Www.diabetesclinic.ca BEDTIME INSULIN IN TYPE 2 DIABETES J. Robin Conway M.D. Diabetes Clinic, Smiths Falls,ON .

www.diabetesclinic.ca

BEDTIME INSULIN IN TYPE 2 DIABETES

J. Robin Conway M.D.

Diabetes Clinic, Smiths Falls,ON



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


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


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


Diabetes in Canada

• Affects 5 - 10 % of population

• Diagnosed: 2.0 million

• Undiagnosed: ???


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


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


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.


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.


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


Type 2 Diabetes: Double Impairment

• Impaired ß cell function: insulin secretion

• Impaired insulin action: insulin resistance

• Results in unacceptable blood glucose control


Insulin resistance: progressive ß-cell failure

Insulin resistance

Hyperinsulinemia

Increasing insulin resistance

ß-cell failure

Insulin deficiency

Impaired glucose tolerance

Hyperglycemia /Type 2 DIABETES



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


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.


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


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.


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


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


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


Type 2 Diabetes: Double Impairment

• Impaired ß cell function: insulin secretion

• Impaired insulin action: insulin resistance

• Results in unacceptable blood glucose control


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


Insulin: Disadvantages

• Hypoglycemia

• Weight gain

• Injections


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


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


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


Novolin®ge NPH

Time-Action Profile

Intermediate-acting insulin

Onset: 1.5 hourMaximum effect: 4-12 hoursDuration: 24 hours


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


Advancing Insulin Therapy Through Device Innovation


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


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


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%)


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


SUMMARY

• If A1c <7% cannot be achieved on OHA, add bedtime insulin

• Use NPH, start with low dose until patient is comfortable

• Titrate up until Fasting Glucose <7

• If daytime glucose remains elevated go to full insulin support

Www.diabetesclinic.ca BEDTIME INSULIN IN TYPE 2 DIABETES J. Robin Conway M.D. Diabetes Clinic, Smiths Falls,ON .

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