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Perspectives on the Perspectives on the M t d P tiM t d P tiManagement and Prevention Management and Prevention

of T2DMof T2DM

Stephen R. Bell, DOStephen R. Bell, DO

Newport Internal MedicineNewport Internal Medicine

www.NewportIM.comwww.NewportIM.com

ObjectivesObjectives•• Identify patients at risk for T2DM & implement Identify patients at risk for T2DM & implement

risk reduction strategiesrisk reduction strategiesD ib h l d h lD ib h l d h l•• Describe the latest treatments and how to apply Describe the latest treatments and how to apply themthem

•• Identify principles by which glycemic control is Identify principles by which glycemic control is optimizedoptimized

•• Identify challenges and barriers to effective Identify challenges and barriers to effective prevention and management of T2DMprevention and management of T2DM

•• Relate the significant of lifestyle change in the Relate the significant of lifestyle change in the prevention of T2DMprevention of T2DM

•• Create simple diet and exercise programsCreate simple diet and exercise programs

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T2DM DefinedT2DM Defined

•• Abnormally high blood glucose levels due to Abnormally high blood glucose levels due to relative lack of insulinrelative lack of insulinrelative lack of insulinrelative lack of insulin

•• Insulin insensitivity due to genetic or metabolic Insulin insensitivity due to genetic or metabolic factorsfactors

•• Risk Factors:Risk Factors:–– Excess caloric intakeExcess caloric intake

–– Minimal exerciseMinimal exercise

–– Genetic predispositionGenetic predisposition

Risk Factors for DiabetesRisk Factors for Diabetes

•• Race/ethnicityRace/ethnicity•• History of GDMHistory of GDM

•• Age 45 and olderAge 45 and older

O i h (BMI ≥ 25)O i h (BMI ≥ 25)History of GDMHistory of GDM•• Physical signs of insulin Physical signs of insulin

resistanceresistance

•• Dx of PreDx of Pre--diabetesdiabetes

•• History of vascular diseaseHistory of vascular disease

•• Overweight (BMI ≥ 25)Overweight (BMI ≥ 25)

•• HypertensionHypertension

•• Abnormal lipid levelsAbnormal lipid levels

•• Family history of Family history of diabetesdiabetes

American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11-61.

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IFG or T2DMIFG or T2DM

Test if patient:Test if patient:Test pat e t:Test pat e t:•• Age 45 or olderAge 45 or older•• An BMI>30, adult and risk factor(s)An BMI>30, adult and risk factor(s)

Order: A1C Order: A1C oror FPG FPG oror 22--hour plasma glucose post 75hour plasma glucose post 75--g g oral glucose challengeoral glucose challenge

Repeat q 3 yrRepeat q 3 yr

American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11--61.61.

Diagnostic Criteria for Diagnostic Criteria for PrePre--diabetes (IFG) & T2DMdiabetes (IFG) & T2DM

CategoryCategory A1CA1C Fasting Plasma Fasting Plasma Glucose Test (FPG)Glucose Test (FPG)

22--Hour Oral Hour Oral Glucose ChallengeGlucose Challenge

AcceptableAcceptable N/AN/A Below 100 mg/dlBelow 100 mg/dl Below 140 mg/dlBelow 140 mg/dl

PrePre--diabetesdiabetes 5.7% 5.7% -- 6.4% 6.4% 100100--125 mg/dl (IFG)125 mg/dl (IFG) 140140--199 mg/dl 199 mg/dl (IGT)(IGT)

American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11American Diabetes Association. Diabetes Care 2011; 34;(Suppl.1):S11--61.61.

(IGT)(IGT)

DiabetesDiabetes ≥ 6.5%≥ 6.5% 126 mg/dl or above 126 mg/dl or above 200 mg/dl or above200 mg/dl or above

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Why do we careWhy do we care-- Glucotoxicity!Glucotoxicity!

•• NonNon--enzymatic glycation of proteins alter their enzymatic glycation of proteins alter their structure and functionstructure and function–– HgbA1C is nothing but glycosylated HemoglobinHgbA1C is nothing but glycosylated Hemoglobin

•• Microvascular damageMicrovascular damage–– NNephropathyephropathy

–– Neuropathy Neuropathy

RetinopathyRetinopathy–– Retinopathy Retinopathy

•• Macrovascular damageMacrovascular damage–– CVDCVD

–– strokestroke

“Lipid Burden” Hypothesis for T2D“Lipid Burden” Hypothesis for T2D

Cusi, K. Curr. Diab. Rep. 2010, 10, 306-315

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How might chronic inflammation in fat tissue lead to How might chronic inflammation in fat tissue lead to insulin resistance…insulin resistance…

