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PowerPoint Presentation - Is there a need for earlier addition to metformin in the management of Type 2 diabetes?

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Insulin initiation OPTIMISING Glycaemic control and Weight Dr C Rajeswaran Consultant Physician Diabetes & Endocrinology Mid Yorkshire NHS Trust * * Reducing HbA1c is ... – PowerPoint PPT presentation

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Title: PowerPoint Presentation - Is there a need for earlier addition to metformin in the management of Type 2 diabetes?


1
Insulin initiation OPTIMISING Glycaemic
control and Weight Dr C Rajeswaran Consultant
Physician Diabetes Endocrinology Mid Yorkshire
NHS Trust
2
UKPDS A 1 decrease in HbA1c is associated with
a reduction in complications
plt0.0001 p0.035
Stratton IM et al. BMJ 2000 321 405412.
3
Glycaemic control and body weight
Weight gain appears unavoidable when patients
with Type 2 diabetes are commenced on
insulin Calculations of average weight gain are
that for every 5 mmol/l reduction in fasting
glucose, or a 2.5 fall in HbA1c, approximate
weight gain is 5 kg (Makimattila et al,
1999) Body weight increases by 2Kg for each
percentage point decrease in HbA1C during the
first year1 1.Makimattila et al Diabetologia
199942406-412
4
Glycosuria is known to occur once fasting glucose
levels reach around 10-12 mmol/l, and if
treatment with insulin is delayed until this
time, weight gain is likely to occur. Gain in
weight mainly represents an increase in fat mass,
which enhances insulin resistance and increases
the risk of obesity related complications. Maki
mattila S, Nikkila K. Yki-Jarvinen H (1999)
Causes of weight gain during insulin therapy with
and without metformin in patients with type II
diabetes mellitus. Diabetologia 42 406-12
5
Insulin in Type 2 Diabetes is aimed
at inhibition of hepatic glucose output
And improvement of peripheral glucose
utilisation
6
Causes of weight gain with treatment ?
7
Insulin and weight
  • Reduced glycosuria
  • Anabolic action of insulin
  • Fluid retention
  • Hypoglycaemia and increased calorie consumption
  • Excess insulin administration
  • Combination of obesity and muscle impairment
    'sarcopenic obesity'.

8
Metabolic Consequences of Weight Gain Patients
with T2 DM often have many other comorbid
conditions increasing their risk for
macrovascular events. Weight gain may have
further deleterious metabolic consequences, such
as worsening hypertension, lowering HDL-C, and
raising LDL-C.1,2 Blood pressure control
and lipid control have both been shown to reduce
cardiovascular events in patients with type 2 DM.
1.Yki-Jarvinen H, Ryysy L, Kauppila M, et al.
Effect of obesity on the response to insulin
therapy in noninsulin-dependent diabetes
mellitus. J Clin Endocrinol Metab.
1997824037-4043. 2.United Kingdom Prospective
Diabetes Study Group. Tight blood pressure
control and risk of macrovascular and
microvascular complications in type 2 diabetes
UKPDS 38. BMJ. 1998317703-713.
9
Adjusted odds ratio for death, by metabolic
category for 51-61years age group Diabetes
2.63 Obesity
0.78 Obesity and diabetes
6.81 Oldridge et al, Jr of
clinical Epidemiology 54(2001)928-934
10
Insulin secretion
11
Contribution of Postprandial Glucose (PPG) to 24
hour hyperglycaemic profile
Mainly target Postprandial hyperglycaemia Repag
linide Nateglinide Acarbose Rapid-acting
insulin
12.5
10.0
7.5
Glucose (mmol/l)
5.0
2.5
0
0600
1200
1800
0000
0600
Hours
Mainly target Basal hyperglycaemia Metformin Secr
etagogues TZDs Basal insulin
Postprandial Hyperglycemia
Basal Hyperglycemia
Adapted from Riddle et al. Diabetes Care.
199013676-686.
12
As patients get closer to HbA1c target, the need
to manage PPG increases
100
80
50
55
60
70
60
Contribution to HbA1c
40
50
45
40
20
30
0
gt10.2
10.2-9.3
9.2-8.5
8.4-7.3
lt7.3
HbA1c Range ()
Fasting Plasma Glucose (FPG)
Post Prandial Glucose (PPG)
Monnier L, et al. Diabetes Care. 200326881-885.
13
How Do We Minimize Weight Gain Associated With
Insulin Therapy? Patients who are started on
insulin treatment may take away mixed messages
about dietary control and think that they can
increase their calorie intake on insulin this
results in excessive weight gain. Lifestyle
intervention should be reinforced with
initiation of insulin therapy. Medical
Nutrition therapy
14
Metformin and insulin Metformin appears to have
an insulin-sparing effect and reduces weight gain
with insulin treatment. Studies using a
combination of 2g metformin with bedtime isophane
insulin, as opposed to twice-daily isophane
insulin, showed that the insulin requirements in
the metformin group were reduced by 47 and
there was 45 less weight gain (Makimattila et
al, 1999). This reduction in weight gain
seemed to be due to reduced energy intake in
those on metformin. Patients with T2DM
should remain on metformin when they convert to
treatment with insulin.
15
Repaglinide with insulin In a RCT, use of
repaglinide resulted in a reduction in HbA1c
compared to twice daily insulin group (1.8
versus 1 drop) and weight gain (2.2 kg
versus 2.9 kg), but less insulin was required
in the repaglinide group (Davies et al, 2002).
Repaglinide in combination with bedtime insulin
and metformin produces a significantly greater
fall in HbA1c compared with the twice-daily
insulin or night time insulin and metformin.
Davies MJ, Howe J, Jarvis J at al (2002) Use
of the combination of insulin and the prandial
glucose regulator repaglinide in patients with
type 2 diabetes mellitus. Diabetic Medicine
19(2) 25
16
Insulin regimes Multiple options
One injection Intermediate-acting insulin or
long-acting analog at bedtimePremixed
formulation before dinner Two injections Breakfa
st and dinner premixed formulation Breakfast and
dinner short-acting or rapid-acting plus NPH or
long-acting insulin analog Three
injections Add a short- or rapid-acting insulin
injection at lunchtime to a 2-injection premixed
regimen Add a third premix injection at lunchtime
to a 2-injection premixed regimen Move the
intermediate- or long-acting insulin analog to
bedtime with short-acting or rapid-acting insulin
analog at breakfast and dinner Multiple
injections Short-acting or rapid-acting insulin
analog at each meal with an intermediate- or
long-acting at bedtime Insulin pump
17
Initiating Insulin Basic Recommendations No set
formula......
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