Diabetic Microvascular Disease:The Role of Glycemic Control and

the Impact on Public Health

Robert E. Ratner, MD

MedStar Research Institute

Georgetown University Medical School

Washington, DC

Diabetes: The Numbers

The National Diabetes Education Program

www.ndep.nih.gov

A joint program of NIH and CDC

December 2006

EVERY 24 HOURS• New Cases – 4,100• Amputations – 230 (60% of non-traumatic

amputations annually)• Blindness – 55 (#1 cause)• Kidney Failure – 120 (#1 cause)

Derived from NIDDK, National Diabetes Statistics fact sheet. HHS, NIH, 2005.

Adjusted ESRD incident rates of ESRD due to diabetes

Incident ESRD patients; adjusted for age, gender, & race.

USRDS, accessed July 13, 2007

Prevalence of Visual Impairment per 100 Adults with Diabetes, by Age, United States, 1997–2003

Source: National Diabetes Surveillance System – CDC website (http://www.cdc.gov/diabetes/statistics/index.htm)

What Complications do People with Diabetes Get?

Ramsey SD. Pharmacoeconomics 3:285, 1999

Cumulative Incidence of Hard End-Points: The Pittsburgh EDC Study

Renal Failure Total CAD

Pambianco G. Diabetes 55:1463, 2006

%%%

Metabolic Pathways Leading to Microvascular Complications

Brownlee M. Diabetes 54:1615, 2005

Metabolic Pathways Leading to Microvascular Complications

Brownlee M. Diabetes 54:1615, 2005

Prevalence of Retinopathy:The AusDiab Study

Tapp RJ. Diabetes Res Clin Pract 73:315, 2006

Prevalence of Microalbuminuria:The AusDiab Study

Tapp RJ. Diabetes Res Clin Pract 73:315, 2006

DCCT: Relationship between Glycemic Control and Retinopathy Progression

Lachin J. Diabetes 57:995, 2008

DCCT: Microvascular Complications and Glycemic Control

Lachin J. Diabetes 57:995, 2008

ukpds

Microvascular Endpoints (cumulative)Microvascular Endpoints (cumulative)

p=0.0099

0%

10%

20%

30%

0 3 6 9 12 15

% o

f pat

ient

s w

ith a

n ev

ent

Years from randomisation

Intensive

Conventional

Risk reduction 25%(95% CI: 7% to 40%)

renal failure or death, vitreous haemorrhage or photocoagulation346 of 3867 patients (9%)

ukpds

Glucose Control Study SummaryGlucose Control Study Summary

The intensive glucose control policy maintained a lower HbA1c by mean 0.9 % over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of:

12% for any diabetes related endpointp=0.029

25% for microvascular endpointsp=0.0099

21% for retinopathy at twelve yearsp=0.015

33% for albuminuria at twelve yearsp=0.000054

ukpds

Microvascular EndpointsMicrovascular Endpoints

0.5

1

10

15

0 5 6 7 8 9 10 11

37% decrease per 1% decrement in HbA1c

p<0.0001

Updated mean HbA1c

Haz

ard

ratio

UKPDS 35. BMJ 2000; 321: 405-12

Steno 2: Long-term Outcomes of Intensive Management

Gaede P. NEJM 358:580, 2008

Steno 2: Long-term Outcomes of Intensive Management

Gaede P. NEJM 358:580, 2008

Steno 2: Long-term Outcomes of Intensive Management

Gaede P. NEJM 358:580, 2008

UKPDS: A1c as Predictor of Micro- and Macrovascular Disease

Microvascular

Myocardialinfarction

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10

5 6 7 8 9 10 11

Updated Mean A1c

Est

. H

azar

d R

atio

Stratton IM et al. BMJ. 2000; 321:405-412.

Temporal Changes in Glycemic Control: NHANES

Hoerger TJ. Diabetes Care 31:81, 2008

Age-adjusted Mortality, age 35-74 yearsNHANES

Gregg EW. Ann Int Med 147:149, 2007

Age-adjusted Mortality, age 35-74 yearsNHANES

Gregg EW. Ann Int Med 147:149, 2007