Diabetes Flashcards
2 types of T1DM
Type 1a: immune mediated (95%)
Type 1b: idiopathic (<5%)
Pathophysiology of T1DM
Autoimmune cell mediated destruction of pancreatic beta cells
Age of onset and rate of B cell destruction is quite variable. Generally rapid in infants and children, and slow in adults i.e. latent autoimmune diabetes of adulthood
Diagnosis of T1DM
Acute onset hyperglycaemia ≥11.1 mmol/L (polydipsia, polyuria, weight loss), ketosis +/- acidosis
HbA1c not used in diagnosis
Low or undetectable plasma C peptide level supports the diagnosis
Other clinical clues
- Personal or FHx of autoimmune disorders
- No FHx of T2DM
- No features of metabolic syndrome (central obesity, HTN, ^lipids)
- Failure to respond to non-insulin treatment options
Autoantibodies not routinely tested but may be positive
- GAD 65
- Insulin (AA)
- Tyrosine phosphatases (IA-2 &IA-2B)
- Zinc transporter 8 (ZnT8)
What’s latent autoimmune diabetes of adulthood (LADA)?
Subtype of T1DM
Slow progressive autoimmune destruction of beta cells
Age of onset >30
Positive titre for at least 1 T1DM antibody
May respond to oral agents initially. However starting insulin early may help preserve beta cell function.
Less likely to have metabolic syndrome
More likely to have FHx or personal history of autoimmune disease
What’s idiopathic T1DM (Type 1b)?
Accounts for <5% of T1DM
No evidence of B cell autoimmunity
Strongly inherited but not HLA associated
Africans and Asians
Permanent insulinopenia (low or undetectable plasma c peptide level) Prone to ketoacidosis
Associated conditions of autoimmune T1DM
Autoimmune thyroid disease e.g. Grave’s
- Monitor TSH, thyroid antibodies every 2 years
Addison’s disease
Coeliac disease
- Monitor coeliac ab every 2 years
Vitiligo
Autoimmune hepatitis
Myasthenia gravis
Autoimmune gastritis –> pernicious anaemia
- Monitor B12 every 2 years
What’s the typical starting dose for insulin?
0.5IU/kg/day (50% should be administered as bolus with meals)
Why should we rotate the areas of insulin administration?
To avoid lipohypertrophy and atrophy = erratic insulin absorption
Rotate between abdomen, thighs, buttock, upper arms
How does insulin analogues compared to human analogues?
Insulin analogues have less hypoglycaemia, less weight gain, achieve lower HbA1c
How does continuous subcutaneous insulin infusion (CSII) compared to multiple daily injections?
Less severe hypoglycaemia
More HbA1c lowering
What’s insulin sensitivity factor?
How much BSL is lowered in 2-4 hours with 1 unit of rapid acting insulin?
What’s insulin carbohydrate index?
How many grams of carbohydrate is covered by 1 unit of insulin?
List treatment options other than insulin for T1DM
Whole pancreas transplant
Islet transplant
Both require lifelong immunosuppression to prevent graft rejection
Downsides to HbA1c
Measures average BSL over 3/12
Doesn’t tell you glycaemic variability or hypoglycaemia
Affected by RBC turnover, blood loss, Hb variants, time in hypoglycaemia
Management of hypoglycaemia
15g glucose (2-3 tsp honey or sugar/100ml soft drink/glucose tab)
Glucagon
Who is at risk of hypoglycaemia unawareness?
Increasing age Long diabetes duration Aggressive glycaemic control Frequent hypoglycaemia Autonomic neuropathy Medications e.g. beta blockers
What’s continuous glucose monitoring?
Measures interstitial glucose level every 1-5 minutes
Correlates well with plasma glucose level
Provides glucose trends over 24h period
Can be connected to mobile or pump
Reduces time in hypoglycaemia without compromising HbA1c, improves HbA1c, improves in target range
What’s continuous subcutaneous insulin infusion (CSII) pump therapy?
Advantages?
Disadvantages?
Insulin is infused continuously to mimic normal basal secretion, and boluses with meals or when BSL is high
Advantages: can lower HbA1c, reduce severe hypoglycaemia rates, less injections, less variable insulin absorption
Disadvantages: $$$, infection risk, pump failure/needle dislodgement (ketoacidosis), need to wear an external pump
What to do with CSII during DKA?
