Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

YEAR 2 SEMESTER 2 > ENDOCRINOLOGY WK 4 > Flashcards

ENDOCRINOLOGY WK 4 Flashcards

1
Q

what hormonal systems and hormones are involved in obesity

A

Regulation of body weight – Hypothalamus
- Efferents Controlling body weight ‘the well-connected hypothalamus’

o	Satiety (default is to eat)
o	Pituitary
	Gonads – sex steroids
	Adrenal cortex – cortisol
	Thryoid – thyroxine
	Growth hormones

o ANS
 PNS – pancreatic B cells – insulin
 Sympathetic – adrenal medulla – adrenaline

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

what afferent signals tell us when to stop eating

A
  • Insulin
  • Gastric distention in small bowel (Ghrelin, PYY, GLP1 etc)
  • Hormones from fat tissue (Leptin and TNFa)
  • Conscious control – willpower
  • Substrate supply protein = CHO>Fat
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

leptin role and as treatment

A
  • Thought that it could turn off appetite in the past
  • Leptin concentrations in blood corresponds with obesity (adiposity)

Leptin treatment for obesity
- Ineffective when (leptin) is high – idiopathic obesity
- Effective when leptin is low
o Leptin deficiency rare
o Anorexia nervosa
o Lipodystrophy
- However doesn’t work on normal obese people as they have ‘ leptin resistance’

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

actions of leptin

A
  • Satiety
  • HPG axis is downregulated – stops…
    o Puberty
    o Fertility
  • HPA axis downregulated
  • HPT axis downregulated
  • Peripheral actions??
    o Adipocytes, pancreatic islets, immune cells…
    PROBABLY MOST IMPORTANT IN LOW ENERGY STATES AS SURVIVAL SIGNAL
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are causes of secondary obesity

A
  • Hypothyroidism
  • Cushing’s syndrome – usually iatrogenic
  • Hypothalamic disease
  • Others
    o Drugs (lestrogen, beta blockers, tricyclic antidepressants, sodium valproate)
    o Insulinoma, GH deficiency
    o Genetic disorders eg Prader Willi syndrome, leptin deficiency etc etc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

spotting endocrine disorders in obese patients

A 
History
-	Always obese/ age of onset
-	Periods irregular/ headache/ thirst, polyuria
-	Diet, eating patern, alcohol, exercise
-	Drugs
-	Complications and effects on lifestyle
Examination
-	Features of cushing’s, hypothyroidism, hypothalamic disease, syndromes
-	BP
Investigations
-	TFTs
-	Blood glucose
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

how is obesity and diabetes linked

A
  • If you are genetically suscpetible and put on weight = resistant to insulin
  • Need to make a lot more insulin to stop you from becoming diabetic
  • Puts a strain on the pancreas B cells
  • B cells become tired and start turning off/ dying
  • Once you’ve lost ~60% of B cells you develo diabetes
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

fat distribution - apple vs pear

A 
Apples
-	Androgens
-	Glucocorticoid
o	Central
o	Visceral
o	Android
-	High risk
Pears
-	Oestrogens
o	Peripheral 
o	Subcutaneous
o	Gynoid
-	Low risk
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

why does central obesity lead to insulin resistance?

A
  • Fat in the belly is broken down and free fatty acids are poured straight to the liver
    o Turned into lipoproteins
    o Secreted into harmful pattern of lipids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

why is fat essential for health?

A

Fat tissue is essential for health!!
- Able to comfortably store demands in a safe place til it’s needed
1- Free fatty acids excess to energy requirements
2- Adipose tissue triglyceride storage capacity
3- Extra-adipose fat stores

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

what happens if you’re potential to expand adipose tissue is low

A

Some people have more potential to expand adipose tissue than others
- If you cannot expand you adipose tissue and it’s stored in small amount in your waist this is bad and can lead to daibetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

adipokines - what secretes them, how do they relate to diabetes

A
  • Secreted from adipocytes or macrophages in adipose tissue
  • Manipulation in mice demonstrate potent effects on insulin sensitivity in other tissues
  • Correlated with insulin sensitivity in other tissues in humans
  • Many candidates published – variabel importance
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

adipose tissue - endocrine effects

A

Fat tissue can take different steroid hormones and converts them to other steroid hormones to activate/ deactivate them

