
Assessment of glycemic control includes
self-monitoring of blood glucose and HbA1c testing
HbA1c testing should be done every 3 months
or at least twice a year in well-controlled patients
Dietary modification in diabetes
helps maintain ideal body weight and achieve proper nutrition
Exercise benefits in diabetes
include improved insulin sensitivity and reduced blood glucose levels
Medications for diabetes
are most effective when combined with diet and exercise
Type 1 diabetes clinical presentation
includes abrupt onset of polyuria
Type 1 diabetes may be triggered
by an unrelated illness or stress on an already-limited islet reserve
Diabetic ketoacidosis may be the first presentation
for a minority of type 1 diabetes patients
Type 1 diabetes incidence increases in winter
due to respiratory viral infections
Puberty and type 1 diabetes
are linked due to insulin resistance from sex and growth hormone secretion
Diabetic ketoacidosis and hyperosmolar hyperglycemic syndrome
are the two main metabolic decompensation syndromes in diabetes
Diabetic ketoacidosis is more common in type 1 diabetes
but can also occur in type 2 under severe stress
Precipitating factors for diabetic ketoacidosis
include infection
Symptoms of diabetic ketoacidosis
include polyuria
Kussmaul respiration and fruity breath odor
are characteristic physical findings in diabetic ketoacidosis
Dehydration
respiratory distress
Laboratory findings in diabetic ketoacidosis
include elevated plasma glucose
Management of diabetic ketoacidosis
requires IV access
Fluid replacement in diabetic ketoacidosis
is critical due to severe dehydration of 7-9% body weight
Initial fluid resuscitation for diabetic ketoacidosis
should be isotonic (0.9%) saline
Insulin therapy in diabetic ketoacidosis
is needed to stop ketogenesis and lower blood glucose
A bolus of 10-15 units of regular insulin
should be followed by a continuous infusion in diabetic ketoacidosis
Blood glucose reduction in diabetic ketoacidosis
should be 50-75 mg/dL per hour
Excessively rapid glucose correction in diabetic ketoacidosis
increases the risk of osmotic encephalopathy
Dextrose infusion should start
when plasma glucose reaches 250 mg/dL to prevent hypoglycemia
Potassium deficit in diabetic ketoacidosis
should be assumed and monitored regardless of initial plasma levels
Bicarbonate therapy in diabetic ketoacidosis
is not routinely needed but may be used in severe acidosis
Type 2 diabetes results from
progressive beta-cell failure and insulin resistance
Type 2 diabetes patients
can develop diabetic ketoacidosis under severe stress
Polyuria
polydipsia
Type 2 diabetes may go undiagnosed
for years before symptoms appear
Severe hyperglycemia in type 2 diabetes
can present as hyperosmolar hyperglycemic syndrome
Type 2 diabetes metabolic defects
worsen over time requiring treatment escalation
Early type 2 diabetes
may be managed with diet and weight loss alone
Most type 2 diabetes patients
eventually require oral medications or insulin therapy
Microvascular complications may be the first sign
of type 2 diabetes in some patients
Treatment goals for type 2 diabetes
are the same as for type 1 diabetes
Type 2 diabetes treatment requires
individualized therapy with lifestyle and pharmacologic interventions
Oral therapy should be started early
if diet and exercise fail to control glucose
Monotherapy for type 2 diabetes
includes insulin secretagogues
Combination therapy or insulin
is needed if monotherapy fails to control glucose
Patients with glucose above 240 mg/dL at diagnosis
should start with combination therapy or insulin
Nonketotic hyperosmolar syndrome is a life-threatening complication
of type 2 diabetes
In 30%-40% of cases
nonketotic hyperosmolar syndrome is
Ketoacidosis is absent in nonketotic hyperosmolar syndrome
due to insulin preventing lipolysis and ketogenesis
Precipitating factors for nonketotic hyperosmolar syndrome
include stress
Nonketotic hyperosmolar syndrome has an insidious onset
with progressive glycemic deterioration and lethargy
Severe dehydration and altered consciousness
are common findings in nonketotic hyperosmolar syndrome
Hyperglycemia above 600 mg/dL and plasma osmolality above 320 mOsm/L
are diagnostic criteria for nonketotic hyperosmolar syndrome
Absence of ketonemia and a pH above 7.3
differentiate nonketotic hyperosmolar syndrome from diabetic ketoacidosis
Nonketotic hyperosmolar syndrome must be distinguished from
hypoglycemia
The first step in treating nonketotic hyperosmolar syndrome
is restoring hemodynamic stability with fluids
Patients with nonketotic hyperosmolar syndrome may require
10-12 L of fluid replacement over 24-36 hours
