Diet and Drugs

Dr Angela Koh

Dr Ester Yeoh

Ms Jasmine Kwan

Case 1

• Miss J, 25 year old – Diagnosed with diabetes in 2007

• HbA1c 15%, weight 67.8 kg BMI 26.1 • Started on Glibenclamide 5mg om then increased to bd

within 1 week with no improvement in BG=> started on Mixtard + metformin thereafter at another hospital

• HbA1c improved to 9.3% but stayed around 9+% • GAD Ab +ve, C-peptide in 2007 was 1130 (no corresponding

glucose) • Switched to MDI regimen with insulatard and actrapid in Sep

2008 – HbA1c worsened, ranging from 12 – 15% for next 3 years in spite

increasing doses of insulin.

• 1st visit Feb 2013: – HbA1c 13.4% Blood glucose 44.3 mmol/L – Symptomatic from hyperglycaemia – polyuria, polydipsia,

weight loss => 58.8kg – Admitted to not taking her insulin shots regularly, esp. pre-

meals – did not like to wait ½ hr after actrapid and would mostly “forget” the insulin

– Started back on insulin regimen, switched to Novorapid with higher pre-meal dosing + metformin

• Apr 2013 – HbA1c >14% (point-of-care) – Home BG monitoring – pre-breakfast and dinner readings

mostly in mid-teens, pre-lunch 8-10 mmol/L – Has put on weight – 65.1kg – Says regular with insulin now, but snacks a lot in between

meals (before dinner and at night) on junk food (potato chips, chocolates, cookies etc.)

How would you manage this patient?

A. She must not be compliant to insulin – scold her some more and ask her to take her insulin regularly

B. Ask her to stop snacking on junk food

C. Ask her to take extra Novorapid when taking snacks

D. Increase insulin dose

E. Refer her to diabetes specialist

Reasons for poor glycaemic control

Medications

Lifestyle Disease Factors

Psychosocial Factors

• Insulin injection technique •When •Where •How

•Compliance

• Diet •Exercise

• Stress

• Depression • Eating Disorders/Body Image Issues

• Diabetes progression • Intercurrent illness • Other diseases/medications causing worsening of glycaemic control e.g. corticosteroid use

Lipohypertrophy

Injection Technique

• Preferred sites: Abdomen > thigh > buttocks

• Needles: generally 4-6 mm

• Change needles for each injection

• Inspect insulin – clarity, bubbles; roll the vial/pen for cloudy insulin

• Inspect site

• Hold time – 10 seconds (pen)

• Avoid insulin leakage, bleeding or bruising

Compliance to Insulin Therapy

• Possible reasons for lack of compliance

– Insulin regime not suitable to lifestyle

• Consider onset, duration and peak action

• Analogues vs regular insulin

Other Options for Therapy

• Education

• Dietary advice

• Non-insulin adjunct therapies to insulin-treated diabetes

– Metformin

– DPP4 inhibitors

– GLP1 RA

– Others - SGLT2 inhibitors

Focus

Shortcomings of insulin treatment

• Other pathophysiological contributors such as glucagon is not treated

• The most “rapid”-acting insulins still peak too late to match postprandial glycaemic peak

• Glucose variability and hypoglycaemia are major problems in optimising glucose control

• Obesity is an increasing problem in diabetes, which insulin treatment can worsen

Incretin-based Therapies with Insulin in T2DM

/DPP4 Inh

DPP4- inhibitors and GLP1 RA in T1DM

• DPP4 inhibitors – small trials, pilot data, 8 weeks follow-up Ellis et al, Diabet Med 2011

– Reduced BG levels (on CGM) with reduced total and prandial insulin dose

– Improved HbA1c (~0.3%)

• GLP1 RA – more data in clinical trials – Reduces insulin dose

– Favours weight loss, attenuates weight gain

– Improved or unaltered glycaemic control

– Reduced or unchanged occurrence of hypoglycaemia Kuhadiya, Endo Pract 2013, Varanasi EJE 2011, Kielgast, Diab Care 2011, Rother Diab Care 2009

All type 1 diabetes patients require insulin therapy. Remind patients not to stop s/c insulin therapy when starting add-on agents!

