necrobiosis lipoidica diabeticorum
Where does diabetes rank in the leading causes of death in the US?
Approximately how many people in the US are affected?
A group of metabolic disorders of impaired glucose tolerance causing hyperglycemia, as well as abnormal and and protein metabolism.
Which cells in the pancreas make insulin?
beta cells (in the islets of Langerhans)
What is amylin?
a substance normally secreted with insulin by beta cells
in diabetes it accumulates around beta cell membranes and converts to amyloid
What happens to the beta cells when they are dying?
Which cells make glucagon?
Which cells make somatostatin?
What does somatostatin do to the alpha and beta cells?
inhibits them (and all gut neuropeptides)
What are the three major complications of diabetes?
blindness before age 70
gangrene of the feet
What is the leading cause of blindness after the age 70?
Can you diagnose diabetes from looking in the eyes?
yes, retinopathy is diagnostic
What are the two types of retinopathy?
nonproliferative and proliferatives (neovascularization)
What will you see on the retina in a nonproliferative case?
microaneurysms (earliest sign)
What happens to the disk to cup ratio with glaucoma?
the disk gets much larger and fills the cup, so the fraction gets larger
What other pathology of the eye is common in diabetics?
What's the risk of DM for Americans born in the year 2000?
1 in 3 for men, 2 in 5 for women
What insulin independent transporter carries glucose into beta cells?
What happens to the glucose once it's in a beta cell?
GLUT-2 tranports it to the mitochondria where ATP activates depolarization of the membrane
Calcium flows in-->release of stored insulin granules
What do beta cells do if hyperglycemia persists?
make more insulin
What activities does insulin cause in the body? (6)
1) transmembrane transport of glucose and amino acids
2) glycogen formation in liver and skeletal muscle
3) production of triglycerides from glucose
4) nucleic acid synthesis
5) protein synthesis
6) lypogenesis by adipose tissue
7) increases cancer growth
I just had the a-ha that perhaps hyperinsulinemia is a major reason for hypertriglyceridemia.
When insulin binds to a receptor on a target cell, what happens to GLUT-4?
it translocates to the cell membrane
What are four hormones that can induce hyperglycemia?
cortisol, catecholamines, thyroxine, glucagon
Why is IDDM now mainly just called Type I Diabetes Mellitus?
because there are others out there who are insulin dependent
because onset can happen later than childhood
What is insulitis?
an auto-immune reaction to one's own islet cell antigens
What are ICA?
islet cell antibodies
What immunoglobulin is present in 90% of type 1 pts?
IgG islet cell antibody
What other auto-immune disorders are found in 10% of type 1 diabetics?
Graves, Addison, thyroiditis, pernicious anemia
Since 1960, how much has the incidence of type 1 increased in the US and western Europe?
What are the sx of type I diabetes?
3P's, ketoacidosis, low serum insulin, high serum and urinary glucose
altered platelets (increasing aggregation, clotting)
copmlications of pregnancy
fatty liver (NASH)
necrobiosis lipoidica, ulcers, gangrene
What viruses may trigger the autoimmune reaction causing type I diabetes?
What chemical toxins are also suspected triggers?
pentamidine = aerosol tx for AIDS pts with pneumocystis carinii
N-nitroso compounds = in bacon? increases gastric cancer risk
vacor = rat poison
If a mother has type 1 diabetes, what should she not feed to her infant to prevent it from developing antibodies to insulin?
gluten containing grains
What food product has a 16 amino acid epitope matching insulin, and potentially causing a crossover reaction?
cow's milk--bovine serum albumin has the epitope
What nutrients are essential for insulin metabolism?
zinc, magnesium, potassium
What nutrients are needed to make glucose tolerance factor?
cromium and niacin
What is glucose tolerance factor?
answer not in SSL's notes
chromodulin = a trivalent chromium-containing molecule which may enhance insulin utilization
other sources say it definitely does this and lots of other things
When glucose attaches to proteins in the body, is it reversible?
at first, yes, later, no-->AGEs = advanced glycosylation end products affecting organs
How do you measure AGEs?
measuring HGB A1C
hemoglobin gets crosslinked with sugars
under 7 is OK
under 5 is better: not diabetic
What else is causes by glycosylation in the body?
