GI - Biochemistry - Diabetes; Other Sugar Metabolism; Bile Acids Flashcards
Of U.S. diabetics, what percentage are type I?
What percentage are type II?
5 - 10%
90 - 95%
What ethnicity is most at-risk for type I diabetes mellitus?
What gender?
What age?
Caucasian > African-American, Hispanic >>> Asian;
men > women;
11 - 13 years of age
What ethnicity is most at-risk for type II diabetes mellitus?
What gender?
What age?
Hispanic, Native American, African-American, Asian > caucasian;
men = women;
> 40
Describe the development of type I diabetes mellitus in terms of cause, timing, and mechanism.
Viral infection induces an autoimmune attack on the pancreatic β-cells (molecular mimicry);
may take up to 10 years post-infection to become a clinical presentation
How is type I diabetes mellitus diagnosed (ADA guidelines)?
(Hint: there are 4 potential tests.)
HbA1c ≥ 6.5%
FPG > 125 mg/dL
OGTT > 200 mg/dL (at 2 hours)
RPG > 200 mg/dL (with classic S/Sy)
What are some of the common signs and symptoms of type I diabetes mellitus?
Polydipsia, polyphagia, polyuria;
unexplained weight loss, lassitude, muscle cramps, blurred vision, peripheral neuropathy, headaches, GI complications
What values for the following tests would indicate prediabetes?
FPG
HbA1c
OGTT
FPG: 110 - 125 mg/dL
HbA1c: 5.6 - 6.4%
OGTT: 140 - 200 mg/dL
What are the normal values for the following tests?
FPG
HbA1c
OGTT
FPG: 70 - 110 mg/dL
HbA1c: < 5.6%
OGTT: < 140 mg/dL
To what conditions is a patient with prediabetes especially predisposed?
Type II diabetes mellitus;
macrovascular disease
Describe the requirements for a patient to be diagnosed with metabolic syndrome.
(I.e. they must have ≥ ____ of which clinical test values?)
Must have ≥3 of the following:
Obesity
Elevated glucose levels (≥ 110 mg/dL FPG)
Dislipidemia (elevated TG and LDL, decreased HDL)
Hypertension
Insulin resistance
Prothrombotic state
Proinflammatory state
To be diagnosed with metabolic syndrome, a patient must have ≥ 3 of what features?
Obesity
Elevated glucose levels (≥ 110 mg/dL FPG)
Dislipidemia (elevated TG and LDL, decreased HDL)
Hypertension
Insulin resistance
Prothrombotic state
Proinflammatory state
Which are the two dominant factors in a patient with metabolic syndrome that especially predispose that individual to T2DM and vascular disease?
Abdominal obesity,
insulin resistance
What percentage of patients with T2DM are obese?
90%
What happens to insulin levels in an individual as they develop T2DM?
An initial compensatory insulin increase;
a steady decrease in insulin production over decades
Describe the changes in serum glucose and insulin in a patient as they develop T2DM.
What are the two features of T2DM development?
Peripheral insulin resistance
+
insufficient insulin-secretory (compensatory) mechanism
What are some of the signs and symptoms of type II diabetes mellitus?
All the S/Sy of T1DM
+
slow-healing sores, itchy skin, frequent yeast infections
Do pregnant women normally develop hyperglycemia or hypoglycemia during pregnancy?
When?
Why?
Hypoglycemia;
intraprandial / during sleep;
fetal glucose need
Does intraprandial hypoglycemia increase or decrease as pregnancy progresses?
Increase
(fetal demand increases)
In non-specific terms, why do some women develop gestational diabetes mellitus?
Susceptible women develop insulin resistance in response to placental steroid and peptide synthesis
A pregnant woman begins to develop insulin resistance in response to the increasing placental steroid and peptide hormone synthesis.
What will occur if her insulin levels are inadequate?
Recurrent postprandial hyperglycemia –>
accelerated fetal growth
What are some of the effects of surging hyperglycemia and hyperinsulinemia (related to gestational diabetes mellitus) on the fetus?
Macrosomia, fetal hypoxia;
hypertension, cardiac remodeling/hypertrophy
What are some of the risk factors for gestational diabetes mellitus?
Consider: age, ethnicity, weight, and medical history.
Age: > 35
Ethnicity: Hispanic, Native American, African-American, Asian > caucasian
Weight: Obesity
Medical History: obstetrical Hx of diabetes or macrosomia; family Hx of DM
How does ethnicity affect a woman’s risk of gestational diabetes mellitus?
What percentage of women with gestational DM will develop overt DM within 5 years of delivery?
~33%
(higher risk ethnicities nearing 50%)
How is gestational DM diagnosed?
When?
2 steps:
1-hour glucose challenge test (GCT)
2-hour OGTT;
between week 24 and 28
(week 13 for those with risk factors)
What is the major acute complication of T1DM?
What is the major acute complication of T2DM?
Diabetic ketoacidosis (DKA);
hyper(HHNC)
Which has a higher mortality rate, diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic non-ketotic coma (HHNC)?
HHNC
True/False.
Both DKA and HHNC are characterized by hyperglycemia and dehydration.
True.
What are some causes of DKA in a patient with T1DM?
New onset of DM,
insulin disruption,
infection
What are some causes of HHNC in a patient with T2DM?
Secondary to DM effects:
infection,
fluid loss,
certain drugs
What are the S/Sy of DKA?
1. Serum glucose > 300 mg/dL
2. Acidosis
3. Low HCO3- (< 15 mEq/L)
4. Ketonemia, ketonuria
5. Acetone breath
What are the S/Sy of HHNC?
1. Serum glucose > 600 mg/dL
2. Hyperosmolarity > 320 mOsm/dL
3. Dehydration
4. Na+/K+ loss (via osmotic diuresis)
How is DKA treated?
Fluids
+
Insulin (after 1st hour)
+
Dextrose (eventually, to prevent hypoglycemia)
How is HHNC treated?
Similar to DKA (fluid –> insulin –> glucose)
+ careful electrolyte monitoring
List some of the chronic complications of diabetes.
Neuropathies,
peripheral vascular disease
diabetic nephropathy,
cataracts, glaucoma, retinopathy,
CVD,
skin lesions
Diabetics should be encouraged to aim for a HbA1c of:
< 7%
What are the main sugar- and insulin-related goals of diabetes medication?
HbA1c < 7%
Postprandial glucose of 90 - 130 mg/dL
Increased insulin secretion
Decreased insulin resistance
Why don’t T2 diabetics get DKA?
They have sufficient insulin secretion to prevent ketone production
Other than meglitinides, thiazolidinediones, and incretins, name three categories of drugs often used to treat T2DM.
Biguanides (metformin)
Sulfonylureas (tolbutamide, glipizide, glyburide)
α-glucosidase (miglitol, acarbose) / SGLT-2 inhibitors (
Other than biguanides, sulfonylureas, and α-glucosidase/SGLT inhibitors, name three categories of drugs used to treat T2DM.
Meglitinides (repaglinide)
Thiazolidinediones (rosiglitazone, pioglitazone)
Incretins (DDP-4 inhibitors; glucose-dependent insulinotropic peptide and GLP-1 analogs)
What results occur with virtually all diabetic medications?
A decrease in FPG and a decrease in HbA1c
Name three diabetic drug types that increase insulin secretion.
Sulfonylureas (long-acting);
meglitinides (short-acting);
incretins
Name a diabetic drug type that decreases glucagon secretion.
Incretins
Name two diabetic drug types that increase insulin sensitivity (in the liver, skeletal muscle, and adipose).
Biguanides (e.g. metformin);
glitazones