  • Probs why fat tissue inc. risk of breast cancer
  • As it can take androgens (male type hormones from adrenal gland) and converts to oestradiol
  • In post menopausal women adipose tissue is a signif. Contributer to circulating amounts of oestrogen – promotes breast cancer
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

what are the endocrine consequences of obesity

A

Altered steroid metabolism in adipose tissue
- Increased oestrone and oestradiol
o Hirsutism and infertility
o Hormone-sensitive cancers
- Increased reactivation of cortisol from cortisone

Altered substrate flux and adipose inflammation
-	Insulin resistance
o	Hyperglycaemia
o	Dyslipidaemia, fatty lover
o	Subfertility

Altered hypothalamic function
- Anovulatory menstrual cycles
o Subfertility

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

strategies for manipulating body weight

A
  • New drugs targeting appetite control/ satiety centres in CNS
  • Altering adipocyte metabolsim
    o Turning on fat burning by activating brown/beige fat
  • Bariatric surgery
    o Medically mimicking surgery (eg combination hormones)
    o Gut microbiota
  • Public health measures
    o Education/ laws/ town planning
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

insulin - where is it secreted, what kind of hormone is it, what does it do

A
  • Hormone secreted in pancreas (islets)
  • Anabolic hormone
  • Essential for fuel storage and cell growth
  • Promotes uptake of glucose into cells for energy
  • Prevents breakdown of fat and protein
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

whats the structure of pancreatic islets

A
  • Beta cell are most prominent = manufacture insulin
  • Alpha cells manufacture glucagon
  • Delta cells = make somatostatin
  • F cell = make oancreatic polypeptide
    Through the islets there are capillaries for hormones to drain into
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

somatostatin - role, therapeutic uses

A
  • An inhibitory hormone which switches off production of other hormoens
  • And so is used therapeutically to treat hormone syndromes (making too much of hormone) eg acromegaly, neuroendocrine tumours
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

what does a tumour of islets lead to

A

If you have tumour of islets that makes lots of pancreatic polypeptide = lots of diarhhoea

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

structure of insulin

A

Alpha subunit and beta subunit that are linked via disulphide bonds by c-peptide

  • Prior to release of insulin free c-peptide is cleaved away by B-cell peptidases
  • Converting pro-insulin to insulin
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

explain the process of coupled insulin secretion and glucose influx

A

GLUT2 allows to go from interstitium into the B-cells without insulin (aka insulin indpendant)

  • It’s concentration dependant so more glucose in interstitium the more in the B-cells
  • Glucose is processed in the mitochondria to produce ATP

ATP dependant K Channel

  • When open allows K from cell to pass out into intersttitium along the conc. Gradient
  • ATP closes the channel
  • Which allows the conc. Of K in the cells to rise
  • Which results in membrane depolarisation
  • Which in turn closes a voltage gated calcium channel
  • This will affect the levels of Ca in cells leading to exocytosis and release of insulin into the blood

So release of insulin is dependant on influx of glucose into the cell
- Due to production of ATP

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

secretion of insulin - when and how

A
  • Biggest surges of insulin occur immediately after geating food as glucose levels rise most in this time
  • In response to eating food insulin secreted in dual phase…
    1- Intial spike occurs quickly, through the release of insulin that’s already manufactured in beta cells in secretory granules
    2- Granules become depleted and beta cells make new insulin to augment insulin repsose (2nd phase)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

c-peptide as a clinical marker

A

insulin secretion in people with diabetes

- Because diabetics inject insulin which does not contain c-peptide and so this doesn’t change endogenous amounts

