Diabetes - Aetiology, Diagnosis and Presentation Flashcards
1
Q
How many people have diabetes
A
3 million people have diabetes
2
Q
at the current rate how many people will have diabetes by 2025
A
- higher than 5 million by 2025
3
Q
what counts for 85-95% of all cases of diabetes
A
type 2 diabetes
4
Q
what percentage of the population have diabetes
A
4-9%
5
Q
How many people at the London have diabetes
A
1 in 5
6
Q
which type of diabetes is more acute
A
- Type 1 diabetes is more acute
- Type 2 diabetes is subacute/ more non specific symptoms such as tiredness
7
Q
What are the classic symptoms of diabetes
A
- polyuria - osmotic diuresis by hyperglycaemia
- polydipsia
- nocturia - osmotic diuresis by hyperglycaemia
- weight loss - glucose coming out of urine
- fatigue - lack of glucose
- blurred vision - osmotic effect on the lens
- pruritic
- recurrent urinary or genitourinary infections
8
Q
Name a word you would use to describe the classic symptoms of diabetes
A
- Osmotic - due to the osmotic effect of hyperglycaemia creating an osmotic diuresis
9
Q
Name two acute emergency presentations of diabetes
A
Hyperosmolar hyperglycaemic syndrome (HHS)
diabetes ketoacidosis (DKA)
10
Q
How can diabetes present with complications
A
skin infections – staphylococcal skin abcesses, oral or genital candidiasis
foot problems – ulcers or neuropathic pain
retinopathy – perhaps found on routine eye test
acute myocardial infarct / stroke – diagnosed whilst in hospital
11
Q
What are the ways to diagnose diabetes
A
- Fasting plasma glucose (FPG) - not a capillary glucose test (fingerpick test)
- Random plasma glucose (RPG)
- 75 gram oral glucose tolerance test (OGTT) - this is when they fast for a minimum of 9 hours, you then check the fasting plasma glucose (FPG) and then give 75g of glucose (lucozade) and check 2 Horus later the plasma glucose
- Haemoglobin A1c( HbA1c) - this is a test that measures for average glucose control over a 3 month period
12
Q
How does a 75 gram oral glucose tolerance test (OGTT) work
A
this is when they fast for a minimum of 9 hours, you then check the fasting plasma glucose (FPG) and then give 75g of glucose (lucozade) and check 2 Horus later the plasma glucose
13
Q
What does haemoglobin A1c( HbA1c) measure
A
- this is a test that measures for average glucose control over a 3 month period
14
Q
What are the normal ranges for Haemoglobin A1c( HbA1c)
A
Normal range <42 mmol/mol
Good control varies from individual to individual (depending on age, co-morbidities etc.)
Generally HbA1c < 53 mmol/mol indicates well controlled diabetes
if HbA1c is greater than 48 mol/mol for two times then you have diabetes
15
Q
For an individual who has no diabetes symptoms how many tests do you have to do
A
two diagnostic tests are required (eg 2x FPG, or HbA1c, but only one abnormal OGTT is required)
16
Q
For an individual with symptoms of diabetes how many tests do you have to do
A
One diagnostic test is enough to diagnose diabetes for someone with symptoms
17
Q
What is the gold standard for diagnosing diabetes
A
75 gram oral glucose tolerance test (OGTT)
18
Q
list the numbers needed for diagnosis of diabetes for each test
- Fasting plasma glucose
- 2 hour plasma glucose
- random plasma glucose
- HbA1c
A
- Fasting plasma glucose = greater than 7 mmol/L
- 2 hour plasma glucose = greater than 11.1mmol/L
- random plasma glucose = greater than 11.1mmol/L
- HbA1c = greater than 48mmol/mol(6.5%)
19
Q
what do you use to measure impaired glucose tolerance and what does it mean
A
can only be diagnosed using an oral glucose tolerance test
- so the 2 hour plasma glucose
- this is between 7.8-11 mol/L - the is not a diagnosis of diabetes but it is abnormal
20
Q
