Prevalence Total: 20.8 million children and adults -- 7.0% of the population -- have diabetes. Diagnosed: 14.6 million people Undiagnosed: 6.2 million

Prevalence Total: 20.8 million children and adults -- 7.0% of

the population -- have diabetes. Diagnosed: 14.6 million people Undiagnosed: 6.2 million people

Under 20 years of age: 176,500, or 0.22% of all people in this age group have diabetes.

$174 billion spent in total direct and indirect cost Medical expenditures 2.4x higher than in patients

without diabetes

American Diabetes Association. Available at http://diabetes.org/diabetes-statistics/prevalence.jspAccessed January 24,2008

American Diabetes Association. Available at http://diabetes.org/diabetes-statistics/prevalence.jspAccessed November 27,2007

Prevalence

Prevalence2000

Center for Disease Control and Prevention, Diabetes Data and Trends http://apps.nccd.cdc.gov/DDTSTRS/default.aspxAccessed November 27, 2007

2005

http://apps.nccd.cdc.gov/DDTSTRS/default.aspx

72

73

74

75

76

77

78

4.04.55.05.56.06.57.07.5

1990 1992 1994 1996 1998 2000

Prevalence of obesity, increased by 61% since 1991

More than 50% of US adults are overweight

Only 43% of obese persons advised to lose weight during checkups

BMI and weight gain major risk factors for diabetes

Diabetes and Obesity: The Continuing Epidemic

Pre

vale

nce

(%

)

DiabetesMean body weight

kg

Year

Mokdad et al. Diabetes Care. 2000;23:1278.Mokdad et al. JAMA. 1999;282:1519.Mokdad et al. JAMA. 2001;286:1195.

Diabetes Definition

American Diabetes Association Position Statements, Diabetes Care 2004; 27American Diabetes Association Position Statements, Diabetes Care 2004; 27

Diabetes is a group of metabolic diseases characterized by:Diabetes is a group of metabolic diseases characterized by:

• Hyperglycemia resulting from defects in insulin secretion, Hyperglycemia resulting from defects in insulin secretion, insulin action, or bothinsulin action, or both

• Long term damage, dysfunction, and organ failure Long term damage, dysfunction, and organ failure associated with chronic hyperglycemia, especially:associated with chronic hyperglycemia, especially:

Eye Kidney Nerves Heart and blood vesselsDiabetic

RetinopathyDiabetic

NephropathyDiabetic

NeuropathAtheroscierosis hypertension,

cardio and cerebrovascular disease

Etiologic Classification

Type Cause

Type 1 β-cell destruction, often with absolute insulin deficiency

Type 2 Insulin resistance with insulin deficiency

Other specific types Genetic defects, drug or chemical induced

Gestational Insulin resistance with β-cell dysfunction

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

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 2002;25(suppl 1):S5-S20; EndocrineWed.com. Symptoms of hyperglycemia. Available at: http://www.endocrineweb.com/diabetes/hyperglycemia.html. Accessed January 7, 2008.

Common Symptoms of Hyperglycemia

Classic Symptoms Polyphagia Polyuria Polydipsia

Other Symptoms Blurred vision Fatigue Weight loss Poor wound healing

(eg, cuts and scrapes) Dry mouth Dry or itchy skin Impotence (male) Recurrent infections (eg, vaginal

yeast infections, groin rash, or external ear infection)

Impairment of growth

Eisenbarth GS. N Engl J Med. 1986;314:1360-1368.

