Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Practical Tips in ManagingUncontrolled Diabetes

SP ChanMBBS (Mal), FRCP (Edinburgh)), AM (Mal)Visiting Professor Consultant EndocrinologistDept of MedicineUniversity of Malaya Medical Centre

Consultant EndocrinologistSubang Jaya Medical Centre

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Understand the Disease & the Patient

• PathophysiologyInsulin resistanceβ-cell secretory dysfunction

• ComplianceDiet & Lifestyle modificationMedication

• Stumbling blocksHypoglycaemiaWeight gain

Disease Burden,Pathophysiology & How are we doing?

8.3

14.9

20.8

6.5

9.510.7

1.8

5.4

10.1

4.3

4.7

5.3

0

5

10

15

20

25

NHMS II (1996) NHMS III(2006)

NHMS 2011

Pre

vale

nce

(%

)

Malaysia : Prevalence of Diabetes, ≥30 years (1996, 2006 & 2011)

Total diabetes

Known

Undiagnosed

IFG

DiabCare 2009: Glucose control

Country Fasting Postprandial A1c A1c >7% (%) A1c ≥6.5% (%)

Indonesia 7.9 11.6 8.1 67.7 81.1

Bangladesh 8.4 8.6 8.6 76.9 86.9

Singapore 7.6 7.5 7.8 65.4 83.5

Malaysia 8 12.7 8.6 76.5 88.2

Taiwan 8 10.6 7.9 69.7 81.3

Thailand 7.9 11 8.2 74.3 84.8

Philippines 7.2 9.4 8 31.8 36.7

2008 DiabCare – Demographics of T2DM

Country Malaysia

Age 57.5 ± 10.9

Sex (F / M) 53 / 47

BMI 27.8 ± 4.5

WC (M>90cm / F>80cm) 73.7 / 89.4

Duration of DM 11.5 ± 8.0

Mafauzy M, Zanariah H & SP Chan. Med J Malaysia 2011; 66: 175-181

n = 1549

Hypertension (80.3%)

Country Malaysia

Mean BP (mmHg)

137.5 ± 19.6 /

78.9 ± 11.3

Patient on anti-hypertensive (%)

75 %

Treatment for HBP (%)

ACE-I : 65.2 %

CCBs : 60.0 %

B-block: 46.3 %

Diuretics: 36.5 %

Country Malaysia

LDL > target 46 %

HDL < 1.0 mmol/L 27.4 %

Tg > target 19.8 %

Rx for dyslipidemia 85 %

Dyslipidaemia (96.1%)

Mafauzy M, Zanariah H, SP Chan. Med J Malaysia 2011

2008 DiabCare

39% < 130/80 mmHg

Fukushima et al. Metabolism 2004;53(7):831-5

Insulin Secretion and Insulin Resistance –across glucose Tolerance in Japanese subjects

1.2 1.5 2.4 60 50 30

β-cell dysfunctionInsulin Resistance

Predominant

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Ethnic Differences in Insulin levels (β-cell function)

0 30 60 90 1200

100

Caucasian1,2

Insulin c

oncentr

ation

(mU

/L)

50

NGT

IGT

DM

Insulin c

oncentr

ation

(mU

/L)

0 30 60 90 120

Japanese3

(Age, weight adjusted)

0

100

50

NGT, normal glucose tolerance; IGT, impaired glucose tolerance; DM, diabetes mellitus

Time (months)Time (months)

1. Adapted from Tripathy et al. Diabetes 2000:49;975–80; 2. Adapted from Fukushima et al. Metabolism 2004:53;831–5; 3. Adapted from and Fukushima et al. Diabetes Res Clin Pract 2004:66(Suppl. 1);S37–43

SP Chan et al. Diabetes Clinical Research & Practice 2010

Hypoglycaemia is a Problem

I in 3 complain of Hypoglycaemia

? FEAR OF Hypoglycaemia

Interview of People with T2DM on oral anti-diabetic Rx

SP Chan et al. Diabetes Clinical Research & Practice 2010

Conducted in 2007

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Case 1: 75 yr Indian ♂, T2DM 35 years. HBP+ Lipid+Height 161 cm, wt 81 kg. Rx gliclazide 80 mg BD, MF 1g BD

HbA1c 6.9 – 7.1 %, SMBG Fasting 6-8; Postprandial gluc 6-12S creat 77 – 81; eGFR 75 ml/min

HbA1c Aug 2012 8.3%, Oct 2012 8.8%, FPG 11.7; 11.8

Q1. How will you manage him ?

