Current and Future Challenges in Diabetes Prevention, Diagnosis

1
Diabetes in the Latino Population A Case-based
Approach to Optimal Management
2
Learner Objectives

• Upon completion, attendees should be able to
• List the medical, social, and economic ways in
  which diabetes impacts the Latino population
• Describe strategies to overcome barriers to
  improving diabetes outcomes in the Latino
  population
• Utilize current standards of care for the
  detection of diabetes and the monitoring of
  complications of diabetes in the Latino patient
• Assess current treatment options to maximize
  glycemic control in order to minimize the
  complications of diabetes in the Latino
  population
• Access appropriate national and local resources
  available to assist in caring for the Latino
  patient with diabetes.

3
Why are We Concerned about Diabetes?

• Every 24 hours...
• 3,600 new cases of diabetes are diagnosed
• 580 people die of diabetes-related complications
• 225 people have a diabetes-related amputation
• 120 people with diabetes progress to end-stage
  renal disease
• 55 people with diabetes become blind

4
Why Are We Concerned about Diabetes Among
Latinos?

• Prevalence of type 2 diabetes is 1.5 times higher
  than in non-Hispanic whites.
• 2 million Latinos 20 years or older have
  diabetes.
• Latinos have a greater number of risk factors for
  diabetes.
• Increased prevalence of retinopathy, nephropathy,
  and peripheral vascular disease in Mexican
  Americans.
• National Diabetes Information Clearinghouse,
  NIDDK 2002

5
A Constellation of Complications
Diabetes
6
Diabetes Care in the U.S. Improvements Needed
NHANES III and Behavioral Risk Factors
Surveillance Study
7
Projected Increase in the US Population with
Diagnosed Diabetes by 2020 by Ethnicity

• Projected Increase ()

Adapted from American Diabetes Association.
Diabetes Care. 200326917-932
8
Geographic Distribution of Latino Americans
Puerto Rican 1.6 million Cuban American
130,000
Mexican American 1.1 million
Mexican American 8.4 million
Mexican American 1 million
Puerto Rican 500,000 Cuban American 830,000
Mexican American 5 million
Adapted from U.S. Census Bureau, Current
Population Survey, March 2000.
9
Clinical Discussion

• Prevalence of diabetes
• Prevalence of complications
• Pathophysiology
• - obesity
• - insulin resistance
• - metabolic syndrome
• Treatment
• - nonpharmacologic
• - medications

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Prevalence of Type 2 Diabetes
Previously undiagnosed diabetes
Physician-diagnosed diabetes
10 8 6 4 2 0
Age-adjusted prevalence ()
Non-Latino African Mexican
Non-Latino African Mexican White
American American White
American American
Harris MI et al. Diabetes Care. 199821518-524.
11
Trends in Diabetes Prevalence (1990-1998)
Age (years)
Ethnicity
50 40 30 20 10 0
80 70 60 50 40 30 20 10 0
Increase
Increase
30-39 40-49 50-59
Non-Latino African
Mexican White American
American

• Prevalence of type 2 diabetes is 2-3 times higher
  in Latinos than Caucasians
• Highly correlated with prevalence of obesity (r
  0.64, P

American Diabetes Association. Facts and Figures.
Mokdad et al. Diabetes Care. 2000231278.
12
Complications of type 2 diabetes in Minorities

• Disparate and Disproportionate prevalence of
  longterm complications of type 2 diabetes in
  minorities vs Whites
• lower leg amputations 2-4x
• retinopathy and blindness 2-4x
• stroke 2x
• ESRD 4-6x

Caballero AE. Diabetes in minority populations.
In Joslins Diabetes Mellitus. LW W 2005.
14th Ed. p 505-524
13
Prevalence of Complications in Type 2 Diabetes
Prevalence of Retinopathy in Type 2 Diabetes
New Cases of End-Stage Renal Disease
Age Range of Amputations per 10,000 DM patients
200
300
160
200
120
Patients ()
(per million/population)
80
100
40
0
0
Caucasian
Mexican-American
African-American
Klein et al. In Harris et al, eds. Diabetes in
America, 2nd ed. 1995. Reiber et al. In
Harris et al, eds. Diabetes in America, 2nd ed.
1995. USRDS. Am J Kidney Dis. 199424879.
14
Cardiovascular Disease in Latinos with Diabetes

• Latinos- more insulin resistance/diabetes but no
  higher rates for CAD when compared to Whites
• A true Hispanic paradox?
• Data are not conclusive - some studies may be
  influenced by changes in the population due to
  migration factors

