Pre Diabetes

PREDIABETES
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Dr FERMIZET RUDY SpPD FINASIM
Burden of Diabetes
The development of diabetes is projected to reach pandemic
proportions over the next10-20 years.
International Diabetes Federation (IDF) data indicate that by

the year 2025, the number of people affected will reach 333
million 90% of these people will have Type 2 diabetes.
In most Western societies, the overall prevalence has

reached 4-6%, and is as high as 10-12% among 60-70-year-
old people.
The annual health costs caused by diabetes and its

complications account for around 6-12% of all health-care
expenditure.
Prediabetes: Impaired glucose tolerance and
impaired fasting glucose
Prediabetes is a term used to distinguish people who are at
increased risk of developing diabetes. People with
prediabetes have impaired fasting glucose (IFG) or
impaired glucose tolerance (IGT). Some people may have
both IFG and IGT.
IFG is a condition in which the fasting blood sugar level is

elevated (100 to 125 milligrams per decilitre or mg/dL) after
an overnight fast but is not high enough to be classified as
diabetes.
IGT is a condition in which the blood sugar level is elevated

(140 to 199 mg/dL after a 2-hour oral glucose tolerance
test), but is not high enough to be classified as diabetes.
Prediabetes: Impaired glucose tolerance and impaired
fasting glucose (cont.)
Progression to diabetes among those with prediabetes is

not inevitable. Studies suggest that weight loss and
increased physical activity among people with
prediabetes prevent or delay diabetes and may return
blood glucose levels to normal.
People with prediabetes are already at increased risk for

other adverse health outcomes such as heart disease
and stroke.
Pre-diabetes is an important risk factor for
future diabetes and cardiovascular
disease
Recent studies have shown that lifestyle

modification can reduce the rate of
progression from pre-diabetes to diabetes
American Diabetes Association, Diabetes Care. 2007:30:S4-41..

Pre-Diabetes in the U.S.
At least 57 million adults ages 20 and
older have pre-diabetes
Pre-diabetes raises the risk for type 2

diabetes and cardiovascular disease
NIDDK, National Diabetes Statistics 2007.

www.diabetes.niddk.nih.gov/dm/pubs/statistics
24 million
with Diabetes
57 million
with Prediabetes
Modifying disease progression
Obesity IGT Diabetes (Uncontrolled)
Prediabetes Type 2 diabetes
Macrovascular complications
What should treatment
Microvascular complications
aim to do?
Plasma Postprandial
glucose 126
(mg/dl)
Fasting
Insulin
resistance
Insulin level
Relative
100
function
Diabetes duration (years) 20 10 0 10 20 30

Adapted from Bergenstal RM, et al. Diabetes mellitus, carbohydrate metabolism and lipid disorders. In Endocrinology. 4th ed. 2001.
Stages in the Natural History
of Type 2 diabetes
Type 2 Disability
Normal IGT Complications
Death
DM
Genetic Preclinical Clinical Disability
predisposition state disease Complications
Death
Primary Secondary Tertiary

prevention prevention prevention
Any abnormality
must be repeated
Fasting Plasma and confirmed on 2-hour Plasma
Glucose a separate day* Glucose On OGTT
Diabetes Mellitus Diabetes Mellitus

126 mg/dL 200 mg/dL
Impaired Fasting Impaired Glucose
Glucose Tolerance
100 mg/dL 140 mg/dL
Normal Normal
Pre-Diabetes
* One can also make the diagnosis of diabetes based on

unequivocal symptoms and a random glucose >200 mg/dL
Adapted from The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
Diabetes Care 2004; Supplement 1
Outcome studies in IGT/IFG/T2DM:
building the picture
Diabetes duration (years)
10 0 10 20
IGT Type 2 diabetes CVD
Can T2DM be Can loss of -cell function and Can CVD risk be
prevented? disease progression be slowed? reduced in T2DM?
DPP UKPDS PROactive

Risk of T2DM decreases in high Conventional antidiabetic agents Pioglitazone improves secondary
risk patients with lifestyle (metformin, SUs) DO NOT improve CV endpoint in T2DM patients
intervention/ metformin -cell function in T2DM with evidence of atherosclerosis
Can other therapies more Can other therapies prevent Can other therapies improve or
effectively prevent progression disease progression in newly prevent CV outcomes in T2DM?
to T2DM in IGT/IFG? diagnosed T2DM?
New and Ongoing outcome

studies
Outcome studies in IGT/IFG/T2DM:
building the picture
10 0 10 20
IGT Type 2 diabetes CVD
Can T2DM be Can loss of -cell function and Can CVD risk be
prevented? disease progression be slowed? reduced in T2DM?
DPP UKPDS PROactive

Risk of T2DM decreases in high Conventional antidiabetic agents Pioglitazone improves secondary
risk patients with lifestyle (metformin, SUs) DO NOT improve CV endpoint in T2DM patients
intervention/ metformin -cell function in T2DM with evidence of atherosclerosis
Can other therapies more Can other therapies prevent Can other therapies improve or
effectively prevent progression disease progression in newly prevent CV outcomes in T2DM?
to T2DM in IGT/IFG? diagnosed T2DM?
RECORD
DREAM ADOPT BARI-2D

ACCORD
Can TZDs affect disease
progression?
ADOPT and DREAM
Intervention studies for diabetes
prevention
Study Intervention RR (%)
Da Qing IGT and Diabetes Study Diet 31

(N = 577) Physical exercise 46
Diet and physical exercise 42
Finnish Diabetes Prevention Study Diet and physical exercise 58
(N = 522)
Diabetes Prevention Program Study Lifestyle intervention 58
(N = 3234) Metformin 31
Troglitazone* 75
TRIPOD (N = 266) Troglitazone* 55
STOP-NIDDM (N = 1418) Acarbose 25
XENDOS (N = 3305) Orlistat 37