collagen cross linking
traps LDL in vessel walls-->atherosclerosis
binds to basement membranes in capillaries-->microangiopathy
binds to receptor sites on endothelial cells
causes WBC's to increase production of cytokines and growth factors
increases permeability, ECM formation, and coagulability
disturbs polyol pathways
What happens when polyol pathways are disturbed?
tissues independent of insulin develop high intracellular glucose
glucose is converted to sorbitol, then to fructose
these raise osmolarity causing injury
What tissues are not dependent on insulin for glucose uptake?
liver, kidney, retina
How does ketoacidosis develop?
when a pt has low blood sugar and low insulin, they still have glucagon
so adipose is broken down to make sugar
lipolysis generates ketones which are toxic to the brain???
What are the sx of ketoacidosis?
early you have weight loss and the 3 P's
later nausea, vomiting, tachylpena, dehydration, abdominal pain
What are the 3 P's?
Why don't type II diabetics get ketoacidosis as often as type I?
because they have high insulin and low glucagon
don't break down fats to generate ketones
What are more of the complications of diabetes?
hyperlipidemia, lowered HDL, high LDL and TG's-->atherosclerosis
increased platelet adhesiveness
increased risk of renal infection: pyelonephritis
necrobiosis lipoidica diabeticorum = shiny red rash with wavy border =
microangiopathic pre-tibial telangiectatic skin lesion
microangiopathy also in skeletal muscle, retina, renal glomeruli and tubules-->leak protein
gangrene with clean ulcers on bottoms of feet
autonomic neuropathy--> incontinence, diarrhea, constipation
What macroscopic changes happen in IDDM skin?
necrobiosis lipoidica diabeticorum
How much protein in a UA counts as albuminuria?
Why do you ask for you microalbuminuria test?
because <300 doesn't show up on the regular UA
What causes gastroparesis?
glycosylation of the vagus nerve
What are the early signs of peripheral neuropathy?
burning sensation, later becomes shocking pain, numbness, tingling, cramping
Besides gastroparesis, what are some signs of autonomic neuropathy?
neurogenic bladder (stress incontinence, retention, enuresis)
erectile dysfunction (both genders)
intestinal perstalsis changes (diarrhea, constipation)
What happens to the infants of diabetic mothers whose blood sugar is poorly controlled?
their pancreas grows more and bigger beta cells, trying to process all the glucose
they grow very large using all that fuel, are hard to birth the old fashioned way
12 pounders with large heads-->C-section
What's the quickest way to get rid of type II diabetes in a 400 pound patient?
bariatric surgery, not that he recommends it
How much insulin does a normal person need when the are either exercising or fasting?
What is C-peptide?
the other half of the protein that is cleaved to make insulin
Why do you test for it?
to find how how much insulin is being made
esp in a person who is taking exogenous insulin
Why is it more accurate to test C-peptide than insulin for insulin deficiency?
because it degrades more slowly and is not used up
What is the honeymoon period in type I diabetes?
the 1st 12-18 months of treatment, when the pancreas is still producing some insulin
later on, after self-administering insulin for a while, the patient becomes insulin resistant
What are the factors involved in metabolic syndrome?
hypertension (over 130/85)
increased uric acid
NASH, most common etio of elevated transaminases >35 in female, >40 in male
hyperlipidemia, TG's over 150 mg/dl, HDL under 40 men under 50 women
What percentage of Americans are type 2 diabetics?
What's the concordance in identical twins for type 2?
What adipokines are released by adipocytes in insulin resistance?
leptin, adiponectin, resistin
What does leptin do?
regulates appetite (-->satiety) and metabolism
downregulated by melatonin at night
improves insulin sensitivity
Where does leptin come from?
produced mainly by white adipose tissue
also: brown adipose tissue, placenta, ovaries, skeletal muscle, stomach (lower part of fundic glands), mammary epithelial cells, bone marrow, pituitary and liver
Who gets leptin resistant?
more on leptin from wikipedia on 5/27/09:
In addition to being a biomarker for body fat, serum leptin levels also reflect individual energy balance. Several studies have shown that fasting or following a very low calorie diet (VLCD) lowers leptin levels. It might be that on short term leptin is an indicator of energy balance. This system is more sensitive to starvation than to overfeeding. That is, leptin levels do not rise extensively after overfeeding. It might be that the dynamics of leptin due to an acute change in energy balance are related to appetite and eventually to food intake. Although this is a new hypothesis, there is already some data that supports it.