Natural History of Type 1 Diabetes-

cell

fun

ctio

n (

% o

f m

ax)

ICA negative ICA positive Normal glucose

metabolism

Progressive impairment in insulin

release

Overt diabetes

“Honeymoon” period or periods of

partial remission

Genetic predisposition

Hyperglycemia

Birth

100

50

0Time (yr)

Clinical CharacteristicsType 1 Diabetes Mellitus

Clinical Characteristics

Insulin Dependent for life

Ketones Frequent

Onset Any age (mainly youth)

Islet cell antibodies Frequently present

HLA antigens Frequent association

Obesity Rare

Pathophysiology of Type 2 Diabetes

CarbohydrateCarbohydrateDIGESTIVE ENZYMESDIGESTIVE ENZYMES

GlucoseGlucose

DefectiveDefective-cell secretion-cell secretion

ExcessExcessglucoseglucoseproductionproduction

Resistance to the action of insulinResistance to the action of insulinResistance to the action of insulinResistance to the action of insulin

Reduced glucoseReduced glucoseuptakeuptake

ExcessiveExcessivelipolysislipolysis

Dinneen SF. Diabet Med. 1997; 14 (Suppl 3): S19-24.

Normal BGNormal BG

Normal Insulin- Normal Insulin- Insulin ResistanceInsulin Resistance

Years

Endogenous InsulinEndogenous Insulin

FBGFBGFBGFBG

Diabetes

Postprandial BGPostprandial BG

IGT

Insulin Insulin ResistanceResistance

Avg Dx9–12 yr

Progressive Nature of Type 2 Diabetes

Insulin Deficiency Due to -Cell Failure

Bergenstal RM et al. In: DeGroot LJ et al, eds. Endocrinology. 4th ed. Philadelphia: WB Saunders; 2001:821. Originally in Type 2 Diabetes BASICS (Minneapolis, International Diabetes Center, 2000). Adapted with permission from International Diabetes Center

Clinical CharacteristicsType 2 Diabetes Mellitus

Clinical Characteristics

Insulin Therapy may be necessary

Ketosis Rare

Onset Any age (mainly adult)

Islet cell antibodies Usually absent

HLA antigens No association

Obesity Frequent – 90%

Insulin DeficiencyInsulin Deficiency

Fat MobilizationFat Mobilization Impaired Glucose Impaired Glucose Uptake in LiverUptake in LiverAdipose and Adipose and Muscle CellsMuscle Cells

GlycogenolysisGlycogenolysis GluconeogenesisGluconeogenesis

KetogenesisKetogenesis Increased AppetiteIncreased Appetite HyperglycemiaHyperglycemia

GlycosuriaGlycosuria Muscle Wasting Muscle Wasting

KetonemiaKetonemia PolydipsiaPolydipsia PolyuriaPolyuria Weight LossWeight Loss

Metabolic Metabolic AcidosisAcidosis

HyperventilationHyperventilation

Renal FailureRenal FailureElectrolyte Losses Electrolyte Losses

Nausea VomittingNausea Vomitting

Coma and DeathComa and Death

HypovolemiaHypovolemia

Reduced CerebralReduced CerebralBlood Flow Blood Flow

DehydrationDehydration

Effects of Insulin DeficiencyEffects of Insulin Deficiency

Adapted from www.emedicine.com

Insulin Resistance:Associated Conditions

Adapted from Consensus Development Conference of the American Diabetes Association. Diabetes Care. 1998;21:310-314.

Atherosclerosis

Type 2 diabetes

Hypertension

Polycysticovary disease

Obesity (central)

DyslipidemiaImpaired

glucose tolerance

Endothelialdysfunction

Hyperuricemia

Decreasedfibrinolytic activity

InsulinResistance

Obesity and Cardiovascular Risk

VisceralObesity

HypertensionLeft ventricular hypertrophy

Congestive heart failure

ProthrombosisFibrinogen

PAI-1

Insulin resistance Glucose intolerance

HyperglycemiaType 2 diabetes

Endothelialdysfunction

DyslipidemiaTotal-C LDL-C

Triglycerides Apo-B HDL-C

RenalHyperfiltrationAlbuminuriaInflammatory

Response

Koch R, Sharma AM. Curr Hypertens Rep 1999;1:127-130;Sowers JR. Clin Cornerstone 2001;4:17-23; Alpert MA. Am J Med Sciences 2001;321:225-326.