Lerman-Garber I, Villa A.R, Caballero AE..
Diabetes and Cardiovascular Disease. Is there a
true Hispanic Paradox? Rev Invest Clinic. 2004
56 (3) 282-296 Available at www.imbiomed.com.mx
15
No Difference In Complications When Good Control
Is Achieved
San Luis Valley Study Caucasian and Latino
(n279) - Similar glucose control in
both study groups - Similar severity of
retinopathy, nephropathy and diabetic neuropathy

Hamman RF et al. Diabetes. 1989 381231.
Hamman RF et al. Diabetes Care. 199114 (suppl
3)655.
16
Diabetes Dual ImpairmentInsulin Resistance and
Impaired b-Cell Function
Insulinresistance
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Insulin Resistance

• Genetic
• Acquired
• Central obesity
• Medications
• In 80-90 of type 2 patients
• Clusters with metabolic disease syndrome
• Associated with increased macrovascular disease

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Visceral Fat, Insulin Resistance and Endothelial
Dysfunction
IL1, IL6, TNF- ?, FFA,, PAI-1, RAS, leptin,
resistin Adiponectin
Increased Visceral Fat
Genes
Genes
Cytokines, Substrates Hormones
Insulin Resistance
Endothelial Dysfunction
Hyperglycemia Hypertension Dyslipidemia
Modified from Caballero AE. Current Diabetes
Reports 2004 4 237- 246
19
Insulin Sensitivity in Healthy Subjects in
Various Ethnic Groups



Insulin Sensitivity Index (?mol L-1 m-2
min-1 pmol-1 L-1)
N34
N9
N18
N16
P 0.0023 vs. Caucasians. Data are geometric
means. Adapted from Chiu KC, et al. Diabetes
Care. 200023(9)1353-1358.
20
Prevalence of the Insulin Resistance Syndrome in
the US Population
Prevalence ( of adults)
Age adjusted 20 years of age
Ford ES et al. JAMA. 2002287356-359
21
Progressive Nature of Type 2 Diabetes
22
UKPDS Glucose Control Study Results
Intensive Blood- Glucose Control
Change in risk P value Any
diabetes-related endpoint ?12 0.029
Diabetes-related deaths ?10
NS Myocardial infarction ?16
0.052 Microvascular disease ?25
0.0099 Stroke ?14 NS
Adapted from UKPDS Group. Lancet. 1998
352837-853.
23
Effect of Each 1 Rise in A1C on Risk of
Developing Complications
10-Year follow-up in older-onset patients
Incidence of retinopathy
Progression of retinopathy
Progression to PDR
Visual loss
Proteinuria Amputation
Ischemic heart death

0.5 1 1.5
2 2.5
Risk Ratio and 95 CI Klein.
Diabetes Care 18258-268, 1995
24
Why Arent Patients Achieving Blood Glucose
Goals?

• Physicians not setting appropriate glycemic
  targets
• Type 2 diabetes is progressive - what works now
  may not work in the future
• Type of medications used and/or doses not
  appropriate
• Insulin therapy only used as a threat

25
American Diabetes Association Standards of
Care
Clinical Practice Recommendations 2004. Diabetes
Care, 27(Suppl1)S15-36.
26
Diagnosing Diabetes
Fasting Plasma
Casual Plasma Oral Glucose Test
Glucose (FPG) Glucose
Tolerance Test
(Preferred Test)
Stage Diabetes
FPG 126 mg/dl Casual plasma
Two-hour plasma glucose 200
mg/dl glucose (2hPG) (plus
symptoms 200 mg/dl

Impaired Impaired Fasting
Impaired Glucose Glucose
Glucose (IFG)FPG Tolerance (IGT)
Homeostasis 100 and
2hPG 140 and Normal FPG 2hPG In the absence of unequivocal hyperglycemia,
these need to be repeated on the second day
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Goals for Glycemic Control
For non-pregnant individuals Diabetes Care, 27
Supp.1.S19, 2004
28
Goals for Blood Pressure, Lipids and Microalbumin

• Blood Pressure
• Lipids (mg/dl)
• LDL-C
• HDL C
• HDL-C 50 (female)
• Triglycerides
• Microalbumin

Diabetes Care, 27 Sup 1. S19, 2004
29
Monitoring Parameters for Control of
Complications

• Every visit Blood Pressure
• Foot Exam (55 achieve goal)
• ______________________________________________
• 3-6 months A1C
• - Every 3 months if treatment changes or
  not meeting goals
• - Every 6 months if stable
• _______________________________________________
• Annual Dilated Eye Examination (63 achieve
  goal)
• Lipid Levels
• Microalbumin
• __________________________________________________
  _____________
• Every 2 years if levels fall in lower risk
  categories

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Goals of Medical Nutrition Therapy

• Achieve blood glucose goals
• Achieve optimal lipid levels
• Provide appropriate calories for
• - Reasonable weight
• - Normal growth and development
• - Pregnancy and lactation
• Prevent, delay or treat nutrition-related
  complications
• Improve health through optimal nutrition

