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Year 2 - Endocrine > Week 2 > Flashcards

Week 2 Flashcards

1
Q

A kg increase in bodyweight leads to what % increase in the risk of developing diabetes?

A kg of weight loss a year after a diagnosis of T2DM is associated with how many months of increased survival?

A

4.5%

3-4 months more survival

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2
Q

How is Lactic Acidosis classified?

A

Type A

  • associated with tissue hypoxaemia e.g. infarcted tissue, cardiogenic shock, hypovolaemic shock

Type B

  • may occur in liver disease
  • may occur in leukaemic states
  • associated with diabetes
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3
Q

What marker is used to screen for diabetic kidney disease?

A

Albumin Creatine Ratio (ACR)

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4
Q

In managing and preventing childhood obesity, what are the 1, 2, 3, 4 steps outlined in the SIGN and NICE guidelines?

A
  1. 1 hour of physical activity a day
  2. less than 2 hours a day of ‘sedentary time’ i.e. TV, computer screens etc.
  3. Food and drink - limit foods high in fat and sugar, discourage multiple snacks and moderate portion size
  4. keep child’s weight within a healthy range
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5
Q

Thiazolidinodiones (TZDs): what do they target? Why does this make them “messy” drugs?

What is the main side effect associated with TZDs?

A

TZDs e.g. pioglitazone targets PPAR gamma, which is involved in the regulation of transcription of many different genes.

Because TZDs are PPAR-gamma agonists, they therefore have numerous side effects

Main side effect is weight gain, which is almost inevitable and can be quite substantial

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6
Q

Metformin is the 1st line drug in treating T2DM, but if a patient is not coping on this alone what other drugs could be added on?

A

Sulphonylureas - cheap and effective, but weight gain is a possible side effect

SGLT-2 inhibitors - better tolerated with weight fluctuation, however are (very rarely) associated with DKA

GLP-1 agonists if the above don’t work - given as an injection either daily or weekly and slow gastric emptying

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7
Q

How is DKA diagnosed biochemically? 3 things

A
  1. Ketonaemia > 3 mmol/L, or significant ketonuria
  2. Blood glucose > 11.0 mmol/L, or known Diabetes
  3. Bicarbonate < 15 mmol/L, or venous pH < 7.3
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8
Q

What newer drugs are available for the treatment of T2DM?

How do they work?

A

Drugs targeting the Incretin Pathway

  • Incretin = Intestinal Secretion of Insulin
  • GIP from K cells and GLP-1 from L cells (Exenatide)
    • promote insulin secretion from the pancreas without the risk of hypoglycaemia (unlike SUs)
    • Suppress glucagon
    • Decreases gastric emptying, resulting in earlier satiety
    • Act on the hypothalamus to cause weight loss
  • DPP-IV inhibitors
    • -gliptins
    • less potent than GLP-1 inhibitors,

SGLT-2 Inhibitors e.g. Dapagliflozin, Canagliflozin, Empagliflozin

  • prevents reabsorption of glucose by the kidneys, causing it to be excreted in the urine
  • Causes weight loss, reduces CV events, death and hospitalisation from heart failure
  • Increased glucose in the urine can result in increased UTIs and Thrush
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9
Q

Glicazide, Glibenclamide and Glimepiride are 1st/2nd gen Sulphonylureas and are long/short acting

Glicazide is the most commonly used, but when would you use Glibenclamide over it? Why?

A

2nd gen (1st gen are rarely used now)

shorter acting

Glibenclamide can be used in pregnancy/gestational diabetes, as it does not cross the placenta

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10
Q

What are the two core defects seen in T2DM?

A

Insulin resistance

Beta cell dysfunction

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11
Q

The “metabolic syndrome” refers to a series of clinical features associated with central obesity - what are these features?

A

Central adiposity a.k.a. ‘apple shapes’ is associated with…

  • High BP
  • High triglycerides
  • Low HDL
  • Insulin resistance
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12
Q

What type of drug is Metformin?

What dosage is given?

A

Biguanide - acts as an insulin sensitiser, primarily acts on the liver to lower glucose production

Usually start at 500mg and titrate up to 1g

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13
Q

Name some sulphonylurea drugs

A

Glimepiride

Gliclazide

Glibenclamide

Glipizide

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14
Q

How is DKA managed?

A

Replace losses

  • fluids
  • insulin
  • potassium

Address risks

  • Naso-gastric tube?
  • monitor potassium
  • prescribe prophylactic LMWH
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15
Q

How might focal neuropathy present itself?

