How to address a complex problem in resource poor regions. Bob Lawrence Alaska Family Doctor September 2009

How to address a complex problem in resource poor regions.

Bob LawrenceAlaska Family Doctor

September 2009

Diabetes Mellitus

Meaning = siphon sweetness

The Modern US Lifestyle is Diabetogenic.

• 23.6 million in the US have DM~ 7.8 % of total population~ 300 million estimated cases by 2025

• 52% of Americans will have DM or Pre-DM by 2020.

• Cause of more deaths than AIDS and Breast cancer combined.

Where is diabetes affecting

Americans?

Source: Mokdad et al., Diabetes Care 2000;23:1278-83.

Diabetes Trends* Among Adults in the U.S.,

(Includes Gestational Diabetes) BRFSS 1990

No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %


(Includes Gestational Diabetes) BRFSS 1991-92


No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %




No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %




No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %




No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %




No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %



Source: Mokdad et al., Diabetes Care 2001;24:412.

No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %



Source: Mokdad et al., J Am Med Assoc 2001;286:10.

No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %



Source: Mokdad et al., J Am Med Assoc 2001;286:10.

No data > 4 % 4-6 % 6-8 % 8-10 % > 10 %

1999

Obesity Trends Among U.S. AdultsBRFSS, 1990, 1999, 2009

(*BMI 30, or about 30 lbs. overweight for 5’4” person)

2009

1990

No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

Obesity Trends Among U.S. Adults1985

(*BMI ≥30, or ~ 30 lbs. overweight for 5’ 4” person)

No Data <10% 10%–14%



No Data <10% 10%–14%



No Data <10% 10%–14%



No Data <10% 10%–14%

Obesity Trends Among U.S. Adults 1989


No Data <10% 10%–14%



No Data <10% 10%–14%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19%



No Data <10% 10%–14% 15%–19% ≥20%



No Data <10% 10%–14% 15%–19% ≥20%

Obesity Trends* Among U.S. Adults1999


No Data <10% 10%–14% 15%–19% ≥20%



No Data <10% 10%–14% 15%–19% ≥20%



No Data <10% 10%–14% 15%–19% 20%–24% ≥25%



No Data <10% 10%–14% 15%–19% 20%–24% ≥25%



No Data <10% 10%–14% 15%–19% 20%–24% ≥25%



No Data <10% 10%–14% 15%–19% 20%–24% ≥25%



No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%



No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%



No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%



No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%



No Data <10% 10%–14% 15%–19% 20%–24% 25%–29% ≥30%

American Indians/Alaska Natives

Age-Adjusted Prevalence of Diabetes* by Race/Ethnicity in the US

Percent

Hispanic/LatinoAmericans

Non-Hispanic Blacks

Non-Hispanic Whites

www.hypertensiononline.org

*In people 20+ years old

CDC. National Diabetes Fact Sheet. 2002.

Sources: 1997-1999 National Health Interview Survey and 1988-1994 National Health and Nutrition Examination Survey (NHANES) estimates projected to year 2000. 1998 outpatient database of the Indian Health Service

19%

15%

14%

7%

Global Trends in Diabetes

<4% 4% 5% 7% 9% ≥ 12%

2010

<4% 4% 5% 7% 9% ≥ 12%

<4% 4% 5% 7% 9% ≥ 12%

2030

Millions of Cases of Diabetes in 2000 and Projections for 2030, with Projected Percent Changes. Data are from Wild et al.

Global Trends in Diabetes

3.8 million DM related deaths world wide in 2007

6% total global mortality rate from DM (the same as HIV/AIDS).

$557.7 billion in lost national income in China, and $236.6 billion in India by 2015.

<4% 4% 5% 7% 9% ≥ 12%

Normal Pre-Diabetes DiabetesImpaired glucose tolerance

Criteria for Diagnosis of Diabetes

OGTT- oral glucose tolerance test



FastingGlucose <100 mg/dL 100-125 mg/dL > 125 mg/dL





Casual >200 mg/dL with symptoms Glucose polyuria, polydipsia, wt loss





Casual >200 mg/dL with symptoms Glucose polyuria, polydipsia, wt loss

2 hour < 140 mg/dL 140-199 mg/dL >200 mg/dL OGTT

OGTT- oral glucose tolerance test using 75 g load



HA1c < 6.0 6.0 - 6.5 > 6.5 %

OGTT- oral glucose tolerance test using 75 g load

Estimating Average Blood Glucose Using

Hemoglobin A1cHb A1c Level Average Blood Glucose

6.0 % …………………………………………… 120 mg/dL7.0 % …………………………………………… 150 mg/dL8.0 % …………………………………………… 180 mg/dL9.0 % …………………………………………… 210 mg/dL10.0 % ……………………………………..…… 240 mg/dL11.0 % ……………………………………….…. 270 mg/dL12.0 % ………………………………………….. 300 mg/dL