Indian Diabetes Prevention Program Lifestyle intervention 38.2
(N = 531) Metformin 28.2
Metformin and lifestyle 60.4
* Troglitazone is no longer available
Pan XR, et al. Diabetes Care 1997; Tuomilehto J, et al. N Engl J Med 2001; Knowler WC, et al. N Engl J Med 2002, 2004;
Buchanan TA, et al. Diabetes 2002;51:27962803; Ramachandran A. 4th World Congress on Prevention of Diabetes and
its Complications, Chennai Feb 2005; Chiasson JL, et al. Lancet 2002; Torgerson JS, et al. Diabetes Care 2004.
Ongoing outcome studies
UKPDS
STENO-2
ADOPT
DREAM
20 10 0 10 20 30
ADOPT: study design
Pre-Screen Screen Run-In Treatment Period*

4 weeks 4-6 years
Rosiglitazone
Diet/Exercise
Recently Dx (< 2 yrs) T2DM Reinforcement
FPG No previous OHA or ins Rx Metformin Long-term
Screen FPG range Observational
126-240 mg/dL F/U
126-240 mg/dL
Glyburide
Randomization/ Monotherapy Study

Baseline Failure End
*All study medication titrated to optimal effect using protocol defined titration steps
Viberti GV, et al. Diabetes Care 2002; 25:17371743.
Ongoing outcome studies in
IGT/IFG populations
UKPDS
STENO-2
ADOPT
DREAM
20 10 0 10 20 30
DREAM: study design
Treatment Period Washout
3 Years from time of last 3 months
patient randomized
Run-In
Screen 17+/- 3 d
RSG + Ramipril Plbo
Ramipril + RSG Plbo

Ages 30 years Placebo
IGT defined as 2-hr glucose 140-199
mg/dL after a 75 g OGTT or isolated IFG
RSG + Ramipril
No Hx T2DM (Hx gestational DM OK)
RSG Plbo + Ramipril Plbo
Randomization/Baseline (N = 5269) Study End
Gerstein HC, et al. Diabetologia. 2004; 47:15191527.

Summary: Can TZDs affect disease progression in type 2
diabetes? ADOPT and DREAM
Previous studies have demonstrated a

reduction in the risk of type 2 diabetes with
lifestyle and pharmacologic interventions
ADOPT and DREAM : TZDs can affect
disease progression in type 2 diabetes:
ADOPT: treatment with rosiglitazone in newly
diagnosed type 2 diabetes
DREAM: treatment with rosiglitazone or
ramipril in IGT/IFG
Thank You
Criteria for the Diagnosis
of Diabetes Mellitus
Diagnosis of diabetes = FPG 126 mg/dL

or
Symptoms (polyuria, polydipsia,
unexplained weight loss) plus casual
plasma glucose 200 mg/dL
or
2-hour plasma glucose 200 mg/dL during
75 g OGTT
ADA. Diabetes Care. 1997;20:1183-1197.

Stages of Glucose Tolerance
Fasting plasma OGTT 2-hr plasma

glucose (mg/dl) glucose (mg/dl)
Normal < 100 < 140
Impaired < 100-125 140-199
Diabetes > 126 > 200
ADA. Diabetes Care. 2003;20:1183-1197.

Type 2 Diabetes
ADA Suggested Treatment Algorithm
Years from -10 -5 0 5 10 15

diagnosis Onset Diagnosis
Step 3: Intensify Insulin

Add TZD or SU
Step 2: Insulin SUs - TZDs
Step 1: Lifestyle - Metformin
Pre-diabetes Type 2 diabetes
Nathan DM et al, Diavetes Care 2006;29:1963-72

Natural History
of Type 2 Diabetes Mellitus
Onset of
Diabetes
Complications
Disability
IGT Ongoing Hyperglycemia Death
Insulin resistance Retinopathy Blindness

Atherosclerosis
Hyperinsulinemia Nephropathy Renal Failure
Hypertension CAD
Dyslipidemia Neuropathy
Amputations
Diabetes Prevention Program
Average follow-up of 2.8 years
12
Cases / 100 person-years
10
31% *
8
6 58% *
4
Placebo Metformin Intensive

Lifestyle
*All pair-wise comparisons significantly different by group sequential log-rank test
The Diabetes Prevention Program Research Group. New Engl J Med 2002;346:393-403.
Values of Diagnosis of Diabetes Mellitus
Pencegahan prediabetes
Prevention or delay of diabetes:
Life style modification
Research studies have found that lifestyle changes can
prevent or delay the onset of type 2 diabetes among high-risk
adults.
These studies included people with IGT and other high-risk

characteristics for developing diabetes.
Lifestyle interventions included diet and moderate-intensity

physical activity (such as walking for 2 1/2 hours each week).
In the Diabetes Prevention Program, a large prevention study

of people at high risk for diabetes, the development of
diabetes was reduced 58% over 3 years.
Prevention or delay of diabetes: Medications
Studies have shown that medications have been successful in
preventing diabetes in some population groups.
In the Diabetes Prevention Program, people treated with the drug
metformin reduced their risk of developing diabetes by 31% over 3
years.
Treatment with metformin was most effective among younger,
heavier people (those 25-40 years of age who were 50 to 80
pounds overweight) and less effective among older people and
people who were not as overweight.
Similarly, in the STOP-NIDDM Trial, treatment of people with IGT
with the drug acarbose reduced the risk of developing diabetes by
25% over 3 years.
Other medication studies are ongoing. In addition to preventing
progression from IGT to diabetes, both lifestyle changes and
medication have also been shown to increase the probability of
reverting from IGT to normal glucose tolerance.
Thank You
Intervensi prediabetes
Intervention Time Window
Changes in glucose concentrations,
insulin sensitivity, and insulin secretion
as much as 36 years before diagnosis
of diabetes in British Civil Servants
(Tabek, et al. Lancet, 2009)
In Pima Indians the timeframe over
which glucose values rose suddenly
was estimated at <4.5 years (Mason et
al. Diabetes 56:20542061, 2007)
Lifestyle Intervention Trials
(All participants had pre-diabetes)
Pan et al. (1997)

Tuomilehto et al. (2001)
DPP Research Group (2002)***
Kosala et al. (2005)
Ramachandran et al (2006)
Effect of Treatment on Incidence of Diabetes in the DPP
(All participants had IGT)
Placebo Metformin Lifestyle
Annual Incidence of diabetes 11.0% 7.8% 4.8%
Relative reduction ---- 31% 58%