Despite normal or high potassium levels
nonketotic hyperosmolar syndrome patients
Insulin therapy plays a secondary role in nonketotic hyperosmolar syndrome
with fluid resuscitation being the priority
For marked hyperglycemia over 600 mg/dL
regular insulin 5-10 units IV
When plasma glucose drops to 250-300 mg/dL
insulin infusion should be reduced
Microvascular complications of diabetes
include retinopathy
Nonproliferative and proliferative retinopathy
are types of diabetic eye disease
Diabetic neuropathy can be
sensory
Diabetic nephropathy
is a major cause of chronic kidney disease
Macrovascular complications of diabetes
include coronary artery disease
Other complications of diabetes
include gastroparesis
Hypoglycemia is caused by low glucose levels
triggering sympathoadrenal activation symptoms
Symptoms of sympathoadrenal activation
include sweating
Neuroglycopenia symptoms include
fatigue
Iatrogenic hypoglycemia
is a major limitation of intensive diabetes therapy
Risk factors for iatrogenic hypoglycemia
include skipped meals
Oral glucose or sugar-containing beverages
are the first-line treatment for conscious hypoglycemic patients
IV dextrose is needed for severe hypoglycemia
or if the patient has altered consciousness
An initial bolus of 20-50 mL of 50% dextrose
should be given followed by maintenance infusion
Glucagon 1 mg IM or SC
is used for severe hypoglycemia when IV access is unavailable
Insulin is synthesized in B-cells of the pancreas
and consists of two polypeptide chains linked by bisulfide bridges
Amylin is synthesized in B-cells
and decreases insulin release by delaying gastric emptying and increasing glycogenolysis
One mg of insulin is equivalent to
22 U
The daily insulin output is 30-40 U
and is controlled by food
Glucose is the main stimulant of insulin release
along with fatty acids and amino acids
GIT hormones such as gastrin and secretin
increase insulin release
Glucagon and growth hormone
increase insulin release
Somatostatin and PGE-1
decrease insulin release
Beta-2 and muscarinic receptor stimulation
increases insulin secretion
Alpha-2 receptor stimulation
decreases insulin secretion
Hypoglycemia and fasting
decrease insulin secretion by stimulating sympathetic transmitters
Sulfonylureas increase insulin release
while phenytoin
Exogenous human insulin
is obtained by genetic engineering
Insulin is not effective orally
and is usually given subcutaneously or intravenously for soluble insulin
Insulin is metabolized in the liver and kidney
by glutathione insulin transhydrogenase and proteolytic enzymes
The insulin receptor consists of
two alpha and two beta subunits linked by bisulfide bonds
The insulin receptor’s action is mediated
through tyrosine kinase phosphorylation
Rapid-acting insulin includes lispro and aspart
with onset within 10-30 minutes and duration of 3-5 hours
Short-acting insulin includes regular insulin
with an onset of 30 minutes and duration of 6-8 hours
Intermediate-acting insulin includes NPH and lente
with an onset of 2 hours and duration of 18-24 hours
Long-acting insulin includes PZI
ultralente
Lispro insulin has a shorter duration and faster action
compared to soluble insulin
Lente insulin consists of
30% semilente and 70% crystalline zinc insulin
Soluble insulin can be acidic or neutral
while PZI is alkaline and should not be mixed with acidic insulin
Insulin therapy is usually given as
a mixture of 30% regular insulin and 70% NPH insulin
Insulin is administered pre-prandially
with 2/3 before breakfast and 1/3 before dinner
Biphasic isophane insulin
is a premixed combination of regular and NPH insulin
Insulin is indicated for type 1 diabetes
and type 2 diabetes uncontrolled by diet and oral antidiabetics
Insulin is used in critical situations
such as pregnancy
Hypoglycemia from insulin therapy
can result from overdose
Hypoglycemia causes sympathetic overactivity
leading to tachycardia
Severe hypoglycemia can cause
mental confusion
Mild hypoglycemia is treated with
a sweet drink or snack
Severe hypoglycemia is treated with
IV glucose or IM glucagon
Insulin allergy is caused by
IgE-mediated histamine release from mast cells
Insulin allergy presents as
localized erythema or systemic anaphylaxis
Purified human insulin
reduces the risk of insulin allergy
Insulin resistance is due to
IgG antibodies neutralizing insulin before receptor binding
A diabetic needing over 200 U of insulin daily
is considered insulin resistant
Insulin lipodystrophy includes
atrophy and hypertrophy at injection sites
Lipohypertrophy is caused by
repeated injections at the same site leading to lipogenesis