Estimating Average Blood Glucose Using

Hemoglobin A1cHb A1c Level Average Blood Glucose

6.0 % …………………………………………… 120 mg/dL7.0 % …………………………………………… 150 mg/dL8.0 % …………………………………………… 180 mg/dL9.0 % …………………………………………… 210 mg/dL10.0 % ……………………………………..…… 240 mg/dL11.0 % ……………………………………….…. 270 mg/dL12.0 % ………………………………………….. 300 mg/dL

Type 2 Diabetes and Prior MI Equally Predict Mortality

Haffner SM, et al. N Engl J Med. 1998;339:229-234.Mukamal KJ, et al. Diabetes Care. 2001;24:1422-1427.

012345678

No MI Prior MI No MI Prior MI

0.3

2.6 2.5

7.3

No Diabetesn=1373

Diabetesn=1059

Even

ts p

er 1

00 P

erso

n Ye

ars

East-West Study

0

0.5

1

1.5

2

2.5

3

No MI Prior MI No MI Prior MI

1.0

1.51.7

2.4

No Diabetesn=1525

Diabetesn=396

Haz

ard

Ratio

Myocardial Infarction Onset StudyAdjusted Total Mortality After MI

Equal Risk

Equal Risk

Diabetes is an eroding cardiovascular

endocrine disorder

The Diabetes Prevention Program

How to stop the coming metabolic

storm


Three treatment options

1) Placebo twice daily2) Metformin 850mg BID3) Intensive lifestyle

modification.• 7% weight loss• 150 min/week exercise


Three treatment options

1) Placebo2) Metformin3) Intensive lifestyle

modification.

---------------------------- No change

Effects of Intervention

---------------------------- 31% risk reduction

---------------------------- 58% risk reduction

Norton Sound Health CorporationDiabetes Prevention Program

Fasting Plasma Glucose Concentrations (Panel A) and Glycosylated Hemoglobin Values (Panel B) According to Study Group. NEMJ Feb 7, 2002.

DiabetesPrevention

ProgramResearch

Group

Knowler W, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM. Reduction in the incidence of type 2 with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403.

DiabetesPrevention

ProgramResearch

Group

Knowler W, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM. Reduction in the incidence of type 2 with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393-403.

RESULTS

Metformin reduces risk of developing diabetes by 31%.

Lifestyle (exercise 150 min/wk, weight loss ~ 7%, and low-fat diet) reduces risk of developing diabetes by 58 %.

NNT = 6.9 patients

1. Insulin Secretion2. Insulin Sensitivity3. Mix of both

Diabetes is caused by a defect in:

• Coronary Artery Disease• Cerebro-Vascular Disease• Peripheral Vascular Disease• Nephropathy• Neuropathy• Retinopathy

Systems Affected

u

The healthy human pancreas monitors prandial glucose (G) levels in the bloodstream and adds the Insulin (I) as needed to induce glucose entry into cells of the body.

Glucose (G) stored for later use in the liver , fat cells, or muscles [or] it is burned as fuel for energy production in every cell of the body.

Insulin (I) acts like a key to open the glucose (G) door of each cell.

u

Diabetes Mellitus is caused by:

u


Reduced insulin production.

u



Increased insulin resistance.

u



Increased insulin resistance.

Combination of both.

Types of Diabetes

Type I Diabetes Mellitus (Insulin Dependent)Type II Diabetes Mellitus (85-95 % of cases world-wide)Gestational Diabetes MellitusMODY (Mature Onset Diabetes of Youth)LADA (Latent Autoimmune Diabetes of Adulthood)Metabolic Syndrome

Type I Diabetes Mellitus

Cause: Auto-immune destruction of pancreatic beta cellsGenetics: 50 % concordance in identical twinsTriggers: Virus? Cows milk allergy?Symptoms: Thirst, urination, appetite, sudden weight lossKetones: Ketoacidosis Age: Usually < 30 years old at onset; peaks in

adolescenceScreening: None Recommended

TREATMENT

TREATMENT = INSULIN

“Whatever it takes”

Type II Diabetes MellitusCause: Insulin resistance and insulin deficiencyGenetics: High, 80-90 % concordance in identical twinsTriggers: Hyper-nutrition, obesity, relative inactivitySymptoms: Often none; fatigue; dry skin; frequent infections;

blurred visionKetones: Usually negativeAge: Adult onset; increasingly seen in teens and

childrenScreening: Every 3 years:

> 45 yrs of age if BMI greater 25 kg/m2< 45 yrs of age if overweight with other risk factors

TREATMENT 1. Weight loss (reduce central obesity)2. Vegetable based diet3. Daily physical activity4. Blood pressure control5. Glucose control 6. Cholesterol control7. Smoking Cessation

Metabolic syndrome is

Diabetes Mellitus in its earliest

detectable form.