(compared with placebo)
Number needed to treat ---- 13.9 6.9

(to prevent 1 case in 3 years)
The DPP Research Group, NEJM 346:393-403, 2002

Intervention Impact by Ethnicity
Lifestyle Metformin Placebo
12
Cases/100 person-yr
0
Caucasian African Hispanic American Asian
(n=1768) American (n=508) Indian (n=142)
(n=645) (n=171)

Natural history DM
COMPLICATION PREDIABETES
Other Complications of Pre-diabetes
5-year risk of total mortality increased 50-
60%
5-year risk of CVD mortality increased
150%
(Barr et al. Circulation 2007;116: July 18 online)
Prevalent retinopathy about 8%

(DPP. Diabet. Med. 2007: 24:137-144)
Further Benefits of Lifestyle Intervention:
Other CVD risk factors are also improved
Hypertension was present in 30% of subjects at entry - then
in placebo and metformin groups, significantly with lifestyle

TG levels in all treatment groups, but significantly more
with
lifestyle intervention
Lifestyle intervention significantly HDL level and LDL
At 3 yr F/U the use of medications to achieve goals in the
lifestyle group was 2728% for hypertension and 25%
for
hyperlipidemia compared with placebo and metformin
groups
DPP. Diabetes Care 28:888894,

2005
US Research Studies that have Translated the DPP
Trial Lifestyle Intervention
13 studies
Core sessions ranged from 16 to 6
Mean sessions attended
16 sessions (9-14)
12 sessions (7-9)
11 sessions (8)
Weight Loss: 6% - 2.7%
The more sessions attended the greater
the wt. loss
National Diabetes Prevention Program
Goal:
Systematically scale the translated model of the Diabetes Prevention
Program (DPP) for high risk persons in collaboration with community-based
organizations that have necessary infrastructure, health payers, public
health, academia, and others to reduce the incidence of type 2 diabetes in
the United States.
Four Key Pillars
(1) Training the work force that can implement the
program cost effectively
CDC established the Diabetes Training and
Technical Assistance Center
(2) Implementing a recognition program that will

contribute to assuring quality, lead to
reimbursement, and allow CDC to develop a
registry of programs for public reporting
CDC currently developing the criteria for
program recognition expected final draft Sept
2010
(3) Implementing sitesFour Key
that will Pillars
build the infrastructure and
some will provide a laboratory for additional
refinement of this prevention system
CDC and Y-USA announced 11 model sites
Y-USA and UnitedHealth Group (UHG) announced 6
model sites
(4) Increasing referrals and utilization of the prevention

system through health marketing and other strategies
CDC contracted with MACRO formative
PR/marketing work and UHG is doing focus group
testing
Prevention of Type 2 Diabetes
The Community Clinic Partnership Model
Community Clinic
Insurers Partnership Zone

}
Employers Reimbursement Proactive Practice
Team
Informed Population Screening for Diagnosis of
High Risk Pre-diabetes Decision Support
Strong Community
Organizations
Structured Lifestyle Information
Programs Systems
Healthy Public
Policy Regular Informed,
Supportive Environments Glucose Activated
Monitoring Patients
Total Population Pre-diabetes Diabetes Complications

Community and policy
System, group,
culture
Family,
friends, small
group
Individual
The health of individuals is inseparable from the health of communities

(Healthy People 2010)
Management
Results:
Treat IFG and IGT with aggressive
lifestyle modification
For certain patients with both IFG and
IGT consider metformin
Nathan D, et al. Impaired Fasting Glucose and Impaired Glucose Tolerance: Implications for Care.
Diabetes Care. 2007 30: 753-759.
40
Placebo
Cumulative Incidence
30
Metformin
of Diabetes (%)
20 Lifestyle
10
0
0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0
Years
Knowler WC, et al. NEJM. 2002;346:393-403.

Study Subjects Intervention Relative Risk
Reduction
Finnish DPS IGT Lifestyle 58%
Behavior
US DPP
IGT Lifestyle 58%
US DPP IGT Metformin 31%

Medication
STOP- IGT Acarbose 25%

NIDDM
TRIPOD Prior GDM Troglitazone 55%
XENDOS IGT Orlistat 45%
DREAM IGT Rosiglitazone/Ramipril 61%/NS
A1C* <7.0%
Preprandial glucose 90-130 mg/dL
Postprandial plasma <180 mg/dL

glucose
* For non-pregnant individuals

As close to normal (<6%) as possible without
significant hypoglycemia
American Diabetes Association. Diabetes Care. 2007:30:S4-41..

Fasting plasma glucose at least every 3 yrs
starting at age 45
Consider at younger age, or more frequently, if
patient is overweight and has one or more of the
following risk factors (or two if not overweight):
Family history of diabetes
Overweight (BMI 25 kg/m2)
Habitual physical inactivity
(continued)

Additional risk factors:
Race/ethnicity (e.g., African-Americans, Hispanic-
Americans, Native Americans, Asian-Americans,
and Pacific Islanders)
Previously identified IFG or IGT
Hypertension (140/90 mmHg in adults)
HDL cholesterol (35 mg/dl [0.90 mmol/l] and/or a
triglyceride level 250 mg/dl [2.82 mmol/l])
History of GDM or delivering baby weighing >9 lbs
Polycystic ovary syndrome (PCOS)

Age 47
Race/ethnicity African American
Gender Male
Family history HTN and diabetes
Overweight/obesity BMI = 29
Abnormal lipid metab TC = 210
Hypertension BP = 146/86
Smoking 1 pack per day
Physical Inactivity Sedentary
Unhealthy diet Fast food diet
Identify at-risk patients by evaluating a
spectrum of predisposing risk factors
The existence of any one risk factor is an
alert to evaluate patient for others
Integrate evidence-based risk management
strategies to target modifiable risk factors
Kahn, et al. The Metabolic Syndrome: Time for a Critical Appraisal: Joint Statement From the American
Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2005;28 (9)2289-2304.
Management
Rationale for
Primary Prevention
Scientific
Economics
What is the
?
Major Studies
Da Qing IGT and Diabetes Study (China)
Diabetes Prevention Study (Finland)
Diabetes Prevention Program (USA)
STOP NIDDM (Europe, Canada)
Troglitazone in the Prevention of Diabetes
(TRIPOD) (USA)
Benefits
Study Reduction in risk (%)
Lifestyle Drug
Da Qing 3146
DPS 58
DPP 58 31
Stop NIDDM 25
TRIPOD 55
Primary prevention
works!!!!
Economics
$$$$$$$$$
Medical Costs of DPP
Interventions
(per participant)
Placebo Metformin Lifestyle

3-Yr. Cost 79 2,542 2,780
- - +2,463 +2,701
Placebo
DPP Research Group, Diabetes Care 2003.

