Diabetes Mellitus Flashcards
define type 1 diabetes
Pancreatic islet β-cells destroyed - autoimmune
Absolute insulin insufficiency
-> lipolysis and ketogenesis
Associated with HLA DR3/4
Define type 2 diabetes?
Associated with obesity, HTN, inactivity, disturbed lipids
Reduced peripheral sensitivity to insulin
Reduced insulin production (over time)
what is the typical presentation of type 1 diabetes
5-15 y/o peak age
Polyuria and polydipsia (osmotic diuresis)
Weight loss (muscle and fat breakdown)
DKA: Abdo pain, N&V, tachypnoea (Kussmaul), coma
what is the typical presentation of type 2 diabetes?
Asymptomatic- picked up routine Ix
RFs present- (truncal) obesity; FHx,
South Asian, black), age
Fatigue
Polydipsia/polyuria
Infections (fungal, cellulitis)
Acanthosis nigricans
what are the causes of type 1 diabetes?
destruction of pancreatic beta-cells -> absolute insulin deficiency
Autoimmune disease with environmental trigger
- HLA-DQ, -DR3/4
Associated autoimmune conditions
- Vitiligo
- Addison’s disease
- Hashimoto’s thyroiditis
what are the causes of type 2 diabetes
- MODY (maturity onset diabetes of the young) – autosomal dominant
- Pancreatic disease e.g.chronic pancreatitis, pancreatic ca.
- Endocrinopathies e.g. Cushing’s syndrome, acromegaly, PCOS
- Drugs e.g. corticosteroids
what are the risk factors of type 2 diabetes?
- Genetic predisposition: 90% concordance amongst monozygotic twins
- Older age
- Physical inactivity
- Obesity - ↑FFAs, hyperglycaemia
- Hypertension
- Dysplipidaemia
- Cardiovascular disease
what are the symptoms and signs of diabetes?
what is HHS and how is it worked out?
hyperglycaemia hyperosomolar state- people with type 2 diabetes
blood glucose levels over 40mmol/L
how is diabetes diagnosed and interpret the results?
when should HbA1c not be used?
- ALL children and young people
- patients of any age suspected of having Type 1 diabetes
- patients with symptoms of diabetes for less than 2 months
- patients at high risk who are acutely ill (e.g.those requiring hospital admission)
- patients taking medication that may cause rapid glucose rise e.g.steroids, antipsychotics
- patients with acute pancreatic damage, including pancreatic surgery
- in pregnancy
- presence of genetic, haematologicand illness-related factors that influence HbA1c and its measurement
interpret the bloodand urine results for a suspected DKA?
Bloods
- FBC – elevated WCC
- U&Es – high urea and Cr
- Glucose >11mmol/l
- Ketones >3mmol/l
- Culture
- ABG – metabolic acidosis with high anion gap (VBG pH <7.3)
Urine
- Glycosuria
- Ketonuria ++
- MC&S
what is the management of type 1 diabetes?
what is the management for DKA?
• IV fluid replacement with 0.9% saline
• Start IV dextrose when glucose reaches 15mmol/l
• Insulin infusion
• Potassium (in fluids)
• Monitor blood glucose, ketones, urine output and venous blood gases
outline the management for type 2 diabetets?
which blood pressure medication should all type 2 diabetics be started with?
BP management in all type II diabetics begins with ACEi/ARB rather than CCB (even if the patient is black or over the age of 55)
outline the step approach for glycaemic control in type 2 diabetics?
If HbA1c >48 on lifestyle interventions, add metformin
If HbA1c >58, try:
- Metformin +DPP-4i e.g., sitagliptin (-gliptin) or
- Metformin +Pioglitazone or
- Metformin +A sulfonylurea e.g., gliclazide or
- Metformin +An SGLT-2i e.g.,dapaglifozin(-gliflozin)
If HbA1c still >58, try:
- Metformin + DPP-4i + sulfonylurea
- Metformin + pioglitazone + sulfonylurea
- metformin, pioglitazoneaor an SU, and an SGLT-2i
- Insulin based treatment
outline the action of metformin?
Inhibits hepatic gluconeogenesis
Also promotes weight loss
Advice is to offer standard release metformin and to increase the dose gradually to avoid adverse effects. If side effects are experienced and intolerable, you can switch to modified release metformin. The patient’s renal function has to be monitored before initiating metformin and during its use.
what are the SE of metformin?
GI upset, MALA
Given Metformin MR if gastro symp don’t go in a month
Why does metformin cause lactic acidosis in liver/renal/heart failure?
