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Insulin initiation OPTIMISING Glycaemic control and Weight Dr C Rajeswaran Consultant Physician Diabetes & Endocri PowerPoint Presentation
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Insulin initiation OPTIMISING Glycaemic control and Weight Dr C Rajeswaran Consultant Physician Diabetes & Endocrinology Mid Yorkshire NHS Trust. 37%. Microvascular complications e.g. kidney disease and blindness *. Amputation or fatal peripheral blood vessel disease*. 43%. HbA 1c.

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slide1

Insulin initiation

OPTIMISING

Glycaemic control and Weight

Dr C Rajeswaran

Consultant Physician

Diabetes & Endocrinology

Mid Yorkshire NHS Trust

ukpds a 1 decrease in hba 1c is associated with a reduction in complications

37%

Microvascular complications e.g. kidney disease and blindness *

Amputation or fatal peripheral blood vessel disease*

43%

HbA1c

1%

21%

Deaths related to diabetes*

14%

Heart attack*

12%

Stroke**

UKPDS: A 1% decrease in HbA1cis associated with a reduction in complications

* p<0.0001

** p=0.035

Stratton IM et al. BMJ 2000; 321: 405–412.

slide3

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

slide4

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

slide5

Insulin in Type 2 Diabetes is aimed at

inhibition of hepatic glucose output

And

improvement of peripheral glucose utilisation

slide7

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'.
slide8

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.

slide9

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

slide11

Contribution of Postprandial Glucose (PPG)

to 24 hour hyperglycaemic profile

Mainly target Postprandial hyperglycaemia:

Repaglinide

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

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 hba 1c target the need to manage ppg increases

30%

70%

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

>10.2

10.2-9.3

9.2-8.5

8.4-7.3

<7.3

HbA1c Range (%)

Fasting Plasma Glucose (FPG)

Post Prandial Glucose (PPG)

Monnier L, et al. Diabetes Care. 2003;26:881-885.

slide13

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

slide14

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.

slide15

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

slide16

Insulin regimes: Multiple options

One injection

Intermediate-acting insulin or long-acting analog at bedtimePremixed 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 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