Lean fat cell (healthy condition)

Glucose

Guilherme et al. Nat Rev Molecular Cell Biol., 2008, 9, 367-377

…Potentially through inhibition of PPAR activity resulting in increased Free Fatty Acids (FFA)

Macrophages

Insulin-mediated

GlucoseAdipocyte

(obese condition)

Insulin

Resistance

Glucose(obese condition)

FFA

Guilherme et al. Nat Rev Molecular Cell Biol., 2008, 9, 367-377http://www.aamdsglossary.co.uk/glossary/m

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Pathogenesis of Type 2 DiabetesPathogenesis of Type 2 Diabetes

Major Underlying PathologiesMajor Underlying Pathologies

PancreasInsulin

Beta-cell dysfunction

Diabetes =Hyperglycemia

Hepatic glucose production

Insulinsecretion

Liver

Glucose uptake

Adapted from American Diabetes Association Diabetes Care 2004;27(suppl 1):S5–S10; Beers MH, Berkow R, eds. Merck Manual of Diagnosis and Therapy, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999.

Muscle

Impaired Glucose Tolerance and Impaired Glucose Tolerance and Development of DiabetesDevelopment of Diabetes

Normal glucose

toleranceDiabetes

Obesityand

increased insulin

resistance

“Prediabetes”(IGT or IFG)

and beta-cell loss

IGT=impaired glucose tolerance; IFG=impaired fasting glucose

Adapted from Weyer C et al Diabetes Care 2001;24(1):89–94; Hedley AA et al JAMA 2004;291:2847–2850.

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Complications of Uncontrolled HyperglycemiaImpaired insulin release Insulin resistance

Increased circulating

free fatty acids

TNF-alphaCRPPAI-1

DyslipidemiaIncreased platelet aggregation

Blood vessel wallabnormalities

Decreasedglucose uptake

Increased lipolysis

Hyperglycemia

Overproduction of glucose

TNF=tumor necrosis factor; CRP=C-reactive protein; PAI-1=plasminogen-activator inhibitor-1; MI=myocardial infarction; PVD=peripheral vascular disease

Adapted from Inzucchi SE JAMA 2002;287(3):360–372; Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philiadelphia: Saunders, 2003:1427–1483; Sheetz MJ, King GL JAMA 2002;288(20):2579–2588; Libby P, Plutzky J. Editorial Circulation 2002;106:2760–2763; Kendall DM et al Coron Artery Dis 2003;14:335–348; DeFronzo RA Ann Intern Med 1999;131:281–303.

Macrovascular risk

• MI• Stroke• PVD

Microvascular risk

• Nephropathy• Retinopathy• Neuropathy

BetaBeta--cellcelldysfunctiondysfunction

Major Targeted Sites of Oral Drug ClassesMajor Targeted Sites of Oral Drug Classes

Pancreas

Sulfonylureas

Hepatic glucoseHepatic glucoseoverproductionoverproduction

InsulinInsulinresistanceresistance

↓Glucose level

Muscle and fatLiver

Biguanides

Glinides

TZDsGut

DPP-4 inhibitors

Glucose Glucose absorptionabsorption

DPP-4=dipeptidyl peptidase-4; TZDs=thiazolidinediones.DeFronzo RA. Ann Intern Med. 1999;131:281–303. Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: WB Saunders; 2003:1427–1483.

g

TZDs Biguanides

Alpha-glucosidase inhibitors

DPP-4 inhibitors

Biguanides

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Pharmaceutical OptionsPharmaceutical Options

SulfonylureasSulfonylureasGlimepiride, Glipizide, Glyburide, etc.Glimepiride, Glipizide, Glyburide, etc.

MOAMOA

RequiresRequires

Drive insulin releaseDrive insulin release

F i iF i i bb llllRequiresRequires

DosedDosed

Major side effectsMajor side effects

DangerDanger

Functioning Functioning betabeta--cellscells

QDQD--BIDBID

Weight gainWeight gain

HypoglycemiaHypoglycemia

Adapted from Siconolfi-Baez L et al Diabetes Care 1990;13(suppl 3):2–8; Riddle MC Am Fam Physician 1999;60(9):2613–2620; DeFronzo RA Ann Intern Med 1999;131:281–303; Glynase™ prescribing information, Pharmacia Corporation, April 2002; Glucotrol™ prescribing information, Pfizer, 2000; Glucotrol XL™ prescribing information, Pfizer, 2003.