What is used to measure impaired fasting glucose and what does it mean
A
- Slightly higher than normal which is less than 6 but it is not quite in the diabetes range yet
- measured by using fasting plasma glucose
- between 6.1-6.9 mol/L
21
Q
What does impaired glucose tolerance and impaired fasting glucose indicate
A
- they indicate a higher risk for developing diabetes
- need to monitor patient carefully
22
Q
List the differences between type 1 and type 2 diabetes
A
Type 1 diabetes - ketone prone - due to lack of insulin and will develop ketoacidosis - insulin deficiency - autoimmune (GAD and ICA antibodies - acute onset - non obese - juvenile onset (usually less than 35 years of age) - HLA DR3 and HLA DR4 present - 50% concordance in MZ twins FH positive in 10%
type 2 diabetes
- non ketosis prone
- insulin resistant or/and deficiency
- Non- autoimmune - associated with metabolic syndrome
- insidious onset
- often obesity associated
- usually greater than 35 years of age but common below this age as well
- No HLA relation
- 100% concordance in MZ twins
- FH positive in 30%
23
Q
what HLA present in type 1 diabetes
A
- HLA DR3 and HLA DR4 present
24
Q
what autoimmune antibodies are present in type 1 diabetes
A
GAD and ICA antibodies
25
List the secondary causes of diabetes
```
- Pancreatic disease
Endocrine disease
Drug induced
Genetic defects of b-cell function
Genetic defects of insulin action
Infections
Genetic syndromes
Gestational diabetes
```
26
How does pancreatic disease lead to the onset of diabetes
- due to damage of the beta cells therefore reducing there production of insulin
27
What can cause pancreatic disease that can lead to type 1 diabetes
- trauma - leading to a pancreatectomy
- pancreatitis
- pancreatic cancer,
- cystic fibrosis causing pancreatic damage to the exocrine gland leading damage to the endocrine gland,
- haemochromatosis/thalassaemia due to iron overload
- Fibrocalculous pancreatopathy (Pancreatic damage associated with malnutrition)
28
Name the endocrine diseases that may cause secondary diabetes
- Acromegaly - excess growth hormone
- Cushing syndrome - excess cortisol
- Glucagonoma - excess glucagon
- phaechromocytoma - excess catecholamines
- Hyperthyroidism - excess thyroid hormone
- Conn's syndrome - excess aldosterone
29
What drugs increase the risk of diabetes
Glucocorticoids - similar to Cushing syndrome
b-blockers - increase risk by about 30%
Thiazide diuretics - increase risk by about 30%
Tacrolimus (used in transplantation – may cause “New Onset Diabetes after Transplantation” [NODAT])
Atypical anti-psychotics – eg. olanzapine, risperidone, clozapine - increase appetite and induce metabolic problems
30
what drug causes NODAT
Tacrolimus (used in transplantation – may cause “New Onset Diabetes after Transplantation” [NODAT])
31
What infections increase the risk of diabetes
Congenital rubella
Cytomegalovirus
32
Type 2 diabetes is a ..
Type 2 diabetes is a heterogenous syndrome
33
what two interactions does the pathogenesis of type 2 diabetes involve
Environmental factors – obesity, poor physical activity
Diabetogenic genes – genes contributing to insulin resistance
(genetic and environmental causes)
34
How does the genetic and environment lead to type 2 diabetes
- causes various combinations of insulin resistance and B cell failure
35
what is insulin resistance and B cell failure exacerbated by
Hyperglycaemia
36
What is glucose toxicity
- High levels of glucose lead to poorer B cell function
- this leads to reduce insulin secretion as they switch off
- therefore if you lower glucose this can help B cell function
37
what is the genetic influence of type 2 diabetes
possibly 40-80% of susceptibility
38
B cell failure gets..