Switch it off (probably pump failure)
Do normal DKA management
Criteria for DKA
Ketosis
BSL >14
Venous pH <7.3 and/or bicarb <20
Features of severe DKA
Ketones >6 pH <7.1 or bicarb <5 K <3.5 GCS <12 SpO2 <92% SBP <90 HR <60 or >100
Criteria for HHS
BSL >30
Minimal ketosis
Serum osmol >320mOsm/kg
Coma present in 1 in 3
DKA vs HHS
A lot of overlap!!
DKA usually has lower BSLs, while HHS BSLs >56!
DKA presents earlier due to ketosis symptoms (dyspnoea) and are generally younger (able to excrete glucose better)
HHS presents in older people –> poor renal function so can’t excrete the glucose
DKA is due to absolute insulin deficiency –> body reverts to lipolysis –> increased FFHA –> ketogenesis –> acidosis
Alot more fluid in HHS (8-10L) compaerd to DKA (3-6L)
HHS
Decreased insulin or resistance –> decreased glucose utilisation in skeletal muscle –> increased fat and muscle breakdown –> increase in glucagon, cortisol and catecholamines + increase in hepatic gluconeogenesis –> increased BSL –> glycosuria + osmotic diuresis (further aggravate dehydration)
Causes of ketosis
DKA
Ketotic hypoglycaemia (occurs in children after a night of fasting)
Starvation ketosis
Alcoholic ketosis
Symptoms and signs of DKA
EARLY
Nausea, vomiting, abdo pain, hyperventilation
Symptoms of hyperglycaemia - polyuria, polydipsia, weight loss
LATE
Lethargy, focal deficits, obtundation, seizure, coma
Precipitants of DKA
Infection Inadequate insulin - new onset diabetes, lack of insulin increase with sick day, non-compliance Myocardial ischaemia, stroke Drugs e.g. steroids Endocrine - hyperthyroidism, Cushing's Pancreatitis Trauma ETOH excess, illicit drugs
Management of DKA in the first hour
Hour 1
x2 IVCs
1) 1L normal saline over 1/24 (cannula 1)
2) If K>3, start IV novorapid 0.1 unit/kg/hr (max starting dose 10 units/hr) (cannula 2)
If K<3, replace K (cannula 2)
3) Other
- Septic screen +/- abx
- Fluid balance chart
- Neuro obs
- Remove CSII pump
- Cardiac monitoring
- DVT prophylaxis
- Give patient’s usual long-acting insulin
4) Monitor
- Do BSL and ketones at the end of hour 1
Management of DKA hour 2-4
1) Continue IVT (cannula 1)
- 500ml/hr for hour 2
- 500ml/hr for hour 3
- 250ml/hr for hour 4
2) Give K infusion over 1 hour via “Y’ site (cannula 1)
If serum K>5 or patient anuric - withhold
If serum K 3.5-5, give 10mmol/100ml
If serum K<3.5, give 20mmol/100ml
3) Insulin + glucose (cannula 2)
- Continue initial insulin rate (novorapid 0.1IU/kg/hr) if BSLs decreasing and pH increasing, and ketones decreasing
- Increase insulin rate if pH is not increasing or if BSLs are not decreasing
- When BSL <14, give 10% glucose 100ml via “Y” site
- Maintain BSL 9-14
- May need to reduce or cease insulin infusion if becoming hypokalaemic
4) Monitor Hourly BSLs UECs and VBG at end of hour 2 and 4 Ketones at end of hour 4 Fluid balance chart (catheter if oliguric)
Subsequent management of DKA after hour 4
1) Continue IVT
- Normal saline 125ml/hr until patient is fluid replete or eating/drinking
2) Continue K replacement to maintain within reference range (cannula 1)
3) Insulin
- Continue insulin at variable rate to maintain BSL 9-14
- Allow oral intake if no clinical evidence of ileus, bowel obstruction or acute abdomen.
