1b T2DM Flashcards

1
Q

What is type 2 diabetes?

A

A condition in which the combination of insulin
resistance and beta-cell failure result in
hyperglycaemia

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2
Q

What is T2DM associated with?

A

Obesity

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3
Q

How is the resultant hyperglycaemia due to T2DM initially managed?

A

changes to diet / weight loss

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4
Q

Can you get diabetic ketoacidosis in T2DM?

A

Yes

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5
Q

What is LADA?

A

Autoimmune diabetes leading to insulin
deficiency can present later in life = latent
autoimmune diabetes in adults

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6
Q

Describe the age distribution of type 2 diabetes?

A

Traditionally thought to be only late adult hood condition

Now increasing evidence that is can occur earlier in life as well

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7
Q

In which ethnic groups is T2DM prevalence the highest?

A

*Greatest in ethnic groups
that move from rural to
urban lifestyle

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8
Q

Above what level of HbA1c levels indicative of Diabetes?

A

greater than or equal to 48 mmol/mol

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9
Q

Between what range of HbA1c levels indicates prediabetes?

A

42-48 mmol/mol

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10
Q

What are some features of prediabetes?

A

Impaired glucose tolerance
Impaired fasting glycaemia

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11
Q

What is needed to make a diagnosis of T2DM?

A

High random glucose with symptoms

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12
Q

Between what levels of fasting glucose would indicate impaired fasting glycaemia?

A

6-7

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13
Q

Between what levels of 2hour oral glucose would indicate impaired glucose tolerance?

A

7.8-11.1

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14
Q

What is meant by an insulin deficiency in T2DM?

A

Insulin is produced by pancreatic beta-cells but not enough to overcome insulin resistance, therefore RELATIVE INSULIN DEFICIENCY

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15
Q

What happens in long-duration diabetes?

A

beta cell failure may progress to complete insulin deficiency - therefore highly important to continue on insulin due to the risk of ketoacidosis

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16
Q

What is lost in patients with type 2 diabetes?

A

The first phase insulin release

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17
Q

Describe the graphs showing plasma insulin levels over time for patients with a normal glucose tolerance and patients with diabetes?

A

After the IV glucose challenge, for the patients with normal glucose tolerance, their plasma insulin levels rapidly shoot up - this represents the first phase insulin release

For patients with type 2 diabetes - there is only a curved, small increase in plasma insulin

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18
Q

What are the effects of T2DM on the skeletal muscle?

A

reduced insulin action causes less uptake of glucose into the skeletal muscle

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19
Q

What are the effects of T2DM on the hepatic glucose production?

A

hepatic glucose production increases due to a reduction in insulin action and increase in glucagon action

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20
Q

What happens to glucagon levels in T2DM and what is the effect?

A

Excessive glucagon mediated glucose output - causes an increase in the hepatic glucose production

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21
Q

What is the relationship between insulin resistance and insulin secretion?

A

Sigmoidal curve - high insulin sensitivity = low insulin secretion

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22
Q

What is the effect of T2DM on the insulin secretion/insulin sensitivity curve

A

They have “Fallen off the curve” - for a given degree of insulin sensativity, they secrete less insulin

Whole curve shifts inwards to the left

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23
Q

In a hyperglycaemic clamp, what is infused continuously to induce an insulin response?

A

Glucose - Hyperglycaemic clamp allows for quantification of beta cell sensitivity to glucose

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24
Q

Explain beta-cell function at diagnosis of T2DM.

A

At the time of diagnosis (t=0), the beta-cell function (%) has a diminished capacity to that prior to diagnosis.

  • Insulin production is compromised.
  • Homeostasis model can be used to calculate beta-cell function (Index).
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25
Q

Under usual circumstances, does hyperglycaemia associate with ketosis?

A

NO

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26
Q

What two factors contribute to increased fasting glucose in patients with T2DM?

A

Decreased glucose disposal and increased hepatic glucose output contributes to increased fasting plasma glucose (FPG) in diabetes mellitus.

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27
Q

In T2DM, what is the excessive amounts of glucose converted into?

A

Lactate

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28
Q

Insulin insufficiency reduces the rate of what?

A

Insulin insufficiency reduces the rate at which glucose-6-phosphate is converted into glycogen

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29
Q

What happens to glucose uptake by the adipocytes and monocytes in T2DM?

A

Reduced uptake by adipocytes and myocytes

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30
Q

What happens to serum triglycerides in Insulin resistance?

A

Elevation in serum triglycerides

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31
Q

What is monogenic?

A

When a single gene mutation causes Diabetes - MODY

32
Q

What is polygenic diabetes?

A

Polymorphisms increasing the risk of developing diabetes - may develop it if high risk and other risk factors

33
Q

Describe the role of GWAS in T2DM?

A

Take people with diabetes and people without

Note the nucleotide changes present in type 2 diabetes group but not the control group

assess the size of the effect seen

34
Q

What is the effect of SNP’s on the risk of developing diabetes?

A

each SNP has a relatively small effect, but cumulatively they have a larger effect

35
Q

what is the role of obesity in T2DM?

A

Large risk factor for diabetes, 80% of people with T2DM are obese - therefore weight reduction treatment is useful

36
Q

What are important in T2DM that relate to Obesity?

A

fatty Acids And adipocytokines

37
Q

What is the difference between central and visceral obesity?

A

Abnormally high deposition of visceral adipose tissueis known as visceral obesity whereas central obesity isan excess accumulation of fat in the abdominal area.