TG = triglycerides; FPG = fasting plasma glucose.Ford ES et al. JAMA. 2002;287:356-359.JAMA. 2001;285:2486-2497.American Association of Clinical Endocrinologists. New ICD-9-CM code for dysmetabolic syndrome X. Available at: http://www.aace.com/members/socio/syndromex.php. Accessed January 10, 2002.

Metabolic Syndrome

Also known as dysmetabolic syndrome, insulin resistance syndrome, syndrome X, the deadly quartet

Prevalence in the United States: approximately 47 million Defined by having 3 of the following:

Abdominal obesity: waist > 40" (men); > 35" (women) TG 150 mg/dL HDL < 40 mg/dL (men); < 50 mg/dL (women) Blood pressure 130/85 mm Hg FPG 100 mg/dL

Testing for Pre-diabetes and Type 2 Diabetes in asymptomatic adults

Age > 45 years old BMI > 25kg/m2

Family history (eg, parents or siblings with diabetes) Habitual physical inactivity Race/ethnicity (eg, African Americans, Hispanic Americans, Native

Americans, Asian Americans, and Pacific Islanders) Previously identified IFG or IGT Hypertension ( 140/90 mm Hg or on therapy in adults) HDL cholesterol 35 mg/dL and/or TG 250 mg/dL History of GDM or delivery of a baby weighing > 9 lbs Polycystic ovary syndrome (PCOS) History of vascular disease Clinical conditions associated with insulin resistance (acanthosis

nigricans)

BMI = body mass index; IFG = impaired fasting glucose.IGT = impaired glucose tolerance; GDM = gestational diabetes mellitus. American Diabetes Association. Diabetes Care. 2008;231(suppl 1):S12-S54

Testing for Type 2 Diabetes in asymptomatic children

Overweight (BMI > 85th percentile for age and gender, or weight > 120% IBW)

PLUS 2 of the Following Risk Factors

Family history of Type 2 Diabetes in a first or second degree relative

Race/ethnicity (eg, African Americans, Hispanic Americans, Native Americans, Asian Americans, and Pacific Islanders)

Clinical conditions associated with insulin resistance (acanthosis nigricans, HTN, PCOS, dyslipidemia)

Maternal history of diabetes or GDM

American Diabetes Association. Diabetes Care. 2008; 31(suppl 1):S12-S54

Diagnosis of Diabetes MellitusThree Methods

Symptoms of diabetes (polyuria, polydipsia, unexplained weight loss,) AND casual plasma glucose > 200 mg/dL on 2 separate occasions

OR Fasting plasma glucose > 126 mg/dL on 2

separate occasions

OR 2 Hour glucose concentration > 200 mg/dL during

a oral glucose tolerance test on 2 separate occasions

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

1197.

Screening for Gestational Diabetes Screening performed between 24 and 28 weeks

gestation Plasma glucose > 140 mg/dl at 1 hour after a 50 gm

glucose = need for 3 hour OGTT Screening not needed for low risk pregnant females

(must meet all of the following): <25 years old normal body weight no 1st degree relative with DM not Hispanic, Native American, African American, or Asian


Diagnosis of Gestational Diabetes Based on OGTT

100 gram oral glucose load. Two values exceeding limits = gestational diabetes.

Fasting > 95 mg/dl

1 hour > 180 mg/dl

2 hour > 155 mg/dl

3 hour > 140 mg/dl


Pre-diabetes

54 million Americans 2 million adolescents (age 12-19)

IFG = 100-125mg/dL IGT = 140-199 mg/dl after 2 hr plasma

glucose)

The Risks Associated with IGT High risk of progressing to type 2 diabetes

40–50% of people with IGT will develop diabetes within ten years

Glucose tolerance deteriorates over the years as pancreatic -cell function declines

Significantly increased risk of cardiovascular disease

Almost always undiagnosed and untreated

Alberti KGMM. Diabetic Medicine 1996; 13: 927-37.