Abdominal Obesity: Waist circumferenceMen > 40 inchesWomen > 35 inches

Triglycerides: > 150 mg/dLHDL- C Men < 40 mg/dL

Women < 50 mg/dLBlood Pressure: > 135/85Fasting Glucose: > 100 mg/dL

Diabetes

Heart Eyes Kidneys

ETC.

Diabetes

Heart Eyes Kidneys

BPETC.

Schrier RW et al. (2007) Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial Nat Clin Pract Nephrol 3: 428–438 doi:10.1038/ncpneph0559

Blood pressure control is more important than blood glucose control in type II diabetes mellitus.

Schrier RW et al. (2007) Appropriate blood pressure control in hypertensive and normotensive type 2 diabetes mellitus: a summary of the ABCD trial Nat Clin Pract Nephrol 3: 428–438 doi:10.1038/ncpneph0559

“All discussions of diabetes control begin with an emphasis on nutrition (DASH and/or Mediterranean

diet), daily physical activity, stress reduction techniques, and smoking cessation.”

Note: Age-adjusted cardiovascular disease mortality rates by leisure time activity in normoglycemic men (n=6,056) versus men with impaired glucose tolerance/diabetes (n=352) in the Whitehall Study (Adapted by Gill and Malakova 2006, (132) from data from the Whitehall Study). P=0.006 for trend in normoglycemic men, P=0.003 for trend in men with IGT/diabetes.

Source: Gill JM, Malkova D. Physical activity, fitness and cardiovascular disease risk in adults: interactions with insulin resistance and obesity. Clin Sci (Lond). 2006 Apr;110(4):409-425. Review. Reproduced with permission.

Blood Pressure Medications

A

C

D

B


ACE/ARBLisinopril CandesartanCaptopril LosartanBenazapril Telmisartan

C

D

B



C

DIURETICHydrochlorothiazideChlorothiazide

B



CCBAmlodipineNifedipine


B



CCBAmlodipineNifedipine


Beta BlockersMetoprololAtenolol

Diabetes

Heart Eyes Kidneys

BPETC.

Diabetes

Heart Eyes Kidneys

BP

GLU

ETC.

Glucose Lowering Medications

Natural Therapy: Insulin (basal and short acting)

Secretagogues: Sulfonylureas (glyburide)

Sensitizers: Metformin and Actos

Incretin memetics: Exenitide

DPP-4 Inhibitor: Sitagliptin and Saxagliptin

Glucose Lowering Medications

Natural Therapy: Insulin (basal and short acting)

Secretagogues: Sulfonylureas (glyburide)

Sensitizers: Metformin and Actos

Incretin memetics: Exenitide

DPP-4 Inhibitor: Sitagliptin and Saxagliptin

Diabetes

Heart Eyes Kidneys

BP

GLU

ETC.

Diabetes

Heart Eyes Kidneys

BP

GLU

BMI

ETC.

Visceral fat causing central obesity is

associated with a higher risk of developing diabetes mellitus.

Diabetes

Heart Eyes Kidneys

BP

GLU

BMI

ETC.

Diabetes

Heart Eyes Kidneys

BP

GLU

BMI

Chol

ETC.

Effects of a Dietary Portfolio of Cholesterol-Lowering Foods vs Lovastatin on Serum Lipids and C-Reactive Protein. JAMA. 2003;290:502-510.

Lipid Lowering Medications

Lower LDL: Statins (simvastatin, atorvastatin)

Lower Triglycerides: Fenofibrate, Niacin, Omega-3 FA

Raise HDL: Niacin, exercise, mod. alcohol

TAKE HOME

Diabetes is a cardiovascular epidemic (not just a sugar problem).Activity and weight management can postpone if not prevent diabetes.The pillars of diabetes treatment are control of blood pressure, blood sugar, BMI, and lipids.

Documents

How to address a complex problem in resource poor regions. Bob Lawrence Alaska Family Doctor September 2009