management of type 2 diabetes focus on insulin therapy

International Diabetes Center Insulin Use in Type 2 Diabetes deficiency and insulin resistance • Purpose of insulin regimen is to mimic normal insulin secretion patterns for glycemic co

Trang 1

Management of Type 2

Diabetes: Focus on Insulin

Therapy

Trang 2

International Diabetes Center

Trang 3

0 50

Beta cell dysfunction

Post Meal Glucose

At risk for Diabetes

Adapted from: UKPDS 33: Lancet 1998; 352, 837-853 DeFronzo RA Diabetes 37:667, 1988

Saltiel J Diabetes 45:1661-1669, 1996 Robertson RP Diabetes. 43:1085, 1994

Medical Nutrition

Metformin Thiazolidinediones

Trang 4

Insulin Use in Type 2 Diabetes

deficiency and insulin resistance

• Purpose of insulin regimen is to mimic normal insulin

secretion patterns

for glycemic control

• Start dose conservatively and adjust dose based on

patterns of BG

– High dose insulin (>1.0 U/kg) often required to overcome

insulin resistance

Trang 5

DiMarchi et al., Peptides-Chemistry and Biology 1992:26-28.

Trang 6

Overcoming Insulin Resistance

Nucleus

Insulin Sensitive Cell (Muscle or Fat)

Insulin Glucose

Insulin Receptor

Glucose Transporter (GLUT4)

G G

G

Trang 7

Meal Meal Meal

Basal Insulin Needs

Bolus insulin needs

Trang 8

Insulins

Bolus (Meal) Insulin

Rapid-acting Insulin lispro, Insulin aspart

Trang 9

30-45 mins

Peak 1-2 hrs

2-3 hrs

Trang 10

Advantages of Rapid Acting

Insulin Analogs

• Modification of human insulin

– Increased rate of subcutaneous absorption (more

physiological )

• Reduced rates of hypoglycemia

• Convenience - increased flexibility

– Taken with meal (onset of action ~ 10 minutes)

– Reduced risk of exercise-induced hypoglycemia

– Limits need for snacks

– Can be used to cover snacks

Trang 11

Basis of Insulin Selection Short-Acting Vs Rapid-Acting

Regular insulin best for

3 Who delay start of meal

after insulin injection

Rapid Acting insulin best for patients who:

1 Desire increased flexibility

or who vary CHO intake

2 Don’t desire consistent snack

3 Have either routine or sporadic exercise

4 Desire injection immediately pre-meal

Trang 12

Insulin Lispro

B28 LYS

S S

A-chain

B28 ASP

S S

S

S A-chain

Trang 13

Lispro vs Aspart Insulin Levels

After 10 Unit Subcutaneous

Injection

in Type 1 Diabetes

Hedman C et al Diabetes Care 2001;24:1120-1121 (abstract #465)

0 50 100

Aspart insulin

Trang 14

Trang 16

Glargine: Activity Profile

30

(Hourly Mean Values)

Time (h) after subcutaneous

injection

=End of observation period

0 1 2 3 4 5 6

Lepore et al Diabetes 1999;48(suppl 1):A97 Abst 416; Study 1015

Trang 17

Rapid (Lispro, Aspart)

Insulin Time Action Curves

Trang 18

Insulin Regimens

• Combination Oral Agent-Insulin

– Single bedtime injection Glargine or NPH

• Physiologic Insulin Stage 4

– Basal/Bolus Regimen

– 4 or more injections/day

• Conventional (Mixed) Insulin Stages 2 and 3

Trang 19

Oral Agent Stage

Type 2 Master DecisionPath

Note: Each stage requires a

pre-set BG target: and a timeline to

reach that goal

Trang 20

Selecting an Insulin Regimen

Consider Combination Oral Agent Insulin or

Insulin Stages 2 or 3 if:

– Consistent in schedule/routine

– Exhibiting barriers to insulin initiation

– Overwhelmed with insulin initiation

– Opposed to multiple insulin injections

– Unable/unwilling to take a noon injection

Trang 21

Selecting an Insulin Regimen

Consider Physiologic Insulin Stage 4 if:

– Desires more schedule flexibility (travel)

– Desire to improve glycemic control

– Works rotating shifts

– Varies food intake in time/amount (skips meals)

– Willing to test post-meal BG

– No barriers to more intensive regimen

Trang 22

Transition from Oral Agent Therapy to

Oral Agent plus Insulin

• Oral Agent and Basal Insulin

– No kidney or liver disease

– HbA1c <11%

– Fasting BG > 126 mg/dL (7.0 mmol/L)

– Post prandial BG < 160 mg/dL (8.9

mmol/L) – Patient resistance to multiple injections

Trang 23

Combination Oral Agent and

• Maintain oral agent(s)

– Sulfonylurea, Metformin or Thiazolidinedione

• Start Bedtime Glargine (or NPH)

– 0.1 U/kg Total Daily Insulin Dose

• Target fasting blood glucose < 120 mg/dL (6.7 mmol/L)

• Increase by 1-4 U based on patterns of blood glucose

• Max dose is 0.4 U/kg at bedtime

• Start pre-meal/bolus insulin based on PPG patterns >160 mg/dL

(8.9 mmol/L)

Trang 24

Secretagogue + Insulin

Pancreas

• Increased and supplemental insulin secretion

Secretagogue

Trang 25

Combination Sulfonylurea (S) and

Glargine (G) Insulin Stage

S – 0 – 0 – G

Combination Sulfonylurea (S) and

S – 0 – 0 – G

Glimepiride ( 4 mg)

Sulfonylurea stimulated

insulin secretion

Trang 26

Metformin + Insulin

Sensitizer

Pancreas

• Supplements insulin secretion

Liver

• Gluconeogenesis

+

Trang 27

Metformin: Suppresses hepatic glucose output

Combination Metformin (M) and

M – 0 – M – G

Combination Metformin (M) and

M – 0 – M – G

Metformin (1000 mg)

Endogenous

Insulin

Trang 28

Thiazolidinedione + Insulin

Sensitizer

Pancreas

• Supplements insulin secretion

Trang 29

Starting Physiologic

Insulin Stage 4

R - R - R – G or N

RA - RA - RA – G or N

Trang 30

Trang 31

Starting Physiologic Regimen:

Trang 32

Add 0.1 U/kg RA before largest meal, increase dose

until pre-BT target is reached or 0.2 U/kg for RA

SMBG

Trang 33

Add 0.1 U/kg RA before next largest meal, increase dose

until 2 hours post meal target is reached or 0.2 U/kg for RA

Trang 34

Add 0.1 U/kg RA before mid-day meal, increase dose

until post meal target is reached or total daily dose reaches 1.5 U/kg

Consider additional injection of RA for snacks

Trang 35

Starting Insulin at Diagnosis of Diabetes

• HbA1c >11%

• Fasting plasma glucose > 300 mg/dL (16.7 mmol/L)

• Casual plasma glucose > 350 mg/dL (19.4 mmol/L)

Trang 36

Trang 38

Trang 39

Alternative and New Means of

Administering Insulin

• Insulin Infusion Pump

• Inhaled Insulin

• Islet Transplant

Trang 40

Insulin Infusion Pump

CLOSING THE LOOP

Trang 41

Innovations: Inhaled Insulin Therapy

RAi-RAi-RAi-G

• Pulmonary inhalation system

• Uses dry powder preparation

• Insulin action - similar to rapid acting insulins

(lispro, aspart)

• Generally requires use of background

insulin

• Limited dosing flexibility

• Significant maintenance needs

Trang 42

Islet Transplants

• Islet Transplants

– Experimental

– Requires one-two pancreases

– Not likely to be used in type 2 diabetes

Trang 43

Summary: Optimal Clinical Effectiveness of

Therapeutic Interventions

*Difference from placebo; based on package insert data and assorted references

O .A C om

bi na tio n

th er

ap y

O .A M on

ot he

ra py

O .A P lu

s BT

In su lin

>-4.0 -3.0 -2.0 -1.0 0

or al

a ge

nt )

>4 %

Trang 44

0 50

Beta cell dysfunction

Post Meal Glucose

At risk for Diabetes

Adapted from: UKPDS 33: Lancet 1998; 352, 837-853 DeFronzo RA Diabetes 37:667, 1988

Saltiel J Diabetes 45:1661-1669, 1996 Robertson RP Diabetes. 43:1085, 1994

Tokuyama Y Diabetes 44:1447, 1995 Polonsky KS N Engl J Med 1996;334:777.

Medical

Metformin Thiazolidinediones

Secretagogue

(11.1 mmol/L)

(7.0 mmol/L)

Trang 45

Oral Agent Stage

Type 2 Master DecisionPath

Note: Each stage requires a

pre-set BG target: and a timeline to

reach that goal

Tiêu đề	Management of Type 2 Diabetes: Focus on Insulin Therapy
Trường học	International Diabetes Center
Chuyên ngành	Diabetes Management
Thể loại	Bài tập tốt nghiệp

Định dạng
Số trang	45
Dung lượng	0,97 MB