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Year 2 - BRS > 3.17 - Type 2 diabetes > Flashcards

3.17 - Type 2 diabetes Flashcards

1
Q

What is T2DM?

A
  • a condition in which the combination of insulin resistance AND beta cell failure results in hyperglycaemia
  • associated with obesity but not always
  • resultant chronic hyperglycaemia may initially be managed by changes to diet/weight loss and may even be reversible
  • with time, glucose lowering therapy including insulin is needed
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2
Q

What makes T2DM harder to diagnose due to overlap with T1DM?

A
  • T2DM may present in youth/young adults
  • diabetic ketoacidosis can be a feature of T2DM
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3
Q

At what ages can T2DM develop and how has our view of this changed?

A
  • traditionally thought to be a condition of adulthood
  • now good evidence that it can present throughout every decade of life
  • increasing in all age groups but rapidly in early adulthood
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4
Q

What is T2DM in youth associated with?

A

An earlier death (whereas developing T2DM at an older age, the life expectancy is similar to a normal person)

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5
Q

What is the prevalence of T2DM like now and how is it predicted to be in the future?

A
  • prevalence of T2DM varies massively between countries
  • increasing prevalence
  • occurring and being diagnosed younger
  • greatest increase predicted in ethnic groups that move from rural to urban lifestyles e.g. India
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6
Q

What are fasting glucose levels like in normal, intermediate state and T2DM?

A
  • normal </=6 mmol/L
  • impaired fasting glycaemia (IFG)
  • T2DM >/=7 mmol/L
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7
Q

What are OGTT (oral glucose tolerance test - 2hr glucose) levels like in normal, intermediate state and T2DM?

A
  • normal <7.7 mmol/L
  • impaired glucose tolerance (IGT)
  • T2DM >/=11 mmol/L
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8
Q

What are HbA1c levels like in normal, intermediate state and T2DM?

A
  • normal <42 mmol/mol
  • intermediate state - pre-diabetes or non-diabetic hyperglycaemia (caused by IFG + IGT)
  • T2DM >/=48 mmol/mol
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9
Q

What is insulin production like in normal, intermediate state and T2DM?

A

Increases during intermediate state, showing the body trying to compensate for the increase in insulin resistance, then starts to fall = by the time you present with T2DM you already have beta cell dysfunction

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10
Q

What is insulin resistance like in normal, intermediate state and T2DM?

A

Increases during intermediate state and is already maxed out by the time you present with T2DM

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11
Q

What are random glucose levels like in normal and T2DM?

A

Normal <11.1mmol/L, T2DM >/=11.1 mmol/L

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12
Q

How can a random glucose test be used to diagnose T2DM?

A

If it is above 11.1 mmol/L and there are symptoms of T2DM e.g. polyuria = diagnosis

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13
Q

What are the beta cell function levels at when you are diagnosed with T2DM?

A

Their function has already decreased to around 50% at time of diagnosis (not enough to overcome insulin resistance)

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14
Q

What is relative insulin deficiency in type 2 diabetes?

A

Insulin is still produced by pancreatic beta cells but not enough to overcome insulin resistance = relative deficiency of insulin

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15
Q

How does the relative insulin deficiency explain why T2DM do not usually get diabetic ketoacidosis?

A
  • ketones typically form when there is no insulin, but here there is still some
  • insulin needed to suppress lipolysis
  • can still present with DKA not spontaneously but because person is unwell (infected/catabolic/septic)
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16
Q

What happens in long duration T2DM?

A
  • beta cell failure may progress to complete insulin deficiency
  • patients usually on insulin at this point, but important not to stop as at risk of ketoacidosis
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17
Q

What is the pathophysiology of T2DM?

A
  • genes, intrauterine environment and adult environment
  • insulin resistance and insulin secretion defects
  • fatty acids important in pathogenesis and complications
  • heterogenous
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18
Q

What does it mean that T2DM is heterogeneous?

A

People develop T2DM at variable BMI, ages and progress differently

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19
Q

What is a hyperglycaemic clamp?

A

When you keep a patient in a steady state with infusions of glucose and insulin

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20
Q

What is insulin response in normal vs impaired glucose tolerance vs T2DM when glucose is added?

A
  • insulin response in normal people - spike as soon as glucose enters blood (IV glucose challenge)
  • IGT - blunted response
  • T2DM - no response = loss of first phase insulin release
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21
Q

What hormone is increased in T2DM and what does this cause?

A

Glucagon increased (as body not responding to insulin) = increased gluconeogenesis + glycogenolysis = increased HGO = increased glucose to peripheral tissues

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22
Q

What does a reduction in insulin action cause in T2DM?

A
  • reduced insulin action causes less uptake of glucose into skeletal muscle
  • HGO also increased due to both reduction in insulin action and increase in glucagon action (liver producing too much glucose despite already hyperglycaemic = dysregulated metabolism)
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23
Q

What is HGO production and glucose clearance like in T2DM?