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GlinidesGlinidesRepaglinide, NateglinideRepaglinide, Nateglinide

MOAMOA

Req iresReq ires

Increase insulin releaseIncrease insulin release

FunctioningFunctioning betabeta--cellscellsRequiresRequires

DosedDosed

Side effectsSide effects

DangerDanger

Functioning Functioning betabeta--cells cells

With mealsWith meals

Weight gainWeight gain

HypoglycemiaHypoglycemia

Adapted from Williams G, Pickup JC, eds. Handbook of Diabetes. 3rd ed. Malden, MA: Blackwell Publishing, 2004; Riddle MC Am Fam Physician 1999;60(9):2613–2620; Del Prato S et al Diabetes Care 2003;26(7):2075–2080; Starlix™ prescribing information, Novartis Pharmaceuticals, December 2000; DeFronzo RA Ann Intern Med 1999;131:281–303.

Biguanide(s)Biguanide(s)MetforminMetformin

MOAMOA Primary:Primary:D d h i l d iD d h i l d i

RequiresRequires

DosingDosing

Decreased hepatic glucose productionDecreased hepatic glucose productionSecondary:Secondary:Increased peripheral glucose uptakeIncreased peripheral glucose uptake

Presence of insulinPresence of insulin

QD QD -- BIDBID

Side effectsSide effects

DangerDanger

Adapted from Kirpichnikov D et al Ann Intern Med 2002;137(1):25–33; DeFronzo RA Ann Intern Med 1999;131:281–303; Glucophage™/Glucophage XR™ prescribing information, Bristol-Myers Squibb, April 2003; Williams G, Pickup JC, eds. Handbook of Diabetes. 3rd ed. Malden, MA: Blackwell Publishing, 2004.

Nausea, anorexia, diarrheaNausea, anorexia, diarrhea

Lactic acidosisLactic acidosis

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AlphaAlpha--Glucosidase InhibitorsGlucosidase InhibitorsAcarbose, MiglitolAcarbose, Miglitol

MOAMOA Delayed CHO absorptionDelayed CHO absorptionMOAMOA

RequiresRequires

DosedDosed

Side effectsSide effects

Delayed CHO absorptionDelayed CHO absorption

Functioning betaFunctioning beta--cells cells

TID with mealsTID with meals

Bloating, abdominal discomfort, diarrheaBloating, abdominal discomfort, diarrheaflatulenceflatulence

DangerDanger

Adapted from Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: Saunders, 2003:1427–1483; DeFronzo RA Ann Intern Med 1999;131:281–303; Glyset™ prescribing information, Bayer Corporation, July 2003.

flatulenceflatulence

Elevations in liver enzymes (rare)Elevations in liver enzymes (rare)

PPARPPARγγ AgonistsAgonists--TZDsTZDsPioglitazone, RosiglitazonePioglitazone, Rosiglitazone

Enhance tissue response to insulinEnhance tissue response to insulin

P f i liP f i li

MOAMOA

R iR i Presence of insulin Presence of insulin

Once or twice dailyOnce or twice daily

Weight gain, edema, anemiaWeight gain, edema, anemia

Congestive heart failure; Congestive heart failure;

RequiresRequires

DosedDosed

Side effectsSide effects

DangerDangerg ;g ;

Need to monitor liver enzymesNeed to monitor liver enzymes

Adapted from Actos™ prescribing information, Takeda Pharmaceuticals, December 2003; Avandia™ prescribing information, GlaxoSmithKline, May 2004; DeFronzo RA Ann Intern Med 1999;131:281–303; Williams G, Pickup JC, eds. Handbook of Diabetes. 3rd ed. Malden, MA: Blackwell Publishing, 2004.

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InsulinInsulinShort Acting (Regular), Fast ActingShort Acting (Regular), Fast Acting--(Aspart,Lispro,Glulisine), Intermediate (Aspart,Lispro,Glulisine), Intermediate

ActingActing--(NPH), Long Acting(NPH), Long Acting--(Detemir, Glargine)(Detemir, Glargine)Fixed MixturesFixed Mixtures-- 70/30, 75/25, 50/5070/30, 75/25, 50/50

Decreased hepatic glucose production Decreased hepatic glucose production MOAMOAIncreased glucose uptakeIncreased glucose uptake

Exogenous source for subcutaneous Exogenous source for subcutaneous injectionsinjections

QD vs continuous pumpQD vs continuous pump

Weight gain, hypoglycemiaWeight gain, hypoglycemia

RequiresRequires

DosedDosed

Side effectsSide effects Weight gain, hypoglycemiaWeight gain, hypoglycemia

HypoglycemiaHypoglycemia

Adapted from Buse JB et al. In: Williams Textbook of Endocrinology. 10th ed. Philadelphia: Saunders, 2003:1427–1483.

