Type 2 Diabetes Flashcards
What is the modern T2D diagnostic criteria?
- Fasting plasma glucose >=126mg/dl on two separate occasions
- Random glucose >200mg/dl with classic symptoms
- 2 hr postprandial glucose >=200mg/dl after consuming 75g carbs (ie oral glucose tolerance test)
- HbA1c>=6.5
What is HbA1c?
Reflects the average plasma glucose level over the past 2-3 mo. Non enzymatic glycosylation of Hb amnio acid residues
What is type 2 diabetes?
May range from predominantly insulin resistance with relative insulin deficiency to a predominantly secretory defect with insulin resistance. Result of multiple defects.
What is a major contributor to the dev of insulin resistance?
Obesity
When does progression to type 2 diabetes occur?
When B cells are no longer able to secrete sufficient insulin to overcome insulin resistance. Before that it is “prediabetes”
What two hormones regulate normal glucose homeostasis?
Insulin and glucagon
When is glucagon secreted
Fasting state, gluconeo and glycogenolysis–>inc blood glucose levels
What causes hyperglycemia?
Insulin resistance at the tissue level causes reduced glucose uptake into fat and muscle. This, in combo with excess glucose output by the liver, causes hyperglycemia
Inherited insulin resistant conditions are…
RARE
What environmental factors worsen insulin resistance?
- Smoking
- Aging
- Obesity
- In-activity
What is glucotoxicity
Toxic effect of sustained hyperglycemia that causes worsening of insulin resistance in skeletal muscle, liver, and also worsens secretory defects in the pancreas
What do high levels of free fatty acids do
Also increase insulin resistance
Why do beta cells fail?
More insulin resistance=more demand on beta cells=start to fail because can’t keep up with demand
Visceral fat
More associated with insulin sensitivity than ‘pear shape’
Describe the adipocyte dysfunction and ectopic lipid deposition model for insulin resistance
Overnutrition can overwhelm adipose ability to store fat and keep it from having toxic effects
XS free FAs travel in portal system and get despised in the liver and skeletal muscle where they interfere with insulin
Can’t store fat safely in adipose tissue..
What is the initial response to insulin resistance?
Hyperinsulinemia and islet hypertrophy
What is the long term response to insulin resistance?
There is a progressive decrease in pancreatic function, beta cells eventually fail, leading to diabetes
What types of toxicity induce beta cell dysfxn
Lipotoxicity and glucotoxicity
What is the sign of beta cell failure?
Loss of first phase insulin response (initial burst of insulin normally shuts down hepatic glucose production). This causes postmeal glucose to start rising
-In type II second phase must now deal with cab load and liver glucose that is pouring out
What is pre-diabetes?
HbA1c: =5.7%
Fasting glucose: =100mg/dl (impaired fasting glucose)
Oral glucose tolerance test (OGTT): =140mg/dl (impaired glucose tolerance)
What % US adults age 20+ have prediabetes
35%
How long do dev type 2?
10 yrs
How much does prediabetes inc risk for CV events?
50%
What helps with prediabets?
modeset lifestyle modifications can lower to normal levels of glucose
What is necessary to dev type 2?
- Insulin resistance
2. Beta cell failure
?What are the secretory defects in T2DM>?
- Reduced insulin
2. Increased glucagon
What does glucagon do?
Major contributor to hepatic glucose output
What are incretins?
Modulators of postprandial glycemia
What causes inc insulin secretion? Oral or IV? Why?
ORAL due to incretins being released from the intestines in response to food ingestion.
What are the incretins we learned?
These stimulate insulin secretion in the presence of glucose:
GLP-1: More potent, works on alpha cells, suppressing glucagon–>suppressing hepatic glucose production. Promotes satiety. Increases insulin secretion, slows gastric emptying (attenutes postprandial glycemia)–>levels are dec in type 2, but fxn remains intact
GIP: les spotent
What is the incretin effect? How does it affect type 2?
Difference in insulin sec when glucose is given intravenously vs orally. This effect is markedly reduced in ppl with type 2
?What are the classic symptoms of T2D
Polyuria
Polydipsia
Polyphagia
Unexplained wt loss
What are the non specific symptoms of T2D?
Fatigue Blurry vision Dry mouth Dry or itchy skin Poor wound healing
What are some complications of T2D?
25%: retinopathy
9%: neuropathy
8%: nephropathy
at time of diag
List some poss physical exam findings with T2D
Obesity, hypertension, skin findings (acanthosis nigricans), fundoscopic changes, changes in feet, genitourinary infections
What are some risk factors for T2D?
Obesity, race, metabolic factors, lifestyle factors, genetics, hx of gestational diabetes, intrauterine effects, microbiome effects
What is the general lifetime risk of dev T2D?
7%
What BMI recommends screening for T2D?
> 25
What reduces incidence of microvascular (retinopathy, nephropathy) complications of T2D?
Lower HA1c
What were the results of lowering glucose late in course of disease?
Intensive glucose lowering in the course of disease only wekaly affects outcomes
-Small reduction in CV events, no effect on mortality, large inc in hypoglycemic episodes
Explain “metabolic memory”
Tells us we need to intervene early to have an effect because microvascular effects persisted even when A1c normalized when treated early
When do we do aggressive treatment?
-Early intensive treatment
-Older pts: long-standing diabetes in whom complications have already dev, can cause harm
-
What is the A1c goal for nonpreg individuals
<6.5% if early
What is the A1c goal for severe individuals
<8%
What are the treatment strategies?
1st lifestyle mods, then oral, then insulin
What drug is recommended for prevention in pts with prediabetes?
Metformin
What are lifestyle interventions affect on CV outcomes?
NONE! No dif in mortality
What is an efective surgery for T2D?
gastric bypass (weight loss–>lower remission rates
Bariatric surgery
-Diabetes remission occurs almost immediately after surgery and before weight loss begins
-benefit to surgery in overall mortality
-
Describe T2D genetic componetn
Has a large genetic component that is highly influenced by environment
What causes T2D?
Insulin resistance and dysfxn of endocrine pancreas
Prediabetes includes:
Impaired fasting glucose
Impaired glucose tolerance
Elevated HbA1c
List the 4 ways to diagnose T2D
- FPG>126mg/dl
- HbA1c >=6.5%
- 2 hours plasma glucose >200mg/dl after 75gm carbs
- Random plasma glucose >200 mg/dl with symptoms
