diabetes Flashcards
what is diabetes mellitus
reduction in insulin action sufficient to cause hyperglycaemia that will result in diabetes specific, microvascular pathology over time eg of eyes, kidneys and nerves
what are the figures for diabetes patients plasma concentrations
> 7 mmol/L fasting
11.1 2h post load
HbA1c>48
what does HbA1c mean
shows glc levels over the past 3 months
=lifespan of RBC
Hb gets exposed to glc in 3 months that it is in RBC
what are the levels for prediabetes/impaired glc tolerance
between 7.8 and 11.1
HbA1c between 42 and 47
what causes T1DM and when does it occur
childhood onset, caused by insulin deficiency from auto-immune destruction of beta cells
what cells secrete what hormone
alpha = glucagon beta = insulin
both in IoL
why are T1DM patients prone to ketosis
bc no insulin at all = burn fat inappropriately instead of glc to form FFA = ketone bodies = acidic
what are the symptoms of T1DM and why
polydipsia - thirst - bc increased urination
polyuria - bc glc lost in urine, hence osmotic effect to draw water out
tiredness - not using energy effectively
weight loss - cells get no glucose, lipolysis attacks and breaks down fatty tissue
how do you treat T1DM
insulin injections into abdomen or thigh (subcutaneous fat)
quick acting, slow acting or bi-phasic
example regimen of insulin injections?
BD biphasic - twice daily premixed insulins by pen eg novomix (uncontrolled type 2 or t1 with reg lifestyle)
QDS regimen- before meals, ultra-fast insulin and bedtime long acting analogue aka rapid acting
OD before bed long acting analogue, good initial in moving from t2 tablets
what are the other types of diabetes
- MODY syndromes - genetic defects b cell function or insulin
- diseases of exocrine (secrete amylase and pancreatic juice) pancreas; cancer, pancreatitis (b cells get destroyed)
-endocrinopathies eg cushing’s (hormones antagonsitic to insulin are affected eg GH cortisol are in excess)
drug induced - steroids, anti-psychotics
what is type 2 diabetes
insulin resistance, combined with b-cell dysfunction (look on ipad for detailed pathophys)
what age does it occur and what is it’s link to ketosis (t2)
adult onset, ketosis resistant; only need a small amount of insulin to stop burning of fat
how does T2DM present
- presence of RF
- may be picked up on routine screening
- may present with the same symptoms as T1DM
what are the risk factors for diabetes and why?
- obesity:
- as BMI increases, insulin resistance increases
- abdominal fat affects it more
- reduced calories improve islet function
- socio-economic deprivation
-ethnicity
black african 3x more likely, SA 6x, bc increased amount of intrab fat
- diet composition
- lack of exercise, exercise improves insulin sensitivity with or without weight loss
what is the twin cycle hypothesis for T2DM?
first cycle:
-increase in liver fat = increase in VLDL triglycerides which are taken up by b cells and reduce their effectiveness = increase in blood glc
- increase in liver fat also means insulin suppression of hepatic glucose production is impaired (insulin resistance)
- which also increases blood glc
diabetic complications
microvascular (neuropathy, retinopathy, nephropathy)
macrovascular (ACS, stroke PVD)
what is the first step in treating T2DM
diet, exercise, weight control
what is the 1st line therapy for T2DM
standard release metformin (if GI side effects = modified-release)
what is the 1st line therapy for T2DM
standard release metformin (if GI side effects = modified-release)
dont give if eGFR is <30
if T2DM is not controlled with dual therapy what do you do?
triple therapy with:
- metformin, SU and DPP4
- metformin, SU and pioglitazone
- metformin, SU, SGLT-2i
if triple therapy not tolerated what do you do?
insulin therapy
or
metformin, SU and GLP-1 mimetic
what are the side effects of T2 drug treatments?
weight gain: sulfonylureas bc increase beta cell activity
hypoglycamiea: all drugs that increase b cell activity
GI symptoms; metformin and incretins, GLP1 agonists
weight loss: metformin, incretins, SGLT-2i
osteoporosis: pioglitazone
headaches - sitagliptin
UTI’s - SGLT-2 inhibitors
what are incretins
gut hormones that decease blood glc by stimulating insulin production after eating
how does metformin work
increases insulin sensitvity by increasing peripheral uptake of glc and decreases hepatic glc production
how do sulfonylureas like gliclazide work?
increases insulin secretion by increasing the b cell activity
how does pioglitazone work?
increases cell’s sensitivity to insulin
how do DPP4 inhibitors work
blocks enzyme DPP4 which is responsible for destroying incretin hormone
sitagliptin
how do SGLT-2’s like empaglifozin work?
sodium glc co-transporter
blocks reabsorption of glucose in the kidneys and promotes excess excretion of glc in urine
how should T2DM be monitored?
urine glucose
blood glc: self-regulation, 4x a day for T1, targeted for those with T2 and on hypoglycaemic risk medications
HbA1c = every 6 month s
what checks should diabetes people get annually other than glc?