Side effectsSide effects

DangerDanger

GLPGLP--1 Analogs1 AnalogsExenatide, LiraglutideExenatide, Liraglutide

••ShortShort--term and longterm and long--term actions term actions of GLPof GLP--11

MOAMOA

Functional beta cellsFunctional beta cells

Injectable Injectable

Preservation or restoration Preservation or restoration of of betabeta--cell functioncell function

RequiresRequires

Route of administeredRoute of administered

Potential benefitsPotential benefits

Nausea, vomiting, diarrheaNausea, vomiting, diarrhea

HypoglycemiaHypoglycemia

Adapted from Holz GG, Chepurny OG Curr Med Chem 2003;10(22):2471–2483; Drucker DJ Endocrinology 2001;142(2):521–527; Drucker DJ Expert Opin Invest Drugs 2003;12(1):87–100.

Side EffectsSide Effects

DangerDanger

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DPPDPP--4 Inhibitors4 Inhibitorslinagliptin, saxagliptin,sitagliptinlinagliptin, saxagliptin,sitagliptin

Inhibit degradation of incretins (e.g., GLPInhibit degradation of incretins (e.g., GLP--1) 1) resulting inresulting in•• Increased insulin release, decreased glucagon Increased insulin release, decreased glucagon secretion,delayed gastric emptying,reduced foodsecretion,delayed gastric emptying,reduced food

MOAMOA

secretion,delayed gastric emptying,reduced food secretion,delayed gastric emptying,reduced food intake, intake,

Functioning beta cellFunctioning beta cell

••OralOral••QDQD--BIDBID-- adjust for renal impairment (sit)adjust for renal impairment (sit)

RequiresRequires

Route of administrationRoute of administrationDosedDosed

••URI, nasopharyngitis, HAURI, nasopharyngitis, HA••Pancreatitis?Pancreatitis?

Adapted from Ahrén B Curr Diab Rep 2003;3:365–372; Schirra J et al J Endocrinol 1998;156(1):177–186; Meier JJ et al Clin Endocrinol Metab2003;88(6):2719–2725; Holz GG, Chepurny OG Curr Med Chem 2003;10(22):2471–2483; Drucker DJ Expert Opin Invest Drugs 2003;12(1):87–100; Gutzwiller JP et al Am J Physiol 1999;76(5 pt 2):R1541–1544; Drucker DJ Endocrinology 2001;142(2):521–527; Holst JJ, Deacon CF Diabetes 1998;47(11):1663–1670.

Side EffectsSide EffectsDangersDangers

Bile Acid SequestrantBile Acid SequestrantColeseveramColeseveram

•• MOAMOA

R iR i

•• UnknownUnknown

F i l b llF i l b ll•• RequiresRequires

•• DosedDosed

•• Side EffectsSide Effects

•• DangerDanger

•• Functional beta cellsFunctional beta cells

•• BIDBID--QDQD

•• Nausea, constipationNausea, constipation

•• Hypertriglyceridemia, Hypertriglyceridemia, Pancreatitis, Drug Pancreatitis, Drug InteractionsInteractions

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Dual PPARDual PPARαα//γγ AgonistsAgonists

Increased insulin sensitivityIncreased insulin sensitivityI d f id kI d f id k

MOAMOA

Note: Agents in this class are not currently approved

Increased fatty acid uptakeIncreased fatty acid uptake

Weight gain, peripheral edema, Weight gain, peripheral edema, fluid retention, which may lead tofluid retention, which may lead toor exacerbate congestive heart failureor exacerbate congestive heart failure

Reduced microvascular andReduced microvascular and

Potential side effectsPotential side effects

Potential benefitsPotential benefits

Reduced microvascular and Reduced microvascular and macrovascular risk in patients with MS macrovascular risk in patients with MS & T2DM& T2DM

Adapted from Doebber TW et al Biochem Biophys Res Comm 2004;318:323–328; Guo Q et al Endocrinology 2004;145(4):1640–1648; Hegarty BD et al Endocrinology 2004;145(7):3158–3164; Bristol-Myers Squibb Research and Development Review, 2004; Verges B Diabetes Metab 2004;30(1):7–12.

United Kingdom Prospective Diabetes Study (UKPDS)

Traditional Monotherapies Do Not Maintain Traditional Monotherapies Do Not Maintain A1C Control Over TimeA1C Control Over Time

10

Conventional*Insulin Glibenclamide (glyburide)

Med

ian

A1C

(%)

6

7

8

9

ADA Goal

*Conventional therapy defined as dietary advice given at 3-month intervals where FPG was targeted at best levels feasible in clinical practice. If FPG exceeded 270 mg/dL, then patients were re-randomized to receive non-intensive metformin, chlorpropamide, glibenclamide, or insulin. If FPG exceeded 270 mg/dL again, then those on SU would have metformin added. If FPG exceeded270 mg/dL after this, then insulin was substituted.Adapted with permission from UK Prospective Diabetes Study (UKPDS 34) Group. Lancet. 1998;352:854-865.

