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Diabetes Flashcards

1
Q

What is type I diabetes mellitus?

A

Autoimmune destruction of the beta cells in the pancreas which produce insulin

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2
Q

What is the only current therapy for type I diabetes mellitus?

A

Insulin injection or insulin pumps to maintain blood glucose

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3
Q

The prevalence of type I diabetes is increasing. T/F?

A

True

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4
Q

Type 2 diabetes is associated with obesity. T/F?

A

True

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5
Q

What is type II diabetes mellitus?

A

Insulin resistance where tissues are no longer sensitive to endogenous insulin

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6
Q

How do sulphonylureas act as hypoglycaemic drugs?

A

These inhibit ATP-sensitive potassium channels to increase the release of insulin

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7
Q

Give examples of sulphonylureas which are used clinically as hypoglycaemic drugs?

A 
Glibenclamide
Gliclazide
Glimepiride
Tolbutamide
Glipizide
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8
Q

Metformin is an example of a biguanide which is used as a hypoglycaemic drug. How does it work?

A

It mimics insulin by inhibiting hepatic gluconeogenesis

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9
Q

How do thiazolidinediones work as a hypoglaemic drug?

A

They stop the inappropriate deposition of lipid in non-adipose tissue by acting as a ligand to stimulate the expression of genes involved in TAG storage. This improves insulin sensitivity

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10
Q

Give an example of a thiazolidineione used as a hypoglycaemic drug?

A

Pioglitazone

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11
Q

What are incretins?

A

GI hormones which potentiate insulin secretion

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12
Q

Give examples of incretins

A

Glucagon like peptide 1

gastric inhibitory peptide

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13
Q

Which enzyme rapidly inactive incretins?

A

dipeptidyl peptidase 4 (DDP-4)

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14
Q

Incretins are endogenous molecules which potentiate the effects of insulin but are rapidly broken down by DDP-4. Give examples of incretin mimics which are used as hypoglycaemic drugs as they are not cleaved by DDP-4?

A

Exenatide

Liraglutide

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15
Q

Give examples of drugs which inhibit DDP4 to increase endogenous incretin mediated increase in insulin secretion?

A

Sidagliptin

Vildagliptin

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16
Q

Canagliflozin, dapagliflozin and empagilflozin are SGLT2 inhibitors. How do these work to reduce hyperglycaemia?

A

These inhibit renal reabsorption glucose through SGLT2

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17
Q

What type of. hypersensitivity reaction is type 1 diabetes mellitus?

A

Type 4 cell mediated hypersensitivity

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18
Q

What antibodies may exist in a patient with type I diabetes?

A

GAD65 - against glutamic acid decarboxylase
IAA - against insulin
I-A2 against tyrosine phosphatase like molecule
ICA - against islet cells
ZnT8 - against beta cell specific zinc transporter

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19
Q

Beta cell destruction proceeds for months or years without detection as inflammation of the beta cells. Often, what percentage of beta cells needs to be destroyed before hyperglycaemia develops?

A

80-90%

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20
Q

How does the lack of insulin in type 1 diabetes lead to hyperglycaemia?

A

GLUT4 not translocated onto muscle, liver or adipose cells so there is limited glucose uptake by these cells. This results in decrease glycogenesis and protein synthesis and an increase in glycogen-lysis, gluconeogenesis and lipolysis

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21
Q

Which HLA genes provide a genetic susceptibility to type 1 diabetes?

A

HLA-DR3

HLA-DR4

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22
Q

As well as genetic factors, environmental factors have been implicated in the development of type 1 diabetes mellitus. What are these environmental factors?

A 
Congenital rubella syndrome 
Human enteroviruses
Vitamin D deficiency
Wheat proteins (gluten)
Cow's milk
Psychological stress
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23
Q

What are some of the microvascular complications of diabetes?

A

retinopathy
neuropathy
nephropathy

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24
Q

What are some of the microvascular complications of diabetes?