A
  • impaired insulin-mediated glucose clearance/disposal
  • excessive glucagon-mediated glucose output/production
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24
Q

What is the relationship between insulin sensitivity (resistance) and insulin secretion in normal vs T2DM?

A
  • normal - least sensitive (most resistant) need a lot of insulin secretion for desired effect and vice versa
  • people developing T2DM have ‘fallen off the curve’ - for any given degree of insulin sensitivity they secrete less insulin
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25
Q

What are the consequences of insulin resistance in the liver?

A

Increased HGO (due to hyperglucagonaemia)

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26
Q

What are the consequences of insulin resistance in adipocytes?

A
  • increased fatty acid uptake from gut
  • triglycerides form unhealthy types of lipid (usually inhibited by insulin)
  • increased fatty acid production
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27
Q

What are the consequences of insulin resistance in muscle?

A

Usually takes up glucose in presence of insulin, but in T2DM there is less uptake by muscle

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28
Q

What is monogenic diabetes?

A
  • single gene mutation means you are born with it and always going to develop it no matter how much you try
  • MODY - maturity onset diabetes of the young
29
Q

How is T2DM polygenic?

A
  • polymorphisms increase the risk of diabetes
  • not born with it but high risk and may develop later depending on other factors
30
Q

How does genetic and environmental risk interact in the chance of developing T2DM?

A
  • low genetic risk + strong environmental factors –> T2DM
  • high genetic risk + weak environmental –> T2DM (why some ethnic groups need lower BMI to get T2DM)
  • high genetic risk + high environmental risk = very likely to get diabetes
  • low genetic risk + weak environmental = relatively protected against T2DM
31
Q

What do genome wide association studies of T2DM show?

A
  • GWAS of T2DM done by taking people with and without T2DM and sequencing their whole genome to look for nucleotide changes present in T2DM but not control
  • they show that each individual SNP has only a mild effect on risk
  • cumulative effect of all SNPs has bigger effect - those with more SNPs more likely to get T2DM
32
Q

What is the role of obesity in T2DM?

A
  • major risk factor for T2DM - 80% obese
  • fatty acids and adipocytokines important in development
  • central vs visceral obesity - people with lower BMIs can get T2DM due to more visceral fat
  • weight reduction is useful treatment
33
Q

What roles do perturbations in gut microbiota have on T2DM cases?

A
  • obesity, insulin resistance T2DM
  • bacterial lipopolysaccharides fermentation to short chain fatty acids, bacterial modulation bile acids
  • inflammation, signalling metabolic pathways
  • most studies correlative
34
Q

What is the role of intra-uterine growth retardation on T2DM?

A
  • if you have underdeveloped in womb or if mother had diabetes, this affects intrauterine growth environment
  • people with intrauterine growth retardation are more likely to develop T2DM
  • babies with lower body weight had higher % of T2DM/IGT
35
Q

How does T2DM present? (7)

A
  • hyperglycaemia
  • overweight
  • dyslipidaemia
  • fewer osmotic symptoms
  • with complications
  • insulin resistance
  • later insulin deficiency
36
Q

What are the risk factors of T2DM? (6)

A
  • age
  • increased BMI
  • ethnicity
  • PCOS
  • family history
  • inactivity
37
Q

How/when can we diagnose T2DM?

A
  • osmotic symptoms
  • infections
  • screening test - incidental finding (e.g. screen for tiredness and find this)
  • at presentation of a complication - acute / chronic
38
Q

What is an acute complication people with T2DM can present with at diagnosis?

A

Hyperosmolar hyperglycaemic state (life threatening state due to high BGC)

39
Q

What are some chronic complications people with T2DM can present with at diagnosis?

A
  • ischaemic heart disease
  • retinopathy
40
Q

What is the first line test for diagnosis of T2DM?

A
  • HbA1c
  • 1 x HbA1c >=48 mmol/mol with symptoms
  • or 2 x HbA1c >= 48 mmol/mol if asymptomatic
41
Q

What is a hyperosmolar hyperglycaemic state?

A
  • diabetic emergency
  • presents commonly with renal failure
  • unchecked gluconeogenesis –> hyperglycaemia –> osmotic diuresis –> dehydration
  • insufficient insulin (not absent) for prevention of hyperglycaemia but sufficient for suppression of lipolysis and ketogenesis
  • absence of significant acidosis
  • often identifiable precipitating event (infection, MI)
42
Q

Table of differences: DKA vs hyperosmolar hyperglycaemic syndrome

A
  • volume status - dehydrated vs hypovolaemic
  • glucose (mmol/L) - >11/known diabetes vs >30
  • urine ketones - +++(+) vs ++(or less)
  • capillary blood ketones (mmol/L) - >3 vs <3
  • pH - <7.3 vs >7.3
  • bicarbonate (mmol/L) - <15 vs >15
  • osmolarity - variable vs >320mosmol/kg
  • IV fluids - immediately vs immediately
  • insulin - immediately at fixed rate infusion of 0.1 units/kg/h vs immediately only if capillary ketones >1 or urine ketones >2 (at 0.05 units/kg/h); otherwise withhold insulin until fluid resuscitated
43
Q

What is the management of T2DM? (6)

A
  • diet
  • oral medication
  • structured education
  • may need insulin later
  • remission/reversal?
  • prevention of diabetes-related complications and their risk factors
44
Q

What are some diabetes-related complications?

A
  • retinopathy
  • neuropathy
  • nephropathy
  • cardiovascular
45
Q

What are the principles of a T2DM consultation?

A
  • glycaemia - HbA1c, glucose monitoring if on insulin, medication review
  • weight assessment
  • blood pressure
  • dyslipidaemia - cholesterol profile
  • screening for complications - foot check, urine check, retinal screening
46
Q

What is an example of dietary recommendations and education for T2DM?

A
  • total calories control
  • reduce calories as fat and refined carbs
  • increase calories as complex carbs and soluble fibre
  • decrease sodium

DESMOND

47
Q

How do we deal with excess hepatic glucose production in T2DM and what drugs can we use?

A
  • reduce hepatic glucose production
  • metformin
48
Q

How do we deal with resistance to action of circulating insulin in T2DM and what drugs can we use?

A
  • improve insulin sensitivity
  • metformin and thiazolidinediones
49
Q

How do we deal with inadequate insulin production for extent of insulin resistance in T2DM and what drugs can we use?

A
  • boost insulin secretion
  • sulphonylureas, DDP4-inhibitors, GLP-1 agonists
50
Q

How do we deal with excess glucose in circulation in T2DM and what drugs can we use?

A
  • inhibit carbohydrate gut absorption - alpha glucosidase inhibitor
  • inhibit renal glucose reabsorption - SGLT-2 inhibitor
51
Q

What one action helps with managing T2DM?

A

Weight loss

52
Q

What does metformin do?

A
  • biguanide type of drug, insulin sensitiser
  • reduces insulin resistance - reduced HGO, increases peripheral glucose disposal
  • GI side effects
53
Q

When is metformin first line?

A

When dietary/lifestyle adjustment has made no difference

54
Q

When is metformin contraindicated? (3)

A
  • severe liver failure
  • severe cardiac failure
  • severe renal failure
55
Q

What do sulphonylureas e.g. gliclazide do?

A
  • bind to ATP-sensitive potassium channel and close it, independent of glucose/ATP = insulin production
  • boost insulin production of beta cells
56
Q

What does pioglitazone do?

A
  • insulin sensitiser, mainly in peripheral tissues
  • makes action of insulin a bit more efficacious at tissue level
  • causes improvement in glycaemia and lipids
  • adipocyte differentiation modified
  • weight gain (peripheral not central)
57
Q

What are some side effects of older types of pioglitazone? (2)

A
  • hepatitis
  • heart failure
58
Q

What is a side effect of some older glucose-lowering therapies?

A

Mild weight gain

59
Q

How does glucagon-like peptide 1 (GLP-1) work?

A
  • gut hormone secreted in response to nutrients in gut
  • transcription product of pro-glucagon gene, mostly from L-cell
  • stimulates insulin, suppresses glucagon
  • increases satiety
  • short half life due to rapid degeneration by DPP4 enzyme
60
Q

What is the gastrointestinal incretin effect?

A

Oral glucose causes an increased plasma insulin level than IV glucose

61
Q

What do GLP-1 agonists do and give examples?

A
  • Liraglutide, Semaglutide
  • injectable - daily/weekly
  • decrease glucagon and glucose
  • weight loss
62
Q

What do gliptins (DDPG-4 inhibitors) do?

A
  • increase half-life of exogenous GLP-1
  • increase GLP-1
  • decrease glucagon and glucose
  • neutral on weight
63
Q

What do SGLT-2 inhibitors do?

A
  • inhibits Na-Glu transporter, increases glycosuria
  • HbA1c lower
  • improve CKD, microalbuminuria
  • improve risk of heart failure, strokes, death
64
Q

What are some examples of SGLT-2 inhibitors? (3)

A
  • empagliflozin
  • dapagliflozin
  • canagliflozin
65
Q

Despite treatment, what happens to beta cell function in T2DM?

A

Continues to decline as there is progressive loss of beta cell function prior to diagnosis

66
Q

How do we push T2DM patients into remission?

A
  • gastric bypass surgery has potential to induce remission
  • very low calorie diet (800kcal a day) for 3-6 months has potential to induce remission, which appears to be sustained at 2 years
  • NHS England remission programme being piloted
67
Q

How is blood pressure managed in T2DM?

A
  • hypertension very common in T2DM
  • clear benefits for reductions, especially with use of ACE inhibitors
68
Q

What are the levels of different types of lipids like in T2DM, and how can this link to management?

A
  • total cholesterol raised
  • triglycerides raised
  • HDL cholesterol reduced
  • clear benefit to lipid-lowering therapy

Year 2 - BRS (84 decks)

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