Most things Diabetes

Question 1

• tide Drug class

Answer 1

GLP 1 agonists

Question 2

• gliptin Drug class

Answer 2

DDP4 inhibitor

Inhibit DDP4 which increases incretins like GLP-1 level (not metaglised ny DDP4) Causes rise in insulin secretion + inhibition of glucagon

Question 3

• glitazones

Answer 3

Thalizodinediones

Question 4

-gliflozins Drug class

Answer 4

SGLT2 inhibitors

Question 5

indications for HDU in HHS

Answer 5

Consider HDU care for those with osmolality > 350, sodium > 160, PH < 7.1, K+ abnormalities, GCS < 12, ↓ O2 sats, SBP < 90, tachy or bradycardic, evidence of significant AKI.

Intubation and ventilation required for severely unwell especially if ↓ GCS

Question 6

management of HHS

Answer 6

1. Aggressive fluid replacement
   
   • 0.9% NaCL + K+ as indicted by U&Es
     
     • Swap to 0.45% NaCl if osmolality is not ↓ with adequate fluid resuscitation
     • Initial ↑ in Na+ is expected, should not prompt change of fluid
   • Aim for 3-6L by 12 hours depending on weight and extent of dehydration
   • Aim to ↓ glucose by no more than 5mM/h and sodium by 10mM/24 hours
   • Encourage oral intake as soon as safe to do so
2. IV insulin infusion
   
   • Only required if glucose no longer falling with fluid resuscitation alone or significant ketonuria (++)
   • 0.05 IU/kg/hour fixed rate
3. Treat the underlying precipitate
4. VTE prophylaxis
5. Monitoring - serial glucose, U&E, neuro obs

Question 7

Ix for HHS

Answer 7

• Bedside
  
  • Weight - guide fluid resuscitation
  • GCS/AVPU
  • Urine dipstick - glucose +++, ketones may be mildly ↑ (+)
  • ECG
• Bloods
  
  • VBG - ↑ glucose, normal pH (pH > 7.3, bicarbonate > 15)
  • Serum osmolality - > 320 mmol/L, normal 290 + 5
  • U&Es (Na+ often ↑)
  • FBC, CRP - exclude infection
  • CK - screen for rhabdo
• Specialist or scoring
  
  • Calculate osmolarity
• assessing for infection - urine/blood MC&S, CXR

Question 8

diagnostic criteria for HHS

Answer 8

Diagnostic criteria - patient is clinically hypovolaemic

• pH > 7.3 (no acidosis)
• Serum osmolarity > 320 mosmol/kg
• Blood glucose > 30mM

Question 9

treatment of DKA

Answer 9

Question 10

criteria for DKA

Answer 10

• pH < 7.3 and bicarbonate < 15
• Plasma glucose > 11mM
• Blood ketones > 3 mM or ++ in urine

Question 11

what is the management of T2DM

Answer 11

• Advice: diet, exercise, reduce CVD risk, foot care, DVLA
  
  • medical
    
    • Conservative – diet and exercise advice, weight loss
    • Metformin - monotherapy
      
      • r/v if eGFR < 45, stop if < 30
      • CI: eGFR < 30, tissue hypoxia (MI, surgery), iodine contrast (stop 24 hrs prior → 48hrs after), alcohol abuse (relative)
    • dual therapy:
      
      • DDP-4 inhibitor (gliptins, e.g. sitagliptin) Good if overweight
      • pioglitazone (thiazolidinedione)
        
        • • sulfonylurea (glibenclamide, gliclazide)
      • SGLT2 inhibitor (e.g. empagliflozin)
    • triple therapy
      
      • can consider GLP-1 analogue if BMI > 35, or BMI < 35 with occupational consequences of insulin treatment
    • Insulin based treatment
      
      • continue metformin for cardio + renal protection

if metformin CI or not tolerated as 1st drug use another for mono → dual → insulin

Question 12

What are the NICE targets for T2DM?

Answer 12

NICE targets:

• 48 mmol/mol HbA1c = diagnostic + target
• if drug associated hypoglycaemia aim for 53 mmol/mol
• If HbA1c not adequately controlled by single drug and rises to over 58 mmol/mol consider intensifying treatment and aim for < 53 mmol/mol

Question 13

Meeran’s guide for T2DM medical treatment (step 1+2)

Answer 13

• Diet + exercise + lifestyle
• Metformin = everyone unless CI
• Step 2 → consult diabetes team for recommendation
  
  • Guidelines have changed to say you can use anything.
  • GLP-1 agonist if obese
    
    • Expensive, currently only injectable, but new ones coming orally
  • SGLT2 if ischaemic heart disease
    
    • Very good if heart failure
  • Gliclazide for everyone else/money important
    
    • Used to be gliclazide as always second line

Question 14

when can HbA1c not be used for diagnosis of DM?

Answer 14

Inappropriate to use HbA1c in paediatrics, ?T1DM, < 2/12 of symptoms, medications impairing glucose metabolism, significant pancreatic damage, pregnancy

Question 15

what are the target BM in DM if on insulin (T1DM mainly)?

