Diabetes Flashcards
define DM
metabolic disorder characterized by persistent hyperglycaemia (random plasma glucose more than 11 mmol/L) with disturbances of carbohydrate, protein, and fat metabolism resulting from defects in insulin secretion, insulin action, or both
type 1 DM pathophysiology
absolute insulin deficiency
autoimmune destruction of insulin producing beta cells
type 1 DM tx
insulin
complications of type 1 DM
Microvascular complications — retinopathy, nephropathy, and neuropathy.
Macrovascular complications — such as myocardial infarction, stroke, and peripheral arterial disease.
Metabolic complications — diabetic ketoacidosis (DKA) and hypoglycaemia (blood glucose less than 3.5 mmol/L).
Psychological complications — anxiety, depression, and eating disorders. In addition in children and young people, behavioural and conduct disorders, family/relationship difficulties, and risk-taking behaviour (including non-adherence to recommended treatment).
Increased risk of developing other autoimmune conditions — including thyroid disease, coeliac disease, Addison’s disease, and pernicious anaemia.
Reduced quality of life and life expectancy.
diagnosis DM type 1
hyperglycaemia with one or more of the fx:
Ketosis.
Rapid weight loss.
Age of onset younger than 50 years (although type 1 diabetes should not be discounted if the person is aged 50 years or older).
Body mass index (BMI) below 25 kg/m2 (although type 1 diabetes should not be discounted if the person presents with a BMI of 25 kg/m2 or above).
Personal and/or family history of autoimmune disease.
children type 1 DM diagnosis
hyperglycaemia + Polyuria., Polydipsia. Weight loss., Excessive tiredness.
referral type 1 DM
if diagnosed - immediate referral to MDT diabetes specialist team
primary care management type 1DM
- appropriate access to specialist team
- education, support for them and family, inuslin tx, managing hypoglycaemia, sick day rules
- manage pt if ill
- identify complications
- minimise risk of long term complications
- screen for other autoimmune conditions where appropriate
- lifestyle factors
- regular check ups
risk factors type 1 DM
genetic - sibling - 6-7% risk, child 1-9%
environment - diet, vit D exposure, obesity, early onset exposure to viruses, decreased gut microbiome
if clinical diagnosis require investigations type 1 DM
C peptide and/or specific autoantibody titres
… as atypical features, guide use of genetic testing, guide tx if classification uncertain
DKA sx
Increased thirst and urinary frequency.
Weight loss.
Inability to tolerate fluids.
Persistent vomiting and/or diarrhoea.
Abdominal pain.
Visual disturbance.
Lethargy and/or confusion.
Fruity smell of acetone on the breath.
Acidotic breathing — deep sighing (Kussmaul) respiration.
Dehydration, which can be classified as:
Mild — only just clinically detectable.
Moderate — dry skin and mucus membranes, and reduced skin turgor.
Severe — sunken eyes and prolonged capillary refill time.
Shock (resulting from severe dehydration)
DKA glucose level
> 11mmol/L
assessment DKA
assess for precipitating factors:
- infection
- physiological stress
- non adherence to tx
- other medocal conditions
- drug tx
investigations DKA
blood ketones
->3mmol/L
although if low - does not exclude
hypoglycaemia sx
Hunger.
Anxiety or irritability.
Sweating.
Tingling lips.
Irritability.
Palpitations.
Tremor.
As blood glucose levels fall lower, the person may experience:
Weakness and lethargy.
Impaired vision.
Incoordination.
Reduced orientation.
Confusion.
Irrational behaviour.
Emotional lability.
Deterioration of cognitive function (when blood glucose levels fall lower than 3.0 mmol/L).
Severe hypoglycaemia may result in:
Convulsions.
Inability to swallow.
Loss of consciousness.
Coma.
target HbA1C adults type 1 DM
48mmol/mol
measure every 3-6 months
sick day rules type 1 DM
never stop insulin
check blood glucose more regularly
check blood or urine ketones regularly
maintain normal meal pattern where possible
drink at least 3L of fluid
blood pressure targets type 1DM
For adults with a urine albumin:creatinine ratio (ACR) less than 70 mg/mmol, aim for a clinic systolic blood pressure less than 140 mmHg (target range 120 to 139 mmHg) and a clinic diastolic blood pressure less than 90 mmHg.
For adults with an ACR of 70 mg/mmol or more, aim for a clinic systolic blood pressure less than 130 mmHg (target range 120 to 129 mmHg) and a clinic diastolic blood pressure less than 80 mmHg.