Metformin inhibits hepatic gluconeogenesis (ie. the regular way in which excess lactate is converted back into sugars). More lactic acid is produced in heart failure. With increased lactate production (in heart failure), a decreased lactate clearance (with metformin use on top of liver failure) and decreased metformin clearance by kidneys (in kidney failure) - lactic acidosis may occur. Metformin is very safe, and you only see lactic acidosis when the drug is taken in large doses in people who shouldn’t be on it (eg severe renal failure, heart failure and liver failure)
outline the action of sulphonylureas and in which group of people they are used in?
not overweight who need rapid hyperglycaemia control due to symp
e.g. gliclazide, glibenclamide
Blocks K+ sensitive channels in beta cells -> insulin release
what are the SEs of sulphonylureas?
hypoglycaemia(which is why you need to make sure patients take before), weight gain
outline the action of thiazelidione?
who is it contraindicated in?
insulin sensitiser
e.g. pioglitazone
Activates PPARγ and ↓ insulin resistance
Contraindicated in Heart Conditions
outline the action of acarbose?
(alpha-glucosidase inhibitor)
Reduces carbohydrate digestion
what are the SEs of acarbose?
bloating, flatulence
outline the action of incretin?
GLP-1 analogue
e.g. exenatide, liraglutide
↑ insulin secretion, ↓ glucagon release, gastric emptying and so increases hypothalmic satiety
what are the side effects of GLP analogues?
GI upset
outline the action of DPP4- inhibitors
-gliptin e.g. sitagliptin, vildagliptin
Increases GLP-1 half life as DPP4 breaks down GLP-1
outline the action of SGLT-2 inhibitors?
glifozin
e.g. canagliflozin
↓ renal threshold for glucose -> ↓ glucose reabsorption
what are the side effects of SGLT-2 inhibitors?
thirst, N, constipation, more UTIs, poluria
outline the use of insulin in T2DM and state what should be monitored carefully?
Very good treatment for T2DM but they ARE NOT dependent on it, unlike with T1DM
T2DM can go on insulin and come off it!!!
Watch potassium and phosphate carefully as insulin causes activation of glut4 which pumps in glucose, potassium and phosph into cells
what are the side effects of insulin?
weight gain, lipid hypertrophy at injection sites
what are the 3 acute metabolic disturbances in diabetes?
Hypoglycaemia (result of treatment)
Diabetic ketoacidosis (mainly T1DM)
Hyperosmolar hyperglycaemic state
what are the long term microvascular complications of diabetes?
- Retinopathy
- Neuropathy
- Nephropathy
what are the long term macrovascular complications of diabetes?
- Ischaemic heart disease
- Cerebrovascular disease
- Peripheral artery disease
what is hypoglycaemia in diabetics?
Low sugar (<3.6 mmol/L)
what are the causes of hypoglycaemia in diabetics?
Missed meals/inadequate snacks
Alcohol
Unaccustomed exercise
Inappropriate insulin regime
Some drugs (sulfonylureas, SGLT-2i
what are the signs of hypoglycaemia in diabetics?
Palpitations (tachycardia), tremor, sweating, pallor, anxiety
Drowsiness, confusion, altered behaviour(aggression), coma
outline the treatment of hypoglycaemia in diabetics?
GIVE SUGAR!
Conscious:
ORAL Glucose (solution/tablet) AND complex CHO
Impaired consciousness:
PARENTERAL: 1mg glucagon IM. If fails, IV dextrose e.g., 10%glucose infusion
compare the DKA and HHS?
what is seen in diabetics retinopathy on fundoscopy and outline the management?
outline diabetic nephropathy?
One of commonest cause of CKD
commonest secondary cause of nephrotic syndrome
Albuminuria, reduction of eGFR, associated with retinopathy
what are the investigations for diabetic nephropathy?
1st- Urinalysis (proteinuria/raised ACR)
eGFR (see chronic kidney disease)
Biopsy is gold standard but rarely needed- Kimmelstiel-Wilson nodules (mesangial expansion)
outline the management of diabetic nephropathy?
Improve glycaemic control
ACEi/ARB
what is diabetic neuropathy?
Commonest cause of neuropathy
Caused by blockage of vasa nervorum
what is the cause of peripheral neuropathy?
Loss of sensation (particularly feet-glove and stocking)
May not sense injury to foot
INSPECT FEET!
Monofilament examination
Loss of ankle jerk/vibration sense/fractures (Charcot’s joint)
what is mononeuropathy?
Sudden motor loss usually
E.g., wrist drop, foot drop, 3rdnerve palsy (eye down and out, pupil responds to light
what is autonomic neuropathy?
GI tract: difficulty swallowing, delayed gastric emptying, bladder dysfunction
Postural hypotension (collapse on standing)
Cardiac autonomic supply
outline the management of diabetic neuroathy?
Glycaemic control
If painful, use neuropathic pain agent
e.g., duloxetine, pregabalin or gabapentin
what is charcot’s arthropathy?
Charcot arthropathy is a progressive degeneration of a weight bearing joint, a process marked by bony destruction, bone resorption, and eventual deformity.
onset is usually insidious
More commonly seen in the lower extremities and caused by a combo of diabetic neuropathy and vasculopathy