Plasma Glucose Goals

ADA AACE

A1c < 7.0% < 6.5%

Preprandial Plasma Glucose

70-130 mg/dl < 110 mg/dl

Post Prandial Plasma Glucose

< 180 mg/dl < 140 mg/dl


AACE DM Guidelines: Endocrine Practice 2007: 13 (Supp 1) S116

Glucose Contributions to HbA1c

++Fasting Glucose Fasting Glucose

influenced by:influenced by:• Hepatic glucose productionHepatic glucose production• Hepatic sensitivity to Hepatic sensitivity to

insulininsulin

..

HbAHbA1c1c = =

Postprandial Glucose Postprandial Glucose influenced by:influenced by:

• Preprandial glucosePreprandial glucose• Insulin secretionInsulin secretion• Glucose load from mealGlucose load from meal• Insulin sensitivity in Insulin sensitivity in

peripheral tissuesperipheral tissues

Relative Contribution of FPG and PPG to Overall Hyperglycemia Depending on A1C Quintiles

n=58 n=58 n=58 n=58n=58

Monnier L et al. Diabetes Care. 2003;26:881–885.

0

20

40

60

80

100

<7.3 7.3–8.4 8.5–9.2 9.3–10.2 >10.2

Postprandial glucose Fasting glucose

A1C

Co

ntr

ibu

tio

n,

%

Correlation Between A1C and Mean Plasma Glucose Level

A1C (%)Mean Plasma

Glucose (mg/dL)

135

170

206

240

275

310

345

6

7

8

9

10

11

12

American Diabetes Association, Diabetes Care. 2003’;26(suppl 1):S33-S50

Standards of Care BP < 130/80 mm Hg Lipid: LDL < 100 mg/dl, optional < 70 mg/dl

HDL > 50 mg/dl Triglycerides < 150 mg/dl

Smoking cessation ASA: 75-162mg daily for patients as

Primary prevention in those with Type 1 or 2 at increased CVD risk, including > 40 years or those with additional risk factors

Secondary prevention in those with diabetes and a history of CVD

Immunizations Influenza: yearly for all patients > 6 months Pneumococcal: At least 1 lifetime dose


Microvascular Complications

Hyperglycemia May Lead to Long-Term Complications in

Multiple Organs

Neuropathy

CerebrovascularDisease

PeripheralVascular Disease

Macrovascular Complications

Retinopathy

12 % of all new cases of blindness

Nephropathy

>40% new cases ESRD

Heart Disease

Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329:977-986.Stratton IM et al. BMJ. 2000;321:405-412 with permission from the BMJ Publishing Groupwww.cdc.gov.

Diagnosed in 37.2% patientswith diabetes > 35 years old

Complications of Diabetes

BrainCerebrovascular disease

• Transient ischemic attack

• Cerebrovascular accident

• Cognitive impairment

HeartCoronary artery disease

• Coronary syndrome• Myocardial infarction• Congestive heart

failure

ExtremitiesPeripheral vascular disease

• Ulceration• Gangrene• Amputation

Macrovascular Microvascular

NervesNeuropathy

• Peripheral• Autonomic

KidneyNephropathy

• Microalbuminuria• Gross albuminuria• Kidney failure

EyeRetinopathyCataractsGlaucoma

Treatment of ComplicationsDrugs of Choice

Macrovascular Cerebrovascular: Aspirin Cardiovascular: HMG-CoA Reductase Inhibitor

Microvascular Nephropathy: ACE inhibitor or ARB Neuropathy

Autonomic Gastrointestinal: Prokinetic agents Erectile Dysfunction: PDE-5 inhibitor

Peripheral: TCA, AnticonvulsantsACE= angiotensin converting enzyme, ARB = angiotensin receptor blockers, PDE = phosphodiesterase- 5, TCA = tricyclic ACE= angiotensin converting enzyme, ARB = angiotensin receptor blockers, PDE = phosphodiesterase- 5, TCA = tricyclic amineamine


