Flashcards in Diabetes Mellitus (DM) Deck (45):
2 key Hormones of the pancreas?
Specifically where and which cell type produces them?
produced in the islets of Langerhans
* A cells produce glucagon;
* B cells produce insulin
What is insulin
an anabolic hormone, that is, it increases the storage of gluco, fatty acids and amino acids in cells and tissues.
What is glucagon?
a catabolic hormone, that is, it mobilizes glucose, fatty acids and amino acids from stores into the blood.
Important effects of Insulin
Insulin causes cells in the liver, skeletal muscles, and fat tissue to take up glucose from the blood. Inhibits gluconeogenesis in the liver and muscle cells.
What regulates insulin production
Blood glucose levels
How is glucose stored?
In the liver and skeletal muscles, glucose is stored as glycogen, and in adipocytes it is stored as triglycerides..
Where is glucose metabolized? Does it always need to cross the cell membrane to be used?
I don't know
General description of diabetes
• Disorder of insulin (I) action and/or secretion
• Causes widespread metabolic issues- beyond carbohydrates (CHO) also proteins and lipids
• Absolute deficiency= no insulin OR relative deficiency is = low levels
o Compromised glucose homeostasis
o CV, ocular, renal, neuro are chronic
o Life threatening if uncontrolled
Micro and macro vascular complications
Macrovascular: stroke, heart disease and HTN,
peripheral vascular disease, ulcers and amputations
Microvascular: diabetic eye disease retinopathy and
cataracts, renal disease, neuropathy, foot problems
What is Prediabetes?
is the state in which some but not all of
the diagnostic criteria for diabetes are met. It is often described as the “gray area” between normal blood sugar and diabetic levels.
What typifies pre diabetes in Diagnotics?
• IFG (impaired fasting glucose) – 6.1-6.9 mmol/L
o Measured after 10hrs of fasting (below 5.5 is normal)
• Hb [alc] (6-6.4%) of glucose nound to Hb
• IGT (glucose tolerance) 7.8-11 mmol/L
o After fasting glucose test, drink some glucose and watch how levels decrease- if abnormally normal decrease of glucose post peak- decreased tolerance
What is metabolic syndrome
Predisposes to Type 2 DM and Cardio Vascular disease
- abdominal obesity (diabesity: abdominal circumference female >35”, male >40”)
- * Insulin resistance
What is insulin resistance?
Body does not use insulin effectively.
Muscle, fat, and liver cells do not respond properly to insulin and thus cannot easily absorb glucose from the bloodstream. As a result, the body needs higher levels of insulin to help glucose enter cells
Cells are less sensitive to insulin, require more insulin to do the same job.
Stop looking deeper!
Difference in prevalence between Type 1 and 2
• Type 1 (~10%) Always absolute insulin deficiency (historically called IDDM)
• Type 1 A
o immune based,
o more prevalent ~90% of type 1]
o immune targeting of beta cells
• Type 2
o idiopathic (~90%) (NIDDM), relative insulin insufficiency
Etiology / Genetic components of Type 1
o Strong genetic influence- familial influence (x10 inc risk with one person who has it in your fam)
o Insulin gene Chr 11 (10% of folks with type 1)
• The gene regulate division and fx of beta cells
o MHC genes on Chr 6 (40%)
NOTE: MHC gene codes for proteins that sit on cell surface and identify them as self. Beta cells with mutated MHC may be targeted in autoimmunity
What are the islets of langerhans?
are the regions of the pancreas that contain its endocrine (i.e., hormone- producing) cells. Human islets display alpha and beta cells in close relationship with each other throughout the cluster.
What is insulitis
inflm of islets of Langerhans because of infiltration of T cells
When and how is insulin being inhibited in Type 1?
• Usually early age onset
• Autoimmune issue (90-95%)
o Genetic predisposition
o Enviro trigger (virus?)
• Immunity destroys beta cells (up to 90%)
o Absolute I deficiency
o Destroyed by t cells
o or antibodies
• islet cell auto antibodies production
• Insulin auto AB production
Etiology Type 2
MODY = Mature Onset Diabetes Young used to be only adults, d/t poor lifestyle
- 50% d/t glucokinase gene on Chr 7 (genetic problem) when glucose gets into the cell you add a phosphate (phospholate glucose) to keep it inside the cell. Glucokinase is an Es that does this phospholate.
Classification of Type 2
- ∼90% Insulin works wrong, or wrong time
- β cells largely intact
- amyloid: normal protein but tells you there is
accumulation of destructive tissue
- production of Insulin can be normal, inc or dec, the problem is wrong time or problem with receptor
- relative Insuline deficiency:
-> delayed secretion
-> defective target cell response
-> Insulin resistance∴ not doing it’s job
usually adult onset (now more youth d/t lifestyle)
->less severe form
What is Renal Threshold and how does it relate to diabetes?
Renal threshold refers to a concentration in circulation at which point kidney begin excretion (compound will appear in urine) Ex. Glucose 10mmol/L. If Compound concentration is higher in filtrate then blood, you will be pulling fluid out of blood as well (inc osmotic pressure).
Associated with MNFTS of Diabetes
polyuria, polydipsia, polyphasia
What is Glycosuria?
