Term
Which of the following is NOT associated with T1DM?
1) Low C peptide
2) GAD antibody
3) Islet cell antibody
4) Low sensitivity to insulin
5) Genetic predisposition |
|
Definition
4-They are highly sensitive
5 Is true, just weaker than T2DM |
|
|
Term
| What are the primary triggers that are thought to put a genetically predisposed individual into full-blown T1DM? |
|
Definition
1) Infection: Mumps, Rubella, Cocksackie, Enterovirus
- Type IV
2) Diet
- Infants exposed to gluten or cow milk protein
3) Hygiene hypothesis
4) Seasonal (winter) |
|
|
Term
| How is anti-GAD antibody used clinically? |
|
Definition
| Number of antibodies correlate to T1DM risk and are used in clinical research to identify patients at high risk. |
|
|
Term
True or False:
T1DM is predominantly a type II antibody-mediated autoimmune condition. |
|
Definition
| False: Cell mediated (T cells) |
|
|
Term
| What are the classic presenting symptoms of a T1 diabetic and why do they occur? |
|
Definition
Osmotic diuresis and dehydration from glucose
1) Polyuria
2) Polydypsia
3) Polyphagia
4) Infection
DKA and HHS (T2) are also acute! |
|
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Term
| Differentiate between the etiology and manifestation of DKA and Hyperglycemic hyperosmolar states. |
|
Definition
Both are acute, dangerous complications.
1) DKA= T1DM , mortality <5%
- absolute insulin deficiency, with plasma glucose > 250 and osmolarity <320
- Ketosis occurs with brisk lipolysis by hormone-sensitive lipase
2) HHS= T2DM, mortality 10-50%
- relative insulin deficiency, with plasma glucose > 600 and osmolarity >320 (due to reduced GFR)
- Does not have HSL, so no ketosis |
|
|
Term
| Describe the basis of Ketosis in T1DM. |
|
Definition
1) Low insulin favors lipolysis of triglycerides to long chain FA and glycerol (hormone-sensitive lipase is required, and it lacking in T2DM, which is why there is HHS instead).
2) As acids enter liver, glucacon favors conversion to acetyl CoA instead of re-esterification, and acetyl CoA enter mitochondria for beta-oxidation
3) Acetyl CoA enters mitochondria via CPT1 and beta oxidation occurs
- malonyl-CoA usually inhibits CPT1, but it is stopped by glucagon
- CPT1 is stimulated by increased carnitine levels
4) Production of acetoacetate (measured in urine) and beta-hydroxybutarate (most prevalent) |
|
|
Term
| What is the clinical presentation of DKA/HHS? |
|
Definition
Diabetic with dry mouth, blurry vision, nausea, vomiting, fatigue and weakness (sort of an anemia diabetic).
**Neuro signs are more common in HHS**
Hyperglycemia: 250-800 (DKA) or >600 (HHS)
Hyperosmolarity: <320 (DKA) or >320 (HHS) |
|
|
Term
| Describe a basic treatment strategy for DKA/HHS |
|
Definition
1) Volume repletion first (slow enough to prevent cerebral edema in kids and cardiac arrest in adults)
2) Insulin replacement
- IV infusion until glucose <250, then add glucose to formula to prevent hypoglycemia
- Start sub-Q insulin 2h BEFORE stopping IV
3) Careful K+ replacement
4) Treat underlying disease |
|
|
Term
| What are the most typical complications of DKA/HHS? |
|
Definition
1) Death (rare in DKA)
2) Potassium (hyper or hypo can cause cardiac arrest)
3) CNS (edema with volume repletion and effects of hypoglycemia)
4) MUST start IV glucose when levels fall <250 (prevent hypoglycemia) and continue IV drip until Ketosis fully resolve. Then, continue IV insulin for 2h into sub-q therapy. |
|
|
Term
| Describe the process of insulin synthesis in pancreatic beta cells. |
|
Definition
1) Transcription in cell nucleus produces pre-pro-insulin, which is transported to RER ribosomes
2) Pre-Pro-insulin cleaved to Pro-insulin in RER
3) Pro-insulin stored in secretory granules, where converting enzymes cleave it to insulin and C-peptide (All 3 components are contained in granules until exocytosis)
4) Glucose uptake into cells (GLUT-2) produces ATP, which triggers K+ channel closure and Ca-mediated granule release. |
|
|
Term
| What factors stimulate insulin release? |
|
Definition
1) Glucose!
2) Amino acids (arginine)
3) Fatty acids
4) Incretin hormones (GLP-1, GIP)
5) Meds (sulfonylurea, meglitinide, incretin) |
|
|
Term
| What is the rationale behind using DPP IV inhibitors to treat diabetes? |
|
Definition
Dipeptidyl peptidase IV breaks down GLP1 (L cells in jejunum) and GIP (K cells in duodenum)
- Increase concentration of incretin, pro-insulin hormones from small intestine (normally secreted after a meal)
Remember, GLP-1 and GIP work best following oral glucose administration |
|
|
Term
| What are the "2 phases" of insulin release? |
|
Definition
1) First
- Rapid release of granules near cell membrane (2 minutes after meal and last 15 minutes)
2) Second
- Insulin secretion from internally located granules that contain newly synthesized insulin and that persists for duration of glucose stimulus. |
|
|
Term
| What are the Maturity-onset diabetes of the young (MODY) syndromes? |
|
Definition
Insulin secretory defects.
Autosomal dominant, T2DM syndromes that occur in young.
1) Hyperglycemia before age 25
2) Lean body
3) No ketosis
4) Mild degree of hyperglycemia
MODY 2= Gluckokinase (no ATP production to stimulate release of insulin)
MODY 3 (65%)= Hepatocyte nuclear factor 1a on chromosome 12, a transactivator of insulin gene in beta cells |
|
|
Term
| What are the 2 most common inherited secretory defects in diabetes? |
|
Definition
AD MODY syndromes (<25 onset of moderate hyperglycemia, with lean body habitus and no ketosis)
1) MODY 2 (15%)-
- Gluckokinase (no ATP production to stimulate release of insulin)
2) MODY 3 (65%)-
- Hepatocyte nuclear factor 1a on chromosome 12, a transactivator of insulin gene in beta cells
- Progressive insulin deficiency ultimately leading to dependence |
|
|
Term
| What abnormalities of insulin secretion are seen in type 2 diabetes? |
|
Definition
1) Impaired glucose-stimulated insulin release
2) Loss of phase 1 release
3) Abnormal pro-insulin: insulin ratio
4) Altered pulstatility
5) Defective glucose recognition. |
|
|
Term
Which of the following is NOT a proposed mechanism to explain beta cell dysfunction in type 2 diabetes?
1) Islet Amyloid polypeptide (IAPP) or "Amylin"
2) Lymphocytic infiltration
3) Reduced beta cell mass
4) Gluco-lipotoxicity |
|
Definition
| 2) Characteristic of Type IV reaction seen in T1DM |
|
|
Term
| What are the 2 major components of exogenous insulin therapy? |
|
Definition
T1DM get both and T2DM only get basal insulin, unless they deteriorate.
1) Keep up basal insulin with long or intermediate-acting insulin (Glargine, Detemir or NPH)
2) Bolus or nutritional insulin following meal with short (regular) or rapid-acting insulin (aspart/lispro/glulisine)
PUMP of RAI will reduce likelihood of low-insulin points |
|
|
Term
How do each of the following oral agent classes work to treat type 2 DM?
1) Biguanides
2) Insulin secretouges
3) DPP IV inhibitors
4) a-glucosidase inhibitors (AGIs)
5) Thiazolidinediones |
|
Definition
1) Metformin= insulin sensitizer
2) Sulfonylurea (Glyburide, Glipizide, Glimepiride)
Meglitinides (Repaglanide/nateglinide)
- Increase secretion
3) Inhibit degradation of GLP-1/GPI from small intestine L and K cells.
4) Acarbose/Miglitol
- Prevent/slow sugar absorption in gut.
5) Ploglitzaone/Rosiglitazone (PPAR-y)
- Increase hepatic and peripheral insulin sensitivity |
|
|
Term
| What are the advantages and disadvantages of using insulin secretagogues to treat T2DM? |
|
Definition
SU's (long acting)_ and Meglitinides ("glanide") are long- and short-acting agents that bind SU receptor on pancreatic beta cells and stimulate ATP-sensitive K+ channels.
1) Advantages
- Cheap, fast-acting and broadly usable
- Miglitinides good for hepatic/renal failure
2) Disadvantages
- SU severe hypoglycemia in high risk patients and cannot be used in hepatic/renal insufficiency
- Meglitinde is a bit more expensive and requires compliance. |
|
|
Term
| What are the advantages and disadvantages of using Biguanides to treat T2DM? |
|
Definition
Metformin increases insulin sensitivity of liver and may inhibit DDP IV.
1) Advantages
- Adresses insulin resistance, cheap and low risk of hypoglycemia
- Secondary weight loss and reduced TG
2) Disadvantages
- No renal/hepatic insufficiency, surgery or hypoxia
- GI SE |
|
|
Term
| What are the advantages and disadvantages of using Dipeptidyl Peptidase inhibitors ("Gliptin" drugs) to treat T2DM? |
|
Definition
Gliptin drugs are NEW agents that inhibit DPP IV, preventing breakdown of small intestine incretins like GLP-1 and GPI (increase post-prandial insulin secretion)
1) Advantages
- Improves post-prandial insulin secretion and are weight neutral
- Safe an no risk of hypoglycemia
2) Disadvantages
- Pancreatitis risk
- Renal insufficiency
- No long-term safety measures |
|
|
Term
| What are the advantages and disadvantages of using Alpha glucosidase inhibitors to treat T2DM? |
|
Definition
Acarbose and Miglitol inhibit brush border enzymes that rapidly degrade nutrients to absorbable glucose
1) Advantage
- Post-prandial glucose control without weight gain
- Safe
2) Disadvantage
- Weak glucose lowering and require carbs to be active
- GI side effects (compliance issue) |
|
|
Term
| What are the advantages and disadvantages of using Thiazolidinediones (TZDs) to treat T2DM? |
|
Definition
Glitazone drugs bind PPAR-y and amplify intracellular responses to insulin binding (increase glucose uptake in fat/skeletal muscle and decrease gluconeogenesis in liver).
1) Advantages
- Improves insulin resistance (like Biguanide) with beneficial metabolic side effects
- Can be used in renal failure
- Works synergistically with other agents.
2) Disadvantages
- Delayed action and $$
- Hepatic failure and weight gain, with contraindication in CHF.
- Fracture risk in women. |
|
|
Term
| What oral agents used in T2DM can be used in hepatic and renal failure? |
|
Definition
1) Miglitinide secretologoue in both
2) Thiazolidinedione (TZD) in renal only. |
|
|
Term
| What are the available non-insulin injectable therapies for T2DM? What are their advantages/disadvantages? |
|
Definition
1) Pramlintide
- Amylin mimic that slows rate of gastric emptying and reduces postprandial glucagon secretion.
- Used in T1 or insulin-treated T2DM
- Safe, but requires separate injections and $$$
2) GLP-1 agonists (Exenatide, liraglutide)
- Mimic GLP-1 to increase post-prandial insulin secretion and reduce circulating glucagon.
- Use in T2DM with preserved islet function. |
|
|
Term
| What is the basic therapeutic strategy for treating T2DM? |
|
Definition
1) Lifestyle intervention
- Diet, exercise and sleep.
2) Pharmacology
- Metformin (insulin sensitivity) is effective,e, cheap and well-tolerated.
- Addition of secretagogues, DPP IV inhibitor, basal insulin, or GLP-1 receptor agonist are all acceptable second line treatment.
- If needed, long and short-acting insulin may be added to achieve glycemic control |
|
|
Term
| What are the major types of vasculopathy underlying chronic complications of diabetes? |
|
Definition
Non-enzymatic glycosylization, Polyol pathway and Insulin resistance.
1) Microangiopathic (small arterioles and capillaries)
- Retina
- Kidney
- Nerves
2) Macrovascular (atherosclerosis of medium/large vessels)
- MI, Stroke, Peripheral vascular disease |
|
|
Term
| Describe the process of non-enzymatic glycosyization. |
|
Definition
1) Glucose attaches to amino groups forming Schiff base adducts on proteins that increase vascular permeability and protein leakage (Chemically reversible)
2) Schiff bases rearrange to stable Amadori-type glycosylation products, which cross-link to form Advanced glycosylation end products (AGEP)
3) AGEP accumulate in endothelial cells, macrophages, Monocytes and LDL particles (trapped and oxidized, becoming toxic)
- Microthrombosis (endothelial and macrophages) and ECM accumulation (TGF-b from monocytes) |
|
|
Term
What affects to advanced glycosylation end products have on each of the following?
1) Endothelial cells
2) Macrophages
3) Monocytes
4) LDL particles
5) Fibroblasts and smooth muscle cells |
|
Definition
Endothelial damage/thrombosis, lipid accumulation and smooth muscle proliferation produce atherosclerosis.
1) Protein leakage and platelet adhesion (microthrombi)
- Destruction leads to vessel wall exposure and further thrombosis
- Reduced PGI2 and NO
2) Increase pro-coagulant activity- microthrombus
3) Migrate and release cytokines like TGF-b, which promotes ECM accumulation
4) Trap them in vascular matrix, leading to oxidation and cytotoxicity to endothelial cells.
5) Enhance proliferation (atherosclerosis) and ECM synthesis (microangiopathy)
- AGEP-modified collagen is resistant to degradation and accumulates in BM |
|
|
Term
| Describe the process of osmotic damage in diabetes |
|
Definition
Polylol Pathway
Glucose accumulates in lens (cataracts), schwann cells (neuropathy) and pericytes (microaneurysm) and is converted to osmotically active sorbitol by aldose reductase, which draws in water and produces damage.
Sorbitol accumulation also lowers Myoinositol, which leads to
- Decreased phosphoinositide metabolism
- Decreased DAG
- Decreased PKC
- Decreased Na/K ATPase activity |
|
|
Term
| What is the normal function of the Polyol pathway that is disrupted in diabetes? |
|
Definition
Allows cells to survive under osmotic stress by converting glucose to osmotically active sorbitol, which can retain water.
In tissues that do not require insulin, however, hyperglycemia leads to an increase in intracellular glucose by mass effect (brain, lens, blood vessels, kidney) |
|
|
Term
| How does insulin resistance produce diabetic complications? |
|
Definition
Insulin binding and signaling increases NO (causing VSM relaxation and inhibiting proliferation) and PGI2 (retards coagulation extracellulary)
Without these factors, you get smooth muscle proliferation and coagulation/sclerosis. |
|
|
Term
Which of the following is NOT a result of microvascular complications in diabetes?
1) Nephropathy
2) Retinopathy
3) Cataracts
4) Peripheral vascular disease
5) Neuropathy |
|
Definition
| 4- This is a macrovascular change of medium/large arteries. |
|
|
Term
| Describe how macrovascular complications occur in diabetes. |
|
Definition
1) AGEPs damage endothelial cells lining medium/large vessels and lead to LDL oxidation and recruitment of monocytes/macrophages
2) Fatty streak develops as macrophages engulf LDL and become foam cells.
3) Fatty streak changes into fibrous plaque as internal elastic lamina is degraded and smooth muscle cells migrate in.
4) Plaques rupture and as erythrocytes adhere, they form a thrombus, which can cause arterial occlusion. |
|
|
Term
| What evidence supports the target of A1c <7% for treatment? |
|
Definition
1) DCCT trial for Type 1
- 50-60% reduction in microvascular complications
2) UKPDS for Type 2
- 20-30% reduction
3) Legacy effect/glycemic memory
- Benefits of both studies sustained for 10 years, even though levels were not
***Keep it under control from the TIME OF DIAGNOSIS** |
|
|
Term
What does the presence of each of the following tell you about the location of a retinal hemorrhage?
1) Flame shape
2) Dot and blot
3) Sub-hyaloid |
|
Definition
1) Most superficial retina
2) Deeper layers of retina
3) Between retinal surface and vitreous |
|
|
Term
| What are the major pathological changes seen in diabetic microangiopathy? |
|
Definition
1) BM thickening
2) Pericyte destruction (mural cells that line capillary) |
|
|
Term
| Why might you see "hard" vs. "soft" exudates in diabetic retinopathy? |
|
Definition
1) Hard
- ADEP cause protein leakage and Lipoprotein deposites accumulate in deeper layers of retina, coalescing into yellow lumps that have solid, circumscribed appearance.
2) Soft (Cotton wool)
- Areas of infarction in nerve fiber layer occuring as result of ischemia (diffuse and not well-circumscribed) |
|
|
Term
| Why does retinal scarring and detachment occur in diabetes? |
|
Definition
1) Leaky capillaries cause edema, which causes ischemia
2) Neovascularization occur, but vessels are superficial and prone to rupture.
3) Ruptured vessels fibrose over time and cause scarring/detachment. |
|
|
Term
| How can you classify diabetic retinopathy as being Background, Pre-proliferative or Proliferative? |
|
Definition
1) Background
- Microaneurysms
- Dot blot hemorrhage
- Hard exudates
2) Pre-proliferative
- Soft exudates
- Edema
3) Proliferative
- Neovascularization
- Fibrosis |
|
|
Term
| What is the biggest determinant of retinopathy progression? |
|
Definition
| Blood pressure! Keep it <130 and get A1c < 7% |
|
|
Term
| What arteries are most vulnerable to PAD in diabetes and how can you catch it? |
|
Definition
1) Mesenteric and Carotids, especially at bifurcation points (turbulent flow).
2) Claudication, just below site of occlusion, with exercise that is improved with rest
- Critical Limb Ischemia (amount of exercise required) will decease with progression of occlusive disease.
- If it occurs at rest, LOOK OUT
- |
|
|
Term
| How can Arterial Doppler Derived pressures with Ankle Brachial Indices (ABI) be used to diagnose PAD? |
|
Definition
Perform if patient is > 50 or younger with risk factors (smoking, hypertension, hyperlipidemia) or if diabetes is duration >10 years.
Compare pulse pressure in posterior tibial and dorsalis pedis to branchial.
Normal ratio is 0.9-1.1
Claudication with <0.7
Ischemic rest pain 0.4-0.6
Tissue death at 0.1-0.3 |
|
|
Term
| How do you alleviate pain, prevent progress and thromboembolism in documented PAD? |
|
Definition
1) Pain
- Exercise
- Stop smoking
- Pentoxifylline (reduce blood viscosity) and Cilostazol (cAMP PDE III inhibitor)
2) Prevent ischemia
- STOP smoking
- Get LDL < 100 mg/dl
3) HTN (SBP < 130 and DBP< 80)
4) Glycemic control- not as powerful
** Remember to give aspirin +/- other agent to prevent thrombosis** |
|
|
Term
True or False:
Achieving an A1c goal of <7% is less effective in older patients, those with pre-existing heart disease or with other co-morbidities (renal failure). |
|
Definition
True: Hypoglycemia risk outweighs benefits!
You DO want this in young patients without CV complications. |
|
|
Term
| What are the key aspects of preventing peripheral neuropathy in diabetic patients? |
|
Definition
1) Stop smoking
2) Tight glycemic control
3) Prevent limb loss (symmetrical polyneuropathy) with foot dare education and early detection of loss of sensation (5.07 monofilament).
4) Symp treatment WITHOUT opiates
**Most facial (cranial) and multifocal mononeuropathies are caused by ischemic events that will recover over weeks/months** |
|
|
Term
| What are the 4 most common forms of diabetic neuropathy? |
|
Definition
1) Distal symmetrical polyneuropathy (most common)
- sensory and can progress to motor (correlates with duration of DM)
- MUST USE 5.07 monofilament to test NOXIOUS stimuli (check for protective ability to prevent limb loss)
2) Focal and multifocal neuropathy
- Cranial: Usually involves CN III (down and out position)
- Peripheral: Median nerve entrapment
- Multifocal: Lumbar polyradiculopathy
3) Autonomic
- CV (resting tachycardia), GI (Gastroparesis), GU (bladder dysfunction), Peripheral (gustatory sweating), Metabolic (hypoglycemic unawareness)
4) Chronic inflammatory Demyelinating Polyneuropathy (CIDP) |
|
|
Term
| Describe the classic presentation of neuropathy in the diabetic foot. |
|
Definition
Major risk factor for ulceration and 7X risk of amputation.
1) Claw-toe de-formative (loss of interosseious innervation)
2) Foot ulcer: heads of 1st and 2nd metatarsals, at point of maximum prpessure
3) Charcot foot: Progressive degeneration of stress-bearing portion of joint, with hypertrophic changes at periphery.
- loss of sensation, both positional and joint feeling |
|
|
Term
| What are the most common lower extremity infections of diabetes? |
|
Definition
Impaired innate and adaptive immunity, with increased colonization by staph, pharyngeal gram negatives, yeast and other fungi.
1) Cellulitis
2) Deep soft tissue infection (mixed aerobe/anaerobe)
3) Osteomyelitis (Staph): seen on PE, not X-ray, and you need bone biopsy |
|
|
Term
| How is wound healing impaired in diabetes? |
|
Definition
Defective formation and excessive loss of granulation tissue: May relate to AGEP deposition and is probably due to defective Apoptosis.
- Increased ROS production because of hyperglycemia leads to cytochrome C release and caspase activation |
|
|
Term
| What are the 2 best prognostic indicators of foot loss in diabetes? |
|
Definition
1) Loss of protective sensation (5.07 microfilament)
2) Loss of pulses (ABI) |
|
|
Term
| What are the major risk factors that predispose individuals with diabetes to get ESRD? |
|
Definition
Type 1 and Type 2 have same chance.
1) Genetic
- Ethnicity (higher in AA, Mexican and native)
- Positive family h/x of hypertension
- Polymorphisms in AT1R
2) Poor glycemic control
3) Hypertension
4) Longer duration of diabetes
5) Male gender
6) Smoking |
|
|
Term
| Describe how non-enzymatic glycosylization contributes to diabetic nephropathy. |
|
Definition
1) Increased glycosylated serum glucose levels causes glucose to bind to other proteins, resulting in reversible formation of Schiff Base.
2) Schiff base rearranges to form stable "Amadori Product," which degrades to form highly reactive AGEP
3) AGEP effects
- Increase GF release and cell number/size/matrix
- Quench NO, damaging endothelial cells and causing constriction
- DNA damage
- Decrease HDL
- Stimulate TNF-b secretion from macrophages
- Loss of negative charge in BM
- Protein trapping |
|
|
Term
| Describe how osmotic damage contributes to diabetic nephropathy. |
|
Definition
Probably not major factor
1) Glomerulus and capillaries contain aldose reductase, meaning that their is sorbitol occumulation
2) Sorbitol decreases Myoinositol (affecting Na/K ATPase activity |
|
|
Term
| What are the pathophysiological mechanisms involved in diabetic nephropathy? |
|
Definition
1) Non-enzymatic glycosylization
- Product AGEP that damage endothelial cells and lead to vessel constriction/narrowing
2) Sorbitol/osmotic damage of glomeruli
3) Increased glucose increases DAG and PKC activity
4) Decreased proteoglycan synthesis (loss of negative charge in BM)
5) Thickened BM (type IV collagen) |
|
|
Term
| What hemodynamic changes occur in diabetic nephropathy? |
|
Definition
1) Vasodilation of afferent arterioles and constriction of efferent arteriole, INCREASED GFR.
2) Depositon of protein in BM and mesangium combined with increased flows cause shear force and endothelial damage.
3) Altered glomerular contractility and ultimately proliferation and fibrosis of glomeruli |
|
|
Term
| What are the morphological changes that take place in the glomeruli of a patient with diabetic neuropathy over time? |
|
Definition
1) At onset, there are none
2) 1.5-2.5 years later you see BM and mesangial thickening (shear forces from protein deposition and increased GFR)
- Glomerular changes: diffuse glomerulosclerosis and Kimmelsteil-Wilson lesion (30%)
- Non-glomerular changes: vascular afferent and efferent arteriolar hyalinosis with small artery changes and interstitial fibrosis |
|
|
Term
| Describe the natural course of GFR and urine protein in diabetic neuropathy over time. |
|
Definition
1) In first 10 years, there is microalbuminuria and high GFR (hyperfiltration)
2) After 10 years, proteinuria increases and GFR decreases. |
|
|
Term
Why do patients with diabetic nephropathy get metabolic acidosis and gastroparesis?
Why do they require less insulin therapy? |
|
Definition
1) Hyporenin hypoaldosteronism produces hyperkalemia/hyperchloremic metabolic acidosis (Type IV RTA)
2) Gastroparesis at high GFR levels
3) Since there is decreased metabolism in insulin, less is needed. |
|
|
Term
True or False:
Albuminuria is a poor predictor of ESRD in T1DM. |
|
Definition
False- It is great in type 1, but poor in type 2, where older individuals tend to have albuminuria.
In T2DM, it indicates cardiac risk |
|
|
Term
| True or False: Late stage ESRD in diabetes does not benefit from tight glycemic control. |
|
Definition
True
Adding an ACE-inhibitor is the BEST to control hypertension.
IF there is hyperkalemia, restrict potassium, give furosemide and/or lower the dose. |
|
|
Term
| What tumors are found in the MEN 1 syndrome and how do you treat? |
|
Definition
Variable penetrance of AD mutation in menin gene (tumor suppressor gene)
1) Hyperparathyroidism (95%)
- Remove 3 1/2 parathyroids
2) Pituitary adenoma (30%)- prolactinoma
3) Pancreatic islet tumor (40%)- gastrinoma |
|
|
Term
| What tumors are found in the MEN 2a syndrome and how do you treat? |
|
Definition
AD RET mutations on 10q (transmembrane TK in neural crest tissues)
MEN2A is extracellular domain missense mutation
1) Medullary thyroid cancer (100% penetrance)
2) Hyperparathyroidism (10-20%)
3) Pheochromocytoma (40-50%) |
|
|
Term
| Describe the tumors found in MEN2B syndrome |
|
Definition
AD RET mutations on 10q (transmembrane TK in neural crest tissues)
MEN2B is intracellular domain missense mutation
1) Medullary thyroid cancer (100% penetrance)
- Earlier and more aggressive than MEN2A (prophylactic thyroidectomy)
2) Oral/GI neurogangliomatosis and marfanoid body habitus
3) Pheochromocytoma (40-50%) |
|
|
Term
| Describe the pathological basis of Famililial hypocalcuric hypercalcemia |
|
Definition
AD mutations in Ca sensor receptor gene (CaSR) in Kidney and Parathyroid.
1) Poor calcium sensing in kidney leads to increased reabsorption
2) Poor sensing in parathyroid leads to moderate parathyroid hyperplasia, leading to high-normal PTH levels despite high calcium levels. |
|
|
Term
| Describe the pathological basis of Hyperparathyroidism-jaw-tumor syndrome |
|
Definition
AD mutuation in tumor suppressor gene HRPT2, which encodes parafibromin.
Early development of cystic parathyroid adenoma(s)
Risk of parathyroid carcinoma and SURGERY is indicated |
|
|
Term
| Describe the basis of VHL syndrome. What cancers is it associated with? |
|
Definition
RCC, Pheochromocytoma, Retinal angioma, Hemangioblastoma (most common)
- AD mutations in VHL protein (tumor suppressor), prevent inactivation of HIF-1a, leading to aberrant vasculogenesis via VEGF, PDGF, ect.
- Type 1 (low risk of pheo)
- Type 2 (pheo is hallmark)
- Risk of renal cell cancer (RCC) in Type 1 and Type 2B, so surveillance is required.
- Hemangioblastomas are most common in cerebellum and spine
- Can see retinal angiomas |
|
|
Term
| What are the major syndromes associated with pheochromocytoma? |
|
Definition
1) VHL (AD mutation in VHL gene)
2) AD SDH mutations with variable penetrance
- Abnormal complex II leads to HIF-1a activation (similar to VHL pathogenesis)
3) MEN 2A and 2B
4) NF-1 |
|
|
Term
How do you treat each of the following?
1) MODY 1
2) MODY 2
3) MODY 3 |
|
Definition
All are genetic causes of diabetes due to abnormal insulin secretion
1) MODY1= HNF-4 alpha defect
- Give insulin/sulfonylurea
2) MODY2= Glucokinase defect
- Exercise and diet to increase ATP delivered
3) MODY3= HNF-1 alpha (MOST COMMON)
- Transactivator on chromosome 12 for insulin gene in beta cells
- Give insulin and sulfonylurea |
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