- BP
- lipids
- UACR (albuminuria for kidney disease)
- eGFR = 78
- foot exam
- diabetic eye screening
what is the pathophys of the vascular changes in diabetes complications
high glc in lumen (in blood) = endothelial cells uptake this glc with no insulin stimulation = ROS and energy
ROS lead to production of PKC and VEGF leading to platelet aggregation and angiogenesis
increases vascular permeability
= monocytes and LDL in tunica intima
atherosclerosis and inflammation and arteriosclerosis
what are the main complications of diabetes
retinopathy, nephropathy, neuropathy, peripheral vascular, CHD
what are the 2 main eye problems
capillary leakage and capillary occlusion
why does capillary leakage occur and what does it lead to
bc of the changes to BV = leakage of plasma into retina causing oedema
if this occurs at fovea = loss of central vision
why does capillary occlusion occur and what does it lead to
retinal ischaemia, causing angiogenesis = bleed into vitreous humour = fibrosis = secondary, new vessel glaucoma
what changes will you physically see in a diabetic patients eye
- cotton wool spots (retinal ischaemia)
- haemorrhages
- hard exudates
- yellow bits indicating loss of vision due to oedema
how do you treat retinopathy
prevention: BG control, retinal screening
this screening: laser treatment to target new blood vessels and stop them from forming
salvage: vitrectomy
nephropathy in diabetes; what are the stages?
leads to CKD and end stage kidney disease
stage 1: kidney damage with normal GFR >90, microproteinuria
stage 2: mild reduction in GFR
etc until stage 4-5 where GFR <30 and then <15 which is failure, and macroproteinuria
why does nephropathy occur
growth factors, activation of RAAS, oxidative stress which lead to an increase in glomerular capillary pressure and endothelial dysfunction
what is the first sign of nephropathy
albuminuria, then scarring and nodule formation and fibrosis
high BP makes it worse
diagnosis of nephropathy?
microalbuminuria 3-30mg/mmol, regression still possible; not on standard dipstick
how do you treat nephropathy
DM control, hba1c control
BP; ACE-I or ARBs to prevent microalbuminuria to macro
sodium restriction
statins to reduce CV risk
what are the 3 things that you can find in a diabetic foot
neuropathy (decreased sensation, absent ankle jerks, swelling, etc)
ischaemia - no foot pulses, necrosis, calluses, fungal infections
foot ulceration: painless, punched out-ulcer but may be infected
what are the symptoms of diabetic foot
burning, cold, tingling, stabbing, allodynia, numbness , blisters etc
how do you get infections in diabetic foot
damage to skin = staph aureus can penetrate, and strep pyrogenes = cellulitis and lymphangitis = septicaemia
secondary to this can get osteomyelitis
what is charcot foot
bone weakness in foot due to significant nerve damage = deformity or amputation may be necessary
what other complications are there of diabetes
cheiroarthropathy - thickened skin and reduced joint motility in hands and fingers
cataracts
gestational diabetes risks to mother and fetus
miscarriage, pre-term labour, pre-eclampsia and then complications of diabetes
in first trimester: congenital abnormalities
in 2nd and 3rd = accelerated growth: intrauterine growth restriction
what are the RF for GDM
age>25, non-caucasion, high weight, HIV+, prev GDM
how do you treat and prevent GDM
monitor BG, folic acid etc
treatment: everything but metformin should be stopped
why would diabetics become hypoglycaemic and why is this dangerous?
sulfonylureas and insulin is high in the body; eg missed meal, increase in activity etc
brain death can occur
hypoglycaemia = <3mmol plasma glucose
link between DM and CV problems
risk is proportional to HbA1c
multi-vessel disease and atheromatous involvement of smaller CA common with DM
prevention of CV events in diabetes
- lifestyle, control glucose, bp and lipids
- should already be on BP control meds and statins
post angina, ACS, MI etc give aspirin, thrombolysis, beta blockers
treatment of CV events in DM
revascularisation
brand names and examples of insulin?
humalog - rapid acting
humulin S and actrapid: short acting
humulin I - intermediate: reaches peak after about 6 hours so can be used for basal
ultra-long acting eg lamtus and levemir: trickles in over 24 hours
humalogmix: mix of humalogue and humulin I
how do insulin pumps work
SC needle which gives insulin over 24 hours, but risk of hyper or dka if pump stops working
What is a hypo?
What causes it?
How is it managed?
• Classed when blood sugar is <4 • ABCDE • If conscious and able to swallow: o 2-3 dextrose tablets or sweets, NOT chocolate as high in fat so will slow glucose absorption o 300ml of Lucozade or coke • If cannot swallow, use glucogel • Otherwise, use glucagon injections • If emergency: 20ml of 20% dextrose IV
caused if diabetic patient has taken medication/insulin but not eaten at the correct time, eaten less than usual or exercised more than usual