DPP4 Inhibitors with Basal Insulin in T2DM

• Addition of DPP4 inhibitors to once daily basal insulin + metformin resulted in greater HbA1c reduction compared to placebo (0.7% vs 0.13%)

– No reduction in FPG but primarily from improvements in PPG

– Lower rates of hypoglycaemia

– Less weight gain (Fonseca, Diabetologia 2007; Rosenstock Diab Obes Metb 2009; Hong ES Diabetes Obes Metab 2012)

• Improvement in HbA1c (Seino, Diabet Obes Metab 2012; DeVries, Diab Care

2012)

• Hypoglycaemia incidence +/- (compared to basal insulin + placebo)

• Will require adjustment of insulin doses on starting GLP1 RA in patients on insulin therapy and frequent SMBG

• Guidelines to insulin dose adjustment – ~20% dose reduction for basal insulin, ~30-50% for

short-acting insulin

GLP1 RA with Basal Insulin in T2DM

Snacking

Frequently Consumed Snacks

1 bowl of rice = 300kcal, 60g CHO

You Tiao 285 kcal, 36g CHO

Hot Dog Bun 199 kcal, 23g CHO

Pandan Chiffon Cake (55g) 199 kcal, 23g CHO

Frozen Yoghurt (120mls) 130 kcal, 32g CHO

Curry Puff (107g) 331 kcal, 37g CHO

Kaya Toast Set 561 kcal, 59g CHO

Potato Chips (1 medium bag, 80g)

405 kcal, 40g CHO

Assorted Kueh (2 pieces)

302 kcal, 37g CHO

• ~100kcal, 15g CHO

Healthier Snack Ideas

Low-Fat/Skim Milk (250mls) Fruit (1 fist size) Wholemeal/Hi-Fibre Bread (1 slice)

Cherry Tomatoes (15 pcs) Corn (½ cob) Sweet Potato (1 Egg Size)

Plain Crackers (3 pieces) Cereal Bar (1 bar) Low-Fat Plain Yoghurt (¾ tub) Oats (3 dessertspoons)

Miss J’s Progress

• April 2013: – Increased Insulatard dose

– Education – carbohydrate counting, matching insulin dose to carbs and blood glucose

– Added sitagliptin (Januvia) 100mg om

– Advised on healthy snacking

• Jun 2013 – HbA1c reduced to 6.9%

– Maintained A1c 6.1 – 6.7% thereafter with slightly reduced dose of insulin

Case 2

• Mr. M: 32 year old CID officer – Diagnosed with DM Aug 2013

• Presented with DKA, started on Glargine and tds Novorapid

• HbA1c gradually decreased from 8.5% to 6.8% in Nov 2013.

– But: • At presentation: weight 110 kg, BMI 30.8; had gained weight

after started on insulin to 124.2 kg

• Worked irregular hours and eats irregularly => has had hypoglycaemia at work; also skips injections sometimes when busy

• HbA1c gradually deteriorated to 7.9% in Jan 2014

• Very concerned and wanted to switch to oral medications

• Does he really need insulin? – GAD Ab negative – C-peptide 2008 Glucose 9.8

• Switched to Glipizide 2.5 mg om, Metformin 500mg bd and Glargine lower dose at bedtime in Jan 2014.

• HbA1c went up from 7.9% in Jan to 8.5% in March 2014 and 8.2% in June 2014.

• Still had hypoglycaemia at work! • Gained more weight – now 126.6 kg.

How will you manage him next?

A. He has hypoglycaemia – it must be due to insulin. Stop Glargine. Keep on Glipizide and Metformin.

B. Hypoglycaemia is happening when he is at work – stop Glipizide, keep metformin and Glargine at night.

C. HbA1c is not at target – increase glargine.

D. HbA1c is not at target – increase glipizide.

E. HbA1c is not at target – increase metformin.

F. HbA1c is not at target and he has hypoglycaemia – let’s try something else…

Barriers to Optimisation of Glycaemic Control

• Hypoglycaemia

• Weight gain

Options for Therapy in these situations

• Dietary advice

• Metformin

• GLP1RA

• DPP4 inhibitors

• SGLT2 inhibitors - focus

Metformin

• Benefits of Metformin

– Weight neutral

– CV benefits

– Established first-line therapy in T2DM (and possible use in type 1 diabetes with the correct indications) (Vella S, Diabetologia 2010)

SGLT2 inhibitors reduce renal glucose reabsorption

Summary of SGLT2 inhibitors in diabetes management

• SGLT2 inhibitors remove excess glucose and associated calories, along with Na -> resulting in reductions in blood glucose, weight and blood pressure

• Less risk of hypoglycaemia

• Less effective in patients with moderate to severe renal impairment (GFR < 60 ml/min)

• Adverse effects – genital and urinary tract infections

Conclusion for Case 1 and Case 2

• Most patients on insulin are not at glycaemic target

• Limitations to adequate dose titration include hypoglycaemia and weight gain

• Insulin combination therapy is effective at glucose lowering

• Combinations with newer agents (DPP4 inhibitors, GLP1 RA and SGLT2 inhibitors) provide an opportunity to get more patients to target

Eating Out on the Run

Fried Vegetarian Bee Hoon

Chappati with Dhal

Fishball/Fish Sliced Bee Hoon Soup

Steamed Vegetable Pau

Currypuff

Roti Prata

= 1 tsp Oil

Eating Out Choices - Breakfast

Battered Fish with French Fries

Mee Soto

Grilled Fish with Boiled Potato & Broccoli

Yong Tau Foo Hokkien Mee

Mee Siam

= 1 tsp Oil

Eating Out Choices – Lunch/Dinner

Eating Out Choices - On the Run

= 1 tsp Oil

<1g fat

Mr M’s Progress

• Seen in June 2014:

– Stopped Glargine and Glipizide.

