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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