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

insulin - secretion pathway and sites of action

A

Insulin from pancreas
- Secreted into portal vein (in high concentrations in portal circulation > systemic)
o Important bc/ giving exogenous insulin this goes into systemic circulation
o In order to get physiological levles into portal circulation you must give supra-physiological amounts into systemic circulation
- Acts first on LIVER
- Passes through liver into systemic circulation (through hepatic vein)
- Acts on MUSCLE (skeletal) and FAT (adipose)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

principle actions of insulin

A
  • Inc. glucose uptake in FAT and MUSCLE
  • Inc. glycogen storage in LIVER and MUSCLE
  • Inc. amino acid uptake in MUSCLE
  • Protein synthesis
  • Inc. lipogenesis in ADIPOSE TISSUE
  • Dec. gluconeogenesis from 3-Carbon precursors
  • Dec. ketogenesis (in LIVER)
  • Inc. cell proliferation
  • Dec. apoptosis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

how does insulin get into cells

A

Insulin causes translocation of GLUT 4 to cell membranes
- GLUT 4 prodominently in muscle and fat cells
GLUT = Glucose Transporter
- This allows insulin-dependant glucose uptake into cells
- Insulin binds to receptor and second messenger cascade cause translocation of GLUT 4

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

glucose homeostasis - sources of glucose (in blood)

A
  • Digested carbohydrates – broken down in gut and passes into portal circulation
  • Resevoir of glycogen in the liver – in times of need broken and down and released into blood
  • In starvation (glycogen depleted) – liver makes glucose via gluconeogenesis from fat and muscle tissue and releases it into the blood
  • Kidneys can do a bit of gluconeogenesis also
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

brains glucose demand

A

o Brain has higest glucose demands
o Has an insulin independent mechanism of glucose transport into brain cells
o GLUT3 works wihtout insulin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

glucose metabolism in the liver - what actions and insulin and glucagon trigger what?

A

Glycogenolysis/ glycoegenese glucose

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

3-carbon precursors for gluconeogenesis

A
  • Alanine (from ingested protein)
  • Pyruvate (from muscle protein)
  • Lactate (from muscle glycogen)
  • Glycerol (from fat)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

insulin deficiency causes

A
  • Removal of pancreas
  • Process leading to destrcution of the islets in pancreas
    o Commonest cause of this is type 1 diabetes
    o Autoimmune destructive process
    o Infiltration of cytotoxic lymphocytes into the islets of pancreas
     Aka insulitis
  • Toxins destroying islest of the pancreas
    o Alcohol -> pancreatitis
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

insulin resistance causes

A

Severe insulin resistance syndromes (don’t need to know these)
- Vv rare genetic syndromes caused by single gene defects…
o Leprechaunism
o Rabson-mendenhall syndrome
o Type A insulin resistance
Due to central obesity
- Central adiposity is much more harmful than peripheral adiposity
- In part due to various hormones released from adipose tissue
- Mechanisms not understood but probs effect multiple parts of insulin resistance cascade
Other
- Acromegaly (Growth hormone excess)
- Pheochromocytoma – adrenal tumour
- Cushing’s syndrome – cortisol excess

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

4 ways to diagnose diabetes

A
  • Fasting glucose >7.0mmol/L
  • Random glucose level of >11.1mmol/l
  • Glucose tolerance test >11.1
  • HbA1c >48mmol/mol
  • If patient is asymtpomatic, the same test should be repeated to confirm diagnosis of diabetes
    o Can do it next day or later that day
    o Usually arranged a week-2 weeks later
    o Bc/ errors can happen and diagnosis is life changing – got to be sure
  • Do not delay urgent care waiitng for a second test
    o Eg if someone has ketoacidosis etc
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

glycated haemoglobin (HbA1c) - what is it, what does it reflect, how and why do we measure it