Is it cost effective?
Societal judgement and is not absolute

Expert panels in developed countries
suggest:
<$20,000/QALY ready uptake
$20-100,000/QALYconsider
>$100,000/QALY less attractive
CE of Primary Prevention DPP* (USA)
Within Group LS/
DPP Generic Met
Cost/QALY US$ US$
Lifestyle vs Placebo 51,600 27,100

Metformin vs Placebo 99,200 35,000
*Societal perspective
DPP Research Group, Diabetes Care 2003.
Who should we target?
High-Risk vs Entire Population
Epidemiology
PreDM (IGT/IFG) have 10 fold higher risk than NGT
Only 10% have IGT/IFG but yield 40-50% new DM
Pathophysiology
Clinical trials in populations with preDM
Human behavior
Health belief model risk and benefit
Narayan et al., BMJ 2002; 325:403.

Participants
Eligibility Study
criteria DaQing DPS DPP Stop TRIPOD
NIDDM
Glucose (mg/dl)
Fasting none none 95-125 100-140 none
2-hr OGTT 140-199 140-199 140-199 140-199 none
5 OGTT sum
>=625
Age (yrs) >25 40-65 >=25 40-70 >=18
BMI (kg/m2) none >=24 >=25 25-40 none
History GDM +
What are the gaps from RCTs?
Isolated IFG not studied

Only one study examined
non-overweight persons with IGT
What is the risk of developing diabetes in

these groups?
International Diabetes Federation IGT/IFG Consensus
Statement:
Report of an Expert Consensus Workshop
Combined IGT and IFG have highest risk

Isolated IFG and IGT have about the same risk
Isolated IGT is more common
About a third who develop diabetes have
normal glucose tolerance at baseline
(dependent on length of follow-up)
Unwin N et al., Diabetic Medicine 2002; 19: 708.

What are the current policy
recommendations?
American Diabetes Association
Pre-diabetes:
Opportunistic screening for IGT or IFG:
>= 45 yrs
Emphasis in those with BMI >25
Consider others if are overweight with
risk factors
ADA Position Statement, Diabetes Care 2004; 27: S47.

recommendations?
IDF IGT/IFG Consensus Statement:

Report of an Expert Consensus Workshop
IGT or IFG should receive lifestyle advice

If lifestyle fails, consider drugs
Target those at highest risk for DM and CVD.
Unwin N et al., Diabetic Medicine 2002; 19: 708.

recommendations?
Finnish National Policy

Prediction models for future risk
Use fewer screening tests
Tailor to the individuals level of risk
Lindstrom J, Diabetes Care 2003; 26: 725.

How do we do find
the at-risk population?
CDC Workshop
National and International researchers

Questions
What populations not studied
Health policy for those not studied
Detection strategies
Further study
Diabetes Therapeutics and Treatments 2004 (in press).

How do we detect targeted populations?
Two general approaches:
1. Measure glucose levels directly

Use clinical and demographic charaterisitics to target
test
Determine current glycemic status
2. Use individual characteristics (clinical, demographic)

Predict future risk for diabetes
Current glycemic status unknown
Detection Strategies:
Measuring Glucose Directly
Three approaches*
Combinations of risk factors with various
cutpoints
Statistical models with risk factors
Risk scores
*NHANES (3 studies), Framingham, SAHS, AusDiab,

NUDS India, INTER-99, Ely Study, Diabetes in Egypt, ARIC
Risk factors
Demographics
Self-report clinical history
Current clinical measures
Administrative data
Laboratory data
Metabolic syndrome criteria
Combinations
Performance
Moderately effective
AUC 0.60-0.80
Sensitivity 60-80%;
Specificity 70-90%
Prediction of Future Risk of Diabetes
Method*
5-10 year risk of diabetes
Risk score or clinical model
Risk factors
Demographic, clinical
Glucose measures not required
Results
0.60-0.85 AUC
Age-dependent performance
*Finrisk-87, JACDS-Seattle, SAHS

Economics
$$$$$$$$$
Random Capillary Blood Glucose Test
All RCBG test
Low-risk population High-risk population

e.g., age < 45 e.g., age 45
RCBG positive RCBG negative
OGTT
IFG or IGT or DM OGTT & FPG negative
Cost per Case of
Undiagnosed Diabetes or Pre-Diabetes Identified by Random Capillary
Glucose Test
Screening for pre-diabetes & diabetes

Screening for diabetes alone
850
Cost/case ($)
650
450
250
50
75 85 95 105 115 125 135 145
Cutoff value (mg/dl)
Zhang et al ADA 2004
Cost per Case Identified at the Most Efficient
Cutoff Point (single-payer perspective)
Test Screening for pre- Screening for diabetes

diabetes & diabetes alone
Cutoff point $/case Cutoff point $/case
RCBG 100 mg/dl $125 120 mg/dl $392
FPG 100 mg/dl $127 110 mg/dl $578
A1C 5.0% $153 5.7% $590
Zhang et al ADA 2004

Follow-up Report on the
Diagnosis of Diabetes Mellitus
The Expert Committee on the Diagnosis and

Classification of Diabetes Mellitus
Diabetes Care 2003; 26: 3160.

