Diabetes Flashcards
Background
Endocrine pancreas:
Pancreas has endocrine and exocrine tissue. Exocrine makes digestive enzymes.
Endocrine pancreas = millions of cells together called Islets of Langerhans. Islets 4 main cells:
- Alpha cells secrete glucagon - increases BG, breaks down glycogen into glucose.
- Beta cells secrete insulin - decreases BG by helping glucose uptake into tissues and helps make glycogen from glucose.
- Delta cells secrete somatostatin which inhibits the secretion of glucagon and insulin from alpha and beta cells
- PP (gamma) cells - secrete pancreatic polypeptide - function unknown
- Beta cells - also secrete amylin (amyloid polypeptide- delays gastric emptying and opposes insulin= stimulates glycogen breakdown in striated muscle.
Diabetes:
Group of metabolic disorders which persistent hyperglycaemia is caused by deficient insulin secretion or resistance to insulin action.
- Leads to Carbs, Fat, protein metabolism issues.
Types:
- Type 1, Type 2 - most common
- Gestational - happens during pregnancy then resolves after birth
- Secondary - causes = pancreatic damage, hepatic cirrhosis, or endocrine disease or treatment with endocrine, antiviral, or antipsychotic drugs.
Risk factors
T1DM:
- Genetics
- Environment - diet, VIT D exposure, Obesity, Early life viruses with islet inflammation
T2DM:
- Obesity and inactivity
- Family history
- HTN +/OR Dyslipidaemia
- Ethnicity - Asian, African, afro-Caribbean 2-4 X more likely
- History of gestational diabetes
- Diet - Low fibre High glycaemic index
- Drugs: Statins, corticosteroids, and combo treatment of thiazide diuretic + a beta-blocker
- PCOS
- Metabolic syndrome
- Low birth weight for gestational age
- Pregnant >30 yrs age or Previously birth to large child, or had gestational DM(GESTATIONAL)
Pre diabetes
Describes impaired glucose tolerance - IGT
Fasting glucose 6.1-7.0 mmol/L
Rises to 7.8mmol/L 2 hrs after oral glucose intake (OGTT)
Clinical manifestations:
* Often none at all.
* Mild polyuria.
* Mild nocturia.
* Mild polydipsia.
Assessments & Diagnosis
Symptoms of polyuria, polydipsia, and unexplained weight loss, +:
* Random venous plasma glucose ≥ 11.1 mmol/L or
* Fasting plasma glucose (FPG) ≥ 7.0 mmol/L or
* Plasma glucose ≥ 11.1 mmol/L after an oral glucose tolerance test (OGTT) [see bottom$].
IF asymptotic dont do diagnosis on 1 test but 1 more result on another day in diabetes range is needed. Can be random, fasting or OGTT.
IF fasting and random aren’t diagnostic then do OGTT results.
- HbA1c (Glycated haemoglobin) = forms when RBCs are exposed to glucose in the plasma. Test reflects average plasma glucose over last 2 to 3 months and helps show glycaemic control. Don’t require special preparation. 48mmol/mol (6.5%) = cut off point for diagnosing diabetes. BUT less dont mean there no diabetes.
WHEN NOT TO USE HbA1c: - ALL children & young
- Any age sus of T1DM
- Diabetes Symptoms <2 months
- Pregnancy
- High diabetes risk and acutely ill
- Treatment with meds that can cause hyperglycaemia
- Acute pancreatic damage
- End-stage CKD;
- HIV infection.
Use HbA1c in caution for people with abnormal haemoglobin, anaemia, altered red cell lifespan, or had a recent blood transfusion.
TYPE 1 DM:
- HbA1c not used as diagnostic. Other glucose tests used
- YOUNG: Random PG ≥11 + Polyuria, polydipsia. weight loss, excessive tiredness.
- ADULT: Random PG ≥11 + can show 1 or + of: Ketosis, rapid weight loss, age <50, BMI <25, Personal/family Hx of autoimmune disease.
