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Transcript of Www.diabetesclinic.ca BEDTIME INSULIN IN TYPE 2 DIABETES J. Robin Conway M.D. Diabetes Clinic,...
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BEDTIME INSULIN IN TYPE 2 DIABETES
J. Robin Conway M.D.
Diabetes Clinic, Smiths Falls,ON
www.diabetesclinic.ca
www.diabetesclinic.ca
Objectives
• Optimize type 2 diabetes management
• Assist you in initiating insulin in your office– When to start insulin therapy?– Insulins, doses, delivery options– Patient training
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Challenges in Initiating Insulin?
1. Patient attitudesPatient attitudes– Fear of needles– Insulin viewed as a threat by patient & physician– Hypoglycemia
2. Physician AttitudesPhysician Attitudes– Discomfort with insulin
• Lack of knowledge and experience
– Fear of needles
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Insulin in Type 2 Diabetes
• 87% of Type 2 Diabetes is treated by Primary Care Providers
• 10% of Type 1 Diabetes is treated by Primary Care Providers
• 23.5% of visits to GP offices involve Diabetics
• Diabetics have multiple comorbidities
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Diabetes in Canada
• Affects 5 - 10 % of population
• Diagnosed: 2.0 million
• Undiagnosed: ???
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Diabetes: mortality
Diabetes in Canada, National Statistics and Opportunities for Improved Surveillance, Prevention, and Control. Minister of Public Works and Government Services Canada, 1999.
Nu
mb
er
of
death
s
YearMale Male projectedFemale Female projected
8000
7000
6000
5000
4000
3000
2000
1000
01950 1958 1966 1974 1982 1990 1998 2006 2014
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Macrovascular Microvascular
Stroke
Heart disease and
hypertension
Foot problems
Diabetic eye disease(retinopathy and cataracts)
Renal disease
Neuropathy
Foot problems
Diabetes: complications
Peripheral vascular disease
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Pathophysiology of Type 2 Diabetes
Insulin resistance
Insulin production
Glucose level
Time
Non-diabete
s
Pre-diabetes
Type 2diabete
sOpara JU, Levine JH, South Med J. 1997;90:1162-1168.
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UKPDS: long-term glucose control
06
7
8
9
0 3 6 9 12 15
Hb
A1
c (
%)
Years of treatment
Conventional
Intensive
ULN = 6.2%
UKPDS Study Group, Lancet, 1998;352:837-853.
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Beta cell function in the UKPDS
Years from diagnosis
Bet
a ce
ll f
un
ctio
n (
%)
100
90
80
70
60
50
40
30
20
10
0–12 –10 –8 –6 –4 –2 0 2 4 6
Holman RR et al. Diabetes Res Clin Pract 1998;40(suppl):S21–S25
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Type 2 Diabetes: Double Impairment
• Impaired ß cell function: insulin secretion
• Impaired insulin action: insulin resistance
• Results in unacceptable blood glucose control
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Insulin resistance: progressive ß-cell failure
Insulin resistance
Hyperinsulinemia
Increasing insulin resistance
ß-cell failure
Insulin deficiency
Impaired glucose tolerance
Hyperglycemia /Type 2 DIABETES
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Diabetes Control and Complications Trial (DCCT) Research Group. Diabetes Control and Complications Trial (DCCT) Research Group. N Engl J MedN Engl J Med. 1993;329:977-986.. 1993;329:977-986.Ohkubo Y et al. Ohkubo Y et al. Diabetes Res Clin PractDiabetes Res Clin Pract. 1995;28:103-117.. 1995;28:103-117.UK Prospective Diabetes Study Group (UKPDS) 33: UK Prospective Diabetes Study Group (UKPDS) 33: LancetLancet.. 1998;352:837-853.1998;352:837-853.
Findings from Clinical Trials• Intensive therapy to reduce glycemia reduces
the risk of microvascular and neurologic complications.
• Insulin therapy does not increase the risk of complications.
• Type 2 diabetes is a progressive disease.
• Managing postprandial glucose is critical to effective diabetes management.
1414
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HbA1c
Retinopathy
Nephropathy
Neuropathy
Macrovascular disease
DCCT
9 7%
63%
54%
60%
41%*
Kumamoto
9 7%
69%
70%
–
–
UKPDS
8 7%
17-21%
24-33%
–
16%*
* not statistically significant* not statistically significant
Good Glycemic Control Reduces Incidence of Complications
1515
Diabetes Control and Complications Trial (DCCT) Research Group. Diabetes Control and Complications Trial (DCCT) Research Group. N Engl J MedN Engl J Med. 1993;329:977-986.. 1993;329:977-986.Ohkubo Y et al. Ohkubo Y et al. Diabetes Res Clin PractDiabetes Res Clin Pract. 1995;28:103-117.. 1995;28:103-117.UK Prospective Diabetes Study Group (UKPDS) 33: UK Prospective Diabetes Study Group (UKPDS) 33: LancetLancet.. 1998;352:837-853.1998;352:837-853.
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Type 2 Diabetes: Key Concepts
• Minimizing the complications of diabetes requires:– Early diagnosis and treatment of diabetes
– Maintaining HbA1C level < 7%
• Achieving HbA1C < 7% requires control of post-prandial and fasting hyperglycemia
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CDA Guidelines (for glycemic control)
Normal Optimal
A1C level (0.04-0.06)
(< 0.07)
Preprandialglycemia(mmol/L)
3.5-6.1 4-7
Postprandialglycemia(mmol/L)
4.4-7.8 7-11
Haars s et al., CMAJ 2003; 159 (Suppl.): S1-29. Gerstein, H.C. et al. CDA views on the UKPDS and revision of the guidelines affected by the results of this study.
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When oral agents are insufficent to achieve target
HbA1c1. Add bedtime insulin to oral agents
Why combine insulin and oral agents rather than just switching to insulin?
• Better glycemic control with smaller insulin dose + fewer injections.
• Less weight gain.
Why just switch, rather than combining?• Cost, simplicity
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Next steps
2. OPTIMIZE INSULIN THERAPY• Increase insulin dose as needed.
3. IF BEDTIME INSULIN THERAPY FAILS TO ACHIEVE SATISFACTORY CONTROL
4. Add daytime insulin according to needs.Consider adding rosiglitazone, metformin or acarbose to insulin regimens to attempt further improvements in glucose control.
5. Once full insulin support is given there is no point in continuing secretagogues
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Indications for Starting Insulin
1. Sub-optimal glycemic control despite maximal doses of oral hypoglycemics
• HbA1C > 7% (NEW CPG SUGGEST 7%)
• AC glycemia > 10 mmol
• PC glycemia > 14 mmol
2. Complications
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Type 2 Diabetes: Double Impairment
• Impaired ß cell function: insulin secretion
• Impaired insulin action: insulin resistance
• Results in unacceptable blood glucose control
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Insulin: Advantages
• Controls ANY patient
• Can be used to overcome glucose toxicity
• Flexibility of dose and lifestyle
• Ease of use with new insulin delivery technology
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PlasmaGlucose,mmol/L
6 AM 10 AM 2 PM 6 PM 10 PM 2 AM 6 AMTime of Day
22.022.0
16.516.5
11.011.0
5.55.5
00
DiabeticControl
BB LL DD
Plasma Glucose Normally Maintained in Narrow Range
Data from Polonsky KS, et al. N Engl J Med. 1988;318:1231-1239. 2424
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American Diabetes Association. American Diabetes Association. Diabetes CareDiabetes Care. 1999; 22(supp 1): S32-S41.. 1999; 22(supp 1): S32-S41.Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders, 3rd ed. ADA Clinical Education Lebovitz HE, ed. Therapy for Diabetes Mellitus and Related Disorders, 3rd ed. ADA Clinical Education Series, 1998. Alexandria, VA: ADA, Inc.Series, 1998. Alexandria, VA: ADA, Inc.
Targets for Glycemic Control HbA1c < 7%
Fasting/preprandial glucose 4-7 mmol/L
Postprandial glucose 5-8 mmol/L
Bedtime glucose 5-8 mmol/L
2525
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BEDTIME INSULIN
• NPH Insulin at Bedtime
• Signalling to liver to decrease hepatic glu
• Decreases Gluconeogenesis
• Dose usually small
• Risk of Hypoglycemia Small
• Patient can adjust dose
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Novolin®ge NPH
Time-Action Profile
Intermediate-acting insulin
Onset: 1.5 hourMaximum effect: 4-12 hoursDuration: 24 hours
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Bedtime Insulin Advantages
• Safe, unlikely to cause Hypoglycemia
• Small doses of Insulin, no weight gain
• One injection a day
• Good starting point
• Learn Insulin adjustment
• Easy to Teach, no mixing, use Pen
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Bedtime Insulin-Pt Selection
• No longer responding to oral agents
• Relative Insulin deficiency
• Pt must have ability & be motivated
• Physically capable of injecting
• Must be self monitoring
• Helps with glucose toxicity
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Bedtime Insulin
• Start at low dose, give the patient time to get used to injections
• Give first injection in the office
• Review in a Month
• Then start insulin adjustment
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Bedtime Insulin-Adjustment
• Start with 10u (or .1-.3 u/kg)
• Target Fasting Glucose <7 mmol/L
• If FBS >7 for 3 days in a row, increase
• Give ceiling dose (+/- 30u)
• Review in a month
• After 3 mo do A1c (goal <7%)
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Bedtime Insulin-Goals
• FBS <7 mmol/L
• A1c <7%
• If Goals not reached look at next highest glucose and treat this
• If Glu >8 in evening, consider Novomix 30/70 or Humalog Mix 25 at supper, or Novolin 30/70, Humulin 30/70