– Added canagliflozin 300mg om to metformin

• HbA1c:

– Decreased to 7.3% in Sep 2014 -> 6.8% in Jan 15

– Decreased in weight to 117.4 kg (9.2 kg in 6 months)

– No hypoglycaemia

Case 3

84 F • DM, Hypertension, Hyperlipidaemia • Good functional status – goes marketing, looks after

grandchildren • On insulatard 10 units om, Glipizide 2.5 mg bd • HbA1c 6.9% • Had sepsis from cellulitis leg – brought to hospital because

of drowsiness – found to be hypoglycaemic by SCDF ambulance officer – Had poor appetite from sepsis but had continued to take her

diabetes medications and insulin.

• All medications discontinued on admission

Glipizide 5 mg om started and up-titrated to 10 mg om

Sick Day Advice

Check blood glucose more frequently

↑stress hormones => ↑BG

Poor oral intake => ↓BG

Reduce dose by 20 – 30% if eating poorly and BG trending low

ORAL AGENTS INSULIN

Stay on long acting

insulin

Short/Rapid acting insulin

Adjust according to food intake

Adjust according to BG**

** may need higher correction dose than usual if BG is persistently high

CAUTION with sulphonylureas and

non-SU secretagogues if

eating poorly

Sick day advice (Medications)

• General sick day advice in diabetes – Simple meals – Drink plenty of water to replace lost fluids – Treat underlying cause e.g. infection – Frequent SMBG – 4 hourly or more – Seek medical attention early

• SU and sick day advice – Food substitutions for low oral intake days – Reduce dose of SU: e.g. if eating half of usual amount, take half

of usual dose – Take SU after food if unsure of appetite

• Insulin and sick day advice e.g. - BG< 13 : continue current dose – BG 13-22 – increase short-acting insulin by 2 units each injection – BG > 22 – increase short-acting insulin by 4 units, even if unable

to eat – Return dose to normal when BG returns to normal

Elderly and Anti-Diabetic Medications

• Considerations

– Cognitive decline

– Variable oral intake

– Glycemic targets

– Medications with less risk of hypoglycaemia

– Frequent SMBG

– Education of caregiver

Sick Day Dietary Advice

If Your Patient Can Eat

1. Stick to regular diet

2. Small frequent meals

– Consume CHO-containing food every 3-4 hours

3. Drink volumes of unsweetened fluids frequently

– 125-250mls (½ - 1 cup) every hour

Sugar-Free Fluids

If Your Patient Cannot Eat Regular Food

• Eat semi-solid food/liquids that have carbohydrates

• Snack foods

Sick Day Foods

• Each item contains ~15g CHO

Oats (3 dessertspoons) Bread (1 slice) Fruit (1 fist size)

3-in-1 Cereal Drink (1 sachet) Plain Crackers (3 pieces) Porridge (½ bowl)

Soon Kueh (1 piece) Popiah (1 roll) Pau (1 small)

Fluids with Carbohydrates

• Each item contains ~15g CHO

Low-fat/Skim Milk (250mls)

Reduced Sugar Soy Milk (250mls)

Glucerna (1 can) Isotonic Drink (¾ can) Fruit Juice (½ cup)

Pudding (½ small tub) Ice cream (1 small scoop)

Milo (2 dessertspoons)

Take Home Messages (1)

• Add on therapies to insulin to achieve glycaemic targets

• Obesity and therapeutic options

– Consider weight neutral agents (Metformin, DPP4 inhibitors) or agents with weight loss (GLP1 RA, SGLT2)

• Hypoglycaemia risk and options

– Less hypoglycaemia risk agents (Metformin, incretin-based therapies, SGLT2 inhibitors)

Take Home Messages (2)

• Sick day advice

– Insulin and OHGA; Diet

• Dietary history

– Match OHGA and insulin to food intake

• Most common cause of hypoglycaemia is insulin/medication- food mismatch

• Prescribe most suitable agent and at timing most appropriate to dietary habits

• Individualised therapy – no ‘one size fits all’

DESMM Approach

iet

xercise

upport/ Stressor*

onitoring

edications

* Support/Stress: Social, Spiritual, $$, Sleep, Smoke, Sex

Thank you