- If eating but still requiring IV insulin, consider giving mealtime subcut insulin
4) Monitor
Hourly BSL until insulin infusion ceased
UEC and VBG at end of hour 8 and 12
Ketone at end of hour 6 then Q4H until ketones <0.6
When to transit people from DKA protocol to subcut insulin?
Patient well and eating/drinking Anion gap is normal <12 Ketones <0.6 Long-acting insulin has been given at least 2h ago (or pump recommenced) pH >7.3 and bicarb >18
Anion gap and bicarb take hours-days to normalise
Ignore mild persistent acidosis if above criteria are met and there is hyperchloraemia
Complications of DKA
Dehydration + electrolyte disturbance –> circulatory instability and arrhythmias
Vascular thrombosis (DVT prophylaxis!) - Coronary, bowel, cerebral, DVT/PE, limb
Sepsis
Aspiration
ARDS
Cerebral oedema
- Mainly Children
- High mortality
- Gradually lower the glucose (3mmol/hr) and Na+ especially when BSLs have been 30+ for weeks (HHS)
Best marker for resolution of DKA
resolution of ketones
Acidosis takes time to resolve
What’s the role of bicarbonate in DKA?
May be used in severe DKA pH <7
Low level balance
What’s the role of phosphate replacement in DKA?
Not routinely replaced
Consider in cardiac dysfunction or respiratory depression if PO4 <1mmol/L
How long should subcut and IV insulin overlap in DKA/HHS management?
2 hours
Complications of hyperglycaemia
Dehydration + electrolyte disturbance
Lactic acidosis (major surgery + metformin)
DKA
Infection
Long-term: CV disease
BSL target in hospital
5-10
What to do with these pre-op?
1) Metformin
2) Sulphonylureas
3) Glitazones (thiazolinediones)
4) Acarbose
5) GLP1 agonist or DPP4
6) SGLTi
7) Long-acting insulin
8) Bolus insulin
1) Withhold day of surgery (or 24h for major surgery)
2) Withhold day of surgery
3) Withhold day of surgery
4) Withhold day of surgery
5) Withhold day of surgery
6) Withhold at least 2 days before surgery and day of surgery
7) Give normal insulin day before
1/2 basal insulin day of surgery
Monitor BSLs Q2H from 1st missed meal to surgery
IV 5% dextrose if BSL <10
Give PRN short acting insulin if BSL >10
8) Withhold short-acting insulin while fasting
Where is glucose reabsorbed in kidneys?
SGLT1+2 transporters in the PCT
Adverse effects of SGLT2i
Increased urogenital infections
Euglycaemic DKA
Urinary frequency
Hypovolaemia (especially if on concurrent diuretics) and hypotension
Increased risk of LL amputation and fracture
How does SGLT2i cause euglycaemic DKA?
Rapid fall in serum glucose –> fall in plasma insulin –> rise in plasma glucagon –> low insulin:glucagon ratio stimulates lipolysis –> mild ketosis –> when combined with severe insulin deficiency e.g. fasting –> ketoacidosis
Precipitants
- Prolonged fasting
- Reduction in insulin when starting on SGLT2i
- Sepsis
- Significant ETOH intake
- Exercise
Mechanism of action of DPP4 inhibitors ‘gliptins’
Eat –> release of active incretins GLP1 and GIP from GI tract –> stimulate beta cells to increase insulin and inhibit glucagon release from alpha cells
Delays gastric emptying –> less nutrients being delivered rapidly to the bowel and gives insulin more time
Acts on hypothalamus to suppress appetite
DPP4 enzymes degrade GLP1 and GIP. By inhibiting DPP4, you get increase in insulin and decrease in glucagon
Do DPP4 inhibitors cause hypoglycaemia?
No unless compared with insulin or SU
They stimulate beta cells to secrete insulin 24/7
Which DPP4 inhibitor can we use in renal impairment?
Linagliptin
Excreted in bile and gut
Mechanism of action of GLP1 agonist
Eat –> release of active incretins GLP1 and GIP from GI tract –> stimulate beta cells to increase insulin and inhibit glucagon release from alpha cells
Delays gastric emptying –> less nutrients being delivered rapidly to the bowel and gives insulin more time
Acts on hypothalamus to suppress appetite
Similar to DPP4 inhibitors
Benefits of DPP4 inhibitors other than BSL effects
Weight loss
No CV benefits
If atherosclerotic CV disease predominates but HbA1c is suboptimal despite metformin, what’s the next drug that should be added?