A

Cardiovascular, cerebrovascular and peripheral vascular disease

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25
In what age group does type I diabetes usually present?
Young people
26
What is the acute complication of type I diabetes mellitus?
Diabetic ketoacidosis
27
A random plasma glucose test above what level may indicate diabetes?
>11mmol/l
28
A fasting plasma glucose above what level may indicate diabetes?
>6.9mmol/l
29
A plasma glucose above what level, two hours after the administration of 75g of oral glucose, may indicate diabetes?
>11mmol/l
30
What is the AC1 test for diabetes?
Tests glycosylated haemoglobin to measure the 3 month average plasma glucose concentration this will be >48mmol/l in patients with diabetes
31
How can the diagnosis of diabetes be determined by investigation?
random plasma glucose, fasting plasma glucose, glucose tolerance test, AC1 test Two positive tests or one positive test plus symptoms indicates diabetes
32
How can the diagnosis of specifically type 1 diabetes be identified?
low c-peptide levels | presence of type 1 diabetes autoantibodies
33
How is good glycemic control obtained in type I diabetes mellitus?
Diet Exercise Insulin therapy
34
Explain the difference between a twice daily insulin regime and a basal-bolus regime?
Twice daily regime - take insulin before breakfast and dinner Basal-bolus routine - intermediate or long-acting insulin given at bedtime to provide a basal level of insulin then a bolus amount of insulin is added using short/rapid acting insulin to cover mealtimes
35
Explain the difference between insulin pumps and insulin pens?
Insulin pens require injection and deliver a metered dose of insulin Insulin pumps deliver insulin subcutaneously, continuously over 24 hrs
36
How is hypoglycaemia defined?
Normal fasting glucose <3.3 mol/l
37
What may be the cause of diabetic hypoglycaemia?
``` Taking too much insulin Not eating enough Postponing or skipping meals or snacks Increasing exercise without eating more or adjusting medications Drinking alcohol ```
38
What are the symptoms of hypoglycaemia?
``` Diaphoresis Anxiety Tremor Hunger Generalised tingling Nausea Palpations Confusion Irritability Blurred vision Drowsiness ```
39
How are mild episodes of hypolglycaemia treated?
Usually be the patient themselves by taking a glucose tablet or by eating/drinking refined sugar
40
How are more severe/acute presentations of hypoglycaemia treated?
Glucose administered by IV | injection of 1mg of glucagon
41
What are the symptoms of type I diabetes mellitus?
``` Polyuria Polyphagia Polydipsia Glycosuria Weight loss Generalised weakness Blurred vision ```
42
What is the prevalence of type I diabetes in the UK population?
0.5%
43
What is the prevalence of type II diabetes in the UK population?
5%
44
What is the prevalence of MODY in the UK population?
0.1%
45
What percentage of pregnant women in Glasgow develop gestational diabetes?
20%
46
Gestational diabetes is caused by a lack of insulin production. T/F?
False - it is the result of insulin resistance
47
Diabetes mellitus can occur secondary to which conditions?
``` Pancreatitis Cystic fibrosis Haemochromatosis Steroid-induced Acromegaly ```
48
What are the associated diseases with diabetes mellitus?
``` Addison's disease coeliac disease thyroid disease Pernicious anaemia Inflammatory bowel disease Premature ovarian failure ```
49
The majority of cases of MODY are caused by a mutation in...?
HNF-1alpha
50
MODY is the result of lack of insulin secretion rather than lack of insulin production. T/F?
True
51
MODY as a result of potassium channel deficiency is commonly diagnosed in neonates. What percentage of cases of MODY does this account for?
1%
52
A mutation in glucokinase can lead to MODY. What percentage of cases of MODY does this account for?
20%
53
5% of cases of MODY are the result of a mutation in...?
HNF-4alpha
54
2% of cases of MODY are the result of a mutation in...?
HNF-1beta
55
How do mutations in HNF-1alpha, HNF-1 beta, HNF-4alpha and glucokinase result in MODY?
By inhibiting the metabolism of glucose meaning that no ATP is produced to close the potassium channels which would lead to the influx of calcium ions that causes insulin release
56
MODY is usually an autosomal dominant condition. T/F?
True
57
What is the best predictor for the onset of type iI diabetes?
Insulin resistance
58
There is no component of genetic susceptibility for T2DM. T/F?
False - family history is a major risk factor for T2DM
59
Which hormone is responsible for informing the hypothalamus about the quantity of stored fat and adiponectin in order to stimulate hunger?
Leptin
60
How is TNF-alpha implicated in insulin resistance?
Interferes with insulin receptor signalling
61
How is resistin implicated in insulin resistance?
Enhances hypothalamic stimulation of glucose production
62
Glucotoxicity can impair beta cell function. T/F?
True
63
What are the aims of treatment for T2DM?
TO prevent diabetes related complications
64
What are the microvascular complications of diabetes mellitus?