Lipodystrophy can be prevented by
rotating insulin injection sites
Insulin therapy can cause
weight gain
Sulfonylureas stimulate insulin release
by blocking ATP-sensitive potassium channels in beta cells
Sulfonylureas require at least 30% functioning beta cells
to be effective in type 2 diabetes
Long-term sulfonylurea therapy
leads to downregulation of sulfonylurea receptors
Sulfonylureas increase insulin sensitivity
by upregulating insulin receptors and glucose transporters
Sulfonylureas decrease hepatic glucose output
by inhibiting glycogenolysis and gluconeogenesis
First-generation sulfonylureas include tolbutamide and chlorpropamide
while second-generation include glibenclamide glipizide and gliclazide
Third-generation sulfonylureas
include glimepiride
Second-generation sulfonylureas are 100 times more potent
but have the same maximal hypoglycemic effect
Sulfonylureas are indicated in
NIDDM not responding to diet and exercise
Sulfonylureas can cause severe hypoglycemia
leading to coma
Sulfonylureas increase appetite
causing weight gain
Sulfonylureas can cause allergic reactions
including rash and photosensitivity
Sulfonylureas can cause
bone marrow depression and teratogenic effects
Glimepiride is effective in a smaller dose
with less hypoglycemia and no weight gain
Biguanides decrease glucose absorption
increase lactate production
Biguanides decrease plasma glucagon
and increase insulin sensitivity
Biguanides do not increase insulin release
so they do not cause hypoglycemia
Biguanides reduce plasma LDL and VLDL
preventing atherosclerosis
Metformin is the only biguanide
available for clinical use
Metformin is indicated for NIDDM
especially in obese patients due to appetite suppression
Metformin is used with sulfonylureas
to reduce hypoglycemia risk in NIDDM
Metformin is combined with insulin
to reduce insulin requirements in insulin resistance
Metformin can cause lactic acidosis
especially in renal hepatic and cardiopulmonary disease
Metformin can cause
anorexia nausea vomiting diarrhea and B12 deficiency
Meglitinides are oral insulin secretagogues
that block ATP-dependent K-channels in B-cells
Meglitinides include
repaglinide and nateglinide
Meglitinides have rapid onset
and are taken 10 minutes before meals to prevent postprandial hyperglycemia
Meglitinides are ineffective in
IDDM
Meglitinides cause less hypoglycemia
than sulfonylureas
Thiazolidinediones include
rosiglitazone and pioglitazone
Thiazolidinediones are called insulin sensitizers
and act via PPAR-gamma receptors
PPAR-gamma receptors are present in
adipose tissue liver and skeletal muscles
Thiazolidinediones increase glucose transport
by increasing GLUT-4 synthesis and translocation
Thiazolidinediones require insulin
for their action
Thiazolidinediones can cause anemia
weight gain edema and hypervolemia
Thiazolidinediones are contraindicated
in hypertension and heart failure
Alpha-glucosidase inhibitors include
acarbose and miglitol
Alpha-glucosidase inhibitors are poorly absorbed
and competitively inhibit carbohydrate absorption in the gut
Alpha-glucosidase inhibitors reduce postprandial hyperglycemia
and promote weight loss
Alpha-glucosidase inhibitors can be used alone
or with insulin or sulfonylureas
Alpha-glucosidase inhibitors cause
flatulence distension and abdominal pain
DPP-4 inhibitors include
alogliptin linagliptin sitagliptin and saxagliptin
DPP-4 inhibitors prevent incretin degradation
increasing insulin release and reducing glucagon
DPP-4 inhibitors can be used alone
or with sulfonylureas metformin or insulin
DPP-4 inhibitors should not be combined
with GLP-1 receptor agonists due to overlapping mechanisms
DPP-4 inhibitors are well absorbed orally
and excreted via the renal or enterohepatic system
Sitagliptin is mostly excreted unchanged
while saxagliptin is metabolized by CYP450 3A4/5
DPP-4 inhibitors can cause
nasopharyngitis headache pancreatitis and joint pain
CYP3A4 inhibitors like ketoconazole
can increase saxagliptin levels
SGLT2 inhibitors include
canagliflozin and dapagliflozin
Empagliflozin reduces cardiovascular mortality
in diabetic patients with heart disease
SGLT2 inhibitors reduce glucose reabsorption
increasing urinary glucose excretion
SGLT2 inhibitors cause osmotic diuresis
and reduce sodium reabsorption
SGLT2 inhibitors can lower systolic blood pressure
but are not used for hypertension treatment
SGLT2 inhibitors should be avoided
in renal dysfunction
SGLT2 inhibitors can cause
urinary tract infections genital infections and increased urination
SGLT2 inhibitors can cause
hypotension in elderly or diuretic users
SGLT2 inhibitors can cause
ketoacidosis in high-risk patients
