SG 3.3: Living with Diabetes Flashcards
A 25 y/o woman has a history of type 1 diabetes for 10 years and presents to you for pre-conception counselling. Her husband does not have diabetes. She asks you what is the risk that her child will develop DM1?
4%
if she has no family history at all it’s .4% but the offspring of an affected mother is 1-4%
offspring of an affected father is 3-5%
offspring with both parents is as high as 30%
A 29 y/o male has a first-degree relative with type 1 diabetes and wants to know the implications of having a positive GAD65 antibody.
Which of the following is true regarding autoimmune type 1 diabetes?
A. Positive antibodies and presence of HLA-DR2 tend to have more rapid progression to hyperglycemia.
B. Oral glucose tolerance tests become abnormal prior to the loss of first-phase insulin release in patients at risk for type 1 diabetes.
C. IA-2 and islet cell antibodies (ICA) are more commonly seen in latent autoimmune diabetes in adults (LADA) than in children with type 1 diabetes.
D. GAD antibody positivity is more predictive of future hyperglycemia development than the presence of multiple islet antibodies.
E. Presence of ICA at diagnosis predicts more rapid decline in β-cell function.
E. Presence of ICA at diagnosis predicts more rapid decline in β-cell function.
islet cell antibodies is a bad prognosis for β-cell function
which of the following is true regarding susceptibility genes related to autoimmune type I DM?
A. HLADR2 increases risk
B. HLADR4 decreases risk
C. DBQ1 confers increased risk
D. HLADR3 reduces risk
E. HLADR3, HLADR4 both confer increased risk
E. HLADR3, HLADR4 both confer increased risk
what is predictive of future DMI?
screening first-degree relatives of individuals with type 1 diabetes can be used to predict both likelihood of developing disease and timing of disease onset
multiple positive antibodies are highly predictive of future disease development, while positivity for only one autoantibody may not lead to diabetes development
which antibodies can be detect prior to manifestation of autoimmune hyperglycemia?
- islet-cell antibodies (ICA),
- insulin antibodies (IAA),
- glutamic acid decarboxylase antibodies (GAD), and
- antibodies to tyrosine phosphatase-like proteins (IA-2, ICA512)
ICA presence, titer, persistence, and association with other autoimmune markers (GAD and IAA) is associated with increasing risk of type 1 diabetes
in individuals with multiple autoimmune antibodies, testing of first-phase insulin release with an IV glucose tolerance test adds to the predictive value for the future development of hyperglycemia or an abnormal oral glucose tolerance test
which antibodies are common in LADA?
While ICA and GAD are common in LADA, IA-2 antibodies and IAA are much less commonly seen in LADA than in type 1 diabetes
what are the major susceptibility genes for type I diabetes?
HLADR3 and 4
HLADR2 is actually protective!
DQB10602 also has reduced risk
what is the pathophysiology of type I DM?
- interactions between genes imparting susceptibility and resistance
- variable insulinitis and B cell sensitivity to injury
- over time you have loss of first phase insulin response which means that when you give IV glucose you don’t have a good insulin response
- glucose intolerance indicates type I diabetes is official; before this it was prediabetes
- C-peptide is undetectable
A 44 y/o Asian American presents for an annual physical exam. He is physically active and strives to eat healthy. Denies any symptoms today except for c/o mild fatigue lately, and states that he has been under a lot of stress at work.
He is requesting for his vitamin D level to be checked, as wants to make sure it’s not low. His vitals are normal, BMI is 23, and he takes a daily multivitamin. His cholesterol was check at a health fair at work 6 months ago and was normal.
You order for fasting blood work and fasting glucose is 150. what is the next best step?
perform 75 g OGTT
blood glucose over 126 is one of the criteria for diagnosing DM so do the OGTT to confirm
if the OGTT comes back at 200 how do you interpret his results if a fasting glucose was 150?
new onset diabetes
criteria for diagnosis of DMII:
1. fasting glucose of over 126
- 2hr plasma glucose is over 200 during oGTT
- A1c over 6.5
- symptoms of hyperglycemia OR hyperglycemic crisis, a random plasma glucose over 200
in the absence of unequivocal hyperglycemia, diagnosis requires 2 abnormal test results from the same sample OR in 2 different test samples
A 50 y/o male with a history of diabetes returns to your office for review of his labs. His A1c is 9.0%, increased from 7.0% at his last visit. His current drug regimen includes glipizide and metformin. He reports that he takes his medications regularly, but his wife is concerned about his diabetes control.
Which of the following labs would best indicate a need for insulin to control this patient’s blood sugar?
A. Anti-GAD antibody
B. C-peptide
C. Fasting blood sugar
D. IGF-1
E. Random blood glucose
B. C-peptide
DM type 2 may result from insulin resistance but ultimately, overworked β-cells stop producing insulin and pts become insulin dependent
one way to determine when insulin therapy is indicated is to check a C-peptide
C-peptide is cleaved when pro-insulin is converted to insulin; normal ranges of C-peptide indicate endogenous production of insulin
what is the anti-GAD antibody used to diagnose?
type I DM or autoimmune diabetes
A 29 y/o Asian woman comes to your office because she has been feeling increasing hunger for the past week and she wants to be seen by an endocrinologist. Her job has been very stressful and she is worried about her pregnancy (currently at 24 weeks). This is her first pregnancy. Pre-pregnancy BMI is 24 kg/m2. She has gained 14 lbs.
She had a 50-g OGTT after an overnight fast by her ob-gyn. Her 1-hr glucose was 148 mg/dl. You tell her:
A. You meet criteria for gestational diabetes and should be started on insulin
B. You meet criteria for gestational diabetes and you can start metformin
C. You do not meet criteria for gestational diabetes and you should have a 100-g OGTT to determine if you have gestational diabetes
D. You can only be diagnosed with gestational diabetes by a 75-g OGTT
C. You do not meet criteria for gestational diabetes and you should have a 100-g OGTT to determine if you have gestational diabetes
Step 1: 50 g OGTT, non-fasting
If 1 hr ≥ 140 mg/dl, then proceed to:
Step 2: 100 g OGTT, fasting and then you can make a diagnosis with 2 or more:
- Fasting ≥ 95 mg/dl
- 1 hr ≥ 180 mg/dl
- 2 hr ≥ 155 mg/dl
- 3 hr ≥ 140 mg/dl
the other test you can do is a 1 step 75 g OGTT at 24-28 weeks after an over night fast and you can make a diagnosis with 1 or more of the following:
1. fasting ≥ 92 mg/dl
- 1 hr ≥ 180 mg/dl
- 2 hr ≥ 153 mg/dl
A 20 y/o woman presents for evaluation of polyuria and polydipsia. She has a history of cystic fibrosis, diagnosed at the age of two. She reports recent weight loss despite compliance with her treatment of exocrine pancreatic insufficiency. She does not have any acute pulmonary symptoms at this time.
On physical exam, she is thin, in no apparent distress; weight is 100 lbs (BMI 19). Her vitals are normal. Random plasma glucose is 147 mg/dl.
Which of the following is the best diagnostic test to diagnose cystic fibrosis related diabetes (CFRD)?
A. Fasting plasma glucose
B. Measurement of glutamic acid decarboxylase antibodies
C. A1c measurement
D. 75-g oral glucose tolerance test
E. Continuous glucose monitoring
D. 75-g oral glucose tolerance test
The OGTT result comes back with a 2 hour plasma glucose of 300. A diagnosis of cystic fibrosis related diabetes is confirmed. How would you management her medically? when would you screen a CF patient for DM complications?
A. Start patient on metformin
B. Start patient on glipizide
C. Start patient on insulin
D. Start patient on liraglutide
E.. 75-g oral glucose tolerance test
C. Start patient on insulin and begin annual monitoring 5 years after CFDM
what is CF-related diabetes?
Cystic fibrosis-related diabetes (CFRD) is unique in that in addition to losing insulin-secreting β cells, there is also loss of α cells thus, pts are at risk for both spontaneous and treatment-induced hypoglycemia.
Occurs in 1 in 2500 live births and is the most common autosomal recessive condition in white population.
In initial stages, pts are able to maintain normal glucose tolerance because of ↑ hepatic glucose production and ↑ peripheral glucose use.
Subsequently pt develops impaired glucose tolerance and diabetes associated with ↓ hepatic insulin sensitivity and ↓ insulin production.
when do you screen screen CF patients for CFDM?
Annual screening with 75-g OGTT is recommended in pts with CF beginning at age 10 years.
Timely diagnosis & initiation of insulin therapy improves nutritional status and may help maintain pulmonary health.
A1c is not as sensitive and can be affected by anemia, ↓ albumin, acute illness, intermittent steroid use, which may all occur frequently in pts with CF.
Screening for complications related to diabetes starts 5 years after the diagnosis of CFRD**
among female children and adolescence what is the first sign of type I DM?
genital candidiasis
there can also be thirst, hunger, blurred vision, etc but the first presenting sign is often type I DM
Type 2 diabetes accounts for approximately what percentage of all cases of diabetes in adults?
90-95%
What percentage of women with gestational diabetes is diagnosed with type 2 diabetes following pregnancy?
5%-10% of women with GDM develop T2DM immediately postpartum6
35%-60% chance of T2DM over next 10-20 years6
what are the causes of GDM?
hormonally induced insulin resistance
resulting in hyperglycemia
eventually progresses into diabetes
what are the risk factors for type 2 diabetes?
- HDL
- physical inactivity
- advancing age
- PCOS due to insulin resistance susceptibility
A 50-year old male comes to the physician because of a 6 month history of numbness and burning sensation in his feet that is worse at rest. He has not been seen by a physician in several years. He is 178 cm (5 ft 10 in) tall and weighs 118 kg (260 lb); BMI is 37.3 kg/m2. Physical examination shows decreased sensation to pinprick, light touch, vibration over the soles of both feet. Ankle jerk is 1+ bilaterally. His hemoglobin A1C is 10.2%. Which of the following pathophysiological processes is most likely to be involved in this patient’s condition?
a) accumulation of islet amyloid polypeptide
b) deposition of antiglutamic acid decarboxylase antibodies
c) complement mediated destruction of insulin receptors
d) expression of human leukocyte antigen subtype DR4
e) lymphocytic infiltration of islet cells
a) accumulation of islet amyloid polypeptide
Accumulation of islet amyloid polypeptide (proamylin) is the most likely process involved in this patient’s type 2 diabetes.
Peripheral insulin resistance creates a huge demand for glucose lowering hormones, resulting in increased production of proinsulin and proamylin.
Pancreatic proteolytic enzymes that convert proinsulin and proamylin into insulin and amylin are not able to keep up with the high levels of production, which leads to the accumulation of proamylin.
Although the exact role of amylin in the pathogenesis of T2DM is unknown, proamylin accumulation is thought to be responsible for the eventual decrease in insulin production in T2DM.
A previously healthy 55-year old male comes to the physician because of a 4-month history of recurrent abdominal pain, foul-smelling, greasy stools, and a 5-kg (11 lb) weight loss despite no change in appetite. Physical examination shows pain on palpation of the right upper quadrant. His fasting serum glucose concentration is 186 mg/dL. Abdominal ultrasound shows multiple round, echogenic foci within the gallbladder lumen with prominent posterior acoustic shadowing. The serum concentration of which of the following substances is most likely to be increased in this patient?
a) somatostatin
b) glucagon
c) serotonin
d) gastrin
e) insulin
f) vasoactive intestinal peptide
a) somatostatin
Somatostatin is likely to be increased in this patient, who has the typical clinical findings of somatostatinoma, illustrating the hormone’s primarily inhibitory effects.
Glucose intolerance and diabetes mellitus result from the inhibition of insulin secretion.
Diarrhea and steatorrhea occur due to inhibition of pancreatic enzymes and bicarbonate secretion, leading to lipid malabsorption
Finally, the inhibition of cholecystokinin release, which reduces gallbladder contractility and leads to bile stasis, causes cholelithiasis
what is the function of somatostatin?
suppresses the release of insulin and glucagon
large pale granules on EM
what is a somatostatinoma?
Rare neuroendocrine tumor that secrete excessive amounts of somatostatin
45% occur in association with MEN1
An extreme reduction in secretion of insulin and causes diabetes.
Classic triad: diabetes/glucose intolerance, cholelithiasis, diarrhea/steatorrhea
A 28-year-old woman, gravida 1, para 0, at 24 weeks gestation comes to the physician for a prenatal visit. She feels well. She has no history of medical illness and takes no medications. Her fasting serum glucose is 91 mg/dL. One hour after drinking a concentrated glucose solution, her serum glucose concentration is 94 mg/dL. The hormone responsible for the observed laboratory changes most likely increases glucose transport into which of the following types of cells?
A. Islet Cells
B. Adipocytes
C. Hepatocytes
D. Placental Cells
E. Erythrocytes
B. Adipocytes
GLUT4 is insulin dependent and is in heart, skeletal muscle and adipose tissue and insulin stimulates uptake of glucose into these tissues
GLUT4 expression is also increased in response to exercise
A 46-year-old man comes to the physician for a follow-up examination. He has type 2 diabetes mellitus and hypertension. Current medications include metformin and lisinopril. He reports that he has adhered to his diet and medication regimen. His hemoglobin A1C is 8.6%. Insulin glargine is added to his medication regimen.
Which of the following sets of changes is most likely to occur in response to his new medication?
glycolysis, glycogenesis, lipolysis and gluconeogenesis
increased glycolysis, increased glycogenesis, decreased lipolysis and decreased gluconeogenesis
what are the effects of insulin?
Insulin is an anabolic peptide hormone that binds to a tyrosine kinase receptor on target tissues (liver, skeletal muscle, and adipose tissue) to regulate the metabolism of carbohydrate, protein, and fats.
Insulin stimulates glucose uptake by increasing the expression of GLUT4 in skeletal muscle and adipose tissue as well as by increasing glucokinase activity in the liver.
Insulin increases glycogenesis by activating glycogen synthase.
Insulin decreases lipolysis in adipose tissue by decreasing the expression of adipocyte triglyceride lipase and increases lipogenesis by increasing the activity of acetyl CoA carboxylase, HMG CoA reductase, and endothelial lipoprotein lipase.
Insulin also promotes amino acids uptake and protein synthesis and decreases ketogenesis.
A 30-year old woman with type 1 diabetes mellitus suddenly develops tremors, cold sweats, and confusion while on a backpacking trip with friends. She is only oriented to person and is unable to follow commands. Her fingerstick blood glucose concentration is 35 mg/dl. Her friend administers an intramuscular injection with a substance that reverses her symptoms. Which of the following is the most likely mechanism of action of this drug?
a) activation of glucokinase
b) inhibition of glucose-6-phosphatase
c) inhibition of α-glucosidase
d) activation of adenylyl cyclase
e) inhibition of glycogen phosphorylase
d) activation of adenylyl cyclase
glucagon!
Glucagon binds to the glucagon receptor, which activates adenylyl cyclase (also known as adenylate cyclase) to create cyclic AMP as a secondary messenger that causes a shift in hepatic cellular metabolism from glucose consumption and storage to glucose production.
Therefore, glucagon reverses this patient’s insulin-induced hypoglycemia by stimulating gluconeogenesis and glycogenolysis to increase blood glucose concentration
how does glucagon work?
Glucagon operates via G-protein signaling to activate Protein Kinase A (PKA)
Here PKA activates enzymes involved in glycogen breakdown and deactivates enzymes involved in glycogen synthesis
In adipose the same type of pathway is used, there the pathway targets enzymes involved in lipolysis
what stimulates and inhibits glucagon secretion?
Glucagon secretion is stimulated by:
1. Low blood glucose
- Amino acid ingestion
- Epinephrine
Glucagon secretion is inhibited by:
1. High blood glucose
- Insulin