Glycosuria or glucosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reclaim all of the filtered glucose back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels
Which cells are insulin independent
Brain cells and erythrocytes are insulin independent
Muscle and adipose common examples of insulin dependent cells
Manifestations of Diabetes
• Polyuria (& frequency)
• Polydipsia (thirst and inc fluid intake)
• Polyphagia (inc food intake) (excreting calories, metabolizing lipids and proteins, rewuires more intake)
• Weight loss (complex issue) (WHY?)
Why does diabetes cause polyuria and polydipsia?
Inuslin def ->impaired glucose utilization & inc hepatic glucogenesis (glycogen break up to glucose)-> hyperglycemia (11 to 67 mmol/L) -> RT exceeded -> inc osmotic pressure in filtrate -> fluid enters filtrate-> polyuria (lots of urine) -> dehydration ->polydipsia (excessive thirst and fluid intake)
Basic outcomes of impaired glucose utilization in cells? How does it affect metabolism and the blood?
• Deficiency in carbohydrates leads to metabolization of lipids and proteins -> inc proteins & lipid (hyperlipidemia) metabolites in blood (eg ketones byproduct lipid metabolism)
o Adds to danger in atherosclerosis
• Accum of ketones (acidic) in excess in blood – ketoacidosis -> acidotic coma and death
• Ketones renal threshold reach -> ketoneuria -> enhances polyuria
Acute Manifestations of Diabetes
• Diabetic ketoacidosis (DKA) T1
• Hyperosmolar hyperglycemic state (HHS) T2
When might Hypoglycemia occur?
• Usually type 1
• Normally hyperglycemia is the problem…why?
o Too much insulin (glucose going to other cells, brain is independent, brain is most affect by lowered BG levels)
o Missing a meal, continuing normal insulin
o Over exertion
Tx of Hypoglycemia
o Mild: 15 g CHO p.o
1) severe hyperglycemia (Dec Insulin, Inc glucagon)
2) ketosis (formation of ketones)
3) metablolic acidosis
symptoms: drunk like, sweet smell on breath, gluconeogenesis = formation of carbohydrates form non- carbohydrate sources
- mostly in Type 2 and the elderly (less fluid reserve)
- severe hyperosmolality, cellular efflux
No ketoacidosis (why?)
o No lipid metabolism, still have some insulin, still getting energy from carbohydrates
- severe hyperglycemia →inc osmolarity→ cellular efflux→glycosuria (glucose in the urine)→water
loss, pulls fluid from blood→dehydration
- d/t inc. Insulin resistance (not able to use as much glucose)
- d/t severe carbohydrate intake→inc glucose level in blood
• ~ 15 yr post disease onset
• most stem from basic problem of vascular damage -> atherosclerosis, MI, CVA
• infections (particularly foot and UTI)\
Describe why there is increased vascular damage?
• Mobilization of lipid and proteins, inc levels in circulation (More damaging debris)
• Metabolism is altered -> abn metabolites accum and inflict damage on vessels and capillary walls
• Hyperglycemia glucose binds to proteins in blood (protein fx reduced or stopped) Protein said to be glycosylated.
o Also larger= more vessel damage
o Ex. When Hb is glycosylated it’s affinity for 02 inc, doesn’t dissociate 02 in tissues as well
• Glycosylated proteins deposition endothelium -> impaired trans capillary exchange
o Platelet aggregation -> blood flow impeded
Why might healing be impaired?
Impaired perfusion and transcapillary exchange
Increase in infection?
• Growth of anaerobic bacteria
o Bacteria that thrives in anaerobic conditions, decreased perfusion creates conditions.
· Inadequate perfusion= macrocytes/leukocytes cant come to help as easily
· Decreased sensation/ Neuropathies
Describe Retinopathy that might occur
• Capillaries damaged -> aneurysms -> rupture -> visual impairement
• Cataracts (opacity of lens) and glaucoma (damage to optic nerve d/t increased ocular pressure) Pressure is not in vessels
•Glomerular damage -> inc renal demands -> renal failure
• Neural ischemia
• Poor conduction (develop neural defecit)
How does DM effect HTN
• Inc prevalence in DM (40%)
• Major risk factor for MI, CVA, nephropathy
DX OF DM
• Hx (polyuria, polydipsia, unexplained wt loss
• Random glucose > 11 mmol.L or
• IFG (>7mmol/L or
• IGT > 11mmol/L
• HbA1c >6.5% (mean over about 4 months)
TX of DM
• Life style modification
• Glycemic control
o Oral hypoglycemic (type ll) (Table 42-6 List of hypoglycemic, know the categories)
o Increase tissue response to insulin
o Stimulate Beta cells
o Dec hepatic gluconeogenesis
• Metformin if HB (A1C) still > 7% after 2-3 months of lifestyle mod
• Metformin + insulin if Hb >9%
• Insulin for Type 1 (injection only, protein could be broken down in GI)
What is Hyalinization
normal tissue deteriorates
Why in diabetes?
amyloid protein being deposited
also happens in Alzheimers
Can type 2 turn to type 1
Yes, but not autoimmune version
What is MHC
Major histamine complex- marker on cell. Protein produced by chrome 6