Diabetes 101 Joint Task Force on Diabetes Prevention and Awareness [PDF]

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Diabetes 101

Joint Task Force on Diabetes Prevention and Awareness

March 8th, 2012 Thomas L. O’Connell, MD

UNC Department of Medicine, Division of Endocrinology thomas_oconnell@med.unc.edu

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What is Diabetes?

Diabetes is a group of diseases

characterized by high levels of blood glucose (blood sugar)

Diabetes can lead to serious health

problems and premature death

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Common Types of Diabetes

Type 1 diabetes in adults
5% of diagnosed cases of diabetes
Type 2 diabetes in adults
90% to 95% of diagnosed cases of

diabetes

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Etiologic Classification of Diabetes Mellitus

Type 1 (<10%) β-cell destruction with lack of insulin Type 2 (>90%) Insulin resistance + insulin deficiency Other specific types

Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20:1183-1197.

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100 200 150 300 250 350

10
5

5 10 15 20 25 30 100 200 50 150 *Postprandial glucose Fasting glucose Insulin resistance Insulin level Years

At risk for diabetes b-cell dysfunction

250 Glucose (mg/dL) % Relative to Normal

Natural History of Type 2 Diabetes

* Post Prandial = 1-2 h ppg Bergenstal RM et al. Management of Type 2 Diabetes in Endocrinology. 4th Edition; Philadelphia, 2001

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Common Types of Diabetes

Gestational Diabetes (GDM)
diagnosed during pregnancy
5% to 10% of women with GDM are found to have

diabetes, usually type 2, immediately following pregnancy

35% to 60% of women with GDM will develop diabetes in

the next 10 to 20 years

affects at least 7% of pregnancies

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Diagnostic Criteria for Diabetes

A1C  6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* OR FPG  126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h.* OR 2-h plasma glucose  200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose  200 mg/dl (11.1 mmol/l)

* In the absence of unequivocal hyperglycemia, should be confirmed by repeat testing.

ADA. Diabetes Care 35 (suppl. 1): s11-63, 2012

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Screening

Testing should be considered in all adults who are overweight (BMI ≥25 kg/m2*)

and have additional risk factors:

– physical inactivity – first-degree relative with diabetes – members of a high-risk ethnic population (e.g., African American, Latino, Native American, Asian American, Pacific Islander) – women who delivered a baby weighing >9 lb or were diagnosed with GDM – hypertension (≥140/90 mmHg or on therapy for hypertension) – HDL cholesterol level <35 mg/dl and/or a triglyceride level >250 mg/dl – women with polycystic ovary syndrome – A1C ≥5.7%, IGT, or IFG on previous testing – other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) – history of CVD

In the absence of the above criteria, testing diabetes should begin at age 45 years
If results are normal, testing should be repeated at least at 3-year intervals, with

consideration of more frequent testing depending on initial results and risk status. *At-risk BMI may be lower in some ethnic groups.

ADA. Diabetes Care 35 (suppl. 1): s11-63, 2012

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U.S. Diabetes Prevalence

All Ages, 2010

25.8 million people have diabetes
Diagnosed: 18.8 million people
Undiagnosed: 7.0 million people

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Estimated percentage of people aged 20 years or older with diagnosed and undiagnosed diabetes, by age group, United States, 2005-2008

Source: 2005–2008 National Health and Nutrition Examination Survey

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Diabetes Incidence

A total of 1.9 million new cases of diabetes were diagnosed in 2010 in the United States among people aged 20 years and older.

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Diabetes Impact

Daily Annually Cost $476,712,329 $174,000,000,000 New cases 4,658 1,700,000 Deaths 641 234,000 Amputations 195 71,000 ESRD 129 47,000 Blindness 66 24,000

Centers for Disease Control and Prevention. National diabetes fact sheet: general information and national estimates on diabetes in the United States, 2007. Atlanta, GA: U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, 2008.