(g y )Metformin

06

Time From Randomization (Years)0 3 6 9 12 15

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Combination MedsCombination Meds-- The Wave of the The Wave of the FutureFuture

1po

ints

)

PioglitazonePioglitazone Added to Added to MetforminMetformin

HbA1c

-2

-1.5

-1

-0.5

0

0.5

1

ge

Fro

m B

asel

ine

(% p

- 0.8% points P0.05 vsMetformin + placebo

***

*

** *

-2.5

-6 0 8 12 16Weeks

Met + Placebo Met + pio 30 mg

Ch

ang

* P0.05 vs baseline

LOCF

.

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Add-on to pioglitazone study2

Mean Baseline A1C: 8 0% 8 1%

Sitagliptin A1C Reductions From Baseline When Added to Sitagliptin A1C Reductions From Baseline When Added to Metformin or PioglitazoneMetformin or Pioglitazone

24-week change from baseline

Mean Baseline A1C: 8 0%

Add-on to metformin study1

Mean Baseline A1C: 8.0%, 8.1%

n A

1C

Fro

m B

as

elin

e, %

n=224

Metforminsitagliptin

–0.6

00

n A

1C

Fro

m B

as

elin

e, %

Mean Baseline A1C: 8.0%

P<0.001*

–0.0%

Metformin+ Placebo

Pioglitazone+ sitagliptin

Pioglitazone+ Placebo

n=453 n=174 n=163

–0.4

–0.2

–0.6

–0.4

–0.2

–0.2%

Me

an

Ch

an

ge

in

–1.0

–0.8

–1.0

Me

an

Ch

an

ge

in

–0.7% P<0.001*

*Compared with placebo.1. Charbonnel B et al. Diabetes Care. 2006;29:2638–2643.2. Rosenstock J et al. Clin Ther. 2006;28:1556–1568.

0.7% placebo-subtracted result

0.7% placebo-subtracted result

–0.9%

–0.8

General Principles to Prescribe By:General Principles to Prescribe By:

•• Partner with your patientPartner with your patientT h ti t h t’ i t (H bA1 ?)T h ti t h t’ i t (H bA1 ?)–– Teach your patient what’s importance (HgbA1c?)Teach your patient what’s importance (HgbA1c?)

–– Don’t scare your patientDon’t scare your patient-- empower with knowledge therapyempower with knowledge therapy

–– They’re the active partnerThey’re the active partner-- you’re the coachyou’re the coach

–– Praise when you can, scold when you have toPraise when you can, scold when you have to

–– Sell, sell, sellSell, sell, sell

•• Make compliance achievableMake compliance achievable•• Make compliance achievableMake compliance achievable–– Meds that are affordableMeds that are affordable-- combinations?combinations?

–– Regimens that are easy to followRegimens that are easy to follow

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The Down SideThe Down Side

•• T2DM is a progressive T2DM is a progressive diseasediseasediseasedisease

•• No modality other than No modality other than obesity surgery has been obesity surgery has been shown to halt disease shown to halt disease progression over the progression over the course of yearscourse of yearscourse of yearscourse of years

•• Even then, is it Even then, is it permanent?permanent?-- no datano data

PreventionPrevention

79 million79 million79 million79 millionAmericans over Americans over 20 have 20 have prepre--diabetesdiabetes

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

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Diabetes Prevention Program (Diabetes Prevention Program (DPP)DPP)•• Clinical trial to see if metformin could prevent/delay Clinical trial to see if metformin could prevent/delay

the onset of T2DM.the onset of T2DM.•• ParticipantsParticipants Presence of IGTPresence of IGT

–– Mean age 51 years Mean age 51 years –– Mean body mass index (BMI) 34Mean body mass index (BMI) 34–– 68% women68% women–– 45% minority groups 45% minority groups –– African AmericansAfrican Americans

Hi p ni /L tinHi p ni /L tin–– Hispanics/LatinosHispanics/Latinos–– American IndiansAmerican Indians–– Asian Americans and Pacific IslandersAsian Americans and Pacific Islanders

••

DPP Research Group. N Engl J Med 2002, Vol.346, No. 6.

DPP MethodsDPP Methods••Patients Randomized to:Patients Randomized to:

––MetforminMetformin

––PlaceboPlacebo

–– TLC (Therapeutic Lifestyle Changes)TLC (Therapeutic Lifestyle Changes)•• 5% to 7% weight reduction5% to 7% weight reduction

•• Healthy lowHealthy low--calorie, lowcalorie, low--fat dietfat diet

•• 30 minutes of physical activity 30 minutes of physical activity

•• 5 days a week5 days a week

DPP Research Group. N Engl J Med 2002, Vol.346, No. 6.