GLP-1 agonist preferred or SGLT2i as 2nd line (if eGFR adequate)
If further therapy needed consider adding DPP4i, basal insulin, TZD, sulphonylurea
(Relative) Contraindications to SGLT2i
eGFR <30 (may be used but lacking data)
Genital thrush infections
Recurrent UTIs or IDC
Ketosis prone
Dehydration - need to drink lots to make up for polyuria (can be difficult in HF patients with FR)
Low BP - may need to reduce antihypertensives/diuretics
Low BMD + frequent falls = high risk of #
If HF or CKD predominates but HbA1c is suboptimal despite metformin, what’s the next drug that should be added?
Particularly HFrEF with LVEF <45% or CKD eGFR 30-60ml/min or UACR >30mg/g (particularly >300mg/g)
SGLT2i preferred (if eGFR adequate) or GLP1 agonist as 2nd line
If further therapy needed, consider adding DPP4i, basal insulin, sulphonylurea
Avoid TZD
Which OHG to avoid in HF?
TZD
Pathophysiology of T2DM
What happens during the course of T2DM from diagnosis to late stage?
In early T2DM, there is insulin resistance –> high glucose despite hypersecretion of insulin by a depleted beta cell mass –> glucotoxicity destroys more beta cells –> absolute insulin deficiency –> requires insulin therapy
What’s the criteria for remission of T2DM
1) Previous diagnosis of T2DM
2) Off anti-diabetic medication for 2 months
3) HbA1c <6.5 OR
Fasting BSL <7 AND 2-hour glucose <11
Which is the most effective bariatric surgery in treatment of T2DM?
Gastric bypass
Can lead to remission of T2DM
Bariatric surgery is very effective in improving glucose tolerance through weight and non-weight related mechanisms
Predictors of T2DM remission
Short duration of DM (before beta cell further deteriorates)
Younger age (Gastric bypass has a high remission rate)
Not requiring insulin or other complex regimen
Macro and microvascular complications of T2DM
Macrovascular
- heart disease
- stroke
- PVD
Microvascular
- Retinopathy
- Neuropathy
- CKD
Mechanism of SGLT2i
Works on PCT and reduces reabsorption of Na and glucose –> lowers BP (osmotic diuresis from glucose and Na), glucose and weight (calories), lowers uric acid (lose uric acid in urine along with glucose), reduces albuminuria (as extra Na pass through the tubular glomerular apparatus, there is negative feedback to the afferent arteriole in the glomerulus to constrict –> reduce intraglomerular pressure –> reduce hyperfiltration)
How are ACEI/ARB renoprotective?
Relax efferent arteriole in glomerulus –> decrease intraglomerular pressure –> initial decrease in eGFR followed by stabilisation –> decreased albuminuria
MOA of metformin
Class: biguanides
MOA:
- Reduce hepatic glucose production
- Increase insulin sensitivity - increase glucose utilisation in peripheral tissues
Disadvantages of GLP1 agonists
Currently only comes as injection
Increased risk of pancreatitis
MOA sulphonylureas
Directly stimulates insulin release by increasing beta cell responsiveness
Disadvantages of sulphonylureas
Weight gain
Hypoglycaemia - highest risk with longer acting agents
MOA of TZD e.g. pioglitazone
Increases insulin sensitivity in peripheral tissue
Decrease liver production of glucose (lesser extent)
Advantages of TZD
Doesn’t cause hypoglycaemia
In patients with T2DM and NASH, improves fibrosis, inflammation and steatosis
Disadvantages of TZD
Increased risk of
- HF
- Oedema
- Fractures
- Weight gain
- Possible small increase in bladder cancer
- Macular oedema
- Hepatotoxicity (hasn’t happened with pioglitazone but did happen for a previous TZD that has subsequently been removed from the market)
Do DPP4i, SGLT2i and GLP1 agonists cause hypoglycaemia?