A
  • Rate formation of glycated haemoglobin is directly proportional to ambient blood glucose concentration
  • Reflects integrated blood glucose (BG) concentrations during lifespand of erthropcyte (120 days)
  • Blood sample can be taken at any time of the day, irrepective of food consumption
  • Gives us a snap shot of what blood sugar levels have been doing over the past ~3 months
    o Aka the lifespan of a RBC
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

situations in which HbA1c should NOT be used as diagnostic test

A
  • Rapid onset diabetes
  • Pregnancy
  • Conditions where red cell survival may be reduced
    o Haemolytic anaemia
    o Severe blood loss
    o Splenomegaly
    o Antiretroviral drugs
    o Haemoglobinopathy
  • Increased red cell survival
    o Splenectomy
  • Renal dialysis
  • Iron and vit B12 deficiency
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

oral glucose tolerance test

A
  • Used to assess state of glucose tolerance
  • 75g oral glucose load
  • No restriction or modification of carbohydrate intake for preceding 3 days
  • fast overnight
  • Test is performed in morning – seated, no smoking
  • Blood samples for plasma glucose taken at 0hrs and 2 hrs
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

impaired glucose tolerance test

A

fasting plasma glucose - <7.0mmol/l
2 hrs after 75g oral glucose load - 7.8-11.0 mmol/l

  • Affects 20% of population aged 40-65 yrs
  • Inc. mortality from cardiovascular disease (2x)
  • Natural history – 15% develop diabetes in 5 yrs, 15% return to normal
  • Check fasting plasma glucose annually
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

impaired fasting glucose (fasting hyperglycaemia) on a oral glucose tolerance test

A

fasting plasma glucose - 6.0-6.9 mmol/l

  • Intermediate state between normal glucose metabolism and diabetes
  • Impaired glucose tolerance often present also (but not always)
  • Found in 5% of population and prevelance increases with age
  • Inc. risk of vasuclar complications
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

pre-diabetic state on a oral glucose tolerance test and HbA1c

A

fasting blood glucose - 6.0-6.9mmol/l
2hr OGTT glood glucose - 7.8=11.0mmol/l
HbA1c - 42-47 mmol/mol

40
Q

genetic component of type 2 diabetes

A
  • Polygenic disorder
  • Genome-wide assoc. studies identified >400 gene variants assoc. with inc. risk of T2 diabetes
  • Most relate to beta cell function or mass, rather than obesity/insulin resistance
  • 40% of overall risk of type 2 is determined by genetic factors
41
Q

age as a risk factor of type 2 diabetes

A
  • Beta cell function reduces with age
    o Pancreas less able to produce insulin
    o Beta cells have died off (ageing/ environment)
  • Obesity increases with age
42
Q

glucose effect on beta cells

A
  • Beta cells making more insulin but not enough to counteract higher glucose levles
  • Progressively beta cell become less effective
  • Higher glucose = toxic effect on beta cells that impairs insulin release
  • Sugar levels go up even higher
  • At any of these stages this can be reversed
43
Q

clinical presentation of type 2 diabetes

A
  • Asymptomatic – found on routine screening
  • Thirst. Polyuria. polydipsia (osmotic symptoms)
    o Due to glucose in urine acting as a diuretic – make more urine
    o If you choose to drink high glucose drinks this adds to the problems
  • Malaise, chronic fatigue
  • Infections eg thrush (candidaiasis); boils
    o Because glucose in urine
  • Blurred vision
    o Due to osmotic drag – fluid dragged into the lenses of the eye which distorts the shape of the lense resulting in blurred vision
  • Complications as presenting problem (eg retinopathy, neuropathy)
44
Q

target organ damage in type 1 vs type 2 diabetes

A
  • Heart, kidney, feet, eyes, arteries
  • Cardiovascular complications more common In type 2 than type 1
  • Type 1 is developed at a younger case
    o Have diabetes much longer
    o Microvascular complications have longer to develop
     Retinopathy etc
45
Q

other medical disorders assoc. with type 2 diabetes

A
  • Obstructive sleep apnoea
    o Central obesity assoc.
  • Polycystic ovarian disease
    o Manifestation of central obesity and insulin resistance
  • Hypogonadotrophic hypogonadism in men
    o More common bc/ men don’t go through menopause but testosterone levels diminish
    o Central obesity inc. rate of decline
    o Probs to do with adipokines feeding back into pituitary and inhibiting gonadotrophin release
    o Element of adipose tissue enhancing the conversion of testosterone to oestrogen which again feedbacks and inhibits gonadotrpophin release
  • Non-alcohol fatty liver disease
    o Central abdominal fat goes into the liver
    o Inc. risk of cirrhosis (8X higher in diabetes) and hepatocellular carcinoma (3x more common)
46
Q

