Diabetes Revision Flashcards
what are the 4 roles of insulin
facilitation of glucose transport into cells (via GLUT4)
stimulation of glycogenesis
inhibition of glycogenolysis
inhibition of gluconeogenesis
what effect does insulin have on fatty acids
encourages entry of fatty acids into adipose tissue
promotes chemical reactions that use fatty acids for triglyceride synthesis
inhibits lipolysis
what is insulins effect on amino acids
promotes uptake bu muscles and other tissues
stimulates protein synthesis
inhibits the degradation of proteins
what other than blood glucose can trigger the release of insulin
GI hormones (glucose dependent insulinotrophic peptide) stimulate release in anticipation of food being ingested
elevated blood amino acids
parasympathetic nervous system stimulates pancreas to secrete insulin (sympathetic decreases secretion e.g. adrenaline)
do babies of mother with diabetes have low birth weight
no tend to be higher than (have usual length)
what birth defect is seen in babies from diabetic mothers
spina bifida, anencephaly, caudal regression
abnormalities of the great vessels
increased fat and skeletal growth and organomegaly
what are the chances of a child developing diabetes if one parent or sibling has it
5-6%
diabetes is teratogenic, when is the risk highest
in the first 8 weeks
why does hyperglycaemia affect the foetus so much
as glucose can cross placenta but insulin cant
is metformin safe in pregnancy
yes
what are diabetic mothers at increased of during pregnancy
still birth and pre eclampsia
what vitamin should diabetic mothers take in pregnancy
folic acid
what four hormones increase blood glucose
glucagon, adrenaline, cortisol, growth hormone
what causes the release of adrenaline
sympathetic stimulation of the adrenal gland
how does adrenaline increase blood glucose
inhibits secretion of insulin, increases synthesis of glucose by inhibiting uptake
how does growth hormone increase blood glucose
stimulated in response to hypoglycaemia, stress, exercise, deep sleep
decreases glucose uptake, increases protein synthesis
why do tissues rely on fat metabolism in type 1DM
as glucose cant enter the cells
what type of diabetes is there amyloid deposition within islets
non insulin dependent diabetes (type 2)
what type of diabetes in insulinitis seen in
type 1- beta cell destruction
what are the diagnostic criteria for diabetes
Fasting plasma glucose >= 7.0 mmol/L
And/or a plasma glucose 2 hours after a 75g oral glucose load OR a random glucose >= 11.1 mmol/L
(one +ve test + symptoms= diagnosis or 2 + tests
Other terms:
Impaired glucose tolerance: 2 hour glucose between 7.0 and 11.1 mmol/L
Impaired fasting glucose: Fasting glucose between 6.0 and 7.0 mmol/L
what is gestational diabetes
diabetes that develops in pregnancy- resolves post natally
what is secondary diabetes
occurs secondary to other pathology (e.g. endocrinopathies- cushings, acromegaly. haemachromatosis, post pancreatitis, cystic fibrosis)
what is monogenic diabetes
due to mutation in gene regulating insulin secretion or action e.g.
