diabetes Flashcards
type 1 Diabetes Mellitus: define type 1 diabetes mellitus, recall the epidemiology, explain the aetiology, pathophysiology, clinical presentations and explain the physiological basis of treatment
appearance of patients with T1DM compared to T2DM
lean, lose a lot of weight, symptomatic from high glucose vs obese and insulin-resistant
typical age of T1DM patient and reason; explain why may be later onset (LADA)
young as autoimmune leading to insulin deficiency; may be insulin deficient over 40 due to latent autoimmune diabetes in adults (LADA) because of antibodies vs pancreas
why is the prevalence of T2DM in children rising
obesity
common consequence of T1DM which can also be present in T2DM
diabetic ketoacidosis
why might a patient present as obese with diabetic ketoacidosis
insulin deficiency as irritation to pancreas in Afro-Caribbean
examples of monogenic diabetes which can present phenotypically as T1DM or T2DM (small proportion)
MODY, mitochondrial diabetes
diseases and circumstances which present with high glucose but not diabetic
pheochromocytoma, Cushing’s syndrome; drinking cause pancreatic insufficiency
triggers/causes and pathway of T1DM
may be environmental trigger (prevalence increases during winter) and/or genetic influence (less predominant than T2DM), causing autoimmune destruction of islet cells, causing insulin deficiency and hyperglycaemia
triggers/causes and pathway of T2DM
genetic influence and/or obesity causing insulin resistance, causing B-cell failure after many years of high insulin output, causing hyperglycaemia
pathogenesis of T1DM
pre-diabetes with gene interactions imparting susceptibility and resistance, environmental triggers and immune dysregulation (autoantibodies) cause variable insulitis B-cell sensitivity to injury, reducing B-cell mass and causing a loss of glucose tolerance until diabetic and low B-cell mass (complete destruction) and undetectable C-peptide
T1DM cyclical relationship between autoreactive effector T cells and Treg cells
increase in autoreactive effector T cells controlled by increase in Treg cells, but over time a gradual disequilibrium cyclical behaviour could occur, leading to autoreactive effector T cells>Treg cells, leading to declining pancreatic islet function
why is immune basis of T1DM important (disease and treatment)
increased prevalence of other autoimmune diseases, risk of autoimmunity in relatives, more complete destruction of B-cells; autoantibodies can be useful clinically, immune modulation offers possibility of novel treatments
genetic susceptibility to T1DM (HLA-DR allele)
HLA markers are on chromosome 6 and alert if more at risk (HLA DR3 and 4 significant risk); research not clinical
why is there a reduction in T1DM prevalence in summer
bacterial/viral conditions in winter lead to pancreatic failure
4 markers for confirming T1DM diagnosis (most patients not needed)
islet cell antibodies (ICA) - group O human pancreas; insulin antibodies (IAA); glutamic acid decarboxylase (GADA; widespread nuerotransmitter); insulinoma-associated-2 autoantibodies (IA-2A; receptor like family)
presentation of T1DM: symptoms
polyuia, nocturia, polydipsia, blurring of vision, thrush, weight loss, fatigue
presentation of T1DM: signs
dehydration, cachexia (if insulin-deficient for a while), hyperventilation (metabolic acidosis), smell of ketones, glycosuria, ketonuria
what 3 organs/tissues are important for glucose regulation
liver, muscles, adipose
effect on glucose if insulin deficient in T1DM
glucose excreted out of liver into circulation, and can’t be taken up by muscle, so a lot left in circulation
effect on amino acids if insulin deficient in T1DM
amino acids broken down by muscle into circulation and liver uses these to produce more glucose
effect on glycerol if insulin deficient in T1DM
glycerol comes out of adipocytes, which liver uses again to make glucose
effect on fatty acids if insulin deficient in T1DM
fatty acids come out of adipocytes then taken out circulation and converted to ketone bodies in liver; some can be uptaken by muscles but not as good as glucose uptake
2 aims of T1DM treatment
reduce early mortality, avoid acute metabolic decompensation
what do T1DM need to preserve life, and what defines if this is deficient
need exogenous insulin, and ketones define insulin deficiency
4 long term complications of T1DM
retinopathy, nephropathy, neuropathy, vascular disease
4 features of controlled T1DM diet to balance distribution of food over course of day (diet more important in T2DM, but still important in T1DM as glucose levels difficult to control)
reduce calories as fat, reduce calories as refined carbohydrate, increase calories as complex carbohydrate, increase soluble fibre
progression of insulin source
animal -> human -> insulin analogues
non-diabetic insulin profile, and impact on insulin treatment
insulin peaks with food intake (glucose), but is a basal production by B-cells all the time; attempt to mirror this by giving short action insulin when eating and background long action basal insulin
examples of insulin analogue acting as short acting insulin with meals
Lispro, Aspart, Glulisine
how is insulin modified to make it last longer as background insulin
non-c bound to zinc or protamine
examples of insulin analogue acting as long acting background insulin
Glargine, Determir, Degludec
when is short acting insulin injected
with meals (dose dependent on size of meal)
when is long acting insulin injected
1/2 times a day (e.g. evening and morning)
features of insulin pump
continuous insulin delivery to mimic programmed basal rate, plus option for bolus amount for meals; doesn’t measure glucose, so no completion of feedback loop
process of islet cell transplant
islet cells in pancreas extracted from donor -> inserted into recipient by portal vein in liver and redistribute around body; must be on immunosuppressant agents for rest of life
criteria for islet cell transplant as very long waiting list
must have very severe hypoglycaemic episodes
how are capillary glucose levels monitored
prick finger -> blood on strip -> machine reads levels, gving trend of glucose throughout day
capillary vs venous glucose accuracy
capillary not as accurate
describe continous glucose monitoring (CGM)
on abdomen and checks instantaneously, giving a reading and trend in real time but is less accurate; can have alarms if entering hypoglycaemia
what is a long term marker of glucose control to show compliance
HbA1c (glucose molecules bound to Hb), which falls in CGM and those who use capillary monitoring more frequently (compliance)
what does HbA1c irreverible non-covalent bonding depend on
Hb levels, RBC lifespand (120 days), glucose levels
HbA1c impacted by different individuals or diseases
rate of glycation is faster in some individuals, with thalassaemia, renal failure etc. causing HbA1c to be unreflective as RBCs have a shorter lifespan
HbA1c correlation with glucose, and levels for diabetes and pre-diabetes
positive correlation, with >6.5% diabetes and 6-6.5% pre-diabetes
what is lowered HbA1c associated with
lower risk of microvascular complications
acute complications of T1DM
ketoacidosis (metabolic acidosis), hyperglycaemia
glucose utilisation and production in hyperglycaemia
reduced tissue glucose utilisation, increased hepatic glucose production
what is metabolic acidosis associated with
osmotic dehydration and poor tissue perfusion
why is there a slightly higher prevalence of diabetic ketoacidosis in T2DM in black
potential insulin deficiency in T2DM before insulin resistance
what consequence is inevitable inevitable when treating diabetes
occasional hypoglycaemic events (major cause of anxiety in patients and families)
criteria for hypoglycaemia
plasma glucose <3.6mmol/l
define severe hypoglycaemia
any hypoglycaemic event (hypo) requiring help of another person to treat
how is hypo risk reduced but consequence of this
keep glucose high, but this risks complications
features of hypo
disorientation, sweaty, confused (if eat will rectify, but if, not risk of going into coma)
hypo: what happens at <3mmol/l
most mental processes impaired
hypo: what happens at <2mmol/l
consciousness impaired
how might severe hypoglycaemia lead to sudden death
contribute to arrhythmia
describe hypoglycaemia unawareness
don’t spot symptoms of sweating etc. and lose awareness, becoming unconscious, because of habituation by recurrent hypos
who are at main risk of hypos
patients with low HbA1c, who strive for tight glucose control but overdo it
when do hypos occur
anytime, but often clear pattern (pre-lunch, nocturnal)
why are nocturnal hypos very common
patient not totally aware and has increased production of adrenaline, so higher glucose level than normal
5 reasons why hypos occur
unaccustomed exercise (doesn’t eat more and keeps same amount of insulin), missed meals (e.g. psychological condition where give less insulin or miss meals so lose weight), inadequate snacks, alcohol, inappropriate insulin regime
hypoglycaemia signs and symptoms due to increased autonomic activation
palpitations (tachycardia), tremor, sweating, pallor/cold extremities, anxiety
hypoglycaemia signs and symptoms due to impaired CNS function
drowsiness, confusion, altered behaviour, focal neurology, coma
how is hypoglycaemia treated if conscious
oral food: glucose solution or tablets, then complex carbohydrates to maintain blood glucose after initial treatment
how is hypoglycaemia treated if consciousness impaired
parenteral: IV dextrose (not concentrated solutions), 1mg glucagon IM (releases glucose from liver, but if thin and fasting, then low glucose reserves in liver so IM glucagon won’t work)
what can precipitate diabetic ketoacidosis
new diagnosis of T1DM, not taking insulin, intercurrent stress (pneumonia, heart attack), fasting and not taking enough insulin, infection
what will happen with deficient [insulin]
high hepatic glucose output and deficient muscle glucose uptake; lipolysis rate will increase, glycerol used to produce glucose in liver; fatty acids produce ketone bodies in liver
what will happen with high plasma [glucose]
glucose exceeds proximal convoluted tubule ability for reabsorption, causing glycosuria (further promoted by SGLT2 inhibitors during treatment)
how is dehydration caused by T1DM
insulin deficiency and stress hormones cause hyperglycaemia -> osmotic diuresis; this and fever with sepsis, along with not drinking enough or vomiting, causes dehydration
where are ketones produced
occurs in non-diabetics as well as in insulin deficiency, and produced in liver from by-products of fatty acids
what 3 things contribute to diabetic ketoacidosis
insulin deficiency, stress hormones, fasting (vomiting and fasting make ketosis worse)
why do T1DM present as lean
lose weight as insulin required to keep triglycerides in adipocytes
what is HCO3- production linked to
H+ excretion (attempt to buffer)
4 features of distal convoluted tubule concerning acid-base homeostasis: filtration, enzyme, Na+ excretion and ketone bodies impact
needs adequate GRF for acid base system to function; needs carbonate dehydratase acid base homeostasis; Na+ excretion linked to H+ or K+ excretion; acid ketone bodies require increased HCO3- buffering
pH, basic lesion and compensation of metabolic diabetic ketoacidosis
low pH, low HCO3-, so compensated by respiratory processes to increase CO2 release (hyperventilation)
diabetic ketoacidosis: why is there a reduction in [HCO3-]
impaired production, increased H+ buffering
diabetic ketoacidosis: what is pH dependent on
HCO3- and PCO2 levels
diabetic ketoacidosis: anion gap
large anion gap (increase in single anion other than Cl-)
why does diabetic ketoacidosis show high [K+], and why is this unreflective
water, Na+ and K+ lost in urine; excess H+ ions in diabetic ketoacidosis drive out K+ from IC into circulation, so high K+ in plasma but total body K+ is low
what does diabetic ketoacidosis lead to (list all things forming cycle)
hyperventilation and vomiting (acid causes irritation of GI tract), which lead to dehydration -> renal hypoperfusion -> impaired H+ excretion -> acidosis
10 clinical features of diabetic ketoacidosis
dehydration; insulin deficiency; hyperglycaemia; total body K+ deficiency despite high plasma [K+]; polyuria and polydipsia (osmotic diuresis); acidotic; hyperventilation (Kussmaul); risk of arrhythmia, infection and dilated stomach; abdominal pain and vomiting; coma; glycosuria and ketonuria
9 investigations for diabetic ketoacidosis
capillary glucose, plasma glucose; creatine (kidney function), K+ and Na+ (electrolyte impalance; all elevated due to dehydration and acidosis, although Na+ could be low if prolonged hyperglycaemia); full blood count (high neutrophil if due to infection); arterial blood gases (through radial artery showing metabolic acidosis; for HCO3- look at venous); amylase (triglyceride; elevated e.g. due to pancreatitis causing insulin deficiency); ECG (check for MI and arrhythmias due to acidosis and low K+); chest x-ray (check for pneumonia precipitant); septic screen (urinary infection, chest infection or gut infection -> CRP high)
4 treatments of diabetic ketoacidosis
fluid (aggressive rehydration with normal saline to improve renal perfusion, allowing HCO3- buffering); insulin (IV, not subcutaneous as tissues are poorly perfused); K+ replacement (insulin drives K+ into cells, causing rapid drop -> hypokalaemia and cardiac arrhythmias); HCO3- (not usual)
diabetic ketoacidosis treatment: why is HCO3- not usual
danger of hypokalaemia, hypernatraemia, rebound alkalosis, CSF acidosis, impaired oxyHb dissociation
6 other measures to monitor and treat diabetic ketoacidosis
cardiac monitor for arrhythmias; catheterise; antibiotics; NG tube (gastroparesis); heparin; arterial or central line
why catheterise patients in diabetic ketoacidosis
as if confused, won’t be able to go to toilet; allows measurement of fluid output to ensure replacing lost fluids
why NG tube patients in diabetic ketoacidosis
ac acidosis worsens vomiting, NG tube through nose into GIT prevents juices going into lungs
why heparin patients in diabetic ketoacidosis
prevents coagulation, reducing risk of DVT and pulmonary embolism
why arterial line or central line patients in diabetic ketoacidosis
arterial line if very acidotic; central line if very elderly or in cardia failure
6 causes of death in diabetic ketoacidosis
overwhelming disease, self-neglect, social factors, delay seeking help, delay primary care, inappropriate treatment
5 ways to prevent diabetic ketoacidosis
education, never stop insulin, check glucose and modify insulin if ill, admit if vomiting, determine cause of diabetic ketoacidosis (underlying condition e.g. gastroparesis)
what 4 things are important in diabetic ketoacidosis genesis
insulin deficiency, other stress hormones, fasting, dehydration