TYPE 2 DM:
Persistent hyperglycaemia =
- HbA1c of ≥48 mmol/mol
- FPG ≥ 7.0
- Random PG ≥ 11.1 with diabetes signs/symptoms
YOUNG: Persistent hyperglycaemia + symptoms (polydipsia, polyuria, nocturia, blurred vision, unexplained weight loss, recurrent infections, tiredness) or Behaviour change (reduced school performance and/or impaired growth) or sign (acanthosis nigricans) or risk factors present.
ADULT: HbA1c hard to read THEN diagnose by FPG.
$ OGTT - Mainly got IGT diagnosis not needed for diagnosis when severe symptoms of hyper glycaemia present.
- IF less severe symptoms and BG conc. dont show/exclude diabetes then OGTT can be used.
OGGT = Measure BG conc. after fasting and then 2 hrs after drinking (75g glucose) standard anhydrous glucose drink or ALT Polycal® or as Rapilose® OGTT oral solution.
Type 1 Diabetes
- Characterised by lack of insulin production due to beta cell defect.
- Caused by T cell mediated autoimmune response causing pancreatic beta cell destruction.
- Destruction and reduced insulin production takes years, symptoms show over days/weeks.
- Occurs any age most common juveniles.
- Islet cell antibodies marker for immune destruction.
TREATMENT
- New diagnosed - offered patient education programme with 6-12 months of diagnosis,
- Diet - Carb counting training should be offered, Dietary advise (Avoid sugary drinks and fruit juices) (eat healthy balanced diet)
- Do physical activity T1DM ppl more risk of CVD.
- Offer Continuous glucose monitoring (CGM) to self monitor.
- Still need capillary BG tests with CGM can be less often
TREATMENT GOALs:
Refer to treatment monitoring
DRUG TREATMENT
Requires insulin replacement with active management of CV risk factors (HTN, High circulating lipids).
1ST LINE - multiple daily basal bolus insulin regimen:
BASAL:
BD insulin detemir OR OD insulin glargine(100 units/ml)/Detemir = long acting.
ALT OD Insulin degludec (long act) - ESP if nocturnal hypoglycaemia a concern.
- ALT IF need Carer/HCP to administer = ultra long acting eg- insulin degludec, or insulin glargine 300 units/ml.
BOLUS:
Rapid-acting insulin analogue B4 meals. (eg ASPART or LISPRO)
ALT TO 1ST LINE: BD human mixed insulin regimen:
IF getting hypoglycaemia that affects life quality with human mixed ALT is BD Analogue mixed regimen.
Disabling hypoglycaemia or High HbA1c (69 or +) with multiple daily injection try = Continuous SC Insulin infusion.
- BUT need specialist to initiate.
Insulin dosing:
Will need to be adjusted according to regular BG results.
Poor glucose control can lead to erratic insulin need to periods of hypoglycaemia. Can happen due to poor adherence, technique, lifestyle (diet, alcohol), mental issue, renal, coeliac, Addison’s disease or gastroparesis.
Increase dose = Infection, stress, accidental or surgical trauma
Decrease dose = Physical activity, intercurrent illness, reduced food intake, impaired renal function, certain endocrine disease.
Insulin REGIMENS T1DM
Multiple daily injection basal-bolus:
- 1 or + separate daily injections of intermediate or long acting insulin- BASAL. PLUS Multiple BOLUS injections of short acting insulin B4 meals.
- Offers flexibility to tailor to each meals carbs demand.
Mixed (biphasic) regimen:
- 1-3 insulin injection/day of short acting mixed with intermediate.
- Insulin preparations may be mixed by the patient at injection time, or can use premixed product.
Continuous SC insulin infusion (insulin pump):
- regular or continuous amount of insulin (usually form of a rapid-acting insulin analogue or soluble insulin), given by programmable pump and insulin storage reservoir via a SC needle/cannula.