Criteria for Diabetes and Pre-Diabetes
Cutpoint
lowered
to >=100
Fasting glucose 2-hour glucose

Number Fasting Glucose Distribution
100 110 126

Glucose level (mg/dl)
Pre-Diabetes in the US population 4074 years of Age
by Old and New Criteria, 2000
OLD NEW
IFG IGT & IGT IFG IFG & IGT IGT

IFG
13 M (4 M) 15 M 35 M (5 M) 16 M
Total = 20 million Total = 41 million

Benjamin et al., CDC unpublished; CDC National Diabetes Fact Sheet.
Detection Issues
Sensitivity, specificity trade-offs
Program goals
Use of resources
Targeted population
New IFG criteria* (adding 100-110 mg/dl)
Benefit unknown/small
89% w 100-109 have other indication for LS
False positive and label side-effect
Schriger and Lorber Diabetes Care 2004; 27: 598.

Burden of Diabetes
Today
TIME
Tomorrow
Knowing it not enough;
we must apply.
Willing is not enough;

we must do.
- Goethe
Criteria for testing for DM in assymptomatic,
undiagnosed patients
> 45 yrs, every 3 yrs (if
normal)
< 45 yrs, every 3 yrs if:
BMI > 25 and any of the following
1st degree relative with DM
Blacks, Hispanic, Native American, Asian
American
Habitually inactive
Hx Gestational Diabetes or baby > 9 lbs
History of vascular disease
Criteria for testing for DM in
assymptomatic, undiagnosed patients
< 45 yrs, every 3 yrs if:
(cont.)
Hypertension (>140/90)
HDL < 35 mg/dl
TG > 250 mg/dl
previous Dx of impaired glucose
tolerance or impaired fasting glucose
Fasting Blood Glucose
> 8 hr fast
DM if FBG > 126 mg/dl
(7.0mM)
on 2 occasions
Pre-Diabetes
Impaired fasting glucose (IFG)
if : 110 - 125 mg/dl
Diagnostic Criteria
DM if [glu] > 200 mg/dl at 2
hours
IGT if [glu] >140 - 199 at 2
hours
normal if [glu] < 140 mg/dl
IGT and IFT recently termed
pre-diabetic
Hemoglobin A1c
glycated hemoglobin
Average lifespan of red blood cells
~ 120 days (4 months)
Glycosylation of blood proteins in proportion
to blood glucose concentration
Normal: 5%
Goal for diabetics: < 7%
What is Pre-diabetes?
Pre-diabetes is a medical condition where
blood glucose levels are higher than normal but
not high enough to be called diabetes
Studies have shown that the onset of type 2

diabetes can be delayed or prevented by:
losing weight, and
increasing physical activity
Screening
Who should you screen?
Adults who are overweight (BMI>25) or
obese(BMI >30) and have 1 or more
additional risk factors
Routine testing for others not meeting criteria
should begin at age 45
If normal repeat every 3 years or more
frequently if risk status changes
Risk Factors
Physical inactivity
1st degree relative with diabetes
High risk ethnic groups(African-
Amer,Latino,Asian-Amer,Pacific Islanders)
Women who delivered a baby >9lbs +GDM
Hypertension
HDL<35 or Trigs >250
Women with PCOS
IGT or IFG on previous testing
Hx CVD
Severe obesity or acanthosis nigricans
PREDIABETES
Those patients with impaired fasting
glucose(100-125) or impaired glucose
tolerance(2hr between 140-199)
Both are risk factors for future DM and
cardiovascular disease.
Diet and Exercise..how much?
Follow up counseling important for success
Metformin may be considered
Screening
Risk Factors
Physical inactivity
Hypertension
Women with PCOS
Hx CVD
PREDIABETES
A) Lifestyle factors
a)Dietary issues
High fat and low carbohydrate diets have been linked

with type diabetes.
Vegetable fat and polyunsaturated fat had reduced
risk.
Trans-fatty acids had increased risk.
No increase of risk associated with high saturated fat
intakes
Our experiences
2. Dietary Fat Intake as Risk Factor for the Development of Diabetes
Multi-Centre Study of the Mediterranean Group for the Study of Diabetes
(MGSD)
AC. Thanopoulou1, BG. Karamanos1,,.....V. Dimitrijevic4, P. Djordjevic4.....and
MTP. Tenconi 9
Diabetes Care 26:302-307, 2003.
Summary:
We have presented data showing that both subjects with recently diagnosed
diabetes and subjects with undiagnosed fasting glycaemia in the diabetic
range, compared with matched control subject, have higher intake of fat and
especially animal fat. Our data support the view that increased animal fat in
diet may contribute to increased incidence of diabetes.
Comment:
In the present study, fat intake especially of animal origin was strongly
associated with both recently diagnosed type 2 diabetes and undiagnosed type
2 diabetes.
Increased fat intake effect maybe mediated through changes in insulin
sensitivity. Saturated fat is inversely related to insulin sensitivity.
Same trend exist for animal fat intake.
Table 2 - Comparison of the energy nutrient intake between subjects with
recently diagnosed diabetes, unknown diabetes, impaired fasting glucose
and their control groups
Control Control Control
RDM RDM UDM UDM IFG IFG
-----------------------------
Fat (g/day) 792 76 2 89 5 83 6 87 6 95 6
Animal fat (g/day) 32 1 29 1 36 3 29 2 31 2 36 3
-----------------------------
Fat (% of total energy) 30.2 0.5 27.8 0.5 34.7 1.5# 30.4 1.2 30.6 1.1 32.1 1.2
Animal fat (% of total energy) 12.2 0.3** 10.8 0.3 14.2 0.9 10.6 0.7 10.9 0.6 12.5 0.7
-----------------------------
Data are means SE. All P values were adjusted for multiple comparison according to Bonferroni
- p=0.043 - p=0.0001 # - p=0.013