type 1 diabetes symptoms at presentation

A

More acute onset, not usually asymptomatic

  • Polyuria, thirst
  • Fatigue, malaise
  • Weight loss
  • Blurred vision
  • Nausea, vomiting
47
Q

type 1 diabetes presentation

A
  • Usually presents in childhood, adolescence or young adulthood
  • Can present at any age
  • Short history (weeks) of florid osmotic symptoms and rapid weight loss, ketonuria/ ketonaemia is usually present
  • High risk of metabolic decompensation – ketoacidosis
    o Can be the cause of acute presentation
48
Q

pathogenesis of type 1 diabetes

A
  • Genetic predisposition – HLA haplotypes (HLA-DR and HLA_DQ) as risk of alleles
    o All to do with the immune system
  • Environmental trigger
    o Viral infection
    o Chemical toxin
  • Autoimmune mechanism activated – can detect antibodies in blood GAD, IA2 and/or ZnT8
  • Destruction of pancreatic beta cells
    o Can take many years
    o Make sit harder to figure out what the trigger actually is
    o Once down to 80% of beta cells are destroyed = hyperglycaemia / symptoms
49
Q

environmental risk of type 1 diabetes

A
  • More likely to get type 1 diabetes in southern europe compared to nothern europe
  • Maybe because some viruses live better in colder climates (but don’t know)
50
Q

autoimmune disorders assoc. with type 1 diabetes

A
  • Thryoid disease
  • Pernicious anaemia
  • Coeliac disease
  • Addison’s disease
  • Vitiligo
51
Q

impact of type 1 diabetes on daily life

A 
-	Hypoglycaemia
o	Driving, employment
-	Risk of ketoacidosis
-	Pregnancy 
o	Hyperglycaemia inc risk of miscarriage, fetal abnormalities, large babies
-	Childhood and adolescense
-	Complications
52
Q

secondary diabetes (not type 2)

A

Diabetes secondary to other health problems

  • Pancreatectomy
  • Trauma
  • Tumours
  • Chronic pancreatitis – alcohol excess
  • Cystic fibrosis
  • Steroid treatment
53
Q

monogenic diabetes or Maturity-onset diabetes of the young

A

Type 1 and 2 are polygenic
There are number of singular gene mutations that lead to diabetes
Features…
- Early-onset diabetes
- Not insulin-dependant diabetes
- Autosomal dominant inheritance
- Obesity unusual
- Caused by a single gene defect altering beta-cell function
- 1-2% of type 2 diabetes
o Often not diagnosed and misdiagnosed as Type 2

If you get correct genetic diagnosis you can tailor the treatment to the patient

54
Q

home blood glucose monitoring (finger prick glucose test) for glycaemic control

A
  • Demonstrates control throughout the day
  • Identifies hypoglycaemia
  • Provides info to adjust insulin dose
  • Allows manipulation of insulin dose during
    o Intercurrent illnes
    o Travel, sport, other activites
  • Assists self-control of diabetes – improves glycaemic control
55
Q

continuous glucose monitoring system (CGMS) for glycaemic control

A
  • Wireless sensory and monitor communcation
  • Hypo- and hyperglycaemia alarms
  • ‘real time’ glucose values
56
Q

HbA1c for glycaemic control

A
  • Checked at the time of a visit to a diabetes clinic or GP surgery
  • Allows evaluation of
    o Efficacy pf therapeutic regimen
    o Patient’s adherence to treatment
    o Risk of developing diabetic complications
  • Enhances clinical decision-making if available at time of clinical consultation
57
Q

aims of treatment of diabetes

A
  • To restore disturbed metabollism to near normal
  • To prevent, delay diabetic complications
  • To educate, motivate and empower diabetics to achieve effective self-management
58
Q

aims of dietary management in diabetes

A
  • To achieve good glycaemic control
  • To reduce hyperglycaemia and avoid hypoglycaemia
  • To ensure adequate nutritional intake
  • To assist with weight management
  • To avoid aggravating diabetic complications
59
Q

treatment of diabetes assoc. with obesity

A 
Weight reducing diet
-	Reduce/eliminate refined carbs and saturated far 
-	Restrict total calories (portion size)
This…
-	Inc. insulin sensitivity
-	Lower blood glucose
-	Lower triglycerides/ LDL-cholesterol

