Disclosure Statement “I have no financial disclosures to report.”
Guidelines for Pre-diabetes Diagnosis and Management http://www.bluenile.com/ Ali A. Rizvi, MD Department of Medicine University of South Carolina School of Medicine
TYPE 2 DIABETES . . . A PROGRESSIVE DISEASENatural History of Type 2 Diabetes Postmeal glucose Plasma Glucose Fasting glucose 126 mg/dL Insulin resistance Relative -Cell Function 10 0 20 20 30 10 Insulin secretion Years of Diabetes
What is pre-diabetes? When a person's blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes “Borderline diabetes” “A touch of sugar” PRE-DIABETES
A1c Derived Average Glucose (ADAG) Study Diabetes Care, August 2008Translating the A1c assay into estimated average glucose • Increased accuracy of HbA1c in reflecting the true average glycemia • Results reported as A1c-derived average glucose “estimated average glucose” – eAG
Role of A1c Testing to Diagnose Diabetes: Joint Recommendations from IDF, EASD, and ADAJune 2009 Advantages of A1c over FPG or OGTT: better indicator of overall glycemic exposure less variability, unaffected by outside factors like stress not a timed test, requires no fasting; more convenient Better at predicting complications ≥ 6.5% seems to be a reasonable cut-point to avoid over-diagnosis. An A1c 5.7-6.4% indicates high risk for developing diabetes: “pre-diabetes”
ADA Diagnostic Criteria for DiabetesClinical Practice Recommendations 2010 In the absence of unequivocal hyperglycemia, criteria 1–3 should be confirmed by repeat testing.
How is pre-diabetes diagnosed?Categories of increased risk for diabetes 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.
ADA Diagnostic Criteria:Normal, Diabetes, and Pre-diabetesClinical Practice Recommendations 2010 In the absence of unequivocal hyperglycemia, criteria 1, 2, and 4 should be confirmed by repeat testing.
The Epidemic of Diabetes and Pre-diabetes Diabetes: 26 million (11.3%) and increasing. By 2015, 37 million (15%) Americans will have diabetes Pre-diabetes: 57 million: About 1/4 (22.6%) of overweight adults aged 45–74 (CDC data) “What lies beneath…” http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf http://www.cdc.gov/diabetes/pubs/factsheets/prediabetes.htm
Pre-Diabetes in the Young and the Old The diabetogenic process begins early – low birth weight and poor nutrition Diabetes epidemic due to: -lack of exercise and overweight in young persons, and -aging of the population Correlation with central obesity, insulin resistance, glucose intolerance, high blood pressure , and dyslipidemia – metabolic syndrome
The Metabolic Syndrome: NCEP ATP III Criteria (May 2001 Guidelines) NCEP ATP III. JAMA. 2001;285:2486-2497.
What are the health risks associated with pre-diabetes? Progression to diabetes: on average, 11% of people with pre-diabetes develop type 2 diabetes each year (DPP) Other studies: majority with pre-diabetes develop type 2 diabetes in 10 years Presence of microvascular complications at onset of diabetes 50% higher risk of CVD: CAD and stroke
CDC Data http://www.cdc.gov/diabetes/pubs/factsheets/prediabetes.htm accessed June 2010 • Among adults with pre-diabetes in 2000, the prevalence of cardiovascular (heart) disease risk factors was high: • 94.9% had dyslipidemia (high blood cholesterol); • 56.5% had hypertension (high blood pressure); • 13.9% had microalbuminuria • 16.6% were current smokers
Population-based and Epidemiologic DataRelationship between A1c and CVD/all-cause mortality is continuous and significant, even in persons without known diabetes EPIC-NORFOLK StudyEach 1% increase in A1c above 5% was associated with a 21% increase in CV events. Ann Intern Med, Sept 2004 Harvard School of Public Health Study on Global CVD mortality: 21% of IHD and stroke deaths attributable to glucose above 90 mg/dl worldwide. Danaei et al, Lancet, Nov 2006 HUNT study20 year f/u of newly diagnosed diabetes. 20% increase in IHD mortality per 1% increment in A1c. Eur Heart J, Feb 2009
Glycated Hemoglobin, Diabetes, and Cardiovascular Risk in Nondiabetic AdultsSelvin et al, NEJM, March 4, 201011,092 adults from the ARIC Study, 1990-92 • HR for stroke were similar • Association between A1c and death from any cause was J-shaped • Compared to fasting glucose, A1c was similarly associated with arisk of • diabetes and more strongly associated with risks ofCVD and death • Evidence supportedthe use of A1c as a diagnostic test for diabetes
Who should get tested for pre-diabetes? Age 45 or older Overweight Family history of diabetes Other risk factors for diabetes or pre-diabetes: sedentary lifestyle, hypertension, low HDL cholesterol, high triglycerides, history of gestational diabetes or giving birth to a baby weighing more than 9 pounds, or belonging to an ethnic or minority group at high risk for diabetes
Acanthosis Nigricans:a Sign of Insulin Resistance • Velvety, light- brown-to-black discoloration usually on the neck, axilla, groin, dorsum of hands • May point to PCOS in females • Insulin sensitivity decreases by 30% at puberty with compensatory increase in insulin secretion
How often should be testing done? Every 3 years if glucose tolerance is normal Every 1-2 years if pre-diabetes is diagnosed