Screening
Risk Factors
Physical inactivity
Hypertension
Women with PCOS
Hx CVD
PREDIABETES
A) Overall, the published information of the effect of
lifestyle changes is encouraging, at least a 50%
reduction in progression from IGT to type 2 diabetes.
However it seems unlikely that significant lifestyle

changes will be achieved in many developed countries
and or maintained long-term in other vise healthy
individuals against a background of unrestrained and
relatively unhealthy behavioral lifestyle choices by the
rest of community. In this setting, it is important to
consider to possibility of pharmacological intervention
Table 3 - Risk factors for type 2 diabetes
Age 45 years
Overweight (BMI 25 kg/m2*)
First degree relative with diabetes
Habitual physical inactivity
Member of a high risk ethnic population (e.g. African-American,
Latino, Native American, Asian-American, Pacific Islander)
Previously identified pre-diabetes (IFG or IGT)
History of GDM or delivery of a baby weighing > 9 lbs
Hypertensive ( 140/90 mmHg)
HDL cholesterol level 35 mg/dl (0.9 mmol/l) and/or a
triglyceride level 250 mg/dl (2.82 mmol/l)
PCOS
History of vascular disease
*May not be correct for all ethnic groups
Prevention strategies
A) Lifestyle interventions:
a) Diet (reduction of obesity by 10% or more)
b) Physical activity (reduction of obesity,
increase insulin sensitivity, persistent effects).
B) Pharmacological treatment
C) Combination: A+B
Fig.1- Proportion of subjects without diabetes during the Trial
Remaining Free of Diabetes

Cumulative Probability of
Tuomilehto J et al. NEMJ 344, 18 May 3, 2001, 1343-50

Title of the Study, Authors 8 1y. WHR: -9.4%, -14.4%, -15.1% respectively
BELGRADE DIABETES PREVENTION 2y. WHR: -11.5%, -16.3%, -17.2% respectively
PROGRAMME, 2000-2003, S&M (former Metabolic and function parameters
YU) 1 y. Surf. bell. ins. curve: RD -21.2%, ID -
DESIGN 32.0%, ID+Ex -33.4%
Plan of the Study HOMA IR:RD -32%,ID -49.9%,ID+Ex-49.7%
Randomized HOMA : RD -21.8, ID -36.8%, ID+Ex -37.4
1. Diet A) Reduction D - RD. B)
Individually D. -ID 2 y. Surf. bell. ins. curve: RD -28.2%, ID -
2. ID + Exercise - ID+Ex 34.1%, ID+Ex -35.3%
3. ID + Ex + Metformin or Placebo HOMA IR:RD -33.5%,ID -51.1%,ID+Ex-
Randomized, double blind, placebo 50.9%
controlled trial (not yet finished)
HOMA : RD -22.6, ID -37.0%, ID+Ex -37.5
Number of the participants - 125 ?
Reduction of incidence of DM
Duration - 3 years 1 y. IGT: RD. 48%, ID 56%, ID + Exercise
Risk factors IGT, Obesity, aged 40-70 years, 60%
Intervention measures 2 years IGT: RD. 52%, ID 60%, ID +
DIET: Exercise 64%
1. RD 1000 kcal/24h 2.ID (aged, sex, BMR, Droop out and side effects
activity level) 1 year RD 4%, ID 0% ID+Ex 0%
For both diet: CH 55-60% fibres 25g/l000 2 years RD 36% ID 16% ID+Ex 20%
kacl, fats bellow 26%, SAT <8%,PUNS 3-
7%, MUNS 11-15% (high CH, high fibre, CONCLUSION, OBJECTIONS
low fats)
Our results confirmed that in the high-
3. Exercise: walking, 1 hour, speed 6km/h
daily risk subjects with IGT, obesity and
GOALS older age type 2 diabetes can be
To prevent Type 2DM
MAIN RESULTS prevented by changes in the lifestyle
Weight and anthropometric parameters
1 y. BMI: RD -153%, ID -21.1%, ID+Ex -22.5%,
Glucose tolerance after 1 and 2 years
Normal 1 year 2 years
RD IGT 16% 16%
DM
IGT 36% 32%
52%
48%
ID
4% 4%
40% 36%
IGT
56% 60%
ID
+
Physical activ. 36%
40%
IGT
64%
60%
Incidence of Diabetes
Percent developing diabetes
Placebo (n=1082)All participants

Metformin (n=1073, p<0.001 vs. Placebo)
Lifestyle (n=1079, p<0.001 vs. Met , p<0.001 vs. Plac )
40 Lifestyle
Metformin(n=1079,
(n=1073,p<0.001
p<0.001 vs.
vs. Metformin
Plac) ,
Placebo (n=1082) p<0.001 vs. Placebo)
Cumulative incidence (%)
Risk reduction
30 31% by metformin
58% by lifestyle
20
10
0
0 1 2 3 4
Years from randomization
Conclusion
T2DM is a preventable disease
Both lifestyle intervention and Metformin were
effective in preventing the development of
T2DM
Lifestyle intervention was more effective in
reducing the risk of T2DM
Title of the Study, Authors 11 Reduction of incidence of DM
STOP NIDDM Study, Multi Nationale (9
Countries), 1996-2001. A) The risk of progression to DM over 3.3 years
DESIGN
was reduced by 2 5%
Plan of the Study
Randomized, Double-blind, Placebo- Acarbose increases the probability that IGT will
controlled, Multicentric Study revert to normal glucose tolerance over time.
A) Acarbose, B) Placebo Weight loss contributed to decreased risk of DM
Number of the participants - 1429 (714 When Acarbose discontinued at the end of the
Acarbose + 715 Placebo) study incidence of DM increased.
Duration - 3,3 years (Mean follow up) Droop out and side effects
Risk factors IGT, BMI, 25-40 kg/m2 , High 29.56% of whom 48% during first year
risk population in particular from first Mainly from G I side effects
degree- relatives of patients with type
to DM. CONCLUSIONS, OBJECTIONS
Intervention measures Farmacological intervention with Acarbose could
FPG: 5.6-7.7 mmol/l. Acarbose 100mg or be used either as an alternative or in addition
Placebo, 3 times daly; 3-day nutritional to changes in lifestyle, to delay development
diary phisical activity recorded 3 days of type 2 DM in patients with IGT.
GOALS
To delay progression from IGT to type 2 Acarbose effectively reduced risk of the
DM developing DM irrespective of age, sex and
Primary endpoint: Development of DM BMI.
MAIN RESULTS
Weight and anthropometric parameters 11 patients with IGT would need to be treated for
Weight: A) 87.6 kg to 87.1 kg (-0.5kg), B) 3-years to prevent 1 case of DM
87.0kg to 87.3 kg (+0.3kg), p=0.018
The Lancet June 2002; vol. 359: 2074
Actual Conclusions
Type 2 DM is a preventable
disease
Type 2 diabetes is cardiovascular

