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Diagnosis of Diabetes


--two types of DM, I and II
--DM I: aka IDDM, 10-15% of all cases, hyperglycemia and propensity to DKA, Tx: insulin, develops in childhood or any age, has AB's to islet cells of pancreas, little or no insulin production, low fasting insulin, flat insulin curve on OGTT
--DM II: aka NIDDM, hyperglycemia w/o DKA propensity, Tx: diet, some may need insulin until diet is controlled, onset usu in adulthood, usu assoc w/ obesity, little to high insulin production
--20% of new pts in childhood of adolescence have type II, increasing proportion with obesity increase
--3/1000 develop type I by age 20

TESTING
--plasma or serum blood sugar levels will read 10-15% higher than whole blood levels
--blood sugar levels in body controlled by actions of insulin and glucagon, also influenced by ACTH, adrenal corticosteroids, epinephrine and thyroxine
--in a whole blood sample, glucose levels will drop 10 mg/dl per hour at room temperature because the RBC's are alive and using the glucose: remove serum asap after clotting to remove this effect, or use grey top blood tubes with sodium flouride (prevents RBC utilization of glucose)
--three ways people monitor their own blood sugar levels:
1) "good": finger stick w/ glucose strip, read color on strip visually, +/- 15% error
2) "better": glucometer reads color electronically, variance of +/- 5% of serum value
3) "cadillac": infrared electronic meter, don't know how accurate but presume it is very because no error value given, costs a couple thousand bucks, Hitachi and Glucowatch G2
--OGTT = oral glucose tolerance testing: assuming other endocrine tests are normal (adrenal, liver, thyroid), pt must be in good health, no dz not even a cold. Eat high carb diet for 3 days prior (carbs in this range: (150-300 g CHO/day for 3 days prior). Oral dose based on body mass, up to 75 gms glucose, 100 gms for pregnant female.
--3 hour OGTT normals in adults: FBS: 7-100 mg/dl, 30min 110-170, 1hr 120-170, 2hr 70-120, 3 hr 70-120
--all timed serum tests in normal range, and all urine samples w/o glucose-->normal OGTT
--2HrGTT: may give a high carb meal instead of the glucose drink,
--so post prandial 2HrPPG = glucose tolerance 2HrGTT
--OGGT: 1 hour reading reflects pancreatic fx and insulin control of BS increase, 1-2 hour: can the liver convert glucose to glycogen for storage, 2-4 hr: can pancreas respond to decreased glucose by secreting glucagon-->glycogenolysis and gluconeogenesis in liver, 4-5 hour: adrenal response, cortisol increases glycogen available, 5-6 hour: anterior pituitary responds with ACTH to stim adrenals
--correlate above info with pt reports of energy rise & fall relative to meals
--old: 5HrOGGT was used to dx reactive hypoglycemia but now the dx is made by demonstrating a low plasma glucose (<50 mg/dl) during a symptomatic episode (doesn't have to be at 5 hours postprandial)

S/SX:
--polydipsia
--polyuria
--polyphagia
--ketonuria
--weight loss

Dx:
--FBS > 126 (2 separate times) --> DM
--FBS > 100 --> IGT, impaired glucose tolerance
--IGT shows normal fasting insulin, delayed rise in curve on OGTT
--FBS normal but 2HrPPG > or = 200 on at least 2 tests --> DM
--if IGT on FBS then follow up with GGT
--urine level over 160 --> follow up with GGT

Dx of children:
--FBS > 120 mg/dl --> DM
--2HrPPG > 200 mg/dl --> DM
--OGTT not necessary to dx IDDM but can exclude dx of diabetes when hyperglycemia and glycosuria are present in absence of typical causes (illness, steroids)
--glucose dose based on body wt: 2g/kg kids under 3, 1.75 g/kg age 3-10, 75g age 10+

Management (curative for type II, helpful for type I):
--low glycemic index foods --> stable glucose level --> stable insulin level
--www.glycemicindex.com
--glycemic index under 55 is low, medium 56-69, high over 70.
--Dr. Bernsteins Diabetes Solution: A Complete Guide to Achieving Normal Blood Sugars 1997

Insulin assay:
--INDICATIONS: fasting hypoglycemia, abn CHO & lipid metabolism, insulinoma = tumor of pancreatic islet beta cells & APUD stem cells causes hyperinsulinemia (>30mU/ml) despite hypoglycemia (slow recovery from hypoglycemia)
--obese pts with NIDDM show persistently high insulin levels and hyperglycemia
--INTERFERING FACTORS: tx with insulin-->AB's to insulin in some, food intake, recent admin of radioisotopes (RIA assay)
--NORMALS: adults 5-24 mU/ml, newborn 3-20, CRITICAL: > 30 mU/ml
--C-peptide: equal ratio with insulin molecules, absent in exogenous insulin, can evaluate reserve insulin production
--ETIO OF INCREASE: insulinoma, Cushing's, obesity, fructose or galactose intolerance, acromegaly, DFI = dietary fructose intolerance (hereditary, lacks liver enzyme Fructose-1-phosphate adolase)