Diabetes doesn’t only effect glucose metabolism – also effects protein and lipid metabolisms

60
Q

how to stop progression of impaired glucose tolerance (IGT) to type 2 diabetes

A
  • Lifestyle changes with dietary modification and exercise delays progression of glucose intolerance (2 hr value of glucose 7.8-11.1mmol/l)
  • Progression from IGT to type 2 diabetes over 6 years is reduced by 40-60%
  • It is vv difficult to maintain lifestyle changes over long periods
61
Q

diabetes and diet - glycaemic index

A
  • Post-prandial rise in blood glucose is influenced by amount and source of carbohydrate
  • GLYCAEMIC INDEX (GI) is a measure of change in blood glucose following ingestion of a particular food
  • Different carbohydrate-containing foods can be ranked by their effect on post-prandial glycaemia
  • Low GI foods produce slow, gradual rise in blood glucose after ingestion (avoids a big insulin spike)
  • Low GI foods starchy foods (rice, spaghetti, granary bread, porridge) and pulses like beans and lentils
62
Q

dietary treatment of type 1 diabetes

A
  • At diagnosis insulin should be started immediately!
  • Dietary modification requires restriction of refined sugar (as it reduces insulin requirement) and saturated fats
  • Diet is weight-maintaining for most people
  • Insulin dosage adjustment is based on carbohydrate content of meals
  • Structured education programmes are available
  • Other lifestyle changes (regular exercise) are supplementary
63
Q

what are the main 3 therapeutic targets for diabetes drugs

A

Insulin resistance

  • One mechanism in insulin resistance is adipocyte depot
  • Insulin resistance dec. glucose uptake by muscle
  • Insulin resistance Inc. hepatic glucose production (liver makes glucose)

B-cell dysfunction

  • Islets as a target
  • Can promote insulin release in type 2 diabetes if there’s some islet function left

Kidneys (a new therapeutic target)

  • When you pass urine you pass glucose
  • Can promote release of more glucose through urine
64
Q

oral hypoglycaemic agents -indications and contraindications

A

Indications
- Type 2 diabetes (if diet alone inadequate)
- Insulin sensitissers in combination with insulin in Type 1 diabetes
Contraindications
- Ketoacidosis
- Severe intercurrent illness

65
Q

sulphonylureas (eg glipizide, gliclazide)

A
  • Stimulate secretion of endogenous insulin
  • Used in non-obese patients may be insulin-deficient
  • Used as monotherpay or in combination with metformin, glitazone or insulin
  • Choice of sulfonylurea is based on duration of action and method of elimination
  • Promote weight gain
  • Main adverse effect is hypoglycaemia
66
Q

biguanide (metformin)

A
  • Decreases hepatic glucose production
  • Increases insulin sensitivity in muscle
  • Encourages weight loss
  • Effective as monotherapy or in combination with sulfonylurea, glitazone, or insulin
  • Side-effects nausea and diarrhoea
  • Contraindicated in renal impairment (risk of lactic acidosis)
67
Q

glucose prandial regulators (glinides) - not used alot

A

Repaglinide (meglitinide)
Nateglinide (amino acid derivative)
- Stimulate secretagogous – direct effect on beta cells
- Stimulate rapid endogenous insulin release when given with meals
- Side-effect weight gain and hypoglycaemia (rare)
- GI side effects common

68
Q

glucose inhibitors - don’t use alot

A

Eg acarbose, miglitol

  • Delay digestion of carbohydrate and slow down postprandial absorption of glucose
  • Do not cause weight gain
  • Limited efficacy; can be used in combination
  • GI side-effects common
69
Q