Examples of insulins:
Rapid act = Aspart (NovoRapid®), lispro (Humalog®)
Short act = Soluble (Actrapid®)
Intermediate act = Isophane (Insulatard®, Humalin I®)
Long act = Glargine (Lanctus®), Detemir (Levemir®), Degludec
Mixed/biphasic = NovoMix®30 (30% insulin Aspart, 70% insulin Aspart protamine)
Types 2 diabetes
Characterised by insulin resistance and insufficient pancreatic insulin production, resulting hyperglycaemia
Basic pathophysiology:
1. Diet high sugars + Carbs = Can cause elevated insulin.
2. Tissues where insulin work become unresponsive:
A- Down regulation insulin receptor
B- Impaired signalling which recruit GLUT 4
3. Insulin sensitive tissue now unresponsive and resistant to insulin effects.
4. Pancreatic Beta cells make more insulin = hyperinsulinemia
5. Beta cell now insulin depleted.
TREATMENT
NON Pharmacological:
- Lifestyle mods (weight loss, eating a healthy diet, smoking cessation, regular exercise)
- Diet (same advise a T1DM)
DRUG TREATMENT:
Initial 1st line:
- Metformin SR (dose should be titrated up). IF GI effects USE Metformin MR.
CHF or Established atherosclerotic CVD or HIGH risk of CVD ADD SGLT2i. But start only after metformin tolerability confirmed.
- Metformin contraindicated ALT DDP4i or pioglitazone, or a sulfonylurea or SGLT2i (1st choice if CVD issues apply)
Repaglinide also ALT BUT only can be used in combo with metformin so ruins treatment pathway.
Further treatment options:
- IF develop CHF or Established atherosclerotic CVD or HIGH risk of CVD ADD SGLT2i.
Monotherapy with metformin fail to control HbA1c CAN ADD DDP-4i or pioglitazone, or a sulfonylurea.
Dual therapy FAIL THEN
Triple therapy - Regimens:
- Metformin + a sulfonylurea, + canagliflozin, dapagliflozin, or empagliflozin; OR
- Metformin + pioglitazone, + canagliflozin or empagliflozin; OR
- Metformin + a DPP-4i and ertugliflozin (only if a sulfonylurea or pioglitazone inappropriate).
ALT to triple = Insulin treatment
* Elderly or renal impaired at risk of hypoglycaemia if on sulfonylurea = use short act (gliclazide/ tolbutamide)
TRIPLE fails then try GLP1 + triple therapy switch 1 drug BUT only use GLP1 IF:
* BMI ≥35 + mental/medical obesity issues OR
* BMI <35 & insulin affect occupation or Weight loss with GLP 1 beneficial.
- Insulin + GLP 1 = specialist.
INSULIN TREATMENT:
- Provide support programme (shows does titration, techniques, self monitor, diets and glucose)
REGIMENS:
* human isophane injected OD or BD
* human isophane injected + Short act either separately or pre mixed prep
* ALT to above 2 - Detemir or Glargine OD
* Biphasic (pre mixed) prep (INC. Short act human analogue - preferable for injecting B4 meal or Hypoglycaemia issues or BG CONC. rises high after meals.
When insulin started bedtime basal insulin to be started and dose titrated for morning (fasting) glucose. isophane, dtermir, glargine to be monitored for short act need B4 meals.
Biphasic monitored for further short act need b4 meals or Change to basal bolus regimen with isophane, detemir, glargine if BG inadequate.
Diabetes - pregnancy and breast-feeding
Already have DM keep HbA1c <48 and advised to take FOLIC ACID.
DRUGS:
ALL drugs except metformin to be stopped b4 pregnancy SUB with insulin.
Metformin used as adjunct if benefit outweigh risk.
BF - Only metformin rest to be avoided.
Insulin:-
Isophane 1st line long act BUT
If already on detemir or glargine and works well can continue.
Continuous SC infusion can be used if injections not working.
-Women with insulin and pregnancy need to know of Hypoglycaemia risk esp. in 1st trimester, Always carry fast act glucose (dextrose tab or glucose drink)
- AFTER birth reduce insulin. BG monitored to find dose
Diabetic complication & pregnancy:
ACEi/ARBs need to be stopped and swapped.
Statins to be stopped b4 planned pregnancy.
Gestational diabetes
Diagnosis:
- FPG level of =/>5.6mmol/l OR
- 2-hour PG level of =/>7.8mmol/l (OGTT)
Management:
Change diet and exercise 1st to reduce BG.
