Diabetes Intro Flashcards
1
Q
How is glucose produced?
A
- Endogenously under the control of glucagon, catecholamines, cortisol and GH
- In the liver and kidney
2
Q
How is insulin used?
A
With insulin, uptake in muscle adipose and liver tissues
3
Q
Where does glucose from the CNS and other organs originate from?
A
-Liver
4
Q
Where does glucose from the liver, muscle/fat and kidney originate from?
A
-Kidney
5
Q
___ of glucose is produced by liver, and ___ of glucose produced by the kidney
A
90%, 10%
6
Q
What does the post-prandial glucose flux feed?
A
- CNS and other organs
- Liver
- Muscle and fat
7
Q
Discuss glucose regulation in a healthy individual PP
A
Low at baseline, will spike a meal and then quickly return to baseline
8
Q
Discuss glucose regulation in a T2DM PP
A
-Higher at baseline, will peak at meal and stay higher for longer before returning to a higher baseline
9
Q
Discuss insulin release in the healthy individual
A
-Low at baseline, and will drastically spike at meals an then gradually return to low baselin
10
Q
Discuss insulin release in the T2DM individual
A
- Low at baseline, will slightly increase but will not achieve a true “spike”
- Delayed and reduced insulin response
11
Q
Discuss glucagon in the healthy individual
A
High in fasted state, an will drastically drop upon insulin release to shut off endogenous processes, then slowly increase ~ hr later
12
Q
Discuss glucagon in T2DM
A
Will remain high as insulin resistance is reduced and insufficient
13
Q
Anabolic effects of insulin of glucose? (Insulin stimulates)
A
- Glucose transport
- Glycolysis
- Glycogenesis
14
Q
Anti-catabolic effect of insulin on glucose? (Insulin inhibits)
A
- Gluconeogenesis
- Glycogenolysis
15
Q
Anabolic effect of insulin on lipid?
A
- Lipogenesis, synthesis of TG and FFA
- Lipoprotein lipase activity (clearing lipid from the blood)
16
Q
Anti-catabolic effect of insulin on lipid?
A
- Lipolysis
- LPL in muscle
- FA oxidation in the liver (B-oxidation)
- Ketogenesis
17
Q
Anabolic effects of insulin on protein?
A
- Increase transport of AA and protein synthesis
- Electrolyte homeostasis: Allow for potassium to enter into the cell
18
Q
Anti-catabolic effects of insulin on protein?
A
-Protein catabolism
19
Q
What is released alongside insulin from the B-cell? What is this indicative of?
A
- C-peptide
- If we want to see if there is any production of “self” insulin, we can check for presence of C-peptide
- Helpful in T1DM or overt T2DM
20
Q
What is the key concept regarding insulin and glucagon in T2D?
A
- Delayed or reduced insulin
- Excessive glucagon
21
Q
How many phases of insulin are there?
A
-2
22
Q
1st phase of insulin? (Acute)
A
- 5-10 mins after B-cell is exposed to rapid increase in glucose
- Important for decreasing hepatic glucose production, decreasing lipolysis and to prepare target cells of the action of insulin
23
Q
2nd phase of insulin?
A
Insulin secretin will rise more gradually, and is directly related to the degree (meal composition, absorption) and duration of the stimulus
24
Q
Initial observations of onset of diabetes?
A
- Polydipsia
- Polyuria
- Polyphage
- Weight loss (type I) or obesity (type 2)
25
Clinical lab tests to asses for diabetes?
- Hyperglycemia
- Glucosuria
- Abnormal Glucose Tolerance Test
26
Diabetes is similar to a ___ but not as efficient
fasting
27
What occurs during the absence of insulin? (1/2)
- Liver is producing glucose via gluconeogenesis
- Muscle and adipose use ketone and fatty acids
- Glycolytic enzyme activity decreases
- Hypoglycemia is more pronounced than fasting
28
What occurs in the absence of insulin (2/2) ?