PRAR gamma agonists

A
  • Activation in fat reduces insulin resistance in liver and muscle
  • Lower plasma free fatty acids
  • Reduces hepatic glucose output
  • Increases glucose uptake into muscle
70
Q

thiazolidnediones

A

EG pioglitazone

  • Slow onset of action – take 2-3 motnhs to achieve max. effect as work at level of the nucleus
  • Promote weight gain – but redistribute body fat to reduce visceral depot
  • Contraindicated in congestive cardiac failure, hepatic impairment, may cause fractures
71
Q

“incretin effect’

A

Plamsa insulin responses to oral and intravenous glucose
- Secretion of insulin is greater in response to oral glucose > IV glucose
- Hormones in GI tract that inc. insulin response to insulin
o Incretins

72
Q

glucagon-like peptide-1 (GLP-1)

A
  • Potent insulintropic hormone (incretin) is released in response to meals
  • Rapidly degraded in plasma by enzyme Dipeptidyl Peptidase 4 (DDP-4)
  • Plasma GLP-1 is lower in people with impaired glucose tolerance (IGT) and type 2 diabetes compared to healthy non-diabetic subjects
73
Q

GLP-1 physiological effects suppressing glucagon secretion

A
  • Upon ingestion of food secreted from the L-cells in the intestine
  • Stimulates glucose-dependant insulin secretion
  • Slows gastric emptying – slows spike in glucose
  • Reduces food intake- appetite suppressor
  • Improves insulin sensitivity
74
Q

what are therapeutic forms of GLP-1

A
  • Incretin mimetic, synthetic exendin-4 (exenatide)
  • GLP-1 analogue (liraglutide)
  • DDP-4 inhibitors (gliptins)
    o These usually breakdown GLP-1 so promotes it if inhibited
75
Q

Exenatide - a synthetic form of GLP-1

A
  • Synthetic form of exendin-4
  • First isolated from the salivary secretions of the Gila monster
  • Found circulating as a meal-related peptide, with GLP-1 actions
76
Q

incretin mimics

A
  • Act like a GLP-1 peptide
  • Have to be given by injection
    o You can have a weekly injection
  • Promote weight loss
  • Given in combination with either metformin or sulfonylurea
  • Main side-effect is nausea
  • Hypoglycaemia is rare
77
Q

gliptins

A

Eg sitafliptin, vildagliptin

  • DDP-4 inhibitors – inhibit degradation of incretin hormones and enhance their actions
  • Oral route – good for older patients
  • Taken in combo
  • Prodcue modest reduction in HbA1c
  • Weight neutral
  • Few side-effects
78
Q

kidney as a target for diabetes treatment - what drug and how does it work

A

Empaglifozin
- acts as a glucuretic to removes glucose that would otherwise be reabsorbed
Sodium-glucose cotransporter-2 (SGLT2) inhibitors
- class fo FDA approved drugs to lower blood sugar in type 2 diabtes
- eg canagliflozin, dapaglifozin, empagliflozin

79
Q

indications for insulin therapy in type 2 diabetes vs type 1

A

INDICATION FOR INSULIN THERAPY in type 2 diabetes

  • persistently elevated blood glucose and HbA1c on max doses of anti-diabetic drugs
  • symptoms of hyperglycaemai and/or infections (eg candidiasis)
  • non-fasting ketonuria

in type 1 diabetes
- if ketosis-prone

80
Q

insulin therapy for type 1 diabetes - problems!

A
  • insulin has to be given by injection
  • biological action is variable as insulin absorption is influenced by many factors (site of injection, ambient temperature, exercise, etc
  • insulin has to be given several times a day
  • insulin regimens are often complicated
81
Q

types of insulin that can be given

A

Short-acting
- soluble
Intermediate-acting
- isophane

82
Q

insulin analogues what are they and what are the types

A
  • substitution of a single amino acid in the insulin chain
  • alters absorption characteristics of insulin
    time actions profile is modified by minor changes in amino acid sequence of insulin molecule…
    Fast-acting
  • insulin lispro
  • insulin aspart
  • insulin glulisine
    long-acting
  • insulin glargine
  • insulin determir
83
Q

what type of insulin is given in type 1 vs type 2 diabetics and when

A

Mixtures of the 2 are given to type 2 diabetics and only get 2 injections a day

In type 1 who can’t make insulin are usually on short-acting insulin with meals (3x) and then 1 long acting per day so 4 a day

84
Q

what are the 3 different insulin regimes commonly used

A

Basal-bolus (multiple injections)

  • short-acting or fast-acting insulin before meals
  • intermediate-acting ot long-acting insulin once daily

Twice Daily
- soluble or fast-acting and isophane (NPH) insulins combined – free-mixing or fixed mixture

Once daily
- intermediate-acting or long-acting insulin, combined with anti-diabetic drugs (Type 2)

85
Q

insulin routes of administration

A

INSULIN ROUTES OF ADMINISTRATION

  • subcutaneous > syringes, pens, pumps
  • intrapulmonary > inhaler
  • intravenous, intramuscular > injection (emergency)
  • intraperitoneal > dialysate (renal failure)
  • transplanted islets
86
Q

side effect of insulin injection

A

Lipohypertrophy at insulin injection sites

  • unsightly
  • slows insulin absorption
  • resolves if site avoided
  • Hypoglycaemia
  • people eat more if they are hypoglycaemic = weight gain
  • lipodystrophy at injection site
  • peripheral oedema
  • insulin antibody formation (animal insulins)
  • local allergy
87
Q

hypoglycaemia - signs and symptoms

A
  • palpitations
  • blurred vision
  • trembling
  • dizziness
  • sweating
88
Q

causes of insulin induced hypoglycaemia

A
  • too much insulin administration for need
  • inadequate consumption of food
  • increased physical exercise
  • alcohol (without food)
    o as alcohol switches of hepatic gluconeogenesis
89
Q

risk factors for severe hypoglycaemia

A
  • duration of diabetes, older age, female
  • impaired awareness fo hypoglycaemia
  • history of previous severe hypoglycaemia
  • strict glycaemic control
  • sleep
90
Q

treatment of hypoglycaemia (mild vs severe)

A

MILD (self-treated)
- oral fast-acting carbohydrate (10-15g)
o glucose drink, tablets, confectionary
- oral supplementary snack

SEVERE (external help required)
-	Parental therapy
o	i.v 20% dextrose (25-20g)
o	i.m glucagon (1mg)
-	Oral therapy
o	Buccal glucose gel, jam, honey
91
Q

how does hypoglycaemia cause morbidity

A

CNS

  • Coma, convulsions
  • Vascular events – stroke, transient ischaemia
  • Cognitive impairment (young children)
  • Brain damage (rare)
Cardiac
-	Arrhythmias
-	MI
Other
-	Accidents, injuries wtc
92
Q

microvascular complications of diabetes

A 
Kidney 
-	Nephropathy
-	Microalbuminuria
-	If uncontrolled leads to renal disease
Peripheral neuropathy
Retina
-	Retinopathy
93
Q

macrovascular complications of diabetes

A

MACROVASCUALR – larger blood vessels

  • Ischaemic heart disease
  • Peripheral vascular disease
  • Cerebrovascular system
94
Q

how to stop/ slow progression of complications of diabetes

A 
HOW DO WE STOP/ SLOW PROGRESSION
-	Good glycaemic control
o	HbA1c
o	Blood glucose monitoring
-	BP control
o	<140/90 with no microvascular disease
o	<135/85 with target organ damage
95
Q

how do we screen for diabetes complications

A 
-	Retinopathy screening
o	At least 2 yearly eyes
o	PAEP in some cases for higher risk
-	Urinary ACR annually
o	Early inidcation fro proteinurea (kidney problems)
Annual foot examination
96
Q

pathophysiology of diabetic complications

A
  • Dyslipidaemia is highly correlated with athersclerosis
  • Both insulin deficiency and insulin resistance promote dyslipidaemia
  • Endothelial dysfunction is present at an early stage
  • Factors combine to promote atherogenicity and thus macrovascular disease

YEAR 2 SEMESTER 2 (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions