Type 2 Diabetes

Question 0

Normally people make more insulin when their cells become more insulin resistant. What happens in Type 2 Diabetes (T2D)?

Answer 0

People are insulin resistant and don’t make enough insulin.

Question 1

Simple definition of insulin resistance?

Answer 1

Cells don’t take up glucose in response to insulin.

Question 2

What are 2 quantifiable measures altered in pre-diabetes?

Answer 2

Impaired glucose tolerance (post-prandial hyperglycemia).

Impaired fasting glucose (fasting hyperglycemia).

Question 3

What differentiates pre-diabetes from diabetes? (not talking about numbers)

Answer 3

In pre-diabetes, increased insulin secretion is still somewhat compensating for decreased insulin sensitivity.

Question 4

By the time T2D gets diagnosed, about how much beta cell function is usually lost?

Answer 4

Usually about 50% is lost by then.

Question 5

What are the cutoffs of fasting glucose for “impaired” (pre-diabetes) and diabetes?

Answer 5

100 mg/dL for pre-diabetes.

126 mg/dL for diabtes.

Question 6

What are the cutoffs for glucose tolerance (2hrs after glucose load) for pre-diabetes and diabetes?

Answer 6

140 mg/dL for pre-diabetes.

200 mg/dL for diabetes.

Question 7

What percentage of US adults over 20 have pre-diabetes?

Answer 7

35%

Question 8

Is T2D just a pancreatic defect?

Answer 8

Nope. All sorts of things (like insulin resistance, increased gluconeogenesis, etc.) are going on.

Question 9

What has been shown, surprising, to happen to glucagon in T2D?

Answer 9

Glucagon levels paradoxically rise after eating.

Question 10

What are the 2 phases of insulin secretion? How is this altered in T2D?

Answer 10

1st phase - pre-formed granules of insulin release
2nd phase - more gradual release.
In T2D, the 1st phase doesn’t occur.

Question 11

Mechanism for altered glucagon activity in T2D?

Answer 11

Amyloid deposition in the islets impairs the ability of beta cells to suppress glucagon release by alpha cells.

Question 12

What are incretins? What are 2 specific molecules?

Answer 12

Incretins are intestinal hormones that stimulate insulin secretion in response to food in the gut.
Glucagon-like peptide 1 (GLP-1)
Gastric inhibitory polypeptide (GIP)

Question 13

How much of the insulin response to eating are incretins responsible for? How do we know this?

Answer 13

60-70%

We know this because IV glucose does not increase insulin nearly as much as oral glucose. (“The Incretin Effect”)

Question 14

How is the incretin effect different in T2D?

Answer 14

The incretin effect is blunted in T2D.

Question 15

What’s the biggest single risk factor for T2D?

Answer 15

Obesity.

Question 16

What’s a pregnancy-related risk factor for diabetes?

Answer 16

Gestational diabetes - strong association with later development of T2D.

Question 17

What kind of genetic associations are seen with risk for T2D?

Answer 17

Having one parent with T2D increases risk, both even more. (the way this is stated doesn’t separate out environmental differences)
GWAS’s have revealed some loci….

Question 18

What are the 4 “classic” symptoms of T2D?

Answer 18

Polyuria
Polydypsia (excessive thirst)
Polyphagia (excessive hunger)
Unexplained Weight Loss

Question 19

Non-specific symptoms of T2D? (name 5ish)

Answer 19

Fatigue
Blurry vision
Dry mucous membranes / itchy skin
Recurrent infections (esp. candidiasis)
Poor wound healing

Question 20

6 categories of signs of T2D?

Answer 20

Skin changes
Obesity
Recurrent yeast infections.
Fundoscopic (eye exam) changes.
Neuro changes (sensation)
Foot problems (ulcers)

Question 21

3 skin changes seen in T2D?

Answer 21

Ancanthosis nigricans (increased pigmentation in skin folds)
Skin tags
Carbuncles and furuncle.

Question 22

4 diagnostic criteria, any of which are sufficient for Dx of T2D?

Answer 22

Fasting glucose > 126 mg/dL.
A1c > 6.5%
Random glucose > 200 mg/dL
2hr post-prandial glucose > 200 mg/dL

Question 23

What is Hb A1c a product of? What is the time range for which is gives you information?

Answer 23

Hb A1c is a product of non-enzymatic glycosylation (sugar gets stuck on when there’s too much).
A1c reflects average blood glucose over past 2-3 months.

Question 24

How is A1c affected by post-prandial glucose rises?

Answer 24

It’s more affected when A1c is low, it’s less affected when A1c is high.
(It’s biased toward higher values, and is more susceptible to being thrown off by meals when glucose is better controlled.)
(probably low yield)

Question 26

Who should be screened for diabetes?

Answer 26

Everyone over 45.

People younger than that who have risk factors.

Question 27

Can weight loss prevent overweight people with pre-diabetes from progressing to diabetes?

Answer 27

Yep.

Question 28

One hypothesis as to why gastric bypass works better than gastric banding for glycemic control in diabetes?

Answer 28

Bypass shunts food more directly to the distal ileum, where GLP-1 is secreted.
More GLP-1 -> more insulin -> better glucose control.