- Liver increased VLDL production
- Muscle glycogen and protein used for energy
- Cardiac and skeletal muscles rely on KB
- Adipose releases FFA
- Hexokinase increased, hyperG and complications
29
Is there a difference between glucose levels after nutrition administered orally vs IV?
No
30
Is there a difference between insulin levels after nutrition administered orally vs IV?
- Yes, when feeds are oral, insulin release is higher and normal
- Response to glucose given if given IV is lower, resembles what is seen in T2DM (delayed and reduced insulin secretion)
31
What can explain the difference in insulin release between oral and IV feeds
-In parenteral nutrition, we bypass the gut which means that we bypass the incretins
32
What are the two main incretins?
-GLP-1 and GIP
33
What is the mechanism of action of incretins?
When glucose enters the enterocytes, incretin will be released from the GI which will elicit an even greater release of insulin
34
Besides incretins and glucose, what else can determine plasma glucose concentration?
- CHO composition of foods
- Rate of gastric emptying
- Rate of glucose absorption
- Concurrent rate of glucose disposal
- Diurnal change in insulin sensitivety
- Activity of hormones
35
How can change in exercise modulate plasma glucose concentration?
Aerobic exercise may decrease blood glucose, and could counteract hyperglycemia during exercise. Anaerobic exercise, may increase blood glucose
36
What else may modulate plasma glucose levels?
- Consumption of alcohol
- Acute illness
- Emotional stress
37
What is type I diabetes?
Pancreatic beta cell destruction which usually leads to absolute insulin deficiency. Can be (1) immune mediated or (2) idiopathic
38
What is type II diabetes?
May range from predominately insulin resistance with insulin deficiency to a predominantly secretory defect with insulin resistance
39
What is gestational diabetes?
-Glucose intolerance with onset or first recognition in pregnancy
40
What is monogenic diabetes?
MODY, special type of diabetes which will require genetic testing and a specific genetic tx as their responsiveness varies greatly
41
T1DM onset?
usually <25 but can occur at any age (but not before age of 6 months)
42
T1DM weight?
Usually thin, but with obesity epidemic can have overweight/obesity (now complicates w/ insulin resistance)
43
T1DM presence of islet auto-bodies?
Present
44
T1DM insulin production?
Absent
45
T1DM Family hx?
Infrequent (5-10%)
46
T1DM DKA?
Common
47
T2DM age on onset?
Usually >24 but incidence increasing in adolescents, paralleling increasing rate of obesity in children and adolescents
48
T2DM weight?
>90% at least overweight
49
T2DM islet auto-bodies?
Absent
50
T2DM C-peptide?
-Normal/high
51
T2DM insulin production?
Present
52
T2DM first line-tx?
- Healthy lifestyle intervention
- Non-insulin antihyperglycemic agents
- Gradual dependence on insulin may occur
53
T1DM first-line tx?
Insulin
54
T2DM family hx?
Frequent (75-90%)
55
T2DM DKA?
Rare
56
What is the consequence of the obesity epidemic and Type 1 DM?
Type 1 Diabetics may now be obese, therefore they have insulin resistance as well as insulin deficiency
57
What is usually required prior to the onset of T1DM?
- A genetic predisposition
| - The "natural" history
58
Discuss the onset of T1DM
There will be a genetic predisposition, and then a trigger to decrease insulin production until in consequently halts (Silent insulin)
-Clinical diabetes is observed when there is no insulin (or C-peptide) released.
59
(T/F) There is a greater genetic risk factor for the offspring of an affected father with T1DM compared to an affected mother
F, greater in mother (1 in 50)
60
Where is there a greater incidence of T1DM? What is a potential hypothesis?
- North America and Australia
| - Potentially Vitamin D, but not confirmed
61
Why isn't T1DM considered a children's disease anymore?
42% of people with T1DM will receive their diagnosis between the ages of 31 and 60
62
What is the clinical presentation of T1DM?
Diabetic Ketoacidosis (DKA)
63
Discuss DKA
The complication of severe insulin deficiency leading to hyperglycemia, causing glucosuria, dehydration and ketogenesis to the eventual acidosis
64
What are common symptoms of DKA?