Diabetes Care 22(1)S42-S45,1999
31
Non-pharmacological Medical Therapy for Type 2
Diabetes
Consistent carbohydrate intake
Monitor blood glucose to adjust therapy
Modify fat and calorie content
Optimize BG Control Improve blood lipids
Control blood pressure
Moderate weight loss
Space meals
Increase physical activity
32
ADA Nutrition Recommendations

• Total Daily Energy Intake
• Carbohydrate 60-70
• Protein 15-20
• Fat
• - 10 from polyunsaturated fats
• -

33
Preventing or Delaying Type 2 Diabetes

• Exercise can lower risk, delay or prevent,
  type 2 diabetes
• Important for individuals with risk factors
• - Obesity
• - Sedentary lifestyle
• - Family history of type 2 diabetes
• - Native American, Hispanic, African American,
  Asian American, Pacific Islander

34
Effects of Exercise

• Increased insulin sensitivity
• Improved lipids
• Lower blood pressure
• Weight control
• Improved blood glucose control in type 2 diabetes

35
Exercise Precautions for Type 2 Diabetes

• Check with referral source for medical clearance
• Lower VO2max may require a gradual training
  program
• Autonomic neuropathy or blood pressure meds do
  not allow for increased heart rate perceived
  exertion important
• Blood pressure may go higher, avoid exercise if
  systolic BP 180-200

36
Exercise Precautions Related to Complications of
Diabetes

• Peripheral neuropathy can cause loss of sensation
  in feet
• Pre-existing CVD can cause arrhythmias,
  myocardial ischemia, or infarction during
  exercise
• Proliferative retinopathy does not increase risk
  for retinal or vitreous hemorrhage with exercise

37
Treatment of Type 2 Diabetes
38
Principles of Diabetes Treatment

• Define target goal
• Diabetes education is essential
• Monitoring glycemic control is necessary
• Lifestyle modification
• Stepwise and combination pharmacologic therapy

39
ADA Recommendations

• Glycemic goals should be individualized
• Certain populations (children, pregnant women,
  and elderly) require special considerations
• Less intensive glycemic goals may be indicated in
  patients with severe or frequent hypoglycemia
• More stringent glycemic goals (i.e. a normal A1C,
  6) may further reduce complications at the cost
  of increased risk of hypoglycemia.
• Postprandial glucose may be targeted if A1C goals
  are not met despite reaching pre-prandial glucose
  goals.

40
Targeted Glucose Control

• Therapy based on glycemic goals
• Monotherapy usually not effective long-term
• Step-wise approach
• Whatever therapy is necessary to achieve glycemic
  goals

41
Pharmacologic Therapy
Selection of therapy should be individualized
based upon potential side effects.
42
Therapeutic Agents for Type 2 Diabetes

• Mechanism of Action
  Agent
• 1. Sensitize the body to insulin ?
  Thiazolidinediones, Biguanides
• 2. Control hepatic glucose production ?
  Biguanides, Thiazolidnediones
• 3. Stimulate the pancreas to
  ? Sulfonylureas
• make more insulin
  Meglitinides
• 4. Slow the absorption of starches
  ? Alpha-glucosidase
• inhibitors
• 5. Decreases hepatic glucose
  ? Insulin
• production and increases
• peripheral glucose uptake

43
Impact of Therapies on A1C Levels

• Therapy A1C Reduction
• Diet and Exercise 0.5 - 2.0
• Sulfonylureas and Glitinides 1.0 - 2.0
• Metformin 1.0 - 2.0
• ?-Glycosidase Inhibitors 0.5 - 1.0
• Thiazolidinedione 0.5- 1.0
• Insulin 5.0
• Nathan, D. Oct 2002. N Engl J Med, Vol. 347,
  No.17

44
Biguanides

• Decrease hepatic glucose production and
  secondarily may increase insulin-mediated
  peripheral glucose uptake
• Efficacy
• - decrease blood glucose 60 mg/dl
• - reduce HbA1c 1.0 - 2.0
• - cause small decrease in LDL-C and
  triglycerides
• - no specific effect on blood pressure
• - no weight gain
• Other Effects
• - diarrhea and abdominal discomfort
• - lactic acidosis if inappropriately prescribed
• - contraindicated in patients with impaired
  renal function

45
Sulfonylureas

• Increase endogenous insulin secretion
• Efficacy
• - decrease blood glucose 60 mg/dl
• - reduce HbA1c 1.0 - 2.0
• - no specific effect on plasma lipids or
• blood pressure
• Other Effects
• - hypoglycemia
• - weight gain