A
  • Inability to focus
  • Double vision
  • Aching behind the eye
  • Bell’s palsy
  • Pain in thigh/chest/lower back
  • Pain on the outside of the foot
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16
Q

Name some SGLT-2 inhibitors

A

Dapagliflozin

Empagliflozin

Canagliflozin

Ipragliflozin

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17
Q

When considering a diagnosis of T2DM, what other conditions need to be ruled out?

A

T1DM

Pancreatic disease

LADA

Medication induced

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18
Q

Outline the current progression of medications for T2DM

A

Metformin

SUs, TZDs, DPP-4 inhibitors, SGLT-2 inhibitors

GLP-1 agonists

Insulin (unlike T1DM, this is usually given as a basal injection without a pre-meal bolus)

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19
Q

By what features is HHS defined?

A

Hypovolaemia

Hyperglycaemia (blood glucose >30 mmol/L), without significant acidosis or ketonaemia

Hyperosmolar (osmolality >320 mosmol/kg)

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20
Q

What are the typical features of Hyperosmolar Hyperglycaemic State (HHS)?

A

Usually older individuals, but may be younger individuals in non-Caucasians

High refined CHO intake pre-event

Risk associations - cardiovascular events, sepsis, medications (glucocorticoids and thiazides)

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21
Q

What are the three types of bariatric surgery that can be performed to tackle obesity? What are patients often prescribed following surgery?

A

Adjustable gastric band (lap band)

Roux-en-Y Gastric Bypass (RNY)

Verticle Sleeve Gastrectomy

Malabsorption disorders are common following these procedures, and patients are commonly prescribed vitamin supplements

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22
Q

HHS - typical biochemical picture

A

Raised blood glucose, higher than that of DKA (mean is 60 mmol/L)

Significant renal impairment

Na may be raised on admission

Significantly raised osmolality e.g. very dehydrated

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23
Q

What are some treatment options for painful neuropathy?

A

amitriptyline, duloxetine, gabapentin, pregabalin - combinations of these are not recommended

If the pain is localised and the patient wishes to avoid oral treatment, then Caspaicin cream can be applied topically

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24
Q

What is the Resting Metabolic Rate? How does it change in obesity and how does it contribute to maintaining weight loss?

A

Amount of energy expended at rest (i.e. minimum energy consumption)

Both fat mass (FM) and fat-free mass (FFM) contribute

RMR is higher in obese individuals and falls with weight loss, HOWEVER, the observed fall in RMR often exceeds that which was predicted (adaptive thermogenesis - body perceives weight loss as a threat to survival)

This makes it harder to maintain weight loss, because the lower the RMR, the harder it is to lose weight

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25
Q

How is osmolality calculated?

A

2x (Na+ plus K+) + Urea + Glucose

26
Q

What hormone, produced by adipose tissue, signals our body to stop eating and tells us that our fat stores are adequate?

A

Leptin

27
Q

What are the 4 key features of the “metabolic syndrome”?

A

High triglycerides

High BP

Low LDL

Insulin resistance

28
Q

Name a drug that enhances glucose excretion by the kidneys

A

SGLT2 inhibitors e.g. empagliflozin, canagliflozin

29
Q

What causes insulin resistance?

A

Accumulation of ectopic fat and an increase in the amount of FFAs in the circulation, as well as increased inflammatory markers (e.g. CRP) results in inhibition of insulin via serine kinases responsible for phosphorylation of Insulin Receptor Substrate-1 (IRS-1)

This leads to a reduction in the insulin-stimulated glycogen synthesis due to reduced glucose transport

Specific factors are numerous and include…

  • intra-abdominal obesity
  • inactivity
  • genetics
  • medication
  • smoking
  • foetal malnutrition
  • PCOS
  • Aging
  • etc. etc.
30
Q

Name each of the following drug types based on the prefix/suffix

Gli-

  • tide
  • gliptin
  • gliflozin
A

Gli- = sulphonylureas (glimepiride, glibenclamide etc.)

  • tide = GLP-1 agonists (exenatide)
  • gliptin = DPP-4 inhibitors (vildagliptin, sitagliptin etc.)
  • gliflozin = SGLT-2 inhibitors (canagliflozin, empagliflozin etc.)
31
Q

Is beta cell dysfunction reversible?

A

Some evidence suggests yes!