- Vomiting
- Abdo pain
- Hyperventilation
- Lethargy
- Confusion
- Dehydration
- Fruity Breath
65
What would we expect in terms of insulin-mediated glucose uptake and mean plasma insulin during OGTT of someone lean and NGT?
-Smaller amount of insulin for same insulin-mediated glucose uptake with normal glucose levels
66
What would we expect in terms of insulin-mediated glucose uptake and mean plasma insulin during OGTT of someone obese and NGT?
-More insulin required for less insulin mediated glucose uptake with normal glucose levels
67
What would we expect in terms of insulin-mediated glucose uptake and mean plasma insulin during OGTT of someone obese and IGT?
-Much higher insulin for much less insulin mediated glucose uptake, and glucose levels begin to rise (higher baseline)
68
What would we expect in terms of insulin-mediated glucose uptake and mean plasma insulin during OGTT of someone Obese and Diabetic (w/ residual insulin signalling)?
- Slightly declining insulin (compared to IGT) for same less amount of insulin-mediated glucose levels
- Glucose levels continue to climb to a higher baseline
69
What would we expect in terms of insulin-mediated glucose uptake and mean plasma insulin during OGTT of someone obese and diabetic (overt)?
-Exhaustion of plasma insulin, very little insulin mediated glucose uptake and highest baseline glucose levels
70
How do we measure beta cell function?
By decreases in either mass, or function
71
When we have a decrease of ___ of b-cell mass we begin to see insulin resistance, or Impaired glucose tolerance
50%
72
Name 5 pathogenic feature of hyperglycemia in type II diabetes
- Decreased incretin effects
- Increased lipolysis and decreased glucose uptake in adipose
- Increased glucose reabsorption and excretion in kidneys
- Increased hepatic glucose prodocution
73
What are the standard insulin requirements?
0.5-1.0 U/kg/day
74
What are the 3 key impacts of insulin resistance?
Will decrease:
1) Ability of insulin to suppress endogenous glucose production in the liver
2) Uptake of glucose in tissues with insulin-dependent glucose transporters (mainly in skeletal muscle)
3) Inhibition of lipolysis
75
Under normal conditions, how does the pancreatic B-cell compensated for insulin resistance?
Will detect the higher-than-normal levels of glucose to:
| Hyper-secretion --> Hyperinsulinemia ---> Formal FPG
76
4 populations who are usually insulin sensitive?
- Children with T1DM
- Lean people with T1DM
- Conditioned athletes
- Newly diagnosis with T1DM
77
6 populations who are usually insulin resistant?
- Children in puberty
- People with T2Dm
- Late term pregnant women
- People ill w/ infections
- People on steroids
- People w/ high stress
78
What are the 4 way to diagnose diabetes?
- FPG
- A1C
- 2hPG in a 75 g OGTT
- Random PG?
79
Diabetes diagnosis FPG?
```
>/= 7.0 mmol/L
-Fasting = no caloric intake for at least 8 hours
```
80
Diabetes diagnosis A1C?
>/= 6.5%
81
Diabetes diagnosis in 2hPG in a 75g OGTT?
>/= 11.1 mmol/L
82
Diabetes diagnosis Random PG?
>/= 11.1 mmol/L
83
Normoglycemia ranges for fasting glycemia and post-prandial glycemia?
1) 5.6-6.1
| 2) 7.8
84
Range for IFG? (fasting glycemia)?
5.6-6.1 - 7.0
85
Range for IGT? (post-prandial glycemia)?
7.8-11.1
86
When is diabetes indicated with postprandial glycemia?
When greater than 11.1
87
When is diabetes indicated with fasting glycemia?
When greater than 7
88
(T/F) A patients IFG is 6.2 (IFG) but his A1C is 6.6%, this is a diagnosis of diabetes.
T
| Any time that A1C is >6.5%, even if other values indicate only IGT or IFG