worse over time
| - even at diagnosis there is already a lot of beta cell function
39
Name a gene associated with type two diabetes
Thrifty genes
40
What are thrifty genes
- These are genes that favour fat storage and or/insulin resistance to help us in times of famine (ancestors survived famines in families)
- these don't help us in times of decrease physical activity and increased energy intake
41
why type of adiposity is not good in type two diabetes
- Abdominal. visceral adiposity is not good
| - pro-inflammatory cytokines from adipocytes contribute to insulin resistance
42
in terms of alpha and beta cells in the pancreas what happens to the percentage of them in type 2 diabetes
- Beta cell mass is preserved (50% at autopsies)
| - alpha cell population is increased - leads to excess glucagon relative to insulin
43
where is the insulin resistance in type 2 diabetes
post receptor insulin resistance
44
when are amyloid peptide deposition happening in type 2 diabetes
Amyloid peptide deposition in the pancreatic islets occurs late in the disease (hence a possible link between diabetes and dementia)
45
What are the factors in metabolic syndrome
- central obesity (waist circumference increase)
- blood pressure abnormalities
- low HDL concentration (lipid abnormalities)
- increase in triglyceride (glucose abnormalities)
46
Who should be screened for diabetes
Overweight / Obese - BMI > 30 kg/m2
Strong family history of diabetes
History of gestational diabetes
Ethnic minorities
▪ South Asian – 6x increased risk
▪ Afro-Caribbean – 2x increased risk
Individuals with known vascular disease
▪ Coronary Heart Disease, Peripheral Vascular Disease, Cerebrovascular disease
Patients on steroids / atypical anti-psychotic therapy / transplants
Unexplained foot ulcers / recurrent candida / skin abscesses
47
What is type 1 diabetes caused by
- Pancreatic B cell destruction leading to absolute insulin deficiency
- autoimmune destruction of pancreatic islets in predisposed individuals (usually islet cell (ICA) AND glutamic acid decarboxylase (GAD antibodies positive)
48
What autoimmune antibodies are present in type 1 diabetes
- islet cell antibodies (ICA)
- glutamic acid decarboxylase (GAD) antibodies positive
- can be idiopathic and antibody negative
49
What is latent autoimmune diabetes in adults
Diagnosed in adulthood
Usually non-acute, hence may be diagnosed at Type 2 diabetes
ICA or GAD+ve
Usually require insulin fairly soon after diagnosis
50
what is the concordance in monozygotic twins for type 1 diabetes v type 2
- Type 1 30-50%
| - Type 2 >90% - stronger
51
what is the evidence of environmental factors for type 1 diabetes
Peak age of onset 5-7 years
Puberty
Seasonal variations
Predominantly Europid populations
52
What is the pathogenic sequence seen in type 1 diabetes
You have a genetic susceptibility:
HLA genes on Chromosomes 6q (MHC) – HLA DR3/4 appears high risk Also genes on chromosomes 2q, 15q, 11q
You get an environmental insult:
Eg Virus such as cocksackie or parvovirus
Possibly exposure to Cows Milk Protein? - breast milk lower risk
You develop an insulitis:
Infiltration of activated T-lymphocytes
You have activation of autoimmunity:
non-self to self transition
You develop an immune attack on b-cells:
isletcell/GADantibodies
cell mediated immunity
You develop diabetes mellitus:
when >90% of b-cells are destroyed
53
what infections can cause diabetes
- Congenital rubella
| - CMV
54
Name some genetic syndromes that are associated with diabetess
- Down syndrome
- Friedreich’s ataxia
- Huntington’s chorea
- Klinefelter syndrome
- Laurence-Moon-Biedl syndrome
- Myotonic dystrophy
- Porphyria
- Prader-Willi syndrome
- Turner syndrome
- Wolfram syndrome
55
name some uncommon forms of immune mediated diabetes
- Stiff person syndrome
| - anti-insulin receptor antibodies
56
What is impaired glucose tolerance (IGT)
- 2hr OGTT - is greater than 7.8 and less than 11.1
57
What is impaired fasting glucose
fasting glucose is greater than 6.1mmol/L and less than 7mmol/l
58
What is prediabetic
- this is when HbA1c is between 42-47mmol/mol or 6-6.4%
59
What factors in obesity contribute to insulin resistance
- Adipokines – due to higher body fat content, especially abdominal/visceral
- Inflammation – chronic low-grade inflammation
- Lipids – accumulation of lipids and their metabolites (eg DAG and FFAs)
60
Define insulin resistance
= diminution in the response of the body’s tissues to insulin, so that higher concentrations of serum insulin are required to maintain normal circulating glucose levels; eventually the islet cells can no longer produce adequate amounts of insulin for effective glucose lowering, resulting in hyperglycaemia
61
Define glucose tolerance
- the boys ability to absorb and use glucose
62
What 4 conditions make up metabolic syndrome
1. central obesity
2. dyslipidemia
3. hypertension
4. imparted fasting glucose
63
What is central obesity
BMI greater than 30 or was it circumference
- Caucasian men = >94cm
- Caucasian women = >80cm
- south asian men = >90cm
- south asian women = > 80cm
64
What is hypertension
- Systolic ≥130mmHg
- Diastolic ≥85mmHg
- or on treatment