There is some controversy regarding the regulation of leptin by melatonin during the night. One research group suggested that increased levels of melatonin caused a downregulation of leptin. However, in 2004, Brazilian researchers found that in the presence of insulin, "melatonin interacts with insulin and upregulates insulin-stimulated leptin expression", therefore causing a decrease in appetite whilst sleeping.
Professor Cappuccio of the University of Warwick has recently discovered that short sleep duration may lead to obesity through an increase of appetite via hormonal changes. Lack of sleep produces higher than normal levels of ghrelin, a hormone that stimulates appetite by lowering leptin levels.
What does adiponectin do?
increases with weight loss, fatty acid catabolism and low MI risk
decreases with obesity and diabetes
levels correlate inversely with BMI
Which gender has higher levels of adiponectin?
What does resistin do?
antagonizes insulin's effects
correlated with inflammation
predictive of coronary atherosclerosis in humans independent of CRP
Which adipokines are insulin sensitizing?
leptin and adiponectin
Which adipokine works against insulin?
If a person can be type II diabetic with a high normal fasting blood sugar, how do you test to know for sure their status?
oral glucose tolerance test, and include an insulin test too
What's a normal fasting insulin level?
How much insulin is too much?
How much is pathological?
If a person's insulin is between 60 and 100 at 2-3 hours post prandial, what's their status?
If a person has anxiety attacks, what condition should be in your differential?
What are some of SSL's treatment for anxiety attacks?
biotin, GABA, other B vitamins
What are some drugs that can encourage or cause type 2 diabetes?
thiazides, loop diuretics
lithium (in big doses used for bipolar)
phenothiazides (for nausea, cause dyskinesia)
phenytoin (old school anti-siezure med)
tricyclic antidepressants (now used for fibromyalgia)
indomethacin (pain killer)
total parenteral nutrition
What happens to normal gut flora when a pt is on total parenteral nutrition?
the pt is being fed by IV and gut flora are starving so they turn invasive
What mineral deficiency can cause insulin resistance all by itself?
What % of pregnant women experience gestational diabetes?
What are some risk factors for gestational diabetes?
family hx of DM
hx of stillbirth or spontaneous abortion
hx of fetal anomalies in previous preg
advanced maternal age
previous large or heavy for dates infants
Describe type 1.5 diabetes, aka LADA?
onset after age 25
initially responds to diet
looks like type 2 wihtout insulin resistance
pts are not obese
family Hx of DM 2
According to Louise Hay, what unresolved emotions are connected with type 2 DM?
longing for what might have been
need to control
deep sorrow--no sweetness left
"issues in the tissues"
What affirmation does Hay suggest for diabetics?
"this moment is filled with joy. I now choose to experience the sweetness of today."
What are some of the effects of high fructose corn syrup that influence diabetes?
increases hepatic triglyceride synthesis
may decrease leptin synthesis
increases de novo lipogenesis
increases atherogenic lipoprotein particles (LDL)
volume: average north americans (Canadians not exempt) said to consume 63 lbs/year
According to the Nurse's Health Study, what is the risk of one soda per day?
doubles diabetes risk in women
increases wt gain in women and children
What surprise country has the highest rate of type I diabetes?
What three countries have the highest numbers of diabetics?
India, China and the US
What racial group in North America has the highest risk of diabetes?
What infections are especially common in folks with type 2 DM?
candidiasis, esp of the intestines
Name the "dirty neck" rash that may appear on youngsters with high blood sugar.
What populations with type 2 DM are more likely to experience ketoacidosis?
black adolescents & adults
native American males who drink and are thin
What is MODY?
maturity onset diabetes of the young
autosomal dominant disruption of insulin production
onset before age 25
no insulin resistance (not type 2)
ICA negative (not type 1 or 1.5)
How many types of MODY are there?
six but I have no idea what they are
one is a transcription factor gene that's wrong
another is an enzyme mutation: glucokinase
MODY is associated with what disease of the kidneys?
cystic kidney dz