Diabetes Flashcards
Diabetic nephropathy.
a) Basement membrane lesions
b) Biochemical finding
c) Management
a) Kimmelsteil-Wilson nodules
b) Proteinuria (raised ACR)
c) ACE inhibitors/ ARBs - reduce proteinuria
Diabetes: classification
a) What is diabetes mellitus?
b) T1DM
c) T2DM
d) Gestational diabetes
e) MODY
f) Secondary causes
a) A disease caused by deficiency or diminished effectiveness of endogenous insulin.
- It is characterised by hyperglycaemia and deranged metabolism, with macrovascular and microvascular complications.
b) Failure to produce sufficient insulin due to autoimmune disease (eg. anti-islet cell antibodies); usually juvenile-onset
c) Insulin resistance, due to chronically persistent hyperglycaemia and high levels of insulin; usually onset over the age of 30
d) Pregnant women with high blood glucose levels during pregnancy and no pre-gestational diabetes
e) Monogenetic (auto-dominant) defects of beta-cell function (impaired insulin secretion), manifesting as mild hyperglycaemia at a young age;
- Usually can be treated with sulfonlyureas (some may require insulin)
f) Accounts for only 1-2% of patients with diabetes mellitus. Causes include:
- Pancreatic disease: CF, chronic pancreatitis, pancreatectomy, pancreatic Ca
- Endocrine: Cushing’s syndrome, acromegaly, thyrotoxicosis, phaeochromocytoma, glucagonoma
- Drug-induced: corticosteroids, thiazide diuretics, atypical antipsychotics, antiretroviral protease inhibitors..
- Genetic: Wolfram’s syndrome (DIDMOAD), Friedreich’s ataxia, haemochromatosis, glycogen storage disease.
T2DM.
a) Risk factors
b) Presentation
c) Diagnosis
a) Obesity (especially truncal), ethnicity (South Asian, African), sedentary, high GI diet, previous GDM, impaired glucose tolerance, metabolic syndrome, PCOS
b) - May be asymptomatic; or present with complications
- Polyuria, polydipsia, lethargy
- Recurrent or prolonged infections; thrush, balanitis
c) - 1 abnormal plasma glucose (random ≥11.1 mmol/L or fasting ≥7 mmol/L) in the presence of diabetic symptoms
- 2 abnormal fasting glucose readings if no symptoms
- HbA1c of 48 mmol/mol (6.5%)
T1DM.
a) Risk factors
b) Presentation
c) Diagnosis
a) Genetic predisposition, FHx (10%), young age
b) - Usually acute onset of polyuria, polydipsia, weight loss, dehydration
- May present with DKA
c) - Symptoms + hyperglycaemia (11.1 mmol +)
- NOT HbA1c
HbA1c.
a) What does it assess?
b) Cut-off for diagnosing T2DM
c) Range for pre-diabetes
d) Situations where HbA1c cannot be used due to its unreliability
e) Targets in T2DM
f) How often should it be monitored in T2DM
a) The proportion of glycated haemoglobin over the last 120 days (the lifespan of a RBC)
b) 48 mmol/mol (6.5%)
c) 42 - 47 mmol/mol (6.0 - 6.4%)
d) - Children, suspected T1DM, or T2DM of acute onset
- GDM
- Haemolytic disorders (RBC lifespan < 120 days)
- Other haematological: e.g. IDA, myelosuppression, etc.
e) - 48 if controlled by diet or monotherapy without risk of hypoglycaemia
- 53 if controlled by drugs with risk of hypoglycaemia
f) Every 3 - 6 months
Pre-diabetes.
a) 3 test results
b) 2 broad categories of pre-diabetes
c) Management
a) - HbA1c 42 - 47 (6.0 - 6.4%) - most widely used test
- Fasting glucose 6.0 - 6.9 mmol/L
- Glucose 7.8 - 11.1 mmol/L two hours after a 75 g oral glucose load (OGTT)
b) - Impaired fasting glucose (fasting glucose 6.0 - 6.9)
- Impaired glucose tolerance (OGTT glucose 7.8 - 11.1)
c) - Lifestyle changes - lose weight, increase activity, stop smoking, reduce alcohol, etc.