TESTING GLYCOSYLATED HEMOGLOBIN
--aka: Glyc, GHb, HgbA1c
--evaluate diabetic tx and pt compliance
--determine hyperglycemia duration in new pt
--GHb elevation occurs 3 weeks after sustained elevation in blood glucose
--after sustained reduction in blood glucose it takes 4 weeks for GHb to decrease
--"brittle diabetics" = glucose changes significantly day to day
--recognize short term hyperglycemia in nondiabetics (dt cortisol: stress, MI)
--HgbA1c indicates average blood glucose level over past 3 months
--NORMALS: adult 4-8%, child 1.8-4%
--6% = approx 135 mg/dl
--7% considered "good" diabetic control
--8% corresponds to glucose > 200 mg/dl (diabetic)
--10% --> 240 mg/dl, not good
--13% DANGER
--ETIO OF INCREASE: new DM dx or poorly controlled DM, non-diabetic hyperglycemia, splenectomy, pregnancy
--ETIO of DECREASE: hemolytic anemia, chronic blood loss, chronic renal failure (??)
--INTERFERING FACTORS: hemoglobinopathies vary quantity of HGB A and affect results

STUDY QUESTIONS FOR FINAL EXAM ON THIS MATERIAL:

III. Endocrine: Parts 1 and 2

1. How would you optimally instruct your patient to prepare for an OGTT?
--pt instructed NOT to restrict carbohydrate intake in the days or weeks before the test (150-300 g CHO/day for 3 days prior)
--test should not be done during an illness (even a cold).

2. What happens to blood GLU and K if you don’t separate RBCs from serum promptly?
--Glucose levels will drop ~10mg/dl per hour at room temp in a whole blood sample dt RBC utilization of glucose (so it’s best to remove serum ASAP after clotting)
--when RBCs sit in serum, leakage of K+ from RBCs can cause a spurious increase in K+ levels

3. Know criteria for diagnosing diabetes.
--Adult FBS: >126 on 2 tests => diabetes dx
--FBS >100 = impaired fasting glucose (2x >100 => pre-diabetes)
--2-Hr postprandial: ≥200 on 2 tests => diabetic
--140-199 on 2 tests = impaired glucose tolerance (IGT) aka insulin resistance, pre-diabetes
--follow up with GTT, challenge via administered glucose drink or post prandial testing of blood starting with fasting, and continuing hourly for 5-6 hours after intake

4. Be familiar with the endocrine interpretation of OGTT.
--OGTT = oral glucose tolerance test
--FBS to 1hr: reflects pancreatic fxn & insulin control of glucose rise after meal
--1-2hr: liver converts glucose→glycogen for storage
--2-4hr: pancreatic secretes glucagon-->glycogenolysis & gluconeogenesis in liver
--4-5hr: adrenals-->cortisol-->increases glycogen breakdown & gluconeogenesis
--5-6hr: anterior pituitary response to ACTH stimulation of adrenals
--the order: pancreas, liver, pancreas, adrenal, ant pit

How would adrenal fatigue affect the outcome of a 5-hour OGTT?
--low cortisol production→hypoglycemia 4-6 hours after meal

5. What are the current criteria to dx reactive (post-prandial) hypoglycemia?
--DX: plasma glucose < 50mg/dL during a symptomatic episode

6. What are the indications for performing an insulin assay?
--fasting hypoglycemia
--abnormal carbohydrate & lipid metabolism
--hyperinsulinemia (mbdt tumor of panc beta cells) worrisome if >30mU/ml w/ hypoglycemia

7. When combining OGTT & insulin tests, what patterns would you find with IDDM, IGT, & NIDDM?
--IDDM: low fasting insulin, flat insulin curves on OGTT
--IGT = impaired glucose tolerance, aka insulin resistance
--IGT: normal fasting insulin, delayed rise in curve on OGTT (insulin rises with sugar, but then is not allowed to go into cells, so pancreas releases MORE insulin when normally it would begin to fall, still can't get into cells)
--NIDDM: persistently high insulin levels and hyperglycemia

Why might Cushing’s Syndrome predispose one to high insulin levels?
--cortisol excess→hyperglycemia→insulin resistance→high insulin levels

8. What level of HgbA1c is considered evidence of good diabetic control?
--7%

How often should the test be repeated?
--every 3 months

Is HgbA1c useful for brittle diabetics?
--yes

QUESTIONS 9-END MOVED TO ADRENAL POST

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