What is the Treatment for Pre-diabetes? Pre-diabetes is a serious medical condition! It CAN be treated TRIALS: Da Qing 1997, Finnish study 2001, DPP 2002: persons with pre-diabetes can prevent the development of T2DM by sustained lifestyle changes 5-10% reduction in body weight coupled with 30 minutes a day of moderate physical activity Reversal of pre-diabetes and return of blood glucose levels to the normal range is possible
DPP: Intensive Lifestyle Changes Reduce the Risk of Developing Type 2 Diabetes • 27 centers nationwide (1998-2002) • Pre-diabetes, av. age 51, BMI 34, 68% women, 45% minority participants • Other groups at high risk: >60, women with h/o GDM, first-degree relative with diabetes • > 7% loss of body weight and maintenance of weight loss • Dietary fat goal -- <25% of calories from fat • Calorie intake goal -- 1200-1800 kcal/day • > 150 minutes per week of physical activity
A Decade Later….DPPOSThe Lancet, Oct 2009 • At end of DPP: participants were offered a 16-session program of intensive lifestyle changes (88% agreed) • Lifestyle group: 34% reduction in diabetes risk maintained • More favorable CV risk factors: BP and TG’s, despite fewer drugs • Benefits more pronounced in elderly: 50% reduction in age >60
Pharmacologic Treatments for Pre-diabetes • Since many individuals with pre-diabetes are generally healthy, benefits of preventive therapy must outweigh any associated side-effects or risks • Expense • None are FDA-approved
NAVIGATOR StudyNEJM online, March 14, 2010Effect of Nateglinide and Valsartan on the Incidence of Diabetes and CV Events9306 persons with IGT with CVD or CV risk factors followed for 5 years • Nateglinide: A postprandial glucose-lowering approach; incidence of diabetes 36% vs. 34%; composite CV outcome 14.2% vs. 15.2%; increased the risk of hypoglycemia • Valsartan: incidence of diabetes 33.1% vs. 36.8% (RR 14%); 38 fewer cases per 1000 pts treated for 5 years; no reduction in rate of CV events
ADA Consensus Statement: Preventive treatment in high-risk individuals with pre-diabetesDiabetes Care 2007 In addition to lifestyle modification, the following individuals should be considered for treatment with metformin: -those who have both IFG and IGT, and -at least one additional risk factor (age <60, BMI ≥35, FH of diabetes in first degree relative, elevated TGs, reduced HDL, or A1C >6%
What proportion of the US population merits consideration for metformin treatment?Rhee et al. Diabetes Care Jan 2010 • 1581 relatively healthy subjects from NHANES • 25-33% had pre-diabetes • 1/3 of IFG, ½ of IGT, and all of IFG/IGT qualified • 96-99% had at least one other risk factor • Overall, 8-9% of all people qualified for metformin • Perform OGTT in persons with IFG to test for IGT (or unrecognized diabetes) and possible metformin
2010 ADA Recommendations for Adults with Diabetes: Importance of Multi-factorial Therapy Diabetes Care,January 2010 Hemoglobin A1c < 7.0% * In Pregnancy < 6.5% Plasma glucose: pre-meal 90-130 mg/dl postprandial < 180 mg/ml *Goals should be individualized. Less intensive glycemic targets may be indicated if there is frequent or severe hypoglycemia (older pts with long-standing disease?) Blood Pressure < 130/80 mmHg In nephropathy< 125/75 mmHg LDL < 100 mg/dl Patients >40 years: statin therapy to achieve LDL reduction of 30-40% In overt CVD <70 using high-dose statins HDL > 40 mg/dl Triglycerides < 150 mg/dl
Multifactorial therapy to reduce Macrovascular risk: Steno-2 TrialDebunking the “gluco-centric” viewNew Engl J Med,2003, 2008 Multifactorial intervention aimed at multiple risk factors, behavior modification and pharmacologic therapy in type 2 diabetes: hyperglycemia hypertension diabetic dyslipidemia microalbuminuria / use of ACE-inhibitors aspirin A 53% reduction in all cardiovascular endpoints and microvascular complications compared with conventional therapy
Preventive Strategies and Evidence-based Interventions that make sense Changes at the individual level Community- and population-based
A 57-year-old accountant has a stressful lifestyle, has gained 12 lbs in the past year, and does not exercise regularly. She has a fasting glucose of 109 mg/dl. She is anxious about her pre-diabetic condition and wants to avoid having diabetes and its complications. Which of the following is NOT accurate advice for her? Pre-diabetes is the same as "borderline diabetes" or a "touch of sugar" and should only be treated aggressively when it progresses to diabetes Pre-diabetes is a serious condition that increases the risk of future diabetes and cardiovascular disease A diagnosis of pre-diabetes mandates that blood pressure and cholesterol be well-controlled
A 63-year-old patient has a fasting blood glucose of 112 mg/dl. He has a BMI of 32, a HbA1c of 6.1%, and a strong family history of type 2 diabetes. What is the most prudent next step? Tell him he has type 2 diabetes and start lifestyle changes Tell him he has pre-diabetes and start lifestyle changes Tell him he needs a glucose tolerance test
You diagnose a 49-year old woman with pre-diabetes on the basis of screening with fasting glucose. In addition to emphasizing sustained lifestyle changes, you advise the patient that Although metformin has been shown to be effective in preventing progression of pre-diabetes, no medications are currently approved for treatment of the pre-diabetic state Metformin is approved for the drug treatment of pre-diabetes All pharmacologic agents approved for the treatment of diabetes can also be used in pre-diabetes