Avoiding Diabetic ComplicationsGPCME, Rotorua- 2015

Dr Manish Khanolkar, MD, MRCP, FRACP

Consultant Physician & Diabetologist, ADHB

Senior Lecturer in Medicine, University of Auckland

Tutor, University of Leicester, Online Diploma Diabetes course (BMJ group)

What I will cover….

• The micro and macrovascular complications of diabetes

• Case scenarios

• Tips on what can be done to delay/ halt complications

• Some medication related issues

• Diabetic foot problems

• Briefly- hypoglycaemia

Micro and Macro vascular complications

Micro

Macro

Others-1. DKA/ HHS2. Hypoglycaemia3. Infections4. Medication related

Association between mean HbA1c and complications - UKPDS

Adapted from Stratton IM et al, on behalf of UKPDS, 2000

Stratton IM et al. on behalf of the UK Prospective Diabetes Study Group. BMJ 2000; 321:405–12.

3 case scenarios…

Case C

50 years, male, T2d for last 5 years

Peripheral neuropathy

Similar BP/ lipids etc

Case B

50 years, male, T2d for last 5 years

Nephropathy

Similar BP/ lipids etc

Case A

50 years, male, T2d for last 5 years

Retinopathy

Similar BP/ lipids etc

1. Retinopathy

2. Peripheral neuropathy

3. Nephropathy

4. All contribute equally

Which diabetes complication correlates the most with cardiovascular risk?

Diabetic Nephropathy

• Irreversible

• Why treat?- slow/stop progression and also REDUCE CV RISK

• Low eGFR and proteinuria- both independent and powerful predictors of CVD/ mortality

• Refer all <75 years and eGFR<45 (stage 3b)/ many when eGFR <60

• Sudden big jump in creatinine or proteinuria always needs to be worked up soon

Nephropathy detection

Urinary ACR

• Early morning spot urine

• 2 out of 3 samples

• Micro when ACR >2.5mg/mmol (M), >3.5mg/mmol (F)

• Macro when ACR >30 mg/mmol

• UTI excluded, also poor control, heavy exertion, acute illness

eGFR- MDRD vs CG calculator

• Stage 1- >90 with proteinuria/haematuria

• Stage 2- 60-90

• Stage 3- a- 45-60

3- b- 30-45

• Stage 4- 15-30

• Stage 5- <15 (ESRD)

• Not calculated in acute/ hospitalised patients- AKI

Key points…

ACE inhibitors or ARBs firstwhether or not hypertension is presentMonitor renal function and K+ carefully esp if any renal impairment

prior to commencing – recheck after 5-7 days

Optimising blood pressure control – often multiple agents, salt restriction, fluid status. Target ideally < 130 SBP

Avoid potentially nephrotoxic medications e.g. NSAIDs

Assess/treat for CV risk and other eye, nerve, foot problems

ACE inhibitors and ARBs

• Creatinine clearance30% increase in serum

creatinine may occur and

25% reduction in eGFR

• More pronounced inDehydration- advice to STOP

Decompensated CHF

Bilateral renal artery stenosis

FIELD

study

www.nzssd.org.nz/cvd

Case study….

49 yrs, Man, T2D for over 5 years

Longstanding poor glycaemia- HbA1c consistently >100 mmol/molfor over 2 years

On Protaphane insulin 30 units bd and metformin 1 g bd

Suddenly gets compliant with diet/ exercise/ insulins etc- HbA1c drops to 61 mmol/mol from 105 mmol/mol 2 months ago

But now feels more miserable- suddenly has developed severe tingling and pain in both feet

Diagnosis- insulin neuritis

But how?

Leow M K S , and Wyckoff J Postgrad Med J 2005;81:103-107

Impact of glycaemic swings on endothelial cells(Ceriello et al)

Management

• Aim for gradual glycaemic improvement

• Exclude other causes- ETOH, Vit B12 def- pernicious/ vegan/ on metformin

• Usually self limiting

• On occasions- tricyclics/ gabapentin/ opiates if significant pain

And remember….

• Similar situation may arise with retinopathy

• Classic scenario- Referred to eye clinic from retinal screening- the penny drops- glycaemia suddenly improves- retinopathy worsens!

• Retina screened regularly during pregnancy …..

AccordThe Action to Control Cardiovascular Risk in Diabetes Study Group

• N=10,000• 1/3 already on insulin/ 1/3 prevalent CVD events

• Age 62/ Diabetes for 10 years

• HbA1c 8.3

Strategy of (ultra) intensive glycaemic control aiming for HbA1c 6 (achieved 6.3)

Accord- results

The mean difference during the trial was 1.1%

Accord

Talking of J curves

AJC 2013; vol 111; 1209-1213

Learning points…

• Cautious with too much intense glycaemic control- esp elderly/ premorbidities

• Go slow and steady….