disease
Effect of Intervention on Metabolic & Risk
Factors
Change in Fasting Insulin
2
Change in Insulin (U/ml)
-1
Lifestyle
-2
Metformin
Placebo
-3
-4
-5
Change in Blood Presure
Systolic Diastolic
0
Change in BP (mmHg)
-1
-2 Lifestyle
Metformin
Placebo
-3
-4
Change in Lipids
Choleterol Triglycerides
0
Change (%)
-5
Lifestyle
Metformin
-10 Placebo
-15
Conclusion
T2DM is a preventable disease
Both lifestyle intervention and Metformin were
effective in preventing the development of
T2DM
Lifestyle intervention was more effective in
reducing the risk of T2DM
Lifestyle intervention and Metformin were
associated with modest improvement in
insulinemia and CVD risk factors
Effect of acarbose treatment on the risk of silent myocardial
infarction in patients with impaired glucose tolerance: results of
randomised STOP-NIDDM trial electrocardiography
Uwe Zeymer, A. Schwarzmaier-Dassie, D. Petzinna, JL Chiasson and for the STOP-
NIDDM Trial Research Group
Eur J Cardiovasc Prev Rehabil 2004; 11:000-000, European Society of Cardiology
Beckground The moderate increase in postprandial plasma glucose in
subject with impaired glucose tolerance has been shown to be a
predictor of cardiovascular disease. In the randomised STOP-
NIDDM trial, we could demonstrated that lowering postprandial
plasma glucose with acarbose in subjects with impaired oral
glucose tolerance could reduced the risk of diabetes.
Methods The current report focuses on the effect of acarbose on
silent ischaemic events evaluated in the electrocardiographic
substudy, using the Minnesota code classification.
Results A total of 1181 patients were included in the ECG substudy.
From these 72 patients had significant changes between the
baseline and end of treatment ECG, 33 in the acarbose and 39 in
placebo group. Higher rates of myocardial infarctions occurred in
the placebo group (p=0.023 with Chi-square test), while there were
no differences between the two groups with ECG changes
classified under the other Minnesota codes.
Conclusions In this prospective intervention study we could show
that acarbose, by decreasing postprandial hyperglycaemia, can
reduce the incidence of silent myocardial infarction in subjects
with impaired glucose tolerance. This approach should therefore
1st International Congress on Prediabetes and the Metabolic Syndrome
Berlin, Germany, April 13-16, 2005.
IS IGT DISEASE?
METABOLIC PARAMETERS OF
ATHEROSCLEROSIS AND
THROMBOGENESIS IN
MACROANGIOPATHY WHICH ALREDY
EXIST
Predrag B. Djordjevic, V. Kanjuh, V. Dimitrijevic-Sreckovic, M. Ostojic,
S. Popovic, F. Canovic, D. Gostiljac, B. Sreckovic,
G. Milic, R. Obrenovic, E. Colak
Diabetes Center
Institute for Endocrinology, diabetes and metabolic diseases
Clinical Center of Serbia
Serbia and Montenegro
METHODS
62 obese patients were included, over 45 years old, with
IGT (criteria - WHOWG 1998.)
48.4% of them was with DMA (CHD, CVD, peripheral
artery disease).
Risk factors for atherosclerosis were established:
insulin sensitivity-HOMA IR, insulin secretion-HOMA ,
lipids profile (total, LDL and HDL cholesterol, triglycerides,
Apo A and Apo B),
atioxidative protection (SOD, GPX, TAS)
homocysteine-HCS
blood pressure
thrombogenesis: PAI-1 and fibrinogen
Statistical significance between groups with and without
DMA was preformed (Students t test).
Lipids
P>0.05 without DMA

8
p<0.05
DMA
6.11.6
6
mmol/L
4.81.2
P<0.05
4.71.2
4 3.30.98 3.41.2
P>0.05
2.10.9
2
1.10.37 0.950.43
0
T-Ch LDL HDL Tg
Blood pressure
P<0.05
without DMA DMA
160 P<0.01
mmHg
120 135 24.3
80 95.5 17.8
121 26.2
40 82.1 12.4
0
Sistolic Diastolic
PAI-1
P<0.01
3.8 1.8
4
3
U/ml
1.7 0.9
2
0
without DMA DMA
CONCLUSION
Diabetic macroangiopathy exist and is frequent

in IGT. It is associated with more frequent
presence of risk factors for atherosclerosis and
thrombogenesis.
Therefore, IGT is cardiovascular disease, too.

There is growing epidemiological
evidence for the association of
postprandial hyperglycaemia and
macrovascular complications in
diabetic patients
infarction in type 2 diabetic patients:
Meta-analysis of seven long-term studies
H. Hanefeld et al.
European Heart Journal 2004; 25: 10-16
Aims
To assess if treatment with the -
glucosidase inhibitor acarbose can

reduce cardiovascular event in type 2
diabetic patients
Conclusion
Intervention with acarbose can
prevent myocardial infarction and
cardiovascular disease in type 2
diabetic patients while most of them
are already on intensive concomitant
cardiovascular medication.
1st International Congress on Prediabetes
and the Metabolic Syndrome
G. Alberti
IDF consensus on the metabolic syndrome:

DEFINITION AND TREATMENT 2004.
The goal was to find effective but

simplest and cheapest parameters
1. Obesity
BMI
Central obesity (sine qua non)
W/H ratio
W circumference (ethnic specific)
2. Triglycerides > 1.7 mmol/l (sine qua non)
3. HDL < 0.9 mmol/l - Male (Gender specific)
< 1.1 mmol/l - Female
4. Blood Pressure > 130 / 85 mmHg
systolic diastolic
or
Treatment of hypertension
5. Dysglicaemia Estimation of insulin resistance (IR) is (very) complex
one for every day praxis and epidemiological studies
because of that we may use following equation :
Central obesity + 2 of cited parameters = IR
6. Raised blood glucose > 5.6 mmol/l or preexisting