After 1 -2 week no change try METFORMIN. ALT/ADD insulin
FPG>7 immediately start insulin +/- metformin
FPG 6-6.9 + complication macrosomia (newborn larger than average) or hydramnios (excess amniotic fluid around baby) = immediate INSULIN +/- metformin
DISCOINTINUE ALL AFTER BIRTH
Monitoring targets / Self management
Self monitoring BG:
Pre meals- 4-9mmol/L
Post meals- 5-9mmol/L at least 90 minutes after
HbA1c (mmol/mol):
T1DM- <48
T2DM- on >1 Drug therapy/Drugs that cause hypoglycaemia: <53
On Lifestyle therapy <48
BP(mmHg):
T1DM-
ACR <70mg/mmol aim <140/90, ACR >70mg/mmol aim <130/80, Aged 80+ <150/90
T2DM- <140/90
CV risk assessment/review:
Kidney damage surveillance:
- 1st urine of the day once yearly – send for estimation of ACR. <30mg/gm = normal. Test helps to identify kidney disease that can come from diabetes.
Eye care surveillance:
On diagnosis refer to eye screening service. Sudden loss of vision, rubeosis iridis, pre retinol or vitreous haemorrhage or retinal detachment or any sudden large unexplained drop in visual acuity – refer to ophthalmologist.
Foot care surveillance:
On diagnosis and at least annually, asses risk of diabetic foot problems. 10mg monofilament foot sensory examination, check for ulceration, callus, infection/inflammation, deformity, gangrene, Charcot arthropathy.
Self management:
Insulin patients monitor:
4-6 times/day b4 and after meals
- Needed to modify dose of insulin and diet
- admin Technique checked yearly
Urine Glucose monitor:
- Rarely used less desirable than blood
- renal threshold of glucose varies between ppl.
- Fluid intake and urine conc. affects results
- Test dont reflect glucose level at results time
- -ve result dont differentiate between hypo or hyper glycaemia
Diabetes Complications
- Microvascular (i.e., retinopathy, nephropathy and neuropathy).
- Macrovascular (i.e., IHD, PVD, cerebrovascular disease).
- Metabolic abnormalities
- Hyperglycaemia:
Symptoms - Excessive thirst, polyuria, tiredness, blurred vision
Causes- Infection, stress , excess CARBS, poor adherence, new meds - Hyperosmolar Hyperglycaemic State (HHS):
Medical emergency, Occurs in T2DM - will need hospitalisation
Develops over weeks, can become unconscious.
Suspect diagnosis if person is unwell with severe hyperglycaemia (BG >30) for several days and exps
dehydration and infection.
Symptoms: Urination, thirst, nausea, dry skin, disorientation and later stages drowsiness + slow loss of consciousness.
Treatment: Underlying cause, normalise BP/osmolality, Replace fluid and electrolyte loss, Prevent arterial/venous thrombosis, cerebral oedema or foot ulceration - Diabetic ketoacidosis (DKA):
More common with T1DM.
Sus diagnosis DKA with diabetes or BG>11 with symptoms: polydipsia and polyuria, weight loss, abdominal pain, N+V, SOB, Lethargy , drowsiness, Confusion, fruity acetone smell breath, tachypnoea, acidotic breathing, tachycardia, dehydration, or shock and Blood or urinary ketones.
Adult: Test 4 Blood or urinary ketones even if BG near normal
Young: Test 4 Blood ketones even if BG levels near normal or arrange for hospital admission.
Ketones: High = Urinary ketones>2 OR capillary blood ketones >3.
Low blood ketones dont exclude DKA.
SGLT2i STOP ASAP if DKA sus.
Don’t Restart SGLT2i IF exp. DKA unless another cause identified and resolved.
Treatment: Fluid replacement, insulin therapy, Correct electrolyte imbalances.
- Diabetic Foot
Ulcers can cause amputations. Caused by PVD (leads to poor circulation = pains + ulcer)
Complicated poorly fitting footwear causing local trauma/ pressure
3 Categories of foot ulcer:
1. Neuropathic - painless depressed appearance and can be deep. Peripheral neuropathy = loss of pain sensation
2. Ischaemic: Painful mainly on end of toes. caused by PVD = reduced blood flow and O2 and nutrients for healing
3. Neuro-ischaemic
From ulceration foot can be infected can lead to AMPUTATION. - Neuropathy
DM damages peripheral nervous tissue, causing neuropathy. 3 main classes: (Table in pack)
1. Autonomic - Joint deformity, Nerve damage CVS = Silent MI masks chest pain, Gastroparesis, diarrhoea, postural Hypotension, sweating
2. Motor - affects nerves transmission to muscles = muscles weakness, deformity and wasting which causes pain.
3. Sensory - Most common Mainly affects feet/legs. loss of sensation, numbness, pain, tingling
Treatment: (EXTRA)
Pain - optimal diabetic control
Acute painful diabetic neuropathy. Self limiting or simple analgesics NO RESPONSE = TCA or SNRi OR pregabalin, gabapentin
Diarrhoea - Tetracycline or codeine or antidiarrheal
Postural hypotension - Fludrocortisone can + flurbiprofen and ephedrine or Midodrine
Sweating - propantheline
- Retinopathy
Early detection prevents
Optimal diabetic and BP control prevents onset and progression. - Nephropathy
Characterised by changes the glomerulus and interstitial tubules
Protein in urine
Life threatening
Defined by raised albumin excretion = >300mg/day or proteinuria (dip stick test). Albumin in urine increase CVD risk.
Usually 20-25 years after DM onset.
Treatment:
BP reduced to lowest possible = slows decline of GFR and reduce proteinuria. ACR ≥3 use ACEi or ARA even if BP normal.
CKD patient + proteinuria: ACEi or ARA monotherapy
T2DM + CKD already on them add SGLT2i if ACR >30. if ACR 3-30 consider it. - CVD
5 fold increase in diabetics. Manage BP and lipids.
Driving/Alcohol advice
Driving:
- AVOID HYPOGLYCAEMIA
- If on insulin have testing device/strips with you
- BG checked 2 hrs b4 driving and every 2 hrs whilst
- BG conc. min 5mmol/L when driving. If below snack should be taken.
- IF BG <4 mmol/L or warning signs show STOP driving ASAP wait 45 min till BG normal (5mmol/L)
ALCOHOL:
- Can mask hypoglycaemia.
- Recommended to consume in moderation or with food.
HYPOGLYCAEMIA RISK & TREATMENT
Mild if self treated. Severe if assistance needed.
Common side effect of insulin and sulfonylureas therapy. Other meds not likely to cause Hypoglycaemia.
Exclude in people with DM who is: acutely unwell, drowsy, unconscious, can’t co-operate, or presenting with aggressive behaviour/seizures.
- Hospital inpatient with DM IF BG <4 mmol/L need treatment
- test Awareness of hypoglycaemia annually - Gold score or Clarke score.
- Increase in frequency of hypoglycaemic eps may reduce the warning symptoms experienced by the patient
- Beta blocker can mask hypoglycaemia symptoms
TREATMENT:
Adults with symptoms and BG conc. >4 - treat with small carbs snack (bread slice, or normal meal if due)
Any patient BG <4 with/without symptoms able to swallow and conscious TREAT WITH Fast acting CARBS by mouth EG:
- Lift® glucose liquid/Glucojuice®,
- Glucose tablets,
- Glucose 40% gels (e.g. Glucogel®, Dextrogel®, or Rapilose®),
- Pure fruit juice, and
- Sugar (sucrose) dissolved in right volume of water)
Oral forms absorbed quicker.
- IF K+ diet due to CKD NO ORANGE JUICE.
- Sugar water NO IF ON ACARBOSE (prevents breakdown of sucrose to glucose)
- AVOID chocolates and biscuits (low sugar high fat - delays stomach emptying)
IF NEEDED REPATS 15 MINS max 3X
Once BG >4 GIVE long act CARB (eg 2 biscuits, bread slice, 200-300mL normal milk)
IF ABOVE FAIL THEN (BG <4 after repeats):
- IM glucagon or glucose 10% IV infusion.
- Alcoholic = Thiamine supplements with or after IV glucose = reduce risk of Wernicke’s encephalopathy.
GLUCAGON NOT USED IF:
Fasted for a prolonged period or has adrenal insufficiency, chronic hypoglycaemia, or alcohol-induced hypoglycaemia
= USE IV glucose.
EMERGENCY:
Decreased consciousness = IM glucagon if FAIL after 10 min = Glucose 10% IV infusion.
Unconscious = seizures, or aggressive IV insulin stop ASAP. Initial Glucagon fail 10 min response ALT glucose 10/20% IV infusion.
WHEN RECOVERD (BG >4) long acting CARB.
- Glucagon user need longer carbs (X2 previous examples)
If insulin injection due dont miss it But review regimen. IV insulin once BG >3.5 restart after reviews. BG monitor next 2-3 days.
Drugs info breif
Metformin- Reduces hepatic glucose production (gluconeogenesis) is increased in T2DM. increases glucose uptake and utilisation in skeletal muscle, reduces CARBS absorption and reduces circulating LDL and VLDL.
Sulfonylureas e.g., gliclazide, glipizide, glimepiride, glibenclamide, Tolbutamide - High affinity receptors for sulfonylureas are present on K+ channel, KIR6.2, ATP-sensitive K+ channel in the pancreatic beta cell. Rise in intracellular levels of ATP, after glucose metabolism inhibits the KIR6.2 channel, sulfonylureas block the outflux of K+. = partial membrane depolarization = activation of voltage-gated Ca2+ channels, Ca2+ entry and exocytosis of secretory granules with insulin.
- AE- Weight gain, Hypoglycaemic risk - moderate/High in elderly, GI issues, (glibenclamide SJS)
- Contraindicated: DKA, acute porphyrias, severe renal/hepatic impairment, avoid in P/BF
Thiazolidinediones
(glitazones) e.g., Pioglitazone -
Bind to PPARg = conformational changes helps binding to PPRE which important in insulin signalling, fat metabolism and fluid volume.
Monitor - LFT Sign of HF (Weight gain, odema)
- AE - Weight gain, bladder cancer, higher risk bone fracture, visual issues, insomnia
- Contraindicated: DKA, HF, Hx HF, Hx or active bladder cancer, haematuria, hepatic impairment,
Alpha Glucosidase inhibitors -Acarbose - Inhibition of this enzyme = delays in CARBS absorption, reducing the postprandial increase in BG = lowering BG
- Contraindicated: Disorders of digestion/absorption; hernia (can worsen it); IBD; predisposition to intestinal obstruction
Dipeptidyl peptidase 4 inhibitors (DDP4i)/ GLIPTINS e.g., alogliptin, sitagliptin, saxagliptin vildagliptin -
Potentiate endogenous incretins by competitively inhibiting this enzyme which breaks down incretins (DDP4)
Incretins (GLP-1. GIP) act on Beta and alpha = stimulate inulin release and inhibit glucagon release
AE- Gi issues, pancreatitis, Hypersensitivity, headache, tremor dizziness
Contraindicated- P/BF, Ketoacidosis, hepatic impairment (alogliptin for severe impairment only), HF vidahliptin - severe/ alogliptin - moderate to severe.
GLP 1 agonists
- Contraindicated: Hypersensitivity, DKA, P/BF, >80, Hx of pancreatitis, severe GI disease, Severe renal impairment (liraglutide), renal impairment (exenatide SR & liraglutide eGFR<30, exenatide MR eGFR<50, liraglutide & semglutide end stage renal disease)
SGLT-2 e.g., canagliflozin, dapagliflozin, empagliflozin - Inhibit sodium glucose transport protein 2 in renal proximal convoluted tubule, to prevent reabsorption of glucose from filtered blood, facilitating glucose urinary excretion.
- AE - Weight loss, UTI, renal impairment.
- Contraindicated: DKA, Severe hepatic impairment, initiation if eGFR<60, continue if eGFR <45, canagliflozin & foot disease
Insulin - Replaces missing 1.
- Weight gain, Hypoglycaemic risk high
- Contraindicated: check individually
