Transcript PowerPoint Presentation - Is there a need for earlier

Insulin initiation
OPTIMISING
Glycaemic control and Weight
Dr C Rajeswaran
Consultant Physician
Diabetes & Endocrinology
Mid Yorkshire NHS Trust
UKPDS: A 1% decrease in HbA1c is associated
with a reduction in complications
37%
Microvascular
complications e.g. kidney
disease and blindness *
43%
Amputation or fatal
peripheral blood vessel
disease*
21%
Deaths related to diabetes*
14%
Heart attack*
HbA1c
1%
* p<0.0001
12%
Stroke**
** p=0.035
Stratton IM et al. BMJ 2000; 321: 405–412.
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 1999;42;406-412
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.
Makimattila 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
Insulin in Type 2 Diabetes is aimed at
inhibition of hepatic glucose output
And
improvement of peripheral glucose utilisation
Causes of weight gain with treatment ?
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'.
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. 1997;82:4037-4043.
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. 1998;317:703-713.
Adjusted odds ratio for death, by metabolic category for 5161years age group
Diabetes
2.63
Obesity
0.78
Obesity and diabetes
6.81
Oldridge et al, Jr of clinical Epidemiology 54(2001);928-934
Insulin secretion
Contribution of Postprandial Glucose (PPG)
to 24 hour hyperglycaemic profile
Mainly target Postprandial
hyperglycaemia:
Glucose (mmol/l)
12.5
Repaglinide
Nateglinide
Acarbose
Rapid-acting insulin
10.0
7.5
5.0
2.5
0
0600
1200
1800
Hours
0000
0600
Mainly target Basal hyperglycaemia:
Metformin
Secretagogues
TZD’s
Basal insulin
Postprandial Hyperglycemia
Basal Hyperglycemia
Adapted from Riddle et al. Diabetes Care. 1990;13:676-686.
As patients get closer to HbA1c target, the need to manage PPG increases
100
30%
% Contribution
to HbA1c
80
70%
55%
60%
50%
60
40
20
70%
30%
40%
45%
50%
10.2-9.3
9.2-8.5
8.4-7.3
0
>10.2
<7.3
HbA1c Range (%)
Fasting Plasma Glucose (FPG)
Post Prandial Glucose (PPG)
Monnier L, et al. Diabetes Care. 2003;26:881-885.
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
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.
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
Insulin regimes: Multiple options
One injection
Intermediate-acting insulin or long-acting analog at bedtime
Premixed formulation before dinner
Two injections
Breakfast 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 rapidacting 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
Initiating Insulin: Basic Recommendations
No set formula......
•If FPG is elevated, start with long-acting (basal) insulin;
•If PPG is elevated, rapid-acting (prandial or bolus) can be used; and
If FPG and PPG are elevated, any of the following would be
appropriate:
•Oral agents with basal insulin
•Premixed insulin analogs
•Basal/bolus as in multiple daily injections (MDI) or an insulin pump.