maturity onset diabetes of the young
what are the chances of getting type 1 diabetes if your parent or twin has it
parent 25%
MZ twins 35%
siblings 6%
what are the chances of getting type 2 diabetes if your parent or twin has it
MZ twins 80-90%
DZ twins 30-40%
sibling 3/4x risk of normal population
if both parents have it then 70-80%
what type of diabetes is more genetic
type 2 (polygenic)
what would you expect insulin concentrations to be in a T1DM patient
low to none
some retain small amounts of insulin secretion
what would you expect insulin concentrations to be in a T2DM patient
normal to high
what antibodies are tested in T1DM/ young T2DM
GAD and IA-2
what HbA1c should T2DM aim for
53
what might precipitate T2DM presentation
infectino
what are the features of secondary diabetes
cushingoid
bronze pigmentation (haemachromatosis)
acanthosis
what should you ask for in PMH in T1DM
pancreatitis, autoimmune conditions, heavy alcohol consumption
what is the relationship between diabetes and corticosteroids
increase blood sugar
how do you calculate plasma osmolarity
2 x (plasma Na+ + plasma K+) + plasma urea + plasma glucose
what is the purpose of the anion gap
evalutaes metabolic acidosis (high= metabolic acidosis)
what is the anion gap formula
= (Na+ + K+) - (Cl- + HCO3-)
what has more microvascular complications T2 or T2 DM
Type 2
what causes the temporary blurry vision seen in diabetes
high blood sugar causes lens of eye to swell
or
blurry/ double vision in hypos
what can cause hypos in T1DM controlled with insulin
too much insulin, exercise not enough carb intake, alcohol., insulin, vomiting/ illness, coeliac, addisons (cortisol deficient), pituitary disease (reduce ACTH reduce cortisol)
even when not eating why when ill might T1DM need more insulin
as stress hormones released when ill will increase blood glucose
what is addisons
a primary renal disease
why are patients with pituitary disease are greater risk of hypos
as also release GH
what is the prevelance of coeliac in normal population and in diabetics
1 in 100 in pop
1 in 20 in diabetics
what can reduce HbA1c
conditions that increase cell turnover
what can cause DKA
infection, surgical abdomen, silent MI
what is the management for DKA
ABC
HX and exam for cause
cardiac monitor + other monitoring if required
IV fluids
IV insulin (no bolus)
watch K+, replace aggressively to prevent hypokalaemia and cardiac arrest
what is the relationship between insulin and potassium
insulin drives K+ into the cells and blood K can drop
should eggs be avoided if you have high cholesterol
no
what are the treatment steps for T2DM
1- metformin
2- metformin + SGLT 2 metformin + GLP-1 metformin + DDP-4 inhibitor metformin + TZD metformin + insulin
(metformin - SGLT 2 - GLP- 1)
what shouldnt be given with TZDs
GLP-1 analogues and DPP-4 inhibitors
what does GLP-1 do
is secreted when food ingested- increases insulin secretion
what does DPP-4 do
breaks down GLP-1
when should metformin be avoided
patient with renal failure or lactic acidosis
what are the main side effects of SUs
hypos (especially in elderly as renal function decreases with age), weight gain, stimulates appetite
what do TZDs
promote fatty acid uptake and adipogenesis
should people with fatty liver disease be given TZD
yes reduce lipid content in the liver and act as insulin sensitisers
who should you not get TZDS to
elderly slim females, heart failurem osteoporosis, bladder cancer
what acts faster gliclazide or metformin
gliclazide 2-3 days
metformin 2-3 weeks
why do you not give fix mix insulin to young people
does not allow flexibility of meals
what do you recommend doing for T1DM ill patients
keep giving insulin, check BG and ketones, get carbs in the patient
what do you recommend a T1DM wanting to do exercise
eat before or reduce insulin dose
what does increased body Na predispose to
hypertension
what does the AGE pathway interfere with
proteoglycans, basement membranes, enzyme activity, cellular receptors, increases nucleic acid damage
what is the relevance of microalbuminuria
shows presence of albumin in urine, suggestive of diabetic nephropathy or hypertension
how do you manage micoralbuminuria
tackle hypertension if present - ace inhibitors
what bad effects might tight glycaemic control cause
hypos, weight gain, worsen vascular complications (ischaemia)
what are the stages of retinal grading
none, background, moderate, severe, proliferative
what is metabolic syndrome
glucose intolerance, impaired glucose tolerance or DM and/or insulin intolerance along with any two of:
- impaired glucose regulation/ diabetes
- insulin resistance
- raised arterial BP
- raised plasma triglycerides and/or low HDL
- central obesity
- microalbuminuria
how is insulin resistance linked to T2DM
is a predisposing factor
what is acromegaly and its link to diabetes
condition caused by excess GH, GH can also cause insulin resistance
what is cushings link to diabetes
excess cortisol can inhibit the uptake of glucose in the muscles- hyperglycaemia and insulin resistance
what names do SUs end in
ide (tolbutamide)
how do SUs work
action dependent on beta cell function (no use in T1DM), depolarise beta cells stimulating the release of insulin
what is the risk in SUs
hypos
what drug has an additive effect when used with SUs
biguanides (metformin)
what impedes the effectiveness of SUs
corticosteroids, thiazide diuretics
how does metformin cause weight loss
suppresses appetite
reduced absorption of glucose from the gut
how does glucose work
reduced absorption of glucose from the gut
facilitates non insulin dependent entry of glucose into tissues
inhibits liver gluconeogenesis
enhances anaerobic glycolysis
what is the most serious side effect of metformin
lactic acidosis
what are the less serious side effects of metformin
nausea, vomiting, diarrhoea, metallic taste in the mouth
who should not get metformin
patients with:
- renal failure
- alcoholism
- cirrhosis
- chronic lung disease
- cardiac failure
- serious current illness
- mitochondrial myopathy
what are glitazones
thiazolidinediones (TZDs)
how do TZDs work
bind to receptors within the cell nucleus and affect gene expression decreasing insulin resistance
what is the only glitazone licensed in the UK
pioglitazone
how do GLP-1 analogues work
mimic the actions GLP-1 which:
- increases secretion of glucagon
- decreases secretion of glucagon
- increases insulin sensitivity in the peripheral tissues
how do DDP-4s work
inhibit DDP which inhibit GLP-1
what are the possible side effects of insulin
hypos
hypers (overcompensation in response to slight hypo after dose- somogyi effect)
reactions at injection site
insulin resistance
what is the poyol/ aldose-reductase pathway
series of biochemical reactions which occur in the presence of raised intracellular glucose (esp in insulin dependent tissues)
attempt to reduce glucose level in insulin dependent tissues that cannot regulate influx of glucose (insulin allows movement of glucose into the cell)
when does the poyol pathway become active
when there is very high intracellular glucose
what is the enzyme in the poyol pathway
aldose reductase
what is the role of aldose reductase
coverts glucose into sorbitol (sugar alcohol)
not all glucose is converted- some go into methylglyoxal and acetol (glycating sugars)
what does sorbitol do
exerts osmotic pressure on the cell (too large to diffuse out) which can cause damage to the cell so sorbitol dehydrogenase converts the sorbitol into fructose which diffuses out
what is AGE
advanced gylcation end products
these are synthesised in the aldose reductase pathway- can cause damage to cells
formed by glycating sugars and excess glucose binding to proteins
why is proteinuria done in diabetes
shows kidney damage either due to hypertension (diabetics more likely to get) or nephropathy
describe the process of nephropathy
the kidneys hypertrophy due to increased glomerular filtration rate- causes the afferent arteriole to dilate which leads to increased intraglomerular pressure = shearing forces which cause glomerular sclerosis (thickening of basement membrane and disruption of protein cross links) = kidney is no longer an effective filter
what is increased creatine a sign of in diabetes
renal failure
what pathway is responsible for the vascular complicationsin T2DM
poyol pathway (sorbitol-aldose-reductase pathway)
why is hypertension predisposed in diabetes
vasodilator effect of insulin blunted in diabetes
action of insulin which increase BP- sodium and water reabsorption
BMI of diabetic patients
patients with nephropathy should target their BP to be what
less than 130/80
how much more common is HPX in diabetics
2x normal population
what size monofilament for foot exams
10 g
how many areas are examined with monofilament on the feet
10 together
how does hyperglycaemic neuropathy present and resolve
discomfort in lower legs
regain glycaemic control
when does acute painful neuropathy occur
rapid weight loss and poor glycaemic control (severe burning and contact sensitivity)
what causes retinopathy
capillary microangiopathy- proteins of vessel wall get more glycosylated, membrane thickens and becomes MORE permeable, increased transduction of protein which has a fibrous response with the retina damaging the retinas neural network
small vessels also dilate causing micro-aneurysms
also thrombosis of some capillaries - promotes neoangiogenesis which also damages the retinae
where do neuropathic food ulcers most commonly occur
high pressure areas e.g. metatarsal heads, big toe