25 million with diabetes, perhaps 70 million with “prediabetes”

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Harris MI. Clin Invest Med 1995;18:231-239 Nelson RG et al. Adv Nephrol Necker Hosp 1995;24:145-156 World Health Organization, 2002;Fact Sheet N° 138

Retinopathy

Microvascular Macrovascular

Diabetic Complications

Nephropathy Neuropathy Stroke Peripheral Vascular Disease Heart Disease

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Diabetes Complications

Diabetes is the leading cause of:

– kidney failure

48,374 people with diabetes began treatment for end stage

kidney disease in 2008

– new cases of adult blindness

4.2 million people with diabetes aged 40 and older had

diabetic retinopathy in 2005-2008

– nontraumatic lower-limb amputations

Over 65,000 nontraumatic lower-limb amputations were

performed in people with diabetes in 2006

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Diabetes Complications

The risk of periodontal disease is two to three

times higher in adults with diabetes

About one-third of people with diabetes have severe

periodontal disease

60% to 70% of people with diabetes have mild to

severe nervous system damage

Almost 30% of people with diabetes aged 40 years and older

have impaired sensation in the feet

People with diabetes are twice as likely to have

depression

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Can we do anything about microvascular complications?

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Comparing intensive to conventional treatment for type 1 diabetes, DCCT achieved separation of A1C and BS

A1C separation, 9.0 vs 7.1 % Average BS separation, 231 vs 155 mg/dL

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Rate per 100 person- years

24 20 16 12 8 4 9 8 7 6 5 4 3 2 1 Mean HbA1c = 11% 10% 9% 8% 7%

Time during study (y)

DCCT Research Group. Diabetes. 1995;44:968-983.

DCCT: Absolute Risk of Sustained Retinopathy Progression by HbA1c and Years of Follow-up

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In the DCCT, compared to conventional therapy, intensive therapy reduced the cumulative incidence of 3-step worsening of retinal photos

Primary prevention cohort Secondary intervention cohort

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Summary of risk reduction -- DCCT

Retinopathy

– 76% reduction of new onset – 54% reduction of progression

Nephropathy

– 39% reduction of occurrence of microalbuminuria – 54% reduction of occurrence of albuminuria

Neuropathy

– 60% reduction of occurrence

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Every 1% reduction in mean HbA1c* translates to:

37% reduction of risk for microvascular complications
21% reduction of risk for death related to diabetes
14% reduction of fatal and nonfatal myocardial

infarction and in all cause mortality

43% reduction of risk of amputation or death from

peripheral vascular disease

Stratton IM, et al. BMJ. 2000;321:405-412. *P<0.0001

Lowering HbA1c and Rates of Diabetes Complications

UKPDS Epidemiologic Data in Type 2 Diabetes

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DCCT Research Group. N Engl J Med. 1993;329:977-986. Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28:103-117. UKPDS 33: Lancet 1998; 352, 837-853.

HbA1c Retinopathy Nephropathy Neuropathy Cardiovascular disease DCCT 9  7.2% 63% 54% 60% 41% (NS) Kumamoto 9  7% 69% 70% Improved

UKPDS

8  7% 17-21% 24-33%

16% (p=0.052)

Intensive Diabetes Therapy: Reduced Incidence of Complications

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What about macrovascular disease?

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Diabetes & Cardiovascular Disease

Cardiovascular disease is the leading cause of death

for people with diabetes

In adults with diabetes:

– 68% die of heart disease or stroke – the risk for stroke is two to four times higher – 67% have high blood pressure – smoking doubles the risk for heart disease

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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10 20 30 40 50 No prior MI Prior MI No prior MI Prior MI

3.5 18.8 20.2 45.0 P<0.001 P<0.001 7-Year Incidence of MI

n=1304 n=69 n=890 n=169

Diabetic Patients Nondiabetic Patients

Type 2 Diabetes and CHD: After 7 yr followup, the presence of diabetes is as great a risk factor for MI, as is a history among nondiabetics of having a prior MI

More recent studies suggest that this is perhaps only true for those with fairly long-standing diabetes – duration over ten years. The risk is about 2-3 times that of non-diabetic individuals without CAD.

Haffner SM et al. N Engl J Med. 1998;339:229; Arch Intern Med. 2011;171:404

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4S: Simvastatin reduced coronary events* — 6 yr

27 45 23 19

10 20 30 40 50 Placebo Simvastatin Placebo Simvastatin n=202

32%

Risk Reduction Patients With Major Coronary Event (%)

55%

Risk Reduction

Pyörälä et al. Diabetes Care. 1997;20:614

n=4242

*CHD death or nonfatal MI

Nondiabetic Patients Diabetic Patients

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Diabetes-related deaths were reduced by tight BP control (UKPDS 38)

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After median 8.8 years post-trial follow-up Aggregate Endpoint 1997 2007 Any diabetes related endpoint RRR: 12% 9% P: 0.029 0.040 Microvascular disease RRR: 25% 24% P: 0.009 0.001 Myocardial infarction RRR: 16% 15% P: 0.052 0.014 All-cause mortality RRR: 6% 13% P: 0.44 0.007

UKPDS: “Legacy Effect”

f Insulin/Sulfonylurea Therapy

RRR = Relative Risk Reduction P = Log Rank

Holman RR, et al. New England Journal of Medicine 2008; 359:1577-1589

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Preventing Diabetes Complications

Blood glucose control
Blood pressure control
Blood lipid control
Preventive care practices for eyes, kidneys, feet,

teeth, and gums

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Diabetes Care 30: S4-41, 2007 (http://care.diabetesjournals.org/cgi/reprint/30/suppl_1/S4) http://www.aace.com/pub/press/releases/diabetesconsensuswhitepaper.php

Glycemic Goals of Therapy

Goal ADA ACE

Premeal plasma glucose (mg/dl) 70-130 <110 Postprandial plasma glucose (mg/dl) (<180) <140 A1C <7% ≤6.5%

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What is Pre-diabetes?

Pre-diabetes is a medical condition where blood

glucose levels are higher than normal but not high enough to be diagnosed as diabetes

Studies have shown that the onset of type 2

diabetes can be delayed or prevented by:

– losing weight, and – increasing physical activity

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Pre-Diabetes

FPG 100 mg/dl to 125 mg/dl [IFG]†
2-h PG in the 75-gram OGTT 140 mg/dl to 199 mg/dl

[IGT]†

A1C 5.7% to 6.4%

* For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at higher ends of the range.

† IFG = impaired fasting glucose, IGT = impaired glucose tolerance

ADA. Diabetes Care 35 (suppl. 1): s11-63, 2012

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Pre-Diabetes in the U.S.

78 million adults aged 20 and older have pre-

diabetes

Pre-diabetes raises the risk for type 2 diabetes

and cardiovascular disease

National Diabetes Fact Sheet, CDC, 2011. http://www.cdc.gov/diabetes/pubs/factsheet11.htm

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Study Subjects Intervention Relative Risk Reduction DaQing Finnish DPS US DPP IGT IGT IGT+“IFG” Diet or Exercise or Both Lifestyle Lifestyle 64%/53%/61% 58% 58% US DPP STOP-NIDDM EDIT TRIPOD XENDOS DREAM ACT-NOW ORIGIN NAVIGATOR IGT+“IFG” IGT IFG Prior GDM IGT IGT IGT IFG + IGT IGT + IFG Metformin Acarbose Metformin or Acarbose or Both Troglitazone Orlistat Rosiglitazone or Ramipril or Both Pioglitazone Glargine or Fish oil or Both Nateglinide or Valsartan or Both 31% 25% NS 35% 45% 61%/NS 72% ~2012 NS/16%

Prevention of Type 2 Diabetes

Behavior Medication*

Li et al., Lancet 2008;371:1783-1789. ADA Position Statement on the Prevention or Delay of Type 2 Diabetes. Diabetes

Care. 2002;25:742-749. Torgerson JS, et al. Diabetes Care. 2004;27:155-161. DREAM Trial Investigators. Lancet.

2006;368:1096-1105. DREAM Trial Investigators. N Engl J Med. 2006;355:1551-1562. DeFronzo RA, et al. ADA 68th Scientific Sessions 2008. Origin Trial Investigators. Am Heart J 2008;155:26-32. Navigator. NEJM 2010.

*No drugs are approved for diabetes prevention or delay by FDA.