Not on their own
List 2 long-acting insulins
Insulin glargine (optisulin) (duration 24h)
Insulin determir (levemir) (duration 12-24h)
Onset 1.5-2h
Plateaus over the next few hours and has a flat duration of action (small peak at 6h)
List 3 rapid-acting insulins
Insulin aspart (novorapid) Insulin lispro (humalog) Insulin glulisine (apidra)
Onset 5-15 minutes
Peak in 1-2 hours
Duration 4-6 hours (affected by the dose)
What’s an intermediate-acting insulin?
NPH Human insulin (Humalog)
Onset 1-2h
Peak 4-6h
Duration 12h
Is actrarapid faster or novorapid?
Novorapid
What are the 2 stages of diabetic retinopathy?
1) Non-proliferative
2) Proliferative
Features of non-proliferative diabetic retinopathy
Non-proliferative: microaneurysms form in the blood vessels of the eye, which can burst to leak blood —–> pre-proliferative: changes are increasingly severe and widespread, and includes bleeding into the retina
Divided in
Mild: microaneurysm (can burst to leak blood)
Moderate: retinal dot and blot haemorrhages, hard exudates or cotton wool spots
Severe: intraretinal haemorrhages, definite venous beading, intraretinal microvascular abnormalities
Features of proliferative diabetic retinopathy
New blood vessels and scar tissue form on the retina, causing loss of vision
Neovascularisation
Vitreous or preretinal haemorrhage
What’s diabetic macular oedema?
Microaneurysms –> vascular leakage and accumulation of plasma constituents (hard exudate) in the macula
Most common renal lesion found in diabetic nephropathy
Diffuse glomerulosclerosis
Nodular glomerulosclerosis is pathognomonic
Stages of diabetic nephropathy
1) Hyperfiltration - increased GFR
2) Microalbuminuria
- 30-300mg/day
- Progression to >300mg/day - detected on dipstick
- Yearly screening recommended to detect disease at early stage
3) Decrease in GFR +/- proteinuria
Management of diabetic nephropathy
With the onset of microalbuminuria, need aggressive treatment
1) Glycaemic control
- Consider SGLT2i
2) BP control
- ACEI/ARB may help slow progression to overt proteinuria/ESKD
- Overt proteinuria >1g/day, aim BP <130/80
Potential environmental triggers of T1DM
Both genetics and environemntal
Enterovirus
Cogenital rubella
Pathogenesis of T1DM
Beta cell destruction (autoimmune is >90%)
Remember it does not include beta cell destruction or failure due to specific causes e.g. CF, post pancreatectomy
Which HLAs (2) are expressed in patients with T1DM?
Which HLA is protective?
What chromosome are they on?
HLADR3 and DR4 are expressed in 95% of white patients with T1DM
HLADR2 is protective
Present as a polymorphic region on chromosome 6
Order the following familial risks for developing T1DM from high to low
Risk for siblings of diabetic patient
Risk for HLA identical sib
Risk of general population
Risk for identical twin
Offspring of type 1 diabetic woman
Offspring of type 1 diabetic man
Both parents with type 1
Risk for identical twin 40%
Both parents with type 1 30%
Risk for HLA identical sib 15%
Risk for siblings of diabetic patient 5-10%
Offspring of type 1 diabetic man 6.1%
Offspring of type 1 diabetic woman 2.1%
General population 0.6%
Name 5 clinically important autoantibodies for T1DM
Out of the 5 of them, which is the most important?
Older ab
Islet cell antibodies
Insulin antibodies
Newer ab
Anti-GAD* - most important
Anti-IA2
Zinc transporter 8
These days we send all 3 of the new ab
Screening for T1DM
Who should be screened?
First degree relatives of T1DM
How do we screen for T1DM?
Measure anti-GAD and anti-IH2 ab
Measure HLA status for DR3 and/or DR4
If all positive, monitor insulin secreting potential (after IV glucose) every year for the next 5 years. If all normal, then stop. If abnormalities, then need close monitoring and need treatment before development of DKA.
This will identify 90% of patients who will develop T1DM.
Won’t catch the sporadic cases.
Pathogenesis of T2DM
Insulin resistance + relative insulin deficiency (not secreting as much as you need)
- Defective glucorecognition - Higher the BSL, the worse the beta cell function (they fail to recognise high BSLs when there’s high BSLs in a subacute setting e.g. over few weeks)
- Beta cell mass loss is late stage
Is T2DM genetically inherited?