In adults aged 80 or more, whatever the ACR, aim for a clinic systolic blood pressure less than 150 mmHg (target range 140 to 149 mmHg) and a clinic diastolic blood pressure less than 90 mmHg.
first line BP for type 1 DM and CKD
ARB
define type 2 DM
persistent hyperglycaemia (HbA1c more than 48 mmol/mol [6.5%] or random plasma glucose more than 11.1 mmol/L) is caused by a combination of deficient insulin secretion and resistance to the action of insulin
risk factors type 2 DM
obesity and inactivity; diet; family history of type 2 diabetes; Asian, African, and Afro-Caribbean ethnicity; drug treatments such as long-term corticosteroids; and history of gestational diabetes.
complications type 2 DM
Macrovascular — cardiovascular disease (CVD) including ischaemic heart disease, stroke disease, and peripheral arterial disease.
Microvascular — diabetic kidney disease, retinopathy, peripheral and autonomic neuropathy.
Foot problems — including foot ulcer, deformity, infection, and Charcot arthropathy.
Metabolic — dyslipidaemia, potentially life-threatening hyperglycaemic emergencies (diabetic ketoacidosis and hyperosmolar hyperglycaemic state).
Psychosocial impact — including anxiety, depression, eating disorders, behavioural and emotional problems.
Reduced life expectancy.
diagnosis type 2 DM
persistent hyperglycaemia
polydipsia, polyuria, weight loss, tiredness; enuresis, behavioural changes, and impaired growth (in children); signs of acanthosis nigricans (suggesting insulin resistance).
management type 2 DM
- individualised care plan
- education, referral
- diabetes identification
- lifestyle measures
- sick day rules
- assess psychsocial
- sexual health
- regular HbA1C monitor
- monitor for complications
risk fx type 2 DM
obesity and inactivity
family hx
ethnicity - asian, african, afro-caribbean
gestational diabetes hx
diet - low fibre, high glucose
- drug -statins, corticosteroids, and combined treatment with a thiazide diuretic plus a beta-blocker
PCOS
metabolic syndrome
low birth weight
persistent hyperglycaemia definition
HbA1c of 48 mmol/mol (6.5%) or more.
Fasting plasma glucose level of 7.0 mmol/L or more.
Random plasma glucose of 11.1 mmol/L or more in the presence of symptoms or signs of diabetes
HbA1c not used in
Children and young people less than 18 years of age.
Pregnant women or women who are 2 months postpartum.
People with symptoms of diabetes for less than 2 months.
People at high diabetes risk who are acutely ill.
People taking medication that may cause hyperglycaemia (for example long-term corticosteroid treatment).
People with acute pancreatic damage, including pancreatic surgery.
People with end-stage renal disease (ESRD). See the CKS topic on Chronic kidney disease for more information.
People with HIV infection
tx targets if associated with hypoglycaemia
Drug treatment associated with hypoglycaemia (such as a sulfonylurea): 53 mmol/mol (7.0%).
tx options type 2 DM
start metformin
if CVD risk - SGLT inhibitor and metformin
if contraindicated or not work - add A dipeptidyl peptidase-4 inhibitor (DPP-4 inhibitor),
Pioglitazone,
A sulfonylurea
along with metformin as dual therapy
if metformin contraindicated - any mix with DPP4 inhibitor
then triple therapy
then consider insulin tx
sick day rules type 2 DM
if ACEI or Nsaids - stop
On metformin — stop treatment if there is a risk of dehydration, to reduce the risk of lactic acidosis.
On sulfonylureas — may increase the risk of hypoglycaemia, particularly if dietary intake is reduced.
On SGLT-2 inhibitors — check for ketones and stop treatment if acutely unwell and/or at risk of dehydration, due to the risk of euglycaemic DKA.
On GLP-1 receptor agonists — stop treatment if there is a risk of dehydration, to reduce the risk of AKI.
- regular monitoring
- ketone monitoring
- normal meal pattern
- advise to seek medical advice if dehydration, vomiting etc
metformin contraindications
Diabetic ketoacidosis.
Estimated glomerular filtration rate (eGFR) less than 30 mL/minute/1.73 m2.
Risk of acute kidney injury, such as dehydration, prolonged fasting, severe infection, or shock.
Conditions that may cause tissue hypoxia, such as cardiac or respiratory failure, recent myocardial infarction, or shock.
Hepatic insufficiency, acute alcohol intoxication.
metformin side effects
GI upset
lactic acidosis
vit b12 defiency
skin reactions
drug interactions metformin
Alcohol — increased risk of lactic acidosis. In addition, the hypoglycaemic effect of metformin may be enhanced by alcohol. Concurrent use is not recommended.
Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment.
Ketotifen — platelet count may be depressed when metformin is given with ketotifen. Avoid concurrent use.
Topiramate — plasma concentration of metformin may be increased by topiramate.
Other antidiabetic drugs — caution is advised when metformin is used in combination (due to the risk of hypoglycaemia).
contraindications DPP4 inhibitor
Ketoacidosis.