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Diabetes Prevention Program Diabetes Prevention Program Outcomes Study (DPPOS)Outcomes Study (DPPOS)

(10 year follow up)(10 year follow up)

TLC: TLC: •• Reduced A1C and FPGReduced A1C and FPG•• slowed rate of dx by 34%, slowed rate of dx by 34%,

–– 4 years4 years•• 49% in patients 60+49% in patients 60+M tf iM tf iMetformin: Metformin: •• Reduced A1C and FPGReduced A1C and FPG•• slowed rate of dx by 18%, 2 yearsslowed rate of dx by 18%, 2 years

DPP Research Group. The Lancet 2009: Vol.374, No. 9702.

Diabetes Prevention TrialDiabetes Prevention Trial

DPP l l d A 2001 ( bjDPP l l d A 2001 ( bj•• DPP results released August 2001 (subjects were DPP results released August 2001 (subjects were followed for 2.8 years) and published 2002followed for 2.8 years) and published 2002

•• Metformin (850mg BID) reduced progressionMetformin (850mg BID) reduced progression–– 31%31%

•• Lifestyle intervention reduced progressionLifestyle intervention reduced progressiony p gy p g–– 58%58%

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Diabetes Prevention TrialDiabetes Prevention Trial

•• Average Weight Loss by GroupAverage Weight Loss by Group

Pl bPl b 0 1 K0 1 K–– Placebo Placebo –– 0.1 Kg0.1 Kg

–– Metformin Metformin –– 2.1 Kg2.1 Kg

–– Lifestyle Intervention Lifestyle Intervention –– 5.6 Kg5.6 Kg

Incidence of DM by GroupIncidence of DM by Group

•• Placebo Placebo –– 28.9%28.9%

•• Metformin Metformin –– 21.7%21.7%

•• Lifestyle Intervention Lifestyle Intervention –– 14.4%14.4%

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Compared BenefitsCompared BenefitsCurrent CAD TherapiesCurrent CAD Therapies

• Smoking cessation 60%• Smoking cessation 60%• Mediterranean diet 65%• Mediterranean diet 65%

E i / W i ht l 50%E i / W i ht l 50%• • Exercise / Weight loss 50%Exercise / Weight loss 50%• • BP control 42%BP control 42%• • Lipid control 25%Lipid control 25%• • ASA for CAD 25%ASA for CAD 25%• • ACE for CHF / MI 22%ACE for CHF / MI 22%•• BB--Blockers for MIBlockers for MI 18%18% BB Blockers for MI Blockers for MI 18%18%• • Tight BS in DM2 Tight BS in DM2 ??• Control of TG’s / HDL ?• Control of TG’s / HDL ?• Vitamins 0• Vitamins 0• HRT 0• HRT 0

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Mastering Preventive MedicineMastering Preventive Medicine

•• Diet/ Exercise are two important modalities that we as Diet/ Exercise are two important modalities that we as physicians address the least in appropriate detailphysicians address the least in appropriate detailphysicians address the least in appropriate detailphysicians address the least in appropriate detail

•• Physicians need not delegate important roles to other Physicians need not delegate important roles to other professionsprofessions

•• And can do a better job!And can do a better job!–– A simpler planA simpler plan–– Deeper understanding of the patientDeeper understanding of the patient–– Better resultsBetter results–– Preserve our role as best patient advocate and most Preserve our role as best patient advocate and most

appropriate deliverer of medical careappropriate deliverer of medical care

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Objectives of Dietary InterventionObjectives of Dietary Intervention

•• Normal Glucose LevelsNormal Glucose Levels

•• Normal Blood PressureNormal Blood Pressure

•• Normal Serum Lipid LevelsNormal Serum Lipid Levels

•• Reasonable Body WeightReasonable Body Weight

•• Promotion of Overall HealthPromotion of Overall Health•• Promotion of Overall HealthPromotion of Overall Health

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Protein IntakeProtein Intake

•• 1212--20% of daily calories20% of daily calories•• Small to medium portion of protein once dailySmall to medium portion of protein once daily•• 33--5oz of meat, fish or poultry daily from both 5oz of meat, fish or poultry daily from both

animal and vegetable sourcesanimal and vegetable sources•• Vegetable source less nephrotoxic than animal Vegetable source less nephrotoxic than animal

proteinproteinpp•• Patient with nephropathy should limit to less Patient with nephropathy should limit to less

than 12% dailythan 12% daily

Fat IntakeFat Intake

•• <35% of total calories<35% of total calories

•• Saturated fat <10% of total caloriesSaturated fat <10% of total calories

•• Polyunsaturated fats 10% of total caloriesPolyunsaturated fats 10% of total calories