Approach to Medical Nutrition Therapy in For Prevention of Diabetes

Moderate weight loss (7% body weight) Regular physical activity (150 min/wk) Increase dietary fiber and whole grain foods

Approach to Medical Nutrition Therapy in Type 2 Diabetes

Weight control < 7% of calories from saturated fat 10%–20% of calories from protein Balance of calories from carbohydrate and

poly- and mono-unsaturated fats Individualized based on weight, glucose

control, and lipid abnormalities Increased dietary fiber intake

Carbohydrates

Recommended to monitor carbohydrate (CHO) intake for glycemic control

Include CHO from various sources for good health Fruits, vegetables, whole grains, legumes, etc

Glycemic Index: Compares postprandial effect of various CHO containing foods

Portion Control

Effectiveness of Medical Nutrition Therapy

in Type 2 Diabetes Management *

†

†

No Nutrition Education1 Visit with Dietitian3 Visits with Dietitian

6.6

6.8

7.0

7.2

7.4

7.6

7.8

8.0

8.28.4

Initial 6 Week 3 Month 6 Month

A1C

(%

)

*P < .05 for 3-visit and 1-visit groups vs no nutrition education.†No significant difference between 3-visit and 1-visit groups: P < .001 significantly less than at entry.

Franz MJ et al. J Am Diet Assoc. 1995;95:1009-1017.

Sigal RJ et al. Diabetes Care. 2006;29:1433-1438.

ADA: Physical Activity/Exercise Recommendations for Patients With Diabetes

Patients with type 2 diabetes should be evaluated prior to initiation of any exercise program beyond brisk walking

Exercise program (absent contraindications) should include:– 150 min/week moderate-intensity (50%-70%

max heart rate) aerobic activity resistance exercise 3 times/week targeting all

major muscle groups

Referrals

Dietician Certified Diabetes Educator (C.D.E.) Pharmacist Podiatrist Optometrist /Ophthalmologist Dentist Social Worker Mental Health Professionals

Completed Diabetes Prevention Trials

Trial Treatment Relative Risk

Finnish Diabetes Intensive D+E vs control 58%

Prevention Study

DPP Intensive D+E vs placebo 58%

Metformin vs placebo 31%

STOP-NIDDM Acarbose vs placebo 21%

Fasting Hyperglycemic Gliclazide or intensive No effect

study lifestyle modification

TRIPOD Troglitazone in GDM 56%

DREAM Rosiglitazone 60%

Current Treatment Paradigm

Problems Glycemic targets often not met Monotherapy not effective long-term Treatment fails to address dual impairments Step-wise approach tends to perpetuate “failure” Glucose toxicity interferes with treatment response

Harris, MI et al. Diabetes Care. 1999; 22: 403-408. Harris, MI et al. Diabetes Care. 1998; 21: 518-524.

Diet Combinations & Monotherapy of oral Insulin

exercise agents

Type 1 and Type 2 SummaryCharacteristic Type 1 Type 2

Percent of Diabetic Population

5-10% 90%

Age of Onset Usually < 30, peak 10-14

Usually over 40, occurring more frequently at a younger age

Pancreatic Function None Defect in insulin secretion. Tissue resistance to insulin.

Hepatic glucose output

Family History Generally not strong Strong

Type 1 and Type 2 SummaryCharacteristic Type 1 Type 2

Obesity Uncommon Common (80-90%)

History of Ketoacidosis

Often present Rare, except in circumstances of unusual stress

Clinical Presentation Moderate to severe symptoms which progress rapidly. (polyuria, polydipsia, fatigue, weight loss, ketoacidosis)

Mild polyuria, fatigue. Often diagnosed on physical exam

Documents

Prevalence Total: 20.8 million children and adults -- 7.0% of the population -- have diabetes. Diagnosed: 14.6 million people Undiagnosed: 6.2 million