Mr LK, 48 years

• Married with 3 young children

• Heavy Goods Vehicle driver

• T2D- 7 years

• Bilateral preproliferative retinopathy/ Macular oedema awaiting macular grid laser/ microalb/ Feet normal sensations

• BP 126/76 mmHg, BMI 36 kg/m2

Current Medications

• Metformin 1 g bd

• Gliclazide 160 mg bd

• Cilazapril 5 mg od

• Simvastatin 20 mg od

Current hbA1c 68 mmol/mol (8.4%)

BG diary

BB AB BL AL BD AD 2-3am

Sunday 8.8

Monday 9.1 11.2

Tuesday 12.1

Wednesday 8.6 9.8

Thursday 9.7 9.9

Friday 8.9

Saturday 12.3 12.2

Will not consider insulin- what are his options…..

Pioglitazone AVOID- significant macular oedema

Insulin sensitizer/ moves visceral fat to subcutaneous sites- valuable in some patients

Use slowly declining- fluid retaining properties- heart failure, pedal oedema

Osteoporosis especially females

Bladder tumours- especially after prolonged use/ higher dose- review use after 2-3 years

What other options….

GLP-1 agonists (Exenatide) or DPP4 inhibitors (gliptins)- not yet funded by pharmac

SGLT2 inhibitors- Forxiga (dapagliflozin)- not funded yet/ polyuria may be unappealing

What else apart from individualised glycaemic management…• BP is to target

• Lipid profile on simvastatin-

T Cholesterol- 3.8 mmol/l, LDL-C- 2.2 mmol/l, HDL-C- 0.8 mmol/l

Triglycerides- 2.6 mmol/l (fasting)- consistent with metabolic syndrome

Any role for adding in a fibrate?

FIELD study

• Fenofibrate Intervention and Event Lowering in Diabetes

• Multinational study- NZ, Australia, Finland

• Around 10,000 T2D subjects/ age 50-75 years

• Fenofibrate 200 mg a day versus placebo

• Laser treatment for retinopathy- prespecified tertiary endpoint

FIELD- results

Fenofibrate use in T2D

• In those with preexisting retinopathy- Reduced 2 step progression of retinopathy/ less need for laser treatment

• Independent of lipid effects- possibly by inhibiting VEGF/ reduced endothelial cell apoptosis/ reduced inflammation

• Benefit within 8 months of treatment/ benefits additive to better glycaemia/ BP control

• BUT….. Not subsidised- hopefully there is a class effect

Learning points…

• Caution with using glitazones in setting of heart failure/ macular oedema

• Review longer term use of glitazones- bladder tumours/ osteoporosis especially in females

• Consider fibrate therapy in T2D patients with established retinopathy-? Role of bezafibrate

Mr MD, 67 years

• T1D for over 30 years

• HbA1c consistently in 70s for last many years

• Bilateral mod-severe retinopathy/ Neuropathy/ no evident nephropathy

• Previous marathoner

Presents with swollen, red, painful left foot-no obvious trigger….

Patient progress…

• Has had multiple antibiotic courses/ NSAIDs

• DVT ruled out/ good pedal pulses

• Waxing and waning of symptoms

• Few months later- ulcer over the area

Imaging….

Confirms acute charcots

Treatment of acute Charcot foot• Treat co-existing infection

• Cellulitis, ulcer or osteomyelitis

• Offloading, offloading and offloading• Immobilise in total contact cast

• Change cast frequently as oedema settles

• Non-weight bearing

• Subsequent protective weight bearing: orthotics

• Anti-resorptive therapy: little evidence

Charcot foot: Why?

• Multiple predisposing factors• Neurotraumatic theory vs. Neurovascular theory

• “Uncontrolled inflammation”

“The goal in the treatment of CN is to achieve a

plantigrade, stable foot that is able to fit into a shoe and to

also prevent a recurrent ulceration”

Talking of diabetic foot ulcers (DFU)…

• Annual incidence of DFU 1-4% with a lifetime risk of 15-25%

• Risk of recurrence 50-70% over 5 years

• 15% of DFU result in LE amputation

• After initial amputation, risk of contralateral amputation- 25-68% in next 3-5 years

• 85% of nontraumatic LE amputations attributed to DM

Alavi et al, J Am Acad Dermatol, 2014

Learning points…..

• Hot/ swollen/ painful foot- think Charcots- long DM history, neuropathy

• Attention to the other foot

• Risk stratify feet- Low risk/ high risk foot/ active foot

• Education is key

• Clear pathways/ access

Mr TH, 75 yrs

• 4 am- Daughter found him collapsed in bathroom/ confused/ slurred speech/rt facial droop/ right sided weakness.

• Bilateral LL pain/ redness for 1/52- not seen GP as concerned would need amputation.

• May have taken extra Glibenclamide previous night (normally takes 1 tab mane).

• Previous IHD/ Emphysema/ No h/o ETOH

Impression- ?Cerebrovascular event

• BG paramedics- 2.3 mmol/l

• Weakness/ confusion improved with hypoglycaemia treatment

• Can hypoglycaemia cause focal neurological deficits- YES

• Does this person need hospital admission- YES

Rajendran R et al, BMJOpen, 2014

Learning points…..

• Hypoglycaemia may present like a TIA

• Caution with sulphonylureas especially in elderly

• Avoid glibenclamide (longer halflife) wherever possible/ switch if necessary

• May need hospital admission especially if severe episode/ cannot monitor and treat oneself- some patients may need octreotide (anti-dote)