One study…

  • 11 people with T2DM
  • 2 months reduced food intake of 800 calories a day
  • 10 retested after 3 months, 7 classed as free of diabetes
  • Exhibited near normal post-prandial insulin production
32
Q

What medications can cause erectile dysfunction?

A

Anti-hypertensive drugs - commonly thiazides and beta blockers, uncommonly CCBs, ACEIs

CNS drugs - antidepressants/tricyclics/SSRIs, tranquilizers, sedatives, analgaesics

33
Q

What are some of the microvascular complications of diabetes?

A

Retinopathy

Nephropathy

Neuropathy

Erectile dysfunction

34
Q

What are the short term complications of Diabetes?

A

Mainly Type I - hypoglycaemia, DKA

Mainly Type II - Hyperosmolar Hyperglycaemic State (HHS)

35
Q

Sulphonylureas: side effects

A

Hypoglycaemia

Weight gain

GI upset, headaches

SUs should be conisdered as an add-on therapy to Metformin, or as a first line T2DM treatment in those who are underweight/cannot tolerate Metformin

36
Q

What are some of the severe complications associated with DKA?

A

ARDS

Severe cerebral oedema

Acute gastric dilation, resulting in possible aspiration

Hypokalaemia

37
Q

Where are SGLT-2 receptors found?

A

In the proximal convoluted tubule in the kidney. Inhibiting them means glucose cannot be reabsorbed and is passed out in the urine

38
Q

What drug helps with weight loss when given as an adjunct to diet modifications? What is the common side effect?

A

Orlistat - inhibits the action of lipases and blocks the absorption of dietary fat

This leads to steatorrhoea, as up to 1/3 of dietary fat is excreted in faeces

39
Q

What are the different types of eye pathology seen in diabetic patients?

A

Diabetic retinopathy

Cataracts - clouding of the lens

Glaucoma - increase in fluid pressure in the eye, leading to damage of the optic nerve

Acute hyperglycaemia - (reversible) visual blurring

40
Q

What are some common precipitating factors of DKA?

A

Infection

Illicit drugs and alcohol

Non-adherence with treatment (main cause)

Newly diagnosed diabetes

41
Q

DKA pathophysiology: the activation of stress hormones due to absolute/relative insulin deficiency results in what 4 events?

What does this lead to?

A
  1. Increased lipolysis, resulting in acidosis
  2. Decreased glucose utilisation, 3. Increase proteolysis, and 4. Increased glycogenolysis, all resulting in Hyperglycaemia
42
Q

Lactic Acidosis: clinical and laboratory findings

A

Clinical

  • Hyperventilation
  • Mental confusion
  • Stupor or coma if severe

Biochemical

  • reduced bicarbonate
  • raised anion gap [(Na + K) - (HCO3 + Cl)]
  • glucose - variable, may often be raised
  • raised phosphate
  • no ketonaemia
43
Q

What is MODY? What is it commonly misdiagnosed as?

A

Maturity Onset Diabetes in the Young

  • autosomal dominant mutations resulting in impaired insulin production
  • non-insulin dependant
  • age of onset usually <25 years old
  • multiple types, but two distinct forms (GCK (MODY2) and Transcription Factor (MODY3)). HNF1A are sensitive to SUs, and GCKs don’t require treatment

Commonly misdiagnosed as T1 or T2 DM

44
Q

What are some of the longer term micro and macrovascular complications associated with Diabetes?

A

Macrovascular

  • TIAs and stroke
  • Angina, MIs and cardiac failure
  • Peripheral vascular disease

Microvascular

  • Diabetic retinopathy
    • non-proliferative
    • proliferative
    • macular oedema
  • Microalbuminuria, Macroalbuminuria, Endstage renal disease
  • Erectile dysfunction
  • Autonomic neuropathy
  • Peripheral neuropathy
  • Osteomyelitis
  • Amputation
45
Q

DKA - classical biochemical presentation

A

Glucose

  • median around 40 mmol/L (normal should be under 6)
  • anywhere from 10 to 100 (lower range known as euglycaemic ketosis)

Potassium

  • usually raised above 5.5 mmol/L
  • beware the low normal - K is taken into cells when insulin is given

Creatine

  • Often raised

Sodium

  • Often low

Lactate

  • Very commonly raised

Blood ketones

  • usually raised above 5 mmol/L
    • blood measure is beta-hydroxybutarate
    • urine is acetoacetate

Bicarbonate

  • above 10 mmol/L in most severe cases

Amylase

  • Very frequently rasied - does not necessarily mean pancreatitis
46
Q

Name some drugs that decrease insulin resistance and reduce hepatic glucose output

A

Metformin

TZDs (pioglitazone)

47
Q

Name some drugs that increase the release of insulin

A

Sulphonylureas

Incretin mimetics i.e. GLP-1 agonists

DPP-4 inhibitors

48
Q

What is the immediate treatment of a hypoglycaemic episode?