38
Q

What is the presentation of a patient with T2DM?

A
  • Hyperglycaemia
  • Overweight
  • Dyslipidaemia
  • Fewer osmotic symptoms
  • With complications
  • Insulin resistance
  • Later insulin deficiency
39
Q

What are the risk factors for T2DM?

A

Age

Increased BMI

PCOS

Ethnicity

Inactivity

Family Hx

40
Q

What is the first lline test for diagnosis of Diabetes?

A

HbA1c

41
Q

What are the two sets requirements for diagnosis of T2DM?

A
  1. 1 x HbA1c >= 48 with SYMPTOMS
  2. 2 x HbA1c >= 48 without symptoms
42
Q

What are the osmotic symptoms of diabetes?

A

Osmotic symptoms: Nocturia, polyuria & polydipsia.

43
Q

What is a hyperosmolar hyperglycaemic state?

A

When there is insufficient insulin for the prevention of hyperglycaemia but sufficient insulin for the suppression of lipolysis and ketogenesis - therefore absense of significant acidosis

44
Q

What do patients with hyperosmolar hyperglycaemia often present with?

A

Renal failure

45
Q

What is the management of T2DM?

A

Diet
oral Medication
Education
may need insulin later
remission / reversal

46
Q

What are the principles of a T2DM consultation?

A

Glycaemia: HbA1c, glucose monitoring if on insulin, medication review

Weight assessment

BP

Dyslipidaemia: cholesterol profile

Screening for complications: foot check, retinal screening

47
Q

What are the dietary requirements / education which would be given to T2DM patients

A

Total calories control

Reduce calories as fat

Reduce calories as refined carbohydrate

Increase calories as complex carbohydrate

Increase soluble fibre

Decrease sodium

48
Q

What is the strategy and drug used to solve the problem of excess hepatic glucose production?

A

Reduce hepatic glucose production - using Metformin

49
Q

What is the strategy and drug used to solve the problem of resistance to action of circulating insulin ?

A

Improve insulin sensativity - metformin
Thioozolidinediones

50
Q

What is the strategy and drug used to solve the problem of Inadequate insulin production for extent of insulin resistance?

A

Boost insulin secretion -
1. Sulphonylureas
DPP4-Inhibitors
GLP-1 Agonists

51
Q

What is the strategy and drug used to solve the problem of excess glucose in circulation?

A

Inhibit Carb gut absorption
Inhibit renal glucose absorption

Alpha Glucosidase Inhibitor
SGLT-2 Inhibitor

52
Q

In what instance is metformin the first line treatment for T2DM?

A

If dietary / lifestyle adjustments has made no difference

53
Q

How does metformin reduce insulin resistance?

A
  1. Reduced Hepatic glucose output
  2. Increases peripheral glucose disposal
54
Q

In which contexts is Metformin contraindicated>

A

Severe liver disease
Severe cardiac Disease
moderate Renal Failure

55
Q

What does normal insulin release require?

A

The closure of the ATP sensitive potassium channel

56
Q

How do Sulphonylureas work?

A

Bind to the ATP-sensitive potassium channel and close it, so more insulin can be released

57
Q

What is the rate limiting step in the secretion of insulin?

A

When glucose enters into the cell, glucokinase converts it into glucose-6-phosphate

58
Q

What is Pioglitazone?

A

Peroxisome proliferator-activated receptor agonists PPAR-y
Insulin sensitiser (peripheral).

59
Q

How does pioglitazone help in the management of T2DM?

A

Adipocyte differentiation modified

Weight gain but peripheral not central

Improvement in glycaemia and lipids (evidence based on vascular outcomes)

-

60
Q

What is GLP-1?

A

A gut hormones which is secretes in response to nutrients in the gut

61
Q

What is the effect of GLP-1?

A

stimulates insulin and suppresses glucagon - also increases the feeling of satiety

62
Q

Why does GLP-1 have a short half life?

A

due to rapid degeneration from enzyme DPP-4

63
Q

What are the names of the two GLP-1 Agonists?

A

Liraglutide and Semaglutide

64
Q

What do GLP-1 agonists do?

A

decrease glucagon and decrease glucose, causes weight loss

65
Q

What is the name of the a DPP-4 inhibitor?

A

Gliptins

66
Q

What are the effects of Gliptins?

A

Increase half life of exogenous GLP-1
Increase GLP-1
Decrease glucagon
Decrease glucose
Neutral on Weight

67
Q

What do sulphonylureas do?

A

Inhibit Na+-Glu transporter which increases glycosuria
Lowers HbA1c
Improves CKD

68
Q

What happens to beta-cell function despite continued insulin treatment

A

Continues to decline

69
Q

What helps to induce remission of T2DM?

A

Gastric bypass surgery
very low calorie diet

70
Q

How is blood pressure managed?

A

ACE Inhibitor

71
Q

What lipids are raised during diabetes?

A

total cholesterol raised
triglycerides raised
HDL cholesterol reduced

72
Q

When does DKA occur in T2DM patients?

A

When lipolysis is not suppressed enough due to illness associated with t2DM

73
Q

What are some factors which affect insulin secretion and action?

A

Body weight
physical activity
smoking
genetic predisposition
gene environment
epignetics

74
Q

What are the two probems of T2DM?

A

beta cell dysfunction and insulin resistance

75
Q

Which fat is pro-inflammatory?

A

Visceral fat - generates adipocytokines

76
Q

What is a hyperglycaemic clamp?

A

research - assess how insulin resistant someone is in a research facility, not clinical