Answer 15

Aim for sugars of: 4-7 pre-meal, < 9 post-meal

Question 16

Types of insulin regime

Answer 16

• Types of regimes
  
  • Basal-bolus regime - 1st line
  • Twice daily regime - biphasic insulin given pre-breakfast and pre-evening meal
    
    • Mixed of intermediate acting with rapid or short acting
  • Pump therapy - continuous SC insulin infusion

Question 17

management of T1DM

Answer 17

• Conservative
  
  • Structure education program (DAFNE course)
  • Advice: reduce CVD risk, foot care advice, DVLA
• Medical
  
  • Aim for sugars of: 4-7 pre-meal, < 9 post-meal
  • Blood sugar monitoring - 1st and last thing in the day, prior to each meals.
  • Insulin therapy
    
    • Short acting - dose calculated using insulin unit: carbohydrate ratio
    • Long-acting
  • Optimise health - statins if ↑ lipids, anti-hypertensives if ↑ BP
• Monitoring
  
  • HbA1c every 3-6 months
  • Annual review: retinopathy (annual), nephropathy, vascular disease, diabetic foot (at clinic), CVD risk factors

Question 18

what is the diagnostic criteria for DM?

Answer 18

Symptomatic + 1 biochemical test indicating hyperglycaemia

• Fasting glucose > 7
• Oral glucose tolerance test with 75g glucose - 2hr blood sugar > 11.1
• Random glucose > 11.1
• HbA1c > 48 (> 6.5%) → only for T2DM
  
  • Normal < 42, pre-diabetes is 42-47 (6-6.4%)

Asymptomatic + 2 biochemical tests indicating hyperglycaemia

Question 19

MOA of DDP-4 inhibitors and examples

Answer 19

secretagon

Inhibitor DDP-4 which increases insulin secretion and decreases glucagon secretion by preventing DDP-4 breakdown of incretins (e.g. GLP-1)

• “gliptin”
  
  • Alogliptin
  • Linagliptin
  • Saxagliptin
  • Sitagliptin
  • Vildagliptin

Question 20

sulfonylurea MOA and examples

Answer 20

• Insulin secretagon
  
  • Augment insulin secretion, requires some residual beta cell function
  • Bind + close ATP-sensitive channels so beta-cells depolarise opening Ca2+ channels and release of insulin granules
  • May inhibit hepatic glucose production
• gliclazide

Question 21

Thiazolidinodiones MOA and example

Answer 21

Bind to PPARs (PPAR-gamma) in adipocytes to promote adipogenesis and fatty acid take up

• “glitazones”
  
  • Pioglitazone

Question 22

Exenatide, liraglutide etc

class:

SE:

Cautions/risk:

benefit:

Answer 22

Exenatide, liraglutide etc

• class: glucagon-like-peptide-1 mimetic (GLP-1 analogue)
• SE:
  
  • GI disturbance
  • Interacts with warfarin
  • Common - ↓ appetite, dizzy, skin reactions
  • Uncommon – drowsy, renal impairment
• Cautions/risk:
  
  • Exenatide + liraglutide are weekly SC injection
  • CI – ketoacidosis, severe GI disease
  • Caution – elderly, pancreatitis
• benefit:
  
  • prevents weight gain, may cause weight loss → good if BMI > 35

Question 23

alogliptin, sitagliptin etc

class:

SE:

Cautions/risk:

benefit:

Answer 23

alogliptin, sitagliptin etc

• class: DDP-4 inhibitor
• SE: headache, constipation, dizzy, skin reaction
• Cautions/risk:
  
  • CI - ketoacidosis
  • hypersensitivity reaction (SJS)
• benefit:
  
  • weight loss
  • reduced CVD deaths

Question 24

gliclazide etc

class:

SE:

Cautions/risk:

benefit:

Answer 24

gliclazide etc

• class: sulphonylurea
• SE:
  
  • hypoglycaemia
  • weight gain
  • hyponatraemia
  • GI disturbance
  • liver dysfunciton
  • agranulocytosis (rare)
• Cautions/risk:
  
  • CI: high BMI, elderly, G6PD deficiency

Question 25

pioglitazone etc

class:

SE:

Cautions/risk:

Answer 25

pioglitazone etc

• class: thiazolidinodiones
• SE:
  
  • weight gain (common)
  • # , infection, numbness visual impairment
• Cautions/risk:
  
  • increased risk of HF, bladder cancer, bone #
    
    • avoid if other RF for this

Question 26

MOA of SGLT2 inhibitors and examples

Answer 26

• Sodium-glucose co-transporter 2 inhibitor → reduced glucose resorption in kidney inducing glycosuria
• “gliflozin”
  
  • Canagliflozin
  • Dapagliflozin
  • Empagliflozin
  • Ertugliflozin

Question 27

Empagliflozin, Dapaglifozin, etc

class:

SE:

Cautions/risk:

benefit:

Answer 27

Empagliflozin, Dapaglifozin

• class: SGLT 2 inhibitors
• SE:
  
  • serious - DKA
  • Common – balanoposthitis hypoglycaemia (if + insulin or sulfonylurea), thirst, urosepsis/UTI,
  • Uncommon – dehydration, dizzy, hypotension, renal failure, syncope
• Cautions/risk: DKA, increased risk of lower limb amputation
• benefit: weight loss, cardioprotective

Question 28

metformin

class:

SE:

Cautions/risk:

benefit:

Answer 28

metformin

class: biguanide

SE: GI upset, altered taste, rare (hepatitis, skin reaction, reduced B12 absorption, lactic acidosis)

Cautions/risks: contraindicated → acute metabolic acidosis, eGFR < 30; caution → other RF for acidosis

benefit: cardio + renal protection, not linked with weight gain

Question 29

biguanides

example medication

mechanism of action

Answer 29

metformin

complex mechanism but helps patient’s utilise insulin better

• decreases hepatic glucose production
• decreases intestinal absorption of glucose
• improves insulin sensitivity by increasing peripheral glucose uptake and utilization