Term
| What are the 3 types of diabetes? |
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Definition
Type 1 - make no insulin/amylin due to autoimmune destruction of beta cells
Type 2 - 80-90%
Gestational - while pregnant. 30% more likely to get type 2 |
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Term
| What is the etiology of type 2 diabetes? |
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Definition
Increased Age
SNP at TCF 7L2
Beta cell failure - insulin resistance
Increased FFA --> decreased insulin secretion
Increased BG --> decr beta cell fxn
Amyloid/amylin deposits
Increase inappropriate glucagon release |
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Term
| What are the mechanisms behind insulin resistance? |
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Definition
IRS from insulin receptor binds to p85. This does not happen in DM2 --> less protein/lipid/glycogen synthesis, NOS decreased
- Increased activity of Shc -- atherosclerosis
- Fasting blood glucose increases
- non-fasting - decreased glucose uptake and decreased incretins |
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Term
| What happens to adipocytes in DM2? |
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Definition
FFA increase --> decrease insulin secretion, increase glucose production, and DECREASE insulin sensitivity.
FFA block phosphorylation of IRS1 - decr insulin sensitivity
TZDs (Actos) increase IRS1 but block Shc |
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Term
| What happens to liver and Incretins in DM2? |
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Definition
- Liver - decreased insulin sensitivity
- GIP - levels normal, response abnormal. Not a drug target
- GLP1 - Low levels in DM2. Give exogenously to increase beta-cell function |
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Term
| What happens to the kidney and the brain in DM2? |
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Definition
- Kidney - max reabsorption of glucose via SGLT increases, increasing BG
- Brain - posterior hypothalamus which controls appetite has decreased sensitivity to glucose |
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Term
| What is the difference between Type 1 and Type 2 DM? |
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Definition
Type 2 occurs with age
BMI is less in type 1, usually genetic (HLA-linked)
Type 1 is auto-immune while type 2 is insulin resistant |
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Term
| What are the effects of hyperglycemia in DM2? |
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Definition
- crosslinking of polypeptides disrupts shape
- Traps proteins, doing damage. Inhibits proteolysis - protein buildup.
- Increased lipid oxidation - inflammation
- NOS deactivated - inflammation --> CAD
- Increase PKC --> retinopathy/blindness, increased vascular permeability, thick basement membrane, new vessels fragile
- Glucose disrupts immune response |
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Term
| What are complications of diabetes? |
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Definition
- Macrovascular: CAD, PVD, cerebral vascular disease. Increased risk of TIA and stroke
- Retinopathy
- Neuropathy: Peripheral (hands/FEET), autonomic (ED), motor focal (loss of limb use)
- Nephropathy - BP goal <130/80 |
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Term
| What is the epidemiology of Type 1 and 2 diabetes? |
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Definition
Type 1 - 10%, autoimmune, zero insulin. CHO not as restricted, can just increase insulin dose
Type 2 - 80-90%, most overweight, due to insulin resistance. Must restrict CHO |
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Term
| What is metabolic syndrome? |
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Definition
Any three of:
- Abdominal obesity: women > 35 in, men > 40 in
- TGs > 150
- HDL < 50 in women, 40 in men
- BP - over 130/85
- fasting BG - 100 - 125 |
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Term
| What are risk factors for type 2 DM? |
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Definition
- Age > 40, 120% IBW
- Race: AA, latino, asian, native american
- Birth of a 9 lb or more baby
- H/o HTN, dyslipidemia, prediabetes
- Sedentary
- Relative w/ diabetes
- Presence of polycystic ovarian syndrome
- Acanthosis nigricans |
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Term
| What are the 3 P's and other S/S's of hyperglycemia? |
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Definition
polyuria, polydipsia, polyphagia
Blurred vision, fatigue, weight loss, dry skin, yeast infections, nausea |
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Term
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Definition
- symptoms + nonfasting glucose > 200
- FBG > 126. Prediabetes = 100-125
- 2-h postload glucose of > 200 (75 g glucose in water)
- A1C > 6.5%. Prediabetes = 5.7-6.5 |
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Term
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Definition
A measure of the average BG over 2-3 months.
Normal: 3-5
Target for DM2: <7 unless frail then <8 |
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Term
| What are important clinical trials in diabetes? |
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Definition
- Diabetes Complications and Control trial - studied insulin effect on type 1. Intensive Tx decreased complications
- UKPDS - Intensive Tx important, will need at least 2 drugs + metformin
- ACCORD - tried a lot of drugs, stopped due to incr cardiac risk
- ADVANCE - Large trial, no significant changes between drugs |
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