4 importance of glycemic control, the potential benefits of new technologies
TRANSCRIPT
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The Importance of Glycemic Control, the Potential
Benefits of New Technologies, and the Need for
Additional Research in Medicare Populations
Presentation to the Medicare Coverage Advisory Committee
Aaron Kowalski Ph.D.
Director, Strategic Research Projects
Juvenile Diabetes Research Foundation (JDRF)
August 30, 2006
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About JDRF
JDRFs mission: to find a cure for diabetes and itscomplications through research
JDRF is the leading charitable funder of type 1diabetes research worldwide ($140 million a year)
JDRF was founded in 1970 by the parents ofchildren with type 1 diabetes, and JDRF'svolunteers -- who have a personal connection to thedisease -- are the driving force behind JDRF's
commitment
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Tight Glycemic Control is the
Recommended Standard of Care
American Diabetes Association (ADA)(ADA, 2006.)
Glycemic control is fundamental to the management of diabetes
The HbA1c (A1c) goal for patients in general is an A1c goal of
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Hemoglobin A1c Levels are Elevated in the
United States and Appear to Have Plateaued
Reported at Diabetes Mellitus Interagency
Coordinating Committee (DMICC) (DMICC, 2005)
CDC: NHANES III Mean A1c 7.7%, NHANES II MeanA
1c 7.6%, 60% >7.0% Kaiser: TRIAD A1cs have stayed the same or declined
slightly over the past 10 years
VA : 59% of people with diabetes above A1c 7.0%
Summary: Many factors, but tools may besuboptimal for reducing A1c below 7.0%
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Hyperglycemia Causes Complications
in Type 1 and Type 2 Diabetes
LowerA1c confers significantly reduced risk ofmicrovascular and macrovascular complications:
Diabetes Control and Complications Trial (DCCT) Type1 (Diabetes Control and Complications Trial Research Group, 1993)
Epidemiology of Diabetes Interventions and Complications(EDIC) Type 1 (DCCT/EDIC Research Group, 2000, Nathan et al., 2005)
UK Prospective Diabetes Trial (UKPDS) Type 2 (UKPDSGroup, 1998)
Benefits were realized in as soon as three years
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There are Common Pathways in
Diabetes Complications
Oxidative
Stress
Cellular
Dysfunction
AGE Formation
Cell
Damage
Hexosamine
Pathway
ROS
ROS
Glucose Peripheral & Autonomic Neuropathy
Nephropathy
Retinopathy
Vascular
Damage
Different complications (eye, kidney, nerve, blood vessels)arise from limited number of triggers perturbing a limitednumber of metabolic pathway(s) (Brownlee, 2001)
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Hypoglycemia Remains a Significant Burden
Hypoglycemia
Is a real obstacle to tight glycemic control (Reportfrom the American Diabetes Association Workgroup on Hypoglycemia,2005, Cryer et al., 2003)
Is a source of significant morbidity in older adultswith diabetes (Kennedy et al., 2002)
Elderly are at increased risk for hypoglycemiccoma (Ben-ami et al., 1999)
Elderly have reduced awareness of theautonomoic symptoms of hypoglycemia (Meneilly etal., 1994)
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Significant Glycemic Variability is Found
in both Type 1 and Type 2 Diabetes
Type 1 Patients (Bode et al., 2005):
9.6% (2.3 hours) hypoglycemic
30% (7.2 hours) hyperglycemic
Type 2 Patients (Bode et al., 2005):
4.2% (1.0 hours) hypoglycemic
28.7% (6.9 hours) hyperglycemic
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Variability May Exacerbate Complications Pathways
Intensive management may reduce risk ofdeveloping complications by both reducingA1c and by reducing variability (Brownlee and Hirsch,2006)
Monnier et al.(2006):
Type 2 Patients Mean Age 63.6
MeanA
1c 9.6% Acute Glucose Swings Activate Oxidative Stress
Pathways
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Tight Glycemic Control Improves Outcomes for all
People with Diabetes the Young and the Elderly
LowerA1c equals:
Less blindness, less renal failure, fewer amputations,fewer strokes, fewer heart attacks
And continues to be critical in the elderly Increased survival for those on dialysis (Oomichi et al., 2006)
Decreased post-operative morbidity (Ben Ami et al., 1999)
Prevents progression of retinopathy (Morisaki et al., 1994)
Prolonged hospitalization with exacerbated congestiveheart failure (Bhatia et al., 2004)
Better cognitive function (Meneilly et al., 1993, Gradman et al., 1993)
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Better Glycemic Control Increases Survival for
People with Diabetes on Dialysis
(Oomichi et al., 2006)
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Better Glycemic Control Reduces Post-Operative
Morbidity in Elderly People with Diabetes
Dronge et al., 2006
Median age = 71 years
Primary outcomes = infectious complications,
including pneumonia, wound infection, urinarytract infection, or sepsis
CONCLUSION: Good preoperative glycemiccontrol (A1c levels
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Better Glycemic Control Reduces Hospitalization
Time for Elderly People with Diabetes and CHF
Bhatia et al., 2004
Patients with diabetes admitted to a tertiary care center withexacerbation of Congestive Heart Failure (CHF)
Mean Age = 76.5
In-hospital glycemic control strongly correlated positively with thenumber of days of hospitalization
Admission blood glucose level also showed a strong positivecorrelation with the days of hospitalization
Mean hemoglobin A1c correlated positively with the number ofdays in the hospital
51 patients with uncontrolled diabetes (A1c >7%) werehospitalized for a mean period of 6.3 +/- 3.2 days, in comparisonwith a mean duration of3.2 +/- 1.9 days for the 49 patients withgood outpatient glycemic control (A1c < or =7%)
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Better Glycemic Control Prevents the Progression
of Retinopathy in Elderly People with Diabetes
Morisaki et al., 1994
Non-insulin-dependent patients with diabetes 60 years ofage
The progression rates of retinopathy as a function of themean A1c during the follow-up were as follows: lower than7%, 2%; 7-8%, 20%; 8-9%, 40%; more than 9%, 61%
Only A1c was a significant risk factor for progression ofretinopathy
CONCLUSIONS: Control of diabetes mellitus is themost important factor associated with prevention of
progression of retinopathy in elderly patients
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Better Glycemic Control Improves Cognitive
Function in Elderly People with Diabetes
Meneilly et al.,1993: Improved glycemic controlin the elderly patient with NIDDM may havebeneficial effects on selective areas of cognition
Gradman et al., 1993: Verbal learning andmemory may improve with improved glycemiccontrol
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New Technologies Hold Potential to
Improve Control
Continuous Glucose Sensors Show ConsiderablePromise in Preliminary Studies(Presentations 2005 and 2005,Garg et al. 2006, Bailey et al., 2006)
Preliminary Studies have shown:
Statistically significant reductions in A1c (Presentations 2005 and2005, and Bailey et al., 2006)
Statistically significant reductions in hypoglycemia (Garg et al.,2006)
Statistically significant increase in time spent in targetrange (Garg et al., 2006A-B)
Benefits in both type 1 and type 2 patients young andadults (Garg et al. 2006A-B, Bailey et al. 2006)
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New Technologies Provide Additional Information
Provide both point-in-time and glucosetrends
Alarm at hyper and hypoglycemic thresholds
Tells people with diabetes whether theirglucose level is trending upwards ordownwards, allowing them to adjust their
insulin, diet and exercise to prevent highsand lows
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JDRF Plans Prospective Studies in Elderly
The JDRF Artificial Pancreas Project
Aims to close the loop tying insulin delivery tocontinuous glucose sensing
Aims to bring new technologies to people withdiabetes that will improve glycemic control anddiabetes outcomes
Plans to fund outcome-based continuous sensortrial in over 65 patients with IDDM
Would like feedback on outcome prioritization
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Potential JDRF Studies will Examine
Diabetes Outcomes in Over 65 patients
Randomized controlled trial
Primary outcomes ofA1c and Hypoglycemia
Secondary outcomes of quality of life,glycemic variability, time in target
Economic analysis i.e. fewerhospitalizations, reduced morbidity
JDRF-funded: Independent
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References
American Diabetes Association. Standards of medical care in diabetes -2006. Diabetes Care. 2006; 29Suppl 1:S4-42.
Bailey T., Kaplan R., Schwartz S. Reduction in A1c with Real-Time Continuous Glucose Monitoring:Interim Results from a 12-Week Clinical Study. ADA Late breaking Abstract 1-LB. 2006 AnnualScientific Sessions.
Ben-Ami H, Nagachandran P, Mendelson A et al. Drug-induced hypoglycemic coma in 102 diabeticpatients. Arch Intern Med 1999; 159: 281284.
Bhatia V, Wilding GE, Dhindsa G, Bhatia R, Garg RK, Bonner AJ, Dhindsa S. Association of poor
glycemic control with prolonged hospital stay in patients with diabetes admitted withexacerbation of congestive heart failure. Endocr Pract. 2004; 10: 467-71.
Bode BW, Schwartz S, Stubbs HA, Block JE. Glycemic characteristics in continuously monitoredpatients with type 1 and type 2 diabetes: normative values. Diabetes Care. 2005; 28: 2361-6.
Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/AmericanGeriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improvingthe care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003; 51(5 SupplGuidelines): S265-80.
Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature. 2001; 414:813-20.
Brownlee M, Hirsch IB. Glycemic variability: a hemoglobin A1c-independent risk factor for diabeticComplications. JAMA. 2006; 295: 1707-8.
Cryer P, Davis SN, and Shamoon, H.,. Hypoglycemia in Diabetes, Diabetes Care. 2003; 26: 1902-12.
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References
Diabetes Control and Complications Trial Research Group. The effect of intensive treatment ofdiabetes on the development and progression of long-term complications in insulin-dependentdiabetes mellitus. N Engl J Med 1993; 329: 977-986.
Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and ComplicationsResearch Group. Retinopathy and nephropathy in patients with type 1 diabetes four years after atrial of intensive therapy. N Engl J Med 2000; 342: 381-389.
DMICCHbA1c, Diabetes and Public Health December 12, 2005 Summary Minutes.http://www.niddk.nih.gov/federal/dmicc/2005/12-12-05/summary.pdf
Dronge AS, Perkal MF, Kancir S, Concato J, Aslan M, Rosenthal RA. Long-term glycemic control andpostoperative infectious complications. Arch Surg. 2006; 141: 375-80.
Garg S., ZisserH., Jovanovic L. Improvement in Glucose Excursions Using a Seven-Day ContinuousGlucose Sensor: Managing the Extremes. Abstract Number: 393-P. ADA Annual ScientificSessions. 2006.
Garg S, ZisserH, Schwartz S, et. al. Improvement in Glycemic Excursions With a Transcutaneous,Real-Time Continuous Glucose Sensor: A randomized controlled trial, Diabetes Care. 2006; 29:44-50.
Gradman TJ, Laws A, Thompson LW, Reaven GM: Verbal learning and/or memory improves withglycemic control in older subjects with non-insulin dependent diabetes mellitus. J Am Geriatr
Soc. 1993; 41: 1305-12.Kennedy RL et al. Accidents in patients with insulin-treated diabetes: increased risk of low-impact
falls but not motor vehicle crashes- a prospective register-based study. J Trauma. 2002; 52:660-6.
Meneilly GS, Cheung E, Tessier D, Yakura C, Tuokko H: The effect of improved glycemic control oncognitive functions in the elderly patient with diabetes. J Gerontol. 1993; 48: M117-21.
Meneilly GS, Cheung E, Tuokko H. Altered responses to hypoglycemia of healthy elderly people. JClin Endocrinol Metab. 1994; 78: 1341-8.
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Morisaki N, Watanabe S, Kobayashi J, Kanzaki T, Takahashi K, Yokote K, Tezuka M, Tashiro J,Inadera H, Saito Y, et al. Diabetic control and progression of retinopathy in elderly patients: five-year follow-up study. J Am Geriatr Soc. 1994; 42: 142-5.
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