•• Cholesterol consumption < 300 mgCholesterol consumption < 300 mg

•• Moderate increase in monounsaturated fats such Moderate increase in monounsaturated fats such as canola oil and olive oil (up to 20% of total as canola oil and olive oil (up to 20% of total calories)calories)

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Carbohydrate IntakeCarbohydrate Intake

•• CHO intake determined after protein and fat CHO intake determined after protein and fat intake have been calculatedintake have been calculated

•

intake have been calculated.intake have been calculated.•• Emphasize on whole grains, starches, fruits, and Emphasize on whole grains, starches, fruits, and

vegetablesvegetables•• Fiber same as for nondiabetics (20g to 35g)Fiber same as for nondiabetics (20g to 35g)•• Rate of digestion related to the presence of fat, Rate of digestion related to the presence of fat,

degree of ripeness, cooking method, and degree of ripeness, cooking method, and preparationpreparation

“Eating alone will not keep a man well; he must also take exercise. For food and exercise, while possessing oppositequalities work together to producequalities, work together to produce health.”Hippocrates, Regimen,5th Century B.C.

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Benefits of ExerciseBenefits of Exercise

•• Improve fitnessImprove fitness •• Maintain bone healthMaintain bone health

II•• Helps in weight Helps in weight managementmanagement

•• Increases insulin sensitivityIncreases insulin sensitivity

•• Improves CD risk factors:Improves CD risk factors:

–– Blood pressureBlood pressure

•• Increases:Increases:

–– EnergyEnergy

–– Muscle strengthMuscle strength

–– EnduranceEndurance

–– FlexibilityFlexibilitypp

–– Lipid profileLipid profile

yy

–– Sense of well beingSense of well being

In T2DM Exercise Improves:In T2DM Exercise Improves:

•• Basal insulin levelsBasal insulin levelsHbA1HbA1•• HbA1cHbA1c

•• Basal glucoseBasal glucose•• Liver glucose productionLiver glucose production•• Insulin stimulated glucose uptakeInsulin stimulated glucose uptake•• GLUT4 receptorsGLUT4 receptors•• GLUT4 receptorsGLUT4 receptors•• Insulin sensitivityInsulin sensitivity•• LipidsLipids

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Exercise PyramidExercise Pyramid

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Exercise Prescription Exercise Prescription Get FITTGet FITT

• F = Frequency:• F = Frequency:Most days of the week; 5 or more.Most days of the week; 5 or more.Most days of the week; 5 or more.Most days of the week; 5 or more.

•• I = Intensity:I = Intensity:Moderate; 50Moderate; 50--70% of max HR or use “sing70% of max HR or use “sing--talk”talk”testtest

•• T = Type:T = Type:Use large muscle groups; Use large muscle groups; something patients likesomething patients like

•• T TiT Ti•• T = Time:T = Time:30 minutes30 minutes

The Exercise PrescriptionThe Exercise Prescription

•• Minimum of 4 days a week Minimum of 4 days a week -- most days of the most days of the kkweekweek

•• 30 30 –– 60 min/day60 min/day

•• Moderate intensityModerate intensity

•• NEJM 2001;344:1343NEJM 2001;344:1343--5050

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Clearance for ExerciseClearance for Exercise-- who gets a who gets a stress test?stress test?

•• If moderate to high intensity exerciseIf moderate to high intensity exerciseIf moderate to high intensity exerciseIf moderate to high intensity exercise•• And/or ADA guideline risk factorsAnd/or ADA guideline risk factors•• Autonomic neuropathyAutonomic neuropathy•• PVD, retinopathyPVD, retinopathy•• + EKG+ EKG

+ St t t+ St t t•• + Stress test+ Stress test

•• Handbook of Exercise in Diabetes Handbook of Exercise in Diabetes 20022002•• Clin Sports Med Clin Sports Med 2009;28:3792009;28:379--9292

ADA guidelinesADA guidelines

•• Age > 35Age > 35•• Type II > 10 yrsType II > 10 yrs

T I 15T I 15•• Type I > 15 yrsType I > 15 yrs•• 2 more CAD risk factors2 more CAD risk factors•• RetinopathyRetinopathy•• NephropathyNephropathy•• PVDPVD•• PVDPVD•• Autonomic neuropathyAutonomic neuropathy

