Optimising glycaemic control and body weight
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Optimising glycaemic control and body weight A
Mix50 Insulin Experience
Dr C RajeswaranConsultant Physician
Diabetes & EndocrinologyDirector. simplyweight
www.simplyweight.co.uk
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UKPDS: A 1% decrease in HbA1c is associated with a reduction in complications
Stratton IM et al. BMJ 2000; 321: 405–412.
Microvascular complications e.g. kidney disease and blindness *
37%
* p<0.0001
** p=0.035
1%HbA1c
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UKPDS: A 1% decrease in HbA1c is associated with a reduction in complications
Stratton IM et al. BMJ 2000; 321: 405–412.
Microvascular complications e.g. kidney disease and blindness *
37%
Amputation or fatal peripheral blood vessel disease*
43%
* p<0.0001
** p=0.035
1%HbA1c
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UKPDS: A 1% decrease in HbA1c is associated with a reduction in complications
Deaths related to diabetes*21%
Stratton IM et al. BMJ 2000; 321: 405–412.
Microvascular complications e.g. kidney disease and blindness *
37%
Amputation or fatal peripheral blood vessel disease*
43%
* p<0.0001
** p=0.035
1%HbA1c
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UKPDS: A 1% decrease in HbA1c is associated with a reduction in complications
Deaths related to diabetes*21%
Stratton IM et al. BMJ 2000; 321: 405–412.
Microvascular complications e.g. kidney disease and blindness *
37%
Amputation or fatal peripheral blood vessel disease*
43%
Heart attack*14%
* p<0.0001
** p=0.035
1%HbA1c
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UKPDS: A 1% decrease in HbA1c is associated with a reduction in complications
Deaths related to diabetes*21%
Stratton IM et al. BMJ 2000; 321: 405–412.
Microvascular complications e.g. kidney disease and blindness *
37%
Amputation or fatal peripheral blood vessel disease*
43%
12% Stroke**
Heart attack*14%
* p<0.0001
** p=0.035
1%HbA1c
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-cell dysfunction, a core defect in T 2 Diabetes
• Genetic and environmental pathophysiology
• One of the two core defects in Type 2 diabetes
• Impaired ability of -cells to compensate for insulin resistance
• Reduced ability of -cells to secrete insulin
• Therapeutic strategies should address both defects
Insulinresistance
-celldysfunction
Type 2diabetes
+ =
Del Prato S & Marchetti P. Diabetes Technol Ther. 2004; 6:719–731.
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ATP-sensitive K+ channel
Insulin
Ca2+-dependent K+ channel
Na+ channel
Cl- channel
UK SmPC Nov 2006’
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Adapted from Riddle et al. Diabetes Care. 1990;13:676-686.
Contribution of Postprandial Glucose (PPG) to 24 hour hyperglycaemic profile
Mainly target Basal hyperglycaemia:MetforminSecretagogues TZD’sBasal insulin
Mainly target Postprandial hyperglycaemia:
RepaglinideNateglinide AcarboseRapid-acting insulin
Glu
co
se
(m
mo
l/l) 10.0
5.0
00600 1200
Hours
1800 0000 0600
7.5
12.5
2.5
Basal Hyperglycemia
Postprandial Hyperglycemia
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As patients get closer to HbA1c target, the need to manage PPG increases
Monnier L, et al. Diabetes Care. 2003;26:881-885.
30%40% 45%
70%60% 55%
>10.2 10.2-9.3 9.2-8.5 8.4-7.3 <7.3
% C
on
trib
uti
on
to
Hb
A1c
HbA1c Range (%)
0
20
40
60
80
100
Fasting Plasma Glucose (FPG)
Post Prandial Glucose (PPG)
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50%
50%
As patients get closer to HbA1c target, the need to manage PPG increases
Monnier L, et al. Diabetes Care. 2003;26:881-885.
30%40% 45%
70%60% 55%
>10.2 10.2-9.3 9.2-8.5 8.4-7.3 <7.3
% C
on
trib
uti
on
to
Hb
A1c
HbA1c Range (%)
0
20
40
60
80
100
Fasting Plasma Glucose (FPG)
Post Prandial Glucose (PPG)
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As patients get closer to HbA1c target, the need to manage PPG increases
Monnier L, et al. Diabetes Care. 2003;26:881-885.
30%40% 45% 50%
70%60% 55% 50%
70%
30%
>10.2 10.2-9.3 9.2-8.5 8.4-7.3 <7.3
% C
on
trib
uti
on
to
Hb
A1c
HbA1c Range (%)
0
20
40
60
80
100
Fasting Plasma Glucose (FPG)
Post Prandial Glucose (PPG)
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Insulin and body weight
Weight gain appears unavoidable when patients with Type 2 diabetes are commenced on insulin
Body weight increases by 2Kg for each percentage point decrease in HbA1C during the first year1
Gain in weight mainly represents an increase in fat mass, which enhances insulin resistance and increases the risk of obesity related complications.
Insulin in T2 DM is aimed at inhibition of hepatic glucose output and improvement of peripheral glucose utilisation
1.Makimattila et al Diabetologia 1999;42;406-412
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Insulin and weight
• Reduced glyosuria
• Anabolic action of insulin
• Fluid retention
• Hypoglycaemia and increased calorie consumption
• Excess insulin administration
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Hyperinsulinaemia should be avoided to prevent weight gain and optimise glycaemic control
GAME regimen: insulin aspart and glimepride
HbA1c decreasedf rom 9.4 to 7.0 and net change in weight 4-5 Kg less than predicted.
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Mix 50 Advantages
The TDS regime uses appropriate dose of prandial insulin (to improve glycaemic control) in conjunction with a reduction in the total daily dose of insulin( facilitating weight loss) while maintaining adequate basal insulin therapy (given TDS) over a 24 hour period
Absorption is better when the dose is split and prevents stacking
Simple dosage regime and single delivery device
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Mix 50 Once a day
With biggest meal along with Metformin
Substituting Mix30 with Mix 50 reduced HbA1C by 0.49%, whereas patients on Mix 30 had a mean Hba1c increase of 0.33%.1
An alternate regime for initiation of insulin with lesser hypoglycaemic episodes
1.Hui et al Comparitive analysis of twice daly insulin regimes during the month of Ramadan in patients with Type 2 diabetes Diabetic Medicine,24(suppl 1), 79-199
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Titration
Total insulin dose - 10% 3
=
Dose of Mix 50
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Mix 50 case studies
NJ Asian 54 years with T2DM
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Summary
• As patients Get Closer to HbA1c target (≤8.0%) post prandial glucose becomes the most significant contributing factor
• Whilst trying to optimise glycaemic control, increase in body weight should be avoided .
• Mix 50 is a credible option in a select group of patients both as once a day and TDS regime
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