46
Thiazolidinediones

• Potentiate insulin action on muscle and adipose
  tissue
• Efficacy
• - decrease FPG 25 - 40 mg/dl
• - reduce HbA1c 0.5 - 1
• - combined with sulfonylureas reduce HbA1c
  0.8 - 1.0
• - combined with insulin reduce HbA1C by 0.8 -
• 1.4
• - Beneficial effect on lipids
• - Possible cardiovascular effects
• Other Effects
• - contraindicated with abnormal liver function
• - weight gain, edema

47
Meglitinides

• Non-sulfonylurea insulin releasing agent taken
  before each meal
• Rapid onset of action with a duration of action
  of several hours
• Efficacy
• - decrease peak postprandial glucose
• - decrease blood glucose 60 - 70 mg/dl
• - reduce HbA1c 1.0 - 2.0
• Other Effects
• - hypoglycemia
• - weight gain
• - safe at higher levels of creatinine than
  sulfonylureas

48
Alpha-Glucosidase Inhibitors

• Competitive inhibitor of alpha glucosidase
  enzymes in small intestines taken before meals
• Efficacy
• - decrease fasting plasma glucose 20-30 mg/dl
• - decrease peak postprandial glucose 40-50
  mg/dl
• - no specific effect on lipids or blood
  pressure
• - reduce HbA1c 0.5-1.0
• Other Effects
• - abdominal discomfort and flatulence
• - contraindicated with inflammatory bowel
  disease or cirrhosis

49
Insulin

• Decreases hepatic glucose production and
  increases uptake and use of glucose by muscle and
  adipose tissue
• Efficacy
• - can lower plasma glucose to any level
• - reduces HbA1c 5.0
• - limited by hypoglycemia
• Other Effects
• - hypoglycemia
• - weight gain

50
Anticipated Response to Treatment
51
Insulin Therapy in Type 2 Diabetes

• Most patients with type 2 diabetes will
  eventually need insulin.
• As insulin deficiency progresses, a more
  physiologic multi-component insulin regimen will
  be required to adequately replace normal insulin
  secretion.
• - Basal insulin
• - Meal-Related (prandial, bolus) insulin

52
Indications for Insulin Therapy in Type 2
Diabetes

• Severe hyperglycemia at glucose toxicity
• To meet glycemic goals
• Hyperglycemia despite maximum doses of oral
  agents
• Most patients with type 2 diabetes will
  eventually need insulin
  

53
Insulin Action Comparison

• Insulins Onset
  Peak
  Duration
• Lispro orAspart 15 minutes
  1 2 hours
  4 6 hours
• Human Regular 30 60 minutes
  2 4 hours
  6 10 hours
• Human
• NPH or Lente 2 4 hours
  6 12 hours
  12 20 hours
• HumanUltralente 4 6 hours
  Unpredictable
  18 24 hours
• Glargine 2 4 hours
  Peakless
  20 26 hours
• Insulin analogs

54
Profiles of Human Insulins and Analogs
Aspart, lispro (46 hours)
Regular (610 hours)
NPH (1220 hours)
Ultralente (1824 hours)
Glargine (20-26 hours)
Plasma insulin levels
2
4
6
8
12
14
16
18
20
22
24
0
10
Hours
55
Pharmacologic TherapyPossible Treatment Steps

• STEP 1
• Add metformin or insulin secretagogue
• STEP 2
• If on metformin, add insulin secretagogue
• If on insulin secretagogue, add metformin
• 
  
  continued

56
Pharmacologic TherapyPossible Treatment Steps

• STEP 3
• Add insulin
• Switch to insulin
• Add a thiazolidinedione
• STEP 4
• Add an oral drug to insulin
• Use multiple component insulin therapy

57
Studies Aimed at Prevention of Type 2 DM

• Lifestyle Modification Studies
• DPP (Diabetes Prevention Program)
• DPS (Diabetes Prevention Study, Finnish Study)
• Da Qing (Chinese Study)
• Malmo Study (Males, Sweden)

• Drug Intervention Studies
• DPP
• Stop-NIDDM (Acarbose)
• - Prevention Evaluation (Ramipril)
• TRIPOD Study (Troglitazone)
• DREAm Study (Rosiglitazone Ramipril)
• Navigator Study (Nateglinide, Valsartan)
• Xendos trial (Orlistat)
• Sibutramine Study

Trial still underway
58
Summary

• The Latino Population is the largest minority
  group in the country
• The prevalence of diabetes and its complications
  is higher in Latinos when compared to the
  non-Latino White group
• Genetic and environmental factors influence the
  development of obesity, metabolic syndrome and
  type 2 diabetes in Latinos
• continued

59
Summary

• Multiple cultural factors influence diabetes care
  in Latinos
• Goals for glycemic control, BP, weight, lipids
  and smoking cessation need to be established
• Aggressive Management to reach these goals is
  important
• Early use of available pharmacologic treatment
  tools needs to be considered