Optimising glycaemic control and body weight A

Mix50 Insulin Experience

Dr C RajeswaranConsultant Physician

Diabetes & EndocrinologyDirector. simplyweight

www.simplyweight.co.uk

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

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

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

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

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

-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.

http://www.simplyweight.co.uk/forum/forum.php

ATP-sensitive K+ channel

Insulin

Ca2+-dependent K+ channel

Na+ channel

Cl- channel

UK SmPC Nov 2006’

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

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)

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)

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)

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

Insulin and weight

• Reduced glyosuria

• Anabolic action of insulin

• Fluid retention

• Hypoglycaemia and increased calorie consumption

• Excess insulin administration

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.

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

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

Titration

Total insulin dose - 10% 3

=

Dose of Mix 50

Mix 50 case studies

NJ Asian 54 years with T2DM

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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