Diabetic retinopathy Diabetic nephropathy Diabetic neuropathy
65
What are the macrovascular complications of diabetes mellitus?
Ischaemic stroke Coronary heart disease Congestive heart failure Peripheral arterial disease
66
What are the non-vascular complications of diabetes mellitus?
Infection Degenerative diseases Depression Cognitive disorders
67
Which cells secrete GLP-1?
Intestinal L cells
68
What is the action of GLP-1 on the pancreas?
Acts on beta cells pancreas to enhance glucose-dependent insulin secretion and acts on the alpha cells to suppress postprandial glucagon secretion
69
What are the actions of GLP-1 on the liver, stomach and brain?
Liver - reduces gluconeogenesis Stomach - slows rate of gastric emptying to reduce rate at which glucose is absorbed into the bloodstream Brain - promotes satiety and reduces appetite
70
Give examples of drugs which are GLP-1 agonists?
Exenatide Liraglutide Dulaglutide Semaglutide
71
Give an example of a drug which prevents glucose absorption in the GI tract?
Acarbose
72
Give examples of DDP-4 inhibitors?
``` Sitagliptin Vildagliptin Saxagliptin Linagliptin Alogliptin ```
73
What percentage of glucose is normally reabsorbed by SGLT2 in the kidney?
90%
74
Give examples of SGLT2 inhibitors?
Dapagliflozin Canagliflozin Empagliflozin
75
T2DM involves deficits in both insulin secretion and insulin action. T/F?
True
76
Which ethnic group is most at risk of T1DM?
Northern European
77
Which ethnic groups are most at risk of T2DM?
Asian, African, Polynesian and Native American
78
What values of fasting plasma glucose and HbA1c are indicative of pre-diabetes?
Fasting plasma glucose 5.6-6.9 mol/l | HbA1c of 39-46mmol/mol
79
What values of fasting plasma glucose and HbA1c are indicative of diabetes?
Fasting plasma plasma >6.9mmol/l | HbA1c of >48mmol/mol
80
There is no genetic component to T2DM. T/F?
False
81
Subclinical inflammatory changes are characteristic of both T2DM and obesity. T/F?
True
82
Which pro-inflammatory cytokines are elevated in both diabetes and obesity?
TNF-alpha | IL-6
83
The accumulation of fat in which particular tissues is associated with diabetes?
Muscle and liver
84
Patients with T2DM usually show deposition of which protein in the interstitial of beta cells?
Amyloid
85
Initially, there is hyperinsulinaemia in T2DM. Why is this?
This is an attempt to counter insulin resistance
86
Glucotoxicity may contribute to beta cell loss in T2DM. T/F?
True
87
What is the biggest cause of death in patients with T2DM?
Cardiovascular problems
88
Why is the accumulation of sorbitol in T2DM dangerous?
This causes changes in vascular permeability, cell proliferation and capillary structure via stimulation of protein kinase C and TDF-beta
89
How is glycemic control measured in diabetic patients?
HbA1c tests
90
What is the normal HbA1c goal for diabetic patients?
<7%
91
What is the normal blood pressure goal for diabetic patients?
<130/80 mmHg
92
What is the normal total cholesterol goal for diabetic patients?
<4.0 mol/l
93
What are the treatment options for patients with T2DM?
``` Diet advice Smoking cessation Increase exercise Hypoglycaemic drugs Statins Antihypertensive drugs Aspirin therapy ```
94
How much exercise per week is recommended for diabetic patients?
30 mins of moderate activity at least 5 days a week gentle strength training two or three times a week also limit time being sedentary
95
What is the most commonly used hypoglycaemic drug in T2DM?
Metformin
96
What class of drugs does metformin belong to?
Biguanides
97
What is the mechanism of action of metformin?
Activates AMP kinase which is involved in the regulation of cellular energy metabolism to reduce the rate of gluconeogenesis
98
What is the mechanism of action of sulphonylureas?
Promote insulin secretion from beta cells by closing the ATP-sensitive potassium channels on the beta cell
99
Meglitindines act as hypoglycaemic drugs by closing the ATP-sensitive K channel on beta cells to promote insulin secretion. Why are these drugs not commonly used?
They are expensive
100
What is the mechanism of action of thiazolidinediones?
Reduce hepatic glucose production and enhance peripheral glucose uptake by acting on a nuclear receptor involved in the regulation of many genes involved in lipid metabolism and insulin action
101
Insulin can be used in the treatment of T2DM. T/F?
True
102
In normal renal glucose handling, what percentage of glucose is reabsorbed by SGLT2?
90%
103
Why is it so important to treat cardiovascular risk factors in diabetic patients?
Diabetic patients are most likely to die from cardiovascular causes. There are much more likely to have strokes and MIs
104
How is blood pressure treated in diabetic patients?
Patients receive ACE inhibitor or angiotensin-II-receptor blocker Black/Caribbean patients receive calcium receptor blockers
105
How is high cholesterol treated in diabetic patients?
Statins
106
Aspirin therapy is used in all patients with T1DM. T/F?
False - it is used in patients who are at increased cardiovascular risk

Endocrine System (12 decks)

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