Hepatic impairment — avoid vildagliptin; avoid saxagliptin and alogliptin if severe hepatic impairment.
Heart failure — avoid vildagliptin if severe heart failure; avoid alogliptin if moderate-to-severe heart failure.
side effects DPP4 inhibitor
GI upset
acute pancreatitis
hepatititis
headache, dizziness
skin reaction
arthralgia
increased risk of infections
drug interactions DPP4 inhibitor
Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment.
Angiotensin-converting enzyme (ACE) inhibitors — there may be an increased risk of angioedema in people taking vildagliptin and ACE-inhibitors concomitantly.
Digoxin — sitagliptin increases plasma concentration of digoxin. No dose adjustment of digoxin is recommended, however monitor people at risk of digoxin toxicity.
Ketoconazole — plasma concentration of saxagliptin may be increased by ketoconazole.
Rifampicin — effects of linagliptin are possibly reduced by rifampicin.
Other antidiabetic drugs — the dose of concomitant sulfonylurea may need to be reduced due to an increased risk of hypoglycaemia.
pioglitazone contraindications
Heart failure or a history of heart failure.
Uninvestigated macroscopic haematuria.
Previous or active bladder cancer.
Hepatic impairment.
side effects pioglitazone
Numbness, visual impairment, weight increase, insomnia.
Increased risk of bone fractures.
Increased risk of infection.
Bladder cancer.
Hepatic impairment (rare)
interactions pioglitazone
Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked when pioglitazone is given with a beta-blocker.
Gemfibrozil — can significantly increase the plasma concentration of pioglitazone. Consider reducing the dose of pioglitazone.
Ketoconazole — the plasma concentration of pioglitazone may be increased by ketoconazole.
Nonsteroidal anti-inflammatory drugs (NSAIDs) — post marketing cases of peripheral oedema and cardiac failure have been reported. Discontinue pioglitazone if any deterioration in cardiac status occurs.
Liver enzyme-inducing drugs — rifampicin can significantly reduce the plasma concentration of pioglitazone (and the pioglitazone dose may need to be increased). Closely monitor blood glucose control during concurrent use of pioglitazone and other liver enzyme-inducers, such as phenytoin, carbamazepine, and St John’s wort, as these may also affect the plasma concentration of pioglitazone.
Other antidiabetic drugs — people taking pioglitazone in dual or triple oral therapy with a sulfonylurea may be at increased risk of hypoglycaemia. It may be necessary to reduce the dose of the sulfonylurea.
blood glucose lowering effects enhanced by
Alcohol.
Anabolic steroids.
Monoamine oxidase inhibitors (MAOIs).
Testosterone.
blood glucosem lowering effects inhibited by
Corticosteroids.
Diuretics (thiazide and related, and loop).
Oestrogens and progestogens.
sulfonylurea contraindications
Acute porphyria (glibenclamide, gliclazide, and tolbutamide).
Ketoacidosis.
Severe renal impairment.
If necessary, tolbutamide (a short-acting sulfonylurea) and gliclazide (which is principally metabolized in the liver) can be used at the lowest dose to provide blood glucose control.
Severe hepatic impairment — increased risk of hypoglycaemia.
side effects sulfonylurea
Gastrointestinal — abdominal pain, nausea, vomiting, diarrhoea, and constipation.
Hepatic impairment.
Skin — rash, pruritus, urticaria, angioedema, erythema, allergic dermatitis (usually in the first 6–8 weeks of treatment), photosensitivity reaction, Stevens-Johnson syndrome (glibenclamide).
Blood — leucopenia, thrombocytopenia, agranulocytosis, pancytopenia, haemolytic anaemia, and aplastic anaemia (tolbutamide).
drug interactions sulfonylurea
Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked when a sulfonylurea is given with a beta-blocker.
Colesevelam — the absorption of glibenclamide, glimepiride, and glipizide may be reduced by colesevelam.
The manufacturer of glimepiride advises that it is taken at least 4 hours before colesevelam.
Other drugs should be taken at least 4 hours before or after colesevelam, to reduce possible interference with absorption.
Fibrates — there may be improved glucose tolerance and an additive effect when a sulfonylurea is given with a fibrate.
Fluconazole — the plasma concentration of sulfonylureas may be increased by fluconazole.
Fluvastatin — the plasma concentration of glibenclamide may be increased by fluvastatin.
Norfloxacin — the effects of glibenclamide may be enhanced by norfloxacin.
Phenytoin and fosphenytoin — tolbutamide transiently increases plasma concentration of these drugs (possibility of toxicity).
Rifamycins — the metabolism of sulfonylureas may be accelerated by rifamycins (reduced effect).
Ritonavir — the plasma concentration of tolbutamide may be increased by ritonavir.
St John’s wort — can cause poor blood glucose control when taken in combination with gliclazide.
Topiramate — the plasma concentration of glibenclamide may be reduced by topiramate.
Trimethoprim — the effects of sulfonylureas may be enhanced by trimethoprim.
Voriconazole and ketoconazole — the plasma concentration of sulfonylureas may be increased by voriconazole, and plasma concentration of tolbutamide may be increased by ketoconazole.
Other antidiabetic drugs — the dose of the sulfonylurea (and in some cases the concomitant antidiabetic drug) may need to be reduced, to reduce the risk of hypoglycaemia.
contraindications SGLT 2 inhibitor
DKA
renal impairment - specific eGFR and HF
Severe hepatic impairment — manufacturer advises to avoid canagliflozin, empagliflozin, and ertugliflozin.
Increasing age — avoid empagliflozin if aged over 85 years, as risk of volume depletion.
Active foot disease
side effects SGLT 2 inhibitors
Vulvovaginitis, balanoposthitis, urinary tract infection (UTI) or urosepsis.
Fournier’s gangrene — this is a rare but potentially life-threatening necrotizing fasciitis of the genitalia and perineum (predominantly in men).
Complicated UTIs including pyelonephritis and urosepsis have been reported in patients treated with canagliflozin. Tubulointerstitial nephritis has been reported in people taking empagliflozin/metformin and dapagliflozin.
Constipation, nausea, thirst, dyslipidaemia, hypotension, syncope.
Lower limb amputation (canagliflozin).
Renal impairment.
interactions SGLT 2 inhibitors
Thiazide and loop diuretics — additive effect of thiazide and loop diuretics and may increase the risk of dehydration and hypotension.
Insulin and insulin secretagogues (such as sulphonylureas) — cause hypoglycaemia. Therefore, a lower dose of insulin or an insulin secretagogue (such as a sulfonylurea) may be required to reduce the risk of hypoglycaemia.
Enzyme-inducers (such as St John’s wort, rifampicin, barbiturates, phenytoin, carbamazepine, ritonavir, efavirenz) — may decrease the efficacy of canagliflozin.
Digoxin — risk of digoxin toxicity, monitored appropriately.
Dabigatran — dabigatran concentrations may be increased with canagliflozin. Monitor for signs of bleeding or anaemia when dabigatran is combined with canagliflozin.
Cholestyramine — may potentially reduce canagliflozin exposure. Dosing of canagliflozin should occur at least 1 hour before or 4–6 hours after administration of a bile acid sequestrant, to minimize possible interference with absorption.
Lithium — dapagliflozin may increase renal lithium excretion and decrease blood lithium levels.
contraindications GLP 1 agonist
ketoacidosis
pancreatitis
renal impairment
hepatic impatiment
severe GI disease eg: IBD
side effects GLP 1
acute pancreatitis
GI upset
headache, dizzy
renal impairment
skin reaction
AV block, sinus tachycardia
drug interactions GLP 1
Beta-blockers — the warning signs of hypoglycaemia (such as tremor) may be masked during concurrent treatment with a beta-blocker.
Paracetamol — lixisenatide possibly reduces the absorption of paracetamol when given 1–4 hours before paracetamol.
Warfarin — exenatide and liraglutide possibly enhance the anticoagulant effect of warfarin. Monitor the international normalized ratio (INR) during concurrent treatment with warfarin. Also consider monitoring INR at the time of initiation or stopping of lixisenatide treatment.
Other orally administered drugs — may need to be taken at least 1 hour before or 4 hours after lixisenatide or exenatide injection or taken with a meal when lixisenatide is not administered, to minimize possible interference with absorption.
Other antidiabetic drugs — due to the increased risk of hypoglycaemia, the dose of concomitant sulfonylurea may need to be reduced.
finerenone
recommended as an option for treating stage 3 and 4 chronic kidney disease (with albuminuria) associated with type 2 diabetes in adults.
contraindications finerenone
eGFR low
high K
severe hepatic impairment
side effects finerenone
electrolyte imbalance
hypotension
pruritus
drug interactions finernone
Potassium-sparing diuretics (such as amiloride and triamterene).
Mineralocorticoid receptor antagonists (such as eplerenone and sprinolactone).
Rifampicin.
Itraconazole.
Clarithromycin.
Other strong CYP3A4 inducers (such as ketoconazole, carbamazepine, phenytoin, phenobarbital, and St John’s wort).
fasting v non fasting
fasting >7 mmol
non fasting >11mmol
if HbA1C borderline high, when do you repeat reading
2 weeks
what is aim of HbA1C if moved beyond metformin?
<53
if can not use HbA1C
fructose level