Diabetes mellitus
We need the prospective studies to estimate
connection between metabolic syndrome and
CVD especially.
In the mean time the investigators should be
asked to evaluate
- sensitivity
- specificity
- predictivity
of all new parameters according its
connection with CVD.
WHO and perhaps IDF should also be asked to
approve any agreed new definition of
Metabolic Syndrome
1st International Congress on Prediabetes
and the Metabolic Syndrome
G. Alberti
Are We Ready to Treat the Metabolic Syndrome?
Purpose of treatment
To prevent CVD
To prevent type 2 DM
At the moment there is no direct proof
that prevention of Metabolic Syndrome
means prevention of CVD and DM
According the etiology of Metabolic Syndrome
(MSy) treatment measures must be directed to
life style management (amount)
diet
physical activity (increase)
pharmacologic treatment
systematic treatment MSy component
insulin sensitizers (metformin, glitazones)
PPR- and agonists for glycaemic and lipid
disorders
antiobesity drugs - new urgently needed
aspirin
antihypertensives (ACE-I and/or A2 and CB1 receptor
blockers)
oral antihyperglycaemic agents
insulin (it will be investigated more precisely)
statin and fibrate
stop smoking
It is unetical not to treat MSy but there is not
magic bullet
Finally we do not have specific therapy but we
Risk Factors for Prediabetes
Age
45 years or older
Younger than 45, overweight, and have one
or more of the following risk factors:
Low HDL cholesterol and high triglycerides
Hypertension
History of gestational diabetes or gave
birth to a baby weighing more than 9
pounds
Minority group background
African American
American Indian, Hispanic American/Latino
Asian American/Pacific Islander)
Scope of the Problem
Total: 20.8 million children and adults -- 7.0%
of the population -- have diabetes.
10.3 million over age 60
Diagnosed: 14.6 million people
Undiagnosed: 6.2 million people
Pre-diabetes: 41 million people
1.5 million new cases of diabetes were
diagnosed in people aged 20 years or older
in 2005.
AACE: Prediabetes Guidelines 2008
FPG 2-hr PG on OGTT

mg/dL mg/dL
126 Diabetes Mellitus 200 Diabetes Mellitus
100 and <126 Impaired Fasting 140 and <200 Impaired Glucose
Glucose Tolerance
<100 Normal <140 Normal
IFG and IGT = prediabetes

progression to diabetes: IGT is 6-10% per year
IFG and IGT, cumulative incidence of DM in 6 years 60%
Risk of prediabetes: IGT increases CHD risk by 50%.
The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care.
2002;25(suppl):S5
AACE: Prediabetes 2008
Treatment Plan
Reduce weight by 5-10%,
Moderate physical activity for 30-60 min daily, 5 days
weekly
high risk (IFG + IGT, and/or MetSynd, CV ds, NAFL ds,
h/o of gestational DM, or PCOS): consider meds
Metformin and acarbose are inexpensive and safe
the same lipid goals as DM: LDLcholesterol, non-HDL
cholesterol, or apoB goals of 100 mg/dL, 130 mg/dl,
and 90 mg/dl.
the same BP as DM: systolic <130, diastolic 80 mmHg,
recognizing the limitations of these data.
Diabetes drugs:
More drugs, more worries
Denker PS, Dimarco PE. Exenatide (exendin-4)-
induced pancreatitis: a case report.
Diabetes Care. 2006 Feb;29(2):471.
FDA ALERT [10/2007]: FDA has reviewed 30
postmarketing reports of acute pancreatitis in
patients taking Byetta. An association between
Byetta and acute pancreatitis is suspected in
some of these cases.
Healthcare professionals should instruct patients
taking Byetta to seek prompt medical care if they
experience unexplained persistent severe
abdominal pain which may or may not be
accompanied by vomiting. If pancreatitis is
suspected, Byetta should be discontinued. If
pancreatitis is confirmed, Byetta should not be
DPP-4 concerns
DPP-4 is a ubiquitous membrane-spanning cell-surface
aminopeptidase
widely expressed in many tissues, such as liver, lung,
kidney, intestinal brush-border membranes,
lymphocytes, and endothelial cells.
DPP-4 preferentially cleaves peptides with a proline or
alanine residue
Many gastrointestinal hormones, neuropeptides,
cytokines, and chemokines are substrates for DPP-4, in
addition to GIP and and GLP-1.
Drucker DL Lancet 2006;368:1696
DPP-4 Concerns
Meta analysis by Amori et al:13 published double
blinded trials (N=4780) increase risk of infections
UTI
Nasopharyngitis
Relative risk of 1.5
Increases the number if new UTI by 1 million new
cases/year
Studies of longer duration are needed
until more safety data are available, it may be prudent
to avoid use of these agents in pts with h/o recurrent
UTI
also a slight increase RR of headache
untill the risk is further defined , it may be prUdent to
avoid use of DPP4 inhibitors in in pts with a h/o chr HA

Amori et al. JAMA 2007;298(2): 194-206
Old Drugs, New Worries
Rosiglitazone Meta-analysis of 42 trials
OR MI 1.43 (p 0.03)
OR death form CV ds 1.64 (p 0.06- borderline significant )
Record Interim Analysis: ~2000 pts ( 1000 rosi +SU v/s 1000 rosi +
met) vs 2000 control (SU +metformin) followed for <4 years
There was no evidence of any increase in death from either
cardiovascular causes or all causes
Rosiglitazone was associated with an increased risk of heart failure
N Engl J Med, Volume 357(1):28-38, July 5, 2007
Short-term therapy with rosiglitazone exerts detrimental skeletal

effects by inhibiting bone formation
J Clin Endocrinol Metab. 2007 Apr;92(4):1305-10.
Thank you for your
attention
Using American Diabetes Association
Standards of Medical Care In the Free Clinic
Setting
DM-2, By the Rules
Gary Greenberg, MD
Medical Director, Open Door Clinic
Urban Ministries of Wake County
(919) 256-2167; GