Diabetes and hypoglycemia (Darrow) - SRS Flashcards
What are three dermatological findings associated with diabetes?
- Diabetic dermopathy
- Finger pebbles
- Bullous Diabeticorum
What is this finding primarily associated with?
What else?
Primarily associated with hyperlipidemia.
Also associated with…
- Diabetes
- Thyroid disease
- Infections
- Malignancy
- Drugs
•A 44 y/o 32 kg/m2 female presents for an annual PE. She has a new rash. She has a waist circumference of 50 inches. WHR is 1.1. BP is 144/90. FBS is 122 mg/dL. HDL-C is 42 mg/dL with triglycerides of 180 mg/dL. You inform her that she has?
Metabolic Syndrome
What are the two characteristic findings from the PE that you will observe in a case of metabolic syndrome?
Waist circumference
- Men > 40 inches
- Women >35 inches
Hypertension
- > 130/85 mmHg
In addition to the 2 physical findings seen in metabolic syndrome, there are three characteristic lab findings. What are they?
- Triglycerides > 150
- HDL-C
- < 40 mg/dL in Men
- <50 mg/dL in women
- Glucose > 100 mg/dL
Which body shape is worse for health, apple or pear?
Apple, this is the shape that kills you.
Adipose tissue is a dynamic endocrine organ that secretes several inflammatory and immune mediators known as?
Adipokines
Adipokines, FFA (triglycerides especially) lead to activation of what immune cells in particular?
Macrophages
Dysregulation of adipokine secretion, free fatty acid toxicity, macrophage infiltration*, and the site-specific differences in abdominal (visceral) versus subcutaneous fat support abdominal obesity as a causal factor mediating what 3 components of the metabolic syndrome?
- Insulin resistance
- Increased risk of diabetes
- Cardiovascular disease
The adipose tissue of lean individuals contains few macrophages, low levels of inflammatory cytokines and relatively high levels of what?
Adiponectin
Characterize the levels of macros, adipokines and adiponectin in the obese patient.
- Adipokines - high
- Macrophages - high
- Adiponectin - low
A 35 y/o male presents with hyperglycemia, abdominal obesity, hypertension, low HDL, and high triglycerides, would also be expected to have?
A.Hypouricemia.
B.large hypodense LDL.
C.Increased plasminogen activator inhibitor-1.
D.decreased platelet adhesion.
E.decreased levels of homocysteine.
C.Increased plasminogen activator inhibitor-1.
What does the increased levels of plasminogen activator inhibitor-1 lead to in obese patients?
Leads to clotting and thickening of the vessel walls.
In both microvascular and macrovascular diabetic disease processes, the initialpathophysiologic step is tissue damage caused by?
hyperglycemia-mediated mitochondrial superoxide production.
What does superoxide production do to LDL?
What does this lead to?
Oxidizes it which leads to engulfment by macrophages.
The patient does not take your advice and returns 6 months later with complaints of polyuria, polydipsia and polyphagia with vaginal itching. A random blood sugar is 205 mg/dL. You inform the patient that she now has (a):
A.type 1 diabetes.
B.type 2 diabetes.
C.maturity onset diabetes of youth.
D.mucormycosis vaginal infection.
E.renal papillary necrosis.
Type II diabetes
What are the four lab test levels that give a dx of diabetes?
- Random glucose > 200 mg/dL with compatible symptoms
- FBS > 126 mg/dL x 2 (prediabetes = 100-125 mg/dL)
- 2 hour post meal > 200 mg/dL x 2 (Prediabetes = 140 - 199 mg/dL)
- HbA1c > 6.5% x 2 (Prediabetes 5.7 – 6.4%)
What are the two main causes of type 2 DM?
- Genetic
- Environmental
What are the identified genetic abnormalities that lead to type 2 DM?
- A predominance of TCF7L2* transcription factor) for Wnt signaling pathway for normal β cell** development and function. Leads to B cell fatigue and death.
- Other not specified genes for obesity, insulin resistance and fat mass
What are the components of the environmental factors that play into type 2 DM?
- Visceral obesity
- Insulin resistance
How many identified loci are there that are associated with type 2 DM?
30
TCF7L2 is the dominant transcription factor associated with type II DM. What does this stand for?
What is it involved with?
Transcription factor 7 like 2 – a member of the Wnt signaling pathways that has to do with
embryogenesis.
What causes polyuria?
“I want you to know this”
(C) - Dripped
Cortisol excess– Cushings and steroid drugs - (increased RBF and inhibition of cortisol/ADH release)
DM
Recovery from renal failure (urea)
Ions- hyper Ca and hypo K
Parkinson’s (nocturnal nocturia)
Psychogenic Polydipsia
Enzyme- vasopressinase (pregnancy; autoimmune DI)
Drugs - lithium, demeclocycline, methicillin
An asthenic 16 y/o male presents with nausea and vomiting and the smell of ketones on his breath. There has been a 20 lb weight loss over the past four months. He had been aware of polyphagia, polydipsia, polyuria, weakness and fatigue.
BP is 90/50 with pulse of 120 bpm. Skin is shown.
Blood glucose is 300 mg/dL. Ketone bodies are in the urine.
- What antibody tests would be positive in this patient most likely (5)
- Glutamic acid decarboxylase 65 (GAD 65)
- Insulin antibodies (IAA)
- Islet cell (ICA)
- Zinc transporter 8 (ZnT8)
- Tyrosine phosphatase (IA-2)
What HLA types are associated with DM?
HLA-DR3
HLA-DR4
A normal weight 44 year old female was diagnosed with type 1 diabetes at age 20 during a pregnancy. Family history is positive for diabetes in both parents. She had been on insulin since that time, but on a recent trip to the caribbean, had forgotten her insulin with no adverse events except for increased polyuria. Evaluation reveals no acanthosis nigricans and lab analysis shows HbA1c of 8.5% with slightly low peptide C levels, no GAD antibodies, and high HDL levels. This patient most likely has:
A.absence of pancreatic alpha cells.
B.abnormal nuclear transcription factor in β cells.
C.cytotoxic T cell attack against zinc transporter ZnT8.
D.pancreatic polypeptide deposition in the pancreatic delta cells.
E.insulin resistance related to abnormal post receptor signaling.
●
B.abnormal nuclear transcription factor in β cells.
A normal weight 44 year old female was diagnosed with type 1 diabetes at age 20 during a pregnancy. Family history is positive for diabetes in both parents. She had been on insulin since that time, but on a recent trip to the caribbean, had forgotten her insulin with no adverse events except for increased polyuria. Evaluation reveals no acanthosis nigricans and lab analysis shows HbA1c of 8.5% with slightly low peptide C levels, no GAD antibodies, and high HDL levels.
What does this patient have?
MODY - maturity onset diabetes of the young
What is the defect in MODY?
What does that lead to?
** TQ **
TFHNF - (transcription factor hepatic nuclear factor)
resulting in decreased apo M and thus decreased clearance of HDL, which in this case is not cardioprotective.
What are four ways that MODY differs from type 1 DM?
- Strong family history
- No ketoacidosis when off insulin for 3 weeks
- negative pancreatic autoantibodies
- detecable C-peptide levels
What are three ways MODY differs from type II DM?
- Unusual to have onset prior to age 25
- not obese and no insulin resistance
- high HDL levels (2.5 mmol/L)
What are the inheritance patterns for DM 2 and MODY?
DM 2 = polygenic
MODY = monogenic/autosomal dominant
What is the usual age of onset for type 2 DM?
MODY?
Type 2 DM = over 40
MODY = under 25 usually
What drugs do most MODY syndromes respond well to?
Sulfonylureas
A 55 year old moderately obese female presents with severe right anterior thigh pain for the past 2 months. She also reports blurred vision and burning of her feet at night. The patient is on 140 units of 70/30 insulin before breakfast. She is also on 130 units of 70/30 before supper.
There is upper body obesity. There is a right carotid bruit. There is a slight right facial droop. There is weakness in the right femoral region. Skin rash is shown. BP is 170/106. BUN is 35mg/dL with Cr of 1.8 mg/dL and urine alb/Cr of 150 mg/g. Triglycerides are 1200 mg/dL. Blood sugar is 350 mg/dL. HbA1c is 12 %.
The most likely cause of this woman’s insulin resistance is:
A.Obesity and hyperglycemia
B.Concomitant Cushings syndrome
C.Occult infection
D.Silent MI
E.Alternating insulin injection sites
A.Obesity and hyperglycemia
What happens with muscle tissue in obesity and type 2 DM?
Excess calories force lipogenesis with excess malonyl CoA leading to blockage of fatty
acyl CoA oxidation and stimulation of TG and LP synthesis with byproducts of diacylglycerol and ceramide. The latter activate PKC pathways that inhibit insulin receptor activity.
Ultimately causing insulin resitance in muscle tissue.
What happens to liver tissue in obesity and type 2 DM?
Insulin resistance leads to increased visceral fat which releases TNF-alpha, which causes increased liver glucose production. Insulin resistance at the liver also leads to problems regulating glycogenolysis and gluconeogensis.
What dysregulation of lipid metabolism may be acquired in diabetes?
Familial Hypertriglyceridemia - hepatic overproduction of VLDL
Familial hypertriglyceridemia may present with eruptive xanthomas, and be associated with diabetes. What is a possible complication of this?
Pancreatitis
What does this patient with a 20 year history of diabetes present with?
A.Cheiropathy.
A 60 year old female presents with a rash. She is a diabetic at 5’4” and 220 lbs. History is also positive for a prior TIA. Father had an MI at age 40. Blood sugars range from 300-450 mg/dL. BP is 168/98. There are bilateral carotid and femoral bruits with poor pedal pulses. There is a pulsatile mass in the umbilical area. Total cholesterol is 300 mg/dL with HDL of 28 mg/dL and triglycerides of 450. She is on HCTZ and lisinopril.
What are the CAD equivalents in this patient?
All 4
- Anyone with CV disease
- Anyone with LDL-cholesterol of > 190 mg/dL
- Anyone with diabetes with age between 40-75
- Anyone with a > 7.5% risk of an MI or stroke in the next 10 years
A 60 year old female presents with a rash. She is a diabetic at 5’4” and 220 lbs. History is also positive for a prior TIA. Father had an MI at age 40. Blood sugars range from 300-450 mg/dL. BP is 168/98. There are bilateral carotid and femoral bruits with poor pedal pulses. There is a pulsatile mass in the umbilical area. Total cholesterol is 300 mg/dL with HDL of 28 mg/dL and triglycerides of 450. She is on HCTZ and lisinopril. To what type of hyperlipidemia does this patient’s profile correspond?
Acquired Type II b Hyperlipidemia
(Familial Combined Hyperlipidemia)
What is increased in Acquired Type II b Hyperlipidemia (Familial Combined Hyperlipidemia)?
Increased hepatic secretion of Apo B 100 and VLDL
Type II b hyperlipidemia involves increased secretion of Apo B 100 and VLDL from the liver. What are the patients typically characterised by? What is noteably absent in this condition?
What patients get the acquired type?
Often hypertensive and obese
No xanthomas
Acquired type in diabetics
What is the most common cause of lactescent plasma?
Acquired Type II b Hyperlipidemia
(Familial Combined Hyperlipidemia)
A 65 y/o type 2 diabetic presents with nausea, gastric retention, bloating and diarrhea.
There is a painless ulceration beneath the first right metatarsal. There is pain and
weakness in the right femoral region of three months’ duration. There is slobbering
out of the left side of the mouth with weakness of the left face. Extremities have
normal strength. There are dot and blot hemorrhages in both eyes with blurred vision.
The BUN is 70mg/dL with creatinine of 6mg/dL with albumin/creatinine ration of 300
mg/g. Pedal pulses are weak with carotid and femoral bruits. There is a rash also, on the dick.
A. normal cholesterol.
B. acanthosis nigricans.
C. acute renal failure.
D. CVA.
E. macrovascular disease and microvascular disease.
This patient most likely has (a), (an):
E. macrovascular disease and microvascular disease.
What is Whipple’ Triad?
- Symptoms and signs of hypoglycemia
- Low glucose at the time of the event (< 50 mg/dL)
- Reversal with correction of the hypoglycemia
What is Whipple’s triad for?
Hypoglycemia and may indicate an insulinoma
What is elevated in the type III hyperlipidemia?
Cholesterol and Triglycerides both
What is elevated in Type II familial hyperlipidemia?
Cholesterol
What are the Sympathoadrenal signs(glucose < 60 mg/dL) of hypoglycemia?
- sweating
- tachycardia
- tachypnea
- anxiety
- tremulousness
- nausea
What are the Neuroglycopenic signs(glucose < 50 mg/dL) of hypoglycemia?
- blurred vision
- fatigue
- dizziness
- headache
- confusion
- siezures
- coma
- death
A 46 year old male presents with early AM confusion blurred vision and headaches relieved by eating breakfast. He also complains of anxiety attacks and impotence. Two days prior, he had a near syncopal PM episode when he skipped lunch, imbibing two highballs instead. He has lost 8 lbs over the prior two months. There is no history of kidney stones. He denies epigastric pain. PE shows bitemporal hemianopsia. Vitals are normal. Finger stick reveals a glucose of 45 mg/dL.
What blood testing should be done next?
- Reconfirm with serum glucose
- serum insulin and C-peptide
- fast up to 72 hours with simulataneous glucose and insulin
- Serum β-hydroxybutyrate
What are two ways we go about confirming the dx of an insulinoma?
- Endoscopic ultrasound
- calcium stimulated angiography - steps up insulin secretion
What are the five components of treatment for insulinomas?
- Surgery
- Frequent feedings
- Diazoxide
- Verapamil
- Octreotide
MOA of diazoxide?
Opens K+ channel
A 36 year old, non-diabetic female nurse is found in a patient’s room having a seizure. She had had a similar episode two weeks prior, shortly after arriving at work. A serum glucose is found to be 30 mg/dL. Serum insulin is 7 μU/mL (normal 5-20 μU/mL). C-peptide is present. What should be done next?
A.8 AM cortisol, TSH, and T4
B.72 hour fast
C.CT of the pituitary
D. Abdominal CT
E. Serum sulfonylurea level
E. Serum sulfonylurea level
A 25 y/o male presents with complaints of post prandial confusion. His wife reports a seizure 2 hours after supper, on the evening prior.
During evaluation over the next week, finger sticks done at 3 hours postprandial show occasional glucose levels of 38, 42, and 45 mg/dL corresponding with episodes of confusion. Simultaneous insulin, C-peptide, and proinsulin levels are disproportionately elevated.
A 72 hour fast fails to produce hypoglycemia. Abdominal US is negative. A pancreatic arterial calcium stimulation test and pancreatic biopsy are carried out.
The patient has:
A. nesidioblastosis.
B.adrenocortical carcinoma.
C.Insulinoma.
D.adrenal insufficiency.
E.factitious insulin usage.
A. nesidioblastosis.
What is a nesidioblastoma?
noninsulinoma pancreatogenous hypoglycemia syndrome (NIPHS) – pancreatic cell hyperplasia – non adenomatous
What is the mnemonic for the causes of hypoglycemia that Darrow gave us?
ReExPLAINS
What does ReExPLAINS stand for?
(apparently he wants us to know this one)
Renal disease (especially dialysis)
Exogenous drugs% (insulin, sulfonylureas, ASA), Exercise
Pituitary insufficiency (hypothyroism), Pregnancy, Post gastrectomy
Liver failure, enzyme problems
Adrenal insufficiency, Acidosis, Alcohol#, Artifactual, Alimentary*
Islet cell tumors (insulinoma, nesidioblastosis), Infection, Immune mediated**
Neoplasms (retroperitoneal sarcoma, hepatocellular carcinoma, etc with IGF-2 release)
Sepsis, Spurious (prolonged storage and leukocytosis, leukemia)
What are the drugs that cause hypoglycemia?
SAP
Sulfonylureas, meglitinides (repaglinide, nateglinide)
Alcohol, ASA (indocin), Antidysrrhythmics (disopyramide, quinidine and quinine), Antibiotics (ciprofloxacin, gatifloxacin), Antimalarials (chloroquine and quinine), Acetaminophen overdose
Pentamidine
How do hypoglycemic events trigger inflammation?
Release of CRP, IL-6 and VEGF
Hypoglycemia has what effect on platelets and neutrophils?
Activated both of them