Handbook of Exercise in Diabetes Handbook of Exercise in Diabetes 20022002Med Sci Sports Exer Med Sci Sports Exer 1997;29:11997;29:1--66

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Sample Exercise PrescriptionSample Exercise PrescriptionStephen R. Bell, DOStephen R. Bell, DO

Newport Internal Medicine Newport Internal Medicine -- www.NewportIM.comwww.NewportIM.comGreat Lakes Weight & Wellness Great Lakes Weight & Wellness -- www.GLWAW.comwww.GLWAW.com

11 A bi E iA bi E i R i i i l l fR i i i l l f1. 1. Aerobic Exercise Aerobic Exercise –– Repetitive movements using large muscle groups for Repetitive movements using large muscle groups for an extended period of timean extended period of time-- such as cycling, crosssuch as cycling, cross--country skiing, snow country skiing, snow shoeing, running/jogging, brisk walking or using exercise machines which shoeing, running/jogging, brisk walking or using exercise machines which simulate those activities.simulate those activities.

2. 2. 3030--45 minutes/day45 minutes/day (more is better)(more is better)3. 3. 55--6 days/week6 days/week (more is better)(more is better)4. 4. Moderate intensityModerate intensity –– there are many ways to calculate this but the easiest is there are many ways to calculate this but the easiest is

to be comfortably breathless. You should be comfortable enough to follow to be comfortably breathless. You should be comfortable enough to follow the dialogue on the TV in front of you at the gym, but unable to hold a the dialogue on the TV in front of you at the gym, but unable to hold a the dialogue on the TV in front of you at the gym, but unable to hold athe dialogue on the TV in front of you at the gym, but unable to hold aconversation without losing your breath or slowing down.conversation without losing your breath or slowing down.

5. You will notice that as you push your body to perform in this way 5. You will notice that as you push your body to perform in this way your your performance will improve, and you will need to move faster to stay at performance will improve, and you will need to move faster to stay at any given level of perceived intensityany given level of perceived intensity. You will also notice that you will be . You will also notice that you will be able to continue with more intense exercise for an increasing span of timeable to continue with more intense exercise for an increasing span of time

•• "If you can't fly "If you can't fly then run, if you then run, if you can't run then can't run then walk, if you walk, if you can't walk then can't walk then crawl, but crawl, but whatever you whatever you do you have to do you have to keep moving keep moving f d "f d "forward." forward." -- Martin Luther Martin Luther King Jr.King Jr.

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Never Give UpNever Give Up

Slides of InterestSlides of Interest

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Sample of a SIMPLE Dietary PlanSample of a SIMPLE Dietary PlanStephen R. Bell, DOStephen R. Bell, DO

Newport Internal Medicine Newport Internal Medicine -- www.NewportIM.com www.NewportIM.com Great Lakes Weight & Wellness Great Lakes Weight & Wellness -- www.GLWAW.comwww.GLWAW.com

Reduced Calorie Diet:Reduced Calorie Diet:•• .Food journal .Food journal –– keep an keep an accurateaccurate record of record of everythingeverything that goes between your teeththat goes between your teeth--

large or small. If you do not know how to record the value of something, don’t eat it! large or small. If you do not know how to record the value of something, don’t eat it! This is your body’s This is your body’s energy checkbookenergy checkbook. It needs to be as accurate as possible to be of . It needs to be as accurate as possible to be of benefit to you.benefit to you.

•• .Get a good calorie counter. We recommend the .Get a good calorie counter. We recommend the Calorie KingCalorie King-- Calorie, Fat and Calorie, Fat and Carbohydrate CounterCarbohydrate Counter. It can be purchased or ordered from any bookstore, but it . It can be purchased or ordered from any bookstore, but it also has a sophisticated web site which has a number of other tools as well.also has a sophisticated web site which has a number of other tools as well.

•• .Use your calorie counter to calculate the number of calories in everything you eat, .Use your calorie counter to calculate the number of calories in everything you eat, both per meal and daily.both per meal and daily.

•• .Aim for ________ calories daily, as suggested by Dr. Bell..Aim for ________ calories daily, as suggested by Dr. Bell.

•• Helpful Tips: Helpful Tips: –– . . Less carbs = less hungerLess carbs = less hunger. The less carbohydrates you eat, the less hungry you . The less carbohydrates you eat, the less hungry you

will be, and your weight loss will be both easier and faster.will be, and your weight loss will be both easier and faster.–– .As you lose weight your body will be more efficient, and your rate of weight loss .As you lose weight your body will be more efficient, and your rate of weight loss

will slow down. You will need to further will slow down. You will need to further reduce your intake of calories reduce your intake of calories and/or increase your exercise and/or increase your exercise to maximize your weight loss.to maximize your weight loss.