- If these fail, consider metformin
- If resistant obesity, consider orlistat
- Monitor HbA1c regularly
Screening for diabetes.
a) Who should be screened
a) Age > 45 (offered at NHS health check), obese, South Asian, sedentary, FHx, CVD, PCOS, other RFs
NHS health check.
a) Who is it offered to?
b) How often is it offered?
c) What is screened for?
a) Adults between ages of 40 - 74, who do not already have diseases like diabetes, hypertension, CVD, CKD or dementia
b) Every 5 years
c) Diseases like diabetes, hypertension, CVD, CKD and dementia
Diabetes: non-drug management
a) DAFNE
b) Other interventions
c) Driving advice
DAFNE.
- Dose adjustment for normal eating (DAFNE) in T1DM
- 1 week course
- Typical patients then self-manage their insulin therapy
- Generally with 2 intermediate-acting daily doses and pre-meal short-acting insulin
- Patients estimate carbohydrate content of each meal, and adjust dose of pre-meal short-acting insulin accordingly
- Should be allowed to self-manage in hospital provided no issues around safety/competenc
Patient education.
- DAFNE in T1DM
- DESMOND programme in T2DM
- Self-management (eg. glucose monitoring, insulin)
Dietary.
- Involve dietician
- Encourage high-fibre, low-GI sources of carbohydrate (eg. fruit, vegetables, wholegrain and pulses)
- Discourage high-GI carbohydrates (eg. white bread, refined sugars, potatoes), saturated fats, alcohol, etc.
Other lifestyle.
- Weight loss and increased exercise
- Smoking cessation, reduce alcohol, etc.
Driving advice.
- DVLA must be informed if on insulin (or oral hypoglycaemic if HGV driver), if > 1 severe hypo in last 12 months, if ever a hypo while driving, or if reduced hypo awareness
- Drivers on insulin should always carry a glucose meter and blood-glucose strips when driving, and check BM within 2 hours of driving and every 2 hours while driving
- If on other hypoglycaemia-inducing drugs, may be required to check BMs (depending on license type and frequency of hypos)
- Should always have stock of carbohydrate snacks
- 5 to drive (if below- have sugary snack)
- If signs of hypo/BM < 4, must wait until BM > 5 for at least 45 mins before driving
- If driver has ‘hypoglycaemia unawareness’ they are not legally allowed to drive
T2DM: pharmacological management
a) 1st line - main choice
b) 1st line - alternatives
c) 2nd line
d) 3rd line
e) Usual next step
f) Alternative next step if BMI > 35 (or other obesity-related risk factors)
a) Metformin: start low dose standard-release metformin (if GI side effects, consider switch to modified-release)
b) If metformin is contraindicated (eg. eGFR < 30) or not tolerated, consider offering one out of:
- Dipeptidyl peptidase-4 (DPP-4) inhibitor (eg. sitagliptin)
- Pioglitazone
- Sulfonylurea (eg. gliclazide)
- SGLT-2 inhibitor (eg. canagliflozin)
c) Dual therapy:
- Metformin plus… DPP-4 inhibitor, pioglitazone, or sulfonylurea (or SGLT-2 inhibitor)
- (Or if metformin contraindicated/not tolerated): dual therapy with two of DPP-4, pioglitazone, sulfonylurea or SGLT-2 inhibitors
d) Triple therapy:
- eg. Metformin + DPP-4 inhibitor + sulfonylurea
e) Start insulin therapy:
- continue metformin unless contraindicated;
- review other glucose-lowering drugs (probably stop)
f) Metformin + sulfonylurea + GLP-1 mimetic (eg. exenatide)
- Continue GLP-1 drug if a reduction of at least 11 mmol/mol (1.0%) in HbA1c and a weight loss of at least 3% in six months
Antihyperglycaemics: pharmacology
a) Metformin
b) Sulfonylureas
c) Pioglitazone
d) DPP-4 inhibitors (gliptins)
e) SGLT-2 inhibitors (gliflozins)
f) GLP-1 mimetic
a) Decreases gluconeogenesis and increases peripheral utilisation of glucose
b) Increase insulin secretion
c) Reduces peripheral insulin resistance
d) Inhibits DPP-4 to increase insulin secretion and lower glucagon secretion
e) Inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal PCT to reduce glucose reabsorption and increase urinary glucose excretion
f) Activates the GLP-1 (glucagon-like peptide-1) receptor to increase insulin secretion, suppress glucagon secretion, and slow gastric emptying (hence, results in weight loss)
Antihyperglycaemics: contraindications/cautions
a) Metformin
b) Sulfonylureas
c) Pioglitazone
d) DPP-4 inhibitors (gliptins)
e) SGLT-2 inhibitors (gliflozins)
f) GLP-1 mimetic
a) eGFR < 30 (CKD stage 4 +)
b) Porphyrias; caution in the elderly
c) Hx of heart failure, previous or current bladder Ca, unexplained haematuria, increased risk of fracture
d) DKA
e) CV disease and elderly (risk of hypotension)
f) Elderly, low BMI
Antihyperglycaemics: side effects
a) Metformin
b) Sulfonylureas
c) Pioglitazone
d) DPP-4 inhibitors (gliptins)
e) SGLT-2 inhibitors (gliflozins)
f) GLP-1 mimetic
a) GI upset (if present on standard-release metformin, try modified-release), AKI
b) Hypoglycaemia, weight gain
c) Increased fracture risk, weight gain, bladder Ca (rare)
d) Hypersensitivity reactions may occur (anaphylaxis, angio-oedema and Stevens-Johnson syndrome)
e) - Genital infections and urinary tract infections; hypotension
- Risk of precipitating DKA - omit if in hospital for major surgery or major medical illness
f) Weight loss, appetite reduction
Insulin: types
a) 3 main types - timing of injections, onset, duration, examples, etc.
b) Regimens used in DM
c) Examples of mixed insulins
Quick-acting insulin.
- Includes short-acting and rapid-acting
- Taken just before, with or just after meals as a bolus dose
- Onset of action: 15 - 30 mins (quick); peak at ~ 1 hour (rapid) to 2 hours (short)
- Duration of action: < 8 hours
- Examples: NovoRapid (rapid), Humalog (rapid), ActRapid* (short), Humulin S** (short)
*Acting as being rapid, but actually just short
** S for short
Intermediate-acting.
- Mimic basal insulin secretion
- Given once/twice daily, usually at bedtime
- Onset of action: 1 - 2 hours
- Duration of action: 12 - 24 hours
- Examples: Humulin I*
I for intermediate
Long-acting.
- Mimic basal insulin secretion
- Given once/twice daily, usually at bedtime
- Onset of action: 1 - 2 hours
- Duration of action: 24 - 36 hours
- Examples: Lantus, Levemir, Insulatard
*L for long-acting
Three regimens used in DM.
- Biphasic regime (usually a mixed insulin):
- 1, 2 or 3 insulin injections per day, usually before meals
- Intermediate +/- short-acting insulin
- Examples: Humulin M3, Humalog Mix25, Novomix30 - Basal/bolus regimen:
- short-acting insulin before meals,
- plus separate basal injections of intermediate or long-acting insulin once/twice daily - Once-daily insulin plus oral hypoglycaemic agents
- Medium- or long-acting insulin, usually at bedtime
(used only in T2DM)
d) Examples of mixed insulin:
Humulin M3*, Humalog Mix25, Novomix30
- M for mixed
- Mix25 = 25% rapid-acting insulin, 75% intermediate; Humalog Mix25 is NEVER given at bedtime
- ** Novomix30 = 30% rapid-acting insulin
Insulin: problems
a) Patient reported problems
b) Dosage issues
a) - Injection site issues - lipohypertrophy, bleeding, infection, insulin leakage
- Needle phobia
- Blood glucose monitoring - painful fingers
b) - INSULIN-SPECIFIC SYRINGES must be used, which show the number of insulin UNITS on the side: a 1 ml syringe will give max dose of 100 units; a 0.5 ml syringe will give max dose of 50 units
- Dosing issues can cause… hypoglycaemia, HHS/DKA
