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Stanford CF Center Cystic Fibrosis Related Diabetes (CFRD). AN UPDATE ON CFRD and Our Center’s PROTOCOL: KEEPING IT SHORT AND SWEET! Annie Coates, MD Pediatric Pulmonary Fellow March 3 rd , 2012. Cystic Fibrosis Related Diabetes:. CFRD Is a Distinct Form of Diabetes:.

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Stanford CF Center Cystic Fibrosis Related Diabetes (CFRD)

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Stanford cf center cystic fibrosis related diabetes cfrd l.jpg

Stanford CF Center Cystic Fibrosis Related Diabetes (CFRD)

AN UPDATE ON CFRD and Our Center’s PROTOCOL:

KEEPING IT SHORT AND SWEET!

Annie Coates, MD

Pediatric Pulmonary Fellow

March 3rd, 2012


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Cystic Fibrosis Related Diabetes:


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CFRD Is a Distinct Form of Diabetes:

Most common age of onset

Usual body habitus

Insulin Secretion

Insulin Sensitivity

Autoimmune etiology

Ketoacidosis

Microvascular complications

Macrovascular complications

Type 1

Type 2

CFRD

<20

Normal

Absent

Yes

Yes

Yes

Yes

>40

Obese

↓ ↓ ↓

No

Rare

Yes

Yes

22-24

Normal

No

Rare

Yes

No

Moran A, et al. Diabetes Res Clin Pract. 1999.


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Microvascular Complications in Individuals with Diabetes > 10 Years Duration:

Schwarzenberg, Moran et al. Diabetes Care. 2007


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Clinical Signs and Symptoms of CFRD:

Excessive thirst or excessive urination

Failure to gain or maintain weight despite nutritional intervention

Failure to grow

Delayed progression of puberty

Chronic decline in pulmonary function

Moran A, et al. Diabetes Res Clin Pract. 1999.


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Outcomes:

Reduced survival

In a study of 448 people with CF, less than 25% with diabetes survived to age 30, whereas nearly 60% of people without diabetes reached this age

Finkelstein et al J Pediatr 1988

Decreased pulmonary function

Cross sectional analysis of 7,566 people enrolled in the European Epidemiologic Registry of CF found lower FEV1% in those with DM vs those without DM at all ages (72% vs 52%)

Koch et al PediatrPulmonol 2001


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Oral Glucose Tolerance Test (OGTT)

Fasting, 30 minute, 1 hour, 2 hour blood draws after glucose beverage

Most sensitive way to detect CFRD without fasting hyperglycemia

Early Identification is KEY!

High risk for progression to fasting hyperglycemia

High risk for excessive decline in pulmonary function

Moran A, et al. Diabetes Res ClinPract. 1999.

MillaCE, et al. Am J RespirCrit Care Med. 2000.


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Glucose Tolerance Prevalence in Individuals with CF

100

23

30

36

80

57

60

27

38

Percent Prevalence

Within Age Group

38

40

27

34

20

20

15

6

15

16

11

3

0

5-9

10-19

20-29

30+

Age (years)

Normal glucose tolerance

Impaired glucose tolerance

CFRD without fasting hyperglycemia

Moran A, et al. J Pediatr. 1998.

CFRD with fasting hyperglycemia


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Insulin Secretion:

Insulin or C-peptide

*

*

Control

CF-PS

CF-no DM

CFRD

PS=pancreatic sufficient

DM=diabetes mellitus

*P<0.001 vs control

Moran A, et al. J Pediatr. 1991.

.


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Insulin Therapy Improves BMI in CFRD Without Fasting Hyperglycemia:

N= 81

Individuals with CFRD without fasting hyperglycemia were treated with insulin vs. Repaglinide or placebo

Insulin group showed improved BMI after one year of therapy whereas the group treated with Repaglinide did not

Moran A. et al. Diabetes Care. 2009.


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Screening Recommendations

  • Use of A1C not recommended

  • Screening: 2 hour OGTT

  • Begin annual screening at age 10

  • In-patient screening: Fasting,

    2 hour post-prandial BS x 48 hours

  • Screening for patients on continuous enteral feeds at time of gastrostomy feeding initiation, then monthly using SMBG

Position Statement

Published in Diabetes Care, December 2010

Joint effort from the American Diabetes Association, CF Foundation, and endorsed by the Pediatric Endocrine Society


Position statement12 l.jpg

Diagnosis Recommendations

  • 2 hour OGTT plasma glucose > 200 mg/dl

  • Fasting plasma glucose > 126 mg/dl

  • A1C > 6.5%

  • Test on 2 separate days to rule out laboratory error

  • Diagnosis can be made during acute illness, when abnormal fasting plasma glucose or 2 hour post prandial levels persist for greater than 48 hours

Position Statement

Published in Diabetes Care, December 2010

Joint effort from the American Diabetes Association, CF Foundation, and endorsed by the Pediatric Endocrine Society


Position statement13 l.jpg

Management Recommendations

  • Refer to Endocrine (initially should be seen quarterly)

  • Treatment with insulin

  • Blood sugar monitoring minimum of three times daily

  • Follow A1C quarterly (goal <7%)

  • Nutrition management with carbohydrate counting (no calorie restriction)

Position Statement

Published in Diabetes Care, December 2010

Joint effort from the American Diabetes Association, CF Foundation, and endorsed by the Pediatric Endocrine Society


Position statement14 l.jpg

Diabetes Complications

  • Education regarding symptoms, prevention and treatment of hypoglycemia

  • Measure blood pressure at every diabetes visit

  • Annual monitoring for micro- vascular complications (>5 years )

  • Annual lipid profile (Pancreatic sufficient patients or if risk factors present)

Position Statement

Published in Diabetes Care, December 2010

Joint effort from the American Diabetes Association, CF Foundation, and endorsed by the Pediatric Endocrine Society


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LPCH CF Center Protocol

  • Annual screening: 6 years and older withcon- current insulin levels

  • Home BG monitoring: Individuals with impaired glucose tolerance

  • Referral to Endocrine: Individuals with CFRD with and without fasting hyperglycemia

  • In-patient monitoring:

    • Fasting, 2 hour post-prandial BG x 48 hours

    • 2 am, immediately post overnight GT feeds for individuals with newly placed gastrostomy tube feedings


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What does more aggressive management mean?

  • Routine screening with annual OGTT for patients aged > 6 years

  • Careful inpatient glucose monitoring and use of insulin as needed

  • Early institution of intensive insulin therapy has become more routine in the last 5 years

  • Pre-meal insulin is prescribed for those with CFRD without fasting hyperglycemia


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Summary:

CFRD is a challenging disease to diagnose and treat

Earlier screening

Improve the health and well being of our patients and families


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Questions?


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Thank you!


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