Strong genetic basis for T2DM
- Monozygotic twins 90% concordance
- Dizygotic twin 40% concordance
- Offspring of T2DM diabetic women have 2-3 fold greater risk of developing diabetes than the offspring of men with this disease
- If both parents have T2DM, 90% of child having T2DM
However little is known about the actual genetics. No HLA association.
Which of the genes is the biggest risk for T2DM?
TCF7L2 gene defect
Maturity onset diabetes of youth (MODY)
Which Genetic defects is most common?
HNF-1alpha = MODY 3 = on chromosome 12q
Very sensitive to sulphonyureas
Develop complications so must treat
Maturity onset diabetes of youth (MODY)
Glucokinase enzyme defect
Explain characteristics
Mild hyperglycaemia Minimal complications MODY 2 Chromosome 7q May not need treatment
Complications of GDM
Large babies
Increased peri-natal mortality rates
Birth defects: not as high as in type 1 pregnancy patients
How to prevent T2 diabetes?
Diet and exercise
- 60% risk reduction in development of diabetes even without weight loss
Metformin also works but not as good as lifestyle
Rosiglitazone
- 60% risk reduction
In T2DM, does very intensive lifestyle prevent CV disease?
No
Sulphonylureas - what allergy are you concerned about?
Sulphur allergy
Don’t use it
Sulphonylurea MOA
Stimulates release of inuslin from the beta cell
Unregulated hence get hypoglycaemia
Which sulphonylurea is preferred?
Gliclazide
Lowest risk of hypoglycaemia
Metformin MOA
Increase insulin action
Decrease hepatic gluconeogenesis
Increase peripheral glucose uptake (less effect)
Minor decreasing glucose absorption in the gut
Do not use metformin if
Ketosis prone diabetes Pregnant Nephropathy Impaired renal function Liver damage HF (low perfusion state)
Acarbose MOA
Alpha-glucosidase inhibitor
Inhibits breakdown of oligo/disaccharides in the brush border of the gut
Decrease HbA1c by 1% at most
Weakest OHG
Do you get hypoglycaemia with acarbose?
no
TZD “glitazones” efficacy
POWERFUL insulin sensitiser
More powerful than metformin
Why don’t we use TZD “glitazones” often?
Side effects +++
Weight gain Fluid retention/CCF ?Cardiac disease (rosiglitazone increases AMI risk; pioglitazone decreases AMI risk) Fractures ?Bladder cancer (pioglitazone)
Incretin mimetics MOA
GLP-1
GIP
Incretins are GIT hormones that are both decreased in T2DM
GLP-1 stimulates insulin release + decreases glucagon release = lower BSL
Increase satiety
DPP4 inhibitor (DPP4 breaks down GLP1)
or
GLP1 analogue injections
GLP1 analogues MOA
Increase insulin Decrease glucagon Slows stomach emptying Decreases appetite Decreases weight (3kg in 6/12, 5kg in 2 years) Decreases food absorpt
Examples GLP1 analogues
Exenatide
- given twice daily or weekly
Dulaglutide
- Human GLP 1
Semaglutide (new)
- Most useful
- Biggest weight lowering effect and biggest HbA1c reduction
Work just like GLP1 but are resistant to breakdown by DPP4! Hence can last up to a week
GLP1 analogues hypos?
No
But can do it with SU or insulin
GLP1 analogues AE
N&V
Delayed Gastric emptying effects are too strong
DPP4 inhibitors examples
Sitagliptin Vildagliptin Saxagliptin Linagliptin ALogliptin
DPP4 advantages and disadvantages
Oral
Less N&V compared to GLP1 analogues
Disadvantage
Relies on endogenous production of GLP1 (low in T2DM) so they’re relatively weak OHGs
No weight loss
SGLT2i MOA
SGLT2 is responsible for reabsorption of glucose (90% of 180g glucose is filtered through the glomerulus)
= If we inhibit this, we block 90% reabsorption
= Lose glucose in urine
SGLT2i advantages
Weight loss (calorie loss)
Lowers BP (osmotic diuresis)
Lowers HbA1c
Low risk of hypos
SGLT2 cons
Genital infections and candidiasis (fungus loves glucose)
Must be eGFR >30
Syncope/hypotension
Euglycaemic DKA
- Stop 3/7 before coming to hospital for planned procedure
If they go to sleep with low BSL and wake up with high BSL.
What’s dawn phenomenon?
What’s somogyi effect?
Dawn: Diurenal rise in cortisol and GH
Rx: increase basal insulin
Somogyi: rebound effect from hypo overnight, get secretion of counterregulatory hormones e.g. cortisol, NA, adrenaline, glucagon, GH which kicks the BSL up before they wake
Rx: decrease basal insulin
Measure the BSL at 3am to tell the difference
What is the longest acting insulin?
Degludec (only found in Ryzodeg)
When to do Insulin infusion pre-op?
Only in T1DM
Intense glucose control in T1DM
Is it good?
Good for retinopathy, microalbuminuria
BUT
no significant change in macrovascular disease
and
3 fold increase in serious hypoglycaemia
Hence we aim Hba1c 6.5-7% in T1DM
Intense glucose control in T2DM
Is it good?
Better HbA1c
Better microvascular end points and almost macrovascular disease (need a long time like 20 year+; and much lower disease if good diabetes control early in the disease)
But
More weight
Don’t lower BSLs too quickly
General HbA1c target for T2DM
≤7%
Except if lots of other comorbidities, then aim higher
No CV dx + metformin ≤6%
No CV dx + anything less than insulin ≤6.5%
Recurrent hypos ≤8%
Do TZDs have increased AMI risk?
Rioglitazone has increased AMI risk
Pioglitazone actually showed decreased AMI risk
DPP4i
CV outcomes?
No difference in AMI risk
BUT saxagliptin and alogliptin showed increased risk of HF-related hospitalisation; but sitagliptin showed decreased risk for HF-related hospitalisation
SGLT2i
Benefits
Decreased CV death, non-fatal MI, HF hospitalisations (including HFpEF)
Renal profective
Weight loss
BP lowering
No hypoglycaemia unless compared with insulin or SU
GLP1 analogue
Benefits
Decreased CV death, non-fatal MI, non-fatal stroke
BUT no HF reduction
Weight loss
BP lowering
No hypoglycaemia unless compared with insulin or SU
Rapid reduction in BSLs can cause
Worsen existing retinopathy but won’t cause NEW retinopathy
Factitious hypo
How do you prove it?
Low/zero c-peptide but high insulin level
Then you know the patient has injected insulin
Exception is SU - get high insulin and high C-peptide, but then you can do a SU-assay which will be high
Not related to meals
Look out for “medical personnel”
Insulinoma hypo
Characteristics
High c-peptide
Late (>8h after meals) hypo
Impaired glucose tolerance hypo
Characteristics
Highest c-peptide
Rapid (~1h after meal) hypo
Eat –> high BSL due to insulin resistance –> body produces more insulin to compensate –> insulin overshoots and causes hypo
Thing that causes most mortality in DKA is
Hypokalaemia
Why is anti VEGF important in diabetic retinopathy?
What does it do?
Good guy in vascular disease –> gives you collateral
Bad guy in oncology and retinopathy (ischaemia –> distressed cells –> secrete VEGF –> neovascularisation of fragile BVs –> bleeds –> traction and fibrosis –> blindness)
So if you inject anti VEGF to those with macular oedema or proliferative retinopathy, we can prevent new vessel formation.
We don’t use laser anymore (destroy vision to preserve central vision)
When to screen for complications of T1DM and T2DM?
T1DM: within 5 years of treatment
T2DM: from diagnosis
Pick it up early to prevent it from getting wrong
Diabetic nephropathy
Management
Control BP
ACEI/ARB (independent of BP lowering)
BP target in T2DM
In general, 140/80
If diabetic nephropathy, then 130/80
Dyslipidaemia in T2DM
Management
1st line: statin
The lower the LDL, the better
2nd line: ezetimibe
3rd line : PCSK9
Fenofibrate doesn’t prevent CV disease, but does slow progression of established retinopathy
Starvation ketosis
Management
Just feed the patient
Not acidotic