A. No need to do anything. This is acceptable

B. Knock him on the head … diet ! Come back in 3 months

C. Increase gliclazide 160 mg BD

D. Start on Bedtime insulin + continue oral agents

E. Add TZD

F. Add DPP 4-inhibitor

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Case 1: 75 yr Indian ♂, T2DM 35 years. HBP+ Lipid+Height 161 cm, wt 81 kg. Rx gliclazide 80 mg BD, MF 1g BD

HbA1c 6.9 – 7.1 %, SMBG F 6-8; PP 6-12S creat 77 – 81; eGFR 75 ml/min

HbA1c Aug – Oct 2012 8.3, 8.8% ; FPG 11.7; 11.8

Q1. How will you manage him ?

Increased gliclazide 160 mg om/80mg pmAdded oral DPP 4i 1 tab daily

Dec 2012 – HbA1c 6.8 % ; no hypos, weight stable 82 kg

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Case 1: 75 yr Indian♂, T2DM 35 years. HBP+ Lipid+, wt 81 kgRx gliclazide 160/80 mg, MF 1g BD, DPP 4i 1 tab daily

HbA1c 6.9 – 7.1 %, SMBG F 6-8; PP 6-12S creat 77 – 81; eGFR 75 ml/minAug 2012 – HbA1c 8.3%, Oct 2010 8.8%; FPG 11.7; 11.8

Q2. How now?

Apr 2013 – HbA1c 6.5 %; no hypos, weight stableVERY HAPPY !

Self monitoring bld gluc: F 4.0 – 7.8; 2HPP 6.2 – 12.9

Dec 2012 – HbA1c 6.8 %; no hypos, weight stable 82 kg

A. Keep it up!B. Reduce gliclazideC. Stop DPP 4iD. Eat more

Cardiovascular Updates for Doctors & Allied Healthcare Professionals

Symposium

Case 1: 78 yr Indian ♂, T2DM 35 years. HBP+ Lipid+Wt 81 kg. Rx gliclazide, MF, DPP 4i

Still on gliclazide 80 mg BD + DPP 4i 1 tab om, MF 1 g BD

Oct 2012 till last week – HbA1c 6.5-6.9 %; no hypos, weight stableSelf monitoring bld gluc: F 4.0 – 7.8; 2HPP 6.2 – 12.9

3 months ago, routine follow-up visitWeight 84 kg Fasting glu 9.2 mmol/L / HbA1c 7.5%

Q: What do you think has happened? What will you do?

A. Recent dietary non-compliance … back on diet!B. This is to be expected … deterioration of glucose controlC. Time to start insulinD. Any other explanation …? He stopped his oral DPP 4i

… no stock!

Cardiovascular Updates for Doctors & Allied Healthcare Professionals Symposium

HbA1c reduction by DPP 4-inhibitor:meta-analysis of Global and Japanese

Sitagliptin

Vildagliptin

Saxagliptin

Linagliptin

Sitagliptin

Vildagliptin

Linagliptin

0.0 1.0 2.0-1.0-2.0

Weighted mean differences (95% CI)

Global

Japanese

HS Park et al. Annals Pharmacother 2012;46:1453-69

Favors DPP 4 inhibitors Favors placebo

SU + MF Failure

• DPP 4 inhibitor efficacy

• Need to monitor glucose

• Dietary modification

Case 2: 43 yr Chinese businessman. T2DM, HBP 8 yrs.Bad knees (OA) – TKR – R done, cannot exerciseHt 1.63 cm, weight 99 kg. Metformin 1g BD, Gliclazide160mg BD, acarbose 100mg TDS, s/c Lantus 40 u nocte

HbA1c 8.0 – 8.8 %; FPG 5 – 12 / PP 10 – 18

Struggling with weight

Q: How will you manage him?

A) Change to basal-bolus (full) insulin

B) DPP-4 inhibitor

C) GLP-1

D) Diet / exercise

E) Give up

BMI 37.2 kg/m2

Case 2: 43 yr Chinese businessman. T2DM, HBP 8 yrs.Bad knees (OA) – TKR – R done, cannot exerciseHt 1.63 cm, weight 99 kg. Metformin 1g BD, Gliclazide160mg BD, acarbose 100mg TDS, s/c Lantus 40 u nocte

HbA1c 8.0 – 8.8 %; FPG 5 – 12 / PP 10 – 18

Struggling with weight

Started s/c Byetta 5 ug BD 10 ug BD

1 month, weight 95 kgGlucose monitoring more stable – F 4.7-8.9 / PP 7-12Less hungry / able to stop eating at buffet dinnerAble to reduce Lantus 26-28 u nocte

3-6 months, weight 91 kgHbA1c 7.2 – 7.5%

BMI 37.2 kg/m2

12-15 months, weight 94 kgHbA1c 7.5 – 7.8%

SU + MF + Basal Insulin FailurePatient Obese

• Efficacy of GLP 1 receptor agonist

• Need to monitor glucose

• Dietary modification

Case 3: 38 yr old man, T2DM Jul 2013

Mechanic

• Ht 167 cm, wt 62.8 kg

• Rx: Diamicron MR 60 mg BD, Janumet 50/850 mg BD

• Diet ++

• FH – Mother DM & CVA at 58 yrs

Oct 2013, unable to wake up, giddy

BMI 22.0 kg/m2

Q: What is the likely problem ?

A. Cerebrovascular accident

B. Hypoglycaemia

C. Hyperglycaemia

D. Hypotension

E. Malingering

Case 3: 38 yr old man, T2DM Jul 2013

Mechanic

• Ht 167 cm, wt 62.8 kg

• Rx: Diamicron MR 60 mg BD, Janumet 50/850 mg BD

• Diet ++, FH – Mother DM & CVA at 58 yrs

• Oct 2013, unable to wake, giddy

BMI 22.0 kg/m2

Q: What is the likely problem ? What investigation ?

HbA1c 5.4 % 2hr post-BF 5.0 mmol/L

S creatinine 85 umol/L Hypoglycaemia

Stop Diamicron

Continue – Janumet 50/850 1 tab BD

Q: What will you do ?

Case 3: 38 yr old man, T2DM Jul 2013

Mechanic

• Ht 167 cm, wt 62.8 kg

• Rx: Diamicron MR 60 mg BD, Janumet 50/850 mg BD

• Diet ++, FH – Mother DM & CVA at 58 yrs

• Oct 2013, unable to wake, giddy

BMI 22.0 kg/m2

Q: What is the likely problem ? What investigation ?

HbA1c 5.4 %

Hypoglycaemia

Stop Diamicron

Continue – Janumet 50/850 1 tab BD

Glucose monitoringF 4.5, 6.32h PP 4.8 – 8.7 (Av ~ 7.0) Latest HbA1c 6.4%

Case 4: 38 yr old woman, T2DM 2 yrs, HBP0

• Ht 165 cm, wt 62 kg, BP 120/75 mmHg – Tennis BD, TDS

• Rx: Metformin 850 mg BD, Hypo - Diamicron MR 30 mg om

• HbA1c 7.4 %, F 7 – 7.8, 2hPP 8 – 11

Q: What will you do – glucose control?

A) Leave alone

B) Resume SU – Amaryl?

C) Insulin secretagogue – Novonorm?

D) Add DPP-4 inhibitor

E) Add Actos

BMI 22.8 kg/m2

Case 4: 38 yr old woman, T2DM 2 yrs, HBP0

• Ht 165 cm, wt 62 kg, BP 120/75 mmHg – Tennis BD, TDS

• Rx: Metformin 850 mg BD, Hypo - Diamicron MR 30 mg om

• HbA1c 7.4 %, F 7 – 7.8, 2hPP 8 – 11

Added Januvia 100 mg daily

HbA1c 6.3 %

Felt good, no hypos

3 years on …. HbA1c ?

BMI 22.8 kg/m2

Hypoglycaemia – a Problem

• Too much Sulfonylurea

• Sulfonylurea – too potent / insulin secretion unrestricted

Case 5. 47 yr old Chinese man. T2DM 10 years. Self medicating.Januvia 100 mg daily, metformin 850 mg BDSymptomatic hyperglycaemia. Diet √

Ht 165 cm; weight 43 kgFPG 18.2 mmol/L; HbA1c 11.8%

Q: How will you manage him ?

BMI 15.8 kg/m2

A) Add SU – Gliclazide MR / glimepiride

B) DPP-4 inhibitor

C) Acarbose

D) Insulin

Case 5. 47 yr old Chinese man. T2DM 10 years. Self medicating.Januvia 100 mg daily, metformin 850 mg BDSymptomatic hyperglycaemia. Diet √

Ht 165 cm; weight 43 kgFPG 18.2 mmol/L; HbA1c 11.8%

Admitted. Initiated on insulin – basal bolus

s/c Novorapid 12-16 units b/f, lunch,

s/c Novomix 18 pre-dinner. Metformin 850 mg BD

1 week later, weight 45 kg

Extremely happy … BUT hypos at 2-4 am x 2.

despite pre-bed 5.8; 9.0

BMI 15.8 kg/m2

changed to s/c Novorapid TDS; Lantus 8 u nocte

Case 5. 47 yr old Chinese man. T2DM 10 years.Januvia 100 mg daily, metformin 850 mg BDSymptomatic hyperglycaemia. Diet √Ht 165 cm; weight 43 kgFPG 18.2 mmol/L; HbA1c 11.8%

s/c Novorapid 8-10 u TDS; Lantus 8 u nocte

Metformin 850 mg BD

BMI 15.8 kg/m2

6 months later, weight 50 kg

Extremely happy … occasional hypos due to poor intake

On Nutren diabetic – dietary supplement

HbA1c 6.4 %

T2DM – β cell exhaustion

Case 6: 43 yr Indian man. T2DM 3 yrs.Ht 1.75 cm, wt 78 kg. Galvusmet 50/850 mg BD

HbA1c 8.7 %; FPG 9 - 12 / PP 10 - 14

Following lifestyle

Q: How will you manage him?

A) Diet and exercise some more

B) Start Insulin - ? which

C) Add sulfonylurea ? Gliclazide MR

D) Change DPP-4 inhibitor

BMI 25.5 kg/m2

Case 6: 43 yr Indian man. T2DM 3 yrs.Ht 1.75 cm, wt 78 kg. Galvusmet 50/850 mg BD

HbA1c 8.7 %; FPG 9 - 12 / PP 10 - 14

Following lifestyle

Q: How will you manage him?

Added sulfonylurea – Gliclazide MR 60 mg daily

BMI 25.5 kg/m2

2-4 wks later: tolerating, no hypos

Self blood glucose monitoring: F 7-8, PP 7-10

Failure of DPP 4i + MF combination

Efficacy of addition of Sulfonylurea

Remember THE PATIENT

Choice of DIET & PHYSICAL ACTIVITY

Common misconceptions / belief

1. Fruits / fruit juice is ok

2. Drinking 3-in-1 coffee / tea or Teh-Tarik “kurang manis” is ok

3. Carbohydrate is BAD – so I skip eating rice/eat only veggies, salads & fruits for dinner (How come still cannot control my diabetes)

4. Medicines will damage my kidneys

How to manage DM…?

Pathophysiology

BMI & Duration of DM: β-cell fxn / Ins resistance

Renal function

Side-effects – drugs (eg metformin)

Hypoglycaemia ? Vulnerability

Co-morbidities – Life expectancy

HbA1c target

Imagine both of these men … Diabetic

SAME Therapies ???

The Answers are not OUT there …

Choose CORRECT Medication / HbA1c

targets