A

consume 15-20grams of glucose or simple carbohydrate

recheck blood glucose after 15 mins. If hypoglycaemia persists, repeat above.

Once BG is under control, eat a small snack if the next planned meal is more than 1-2 hours away

If severe:

  • 1 mg Glucagon injected into buttock/arm/thigh
49
Q

Of all the approaches to take when trying to lose weight, what appears to be the single most effective in terms of total weight lost?

A

Diet

50
Q

DKA - clinical presentation

A

Osmotic related

  • Thirst and polyuria
  • Dehydration

Ketone body related

  • Flushing
  • Vomiting
  • Abdo pain and tenderness
  • Breathlessness - Kussmaul’s breathing
  • Ketone-smelling breath (in some)

Associated conditions

  • underlying sepsis
  • gastroenteritis
51
Q

How is beta cell dysfunction brought about?

A

Initially beta cells compensate for increasing insulin resistance, however eventually their function declines over time and blood glucose levels increase

Insulin resistance leads to glucotoxicity (hyperglycaemia) and lipotoxicity (excess FFAs, TGs etc.), both of which result in a decline in beta cell function

52
Q

Describe the “therapy staircase” of T2DM management

A

1st step - diet and exercise

2nd step - oral monotherapy

3rd step - oral combination of therapies

4th step - injectable and oral therapy

53
Q

As well as leptin, name some other substances that arise from adipose tissue

A
  • adiponectin
  • CRP
  • TNF alpha
  • IL-6
  • PAI-1
  • Oestrogen
  • Cortisol
  • FFAs
54
Q

Compare DKA and HHS in terms of the following:

  • Age
  • Cause
  • Type of Diabetes
  • Precipitant
  • Mortality
  • Treatment
A

DKA

  • younger individuals
  • insulin deficiency
  • Type 1 DM
  • Insulin omission
  • <2%
  • Insulin

HHS

  • older individuals
  • Diuretics and/or steroids. Also fizzy drinks
  • Type 2 DM
  • new diagnosis, infection
  • 10 to 50%
  • Diet/OHA/Insulin(may not require insulin)
55
Q

Lactic Acidosis: treatment

A

Treat underlying condition - fluids and antibiotics

Withdraw offending medication if this is the cause

56
Q

What is the name of the cell type that provides a lot of the same functions as macrophages but is found in fat tissue?

A

Adipocytes

57
Q

What are the 4 types of neuropathy? Give an example of each

A

Peripheral - pain/loss of feeling in feet, hands, sensitivity to touch, loss of balance etc. (associated with Charcot’s foot)

Autonomic - changes in bowel/bladder function, sexual response, sweating, heart rate, BP etc.

Proximal - pain in the thighs, hips or buttocks leading to leg weakness

Focal neuropathy - sudden weakness in one nerve or group of nerves causing muscle weakness/pain

58
Q

Define diabetic ketoacidosis (DKA)

A

DKA is a disordered metabolic state that usually occurs in the context of an absolute or relative insulin deficiency, accompanied by an increase in the counter-regulatory hormones i.e. glucagon, adrenaline, cortisol and growth hormone.

By definition, DKA can occur in both T1DM and T2DM, however more commonly occurs in T1

59
Q

How are ketones monitored?

A

Blood ketone testing for beta-hydroxybutarate

Urinary ketone testing for acetoacetate

60
Q

Explain the general concept of Insulin resistance in comparison to normal insulin activity

A

Normal activity - insulin binds to receptors triggering the production of glucose transport proteins and allowing glucose into the cell

Insulin resistance - receptors aren’t as responsive to insulin, meaning less glucose is brought into cells and instead remains in the blood stream

61
Q

Metformin is a brilliant drug! BUT! What side effects does it have?

How are these avoided?

A

GI side effects (most common, seen in up to 25% of patients) - anorexia, nausea, vomiting, diarrhoea, abdo pain

Interference with Vit B12 and folic acid absorption

Lactic acidosis - 1/100,000, but can be fatal

Liver failure - also v. rare

Rash

“Start low, go slow”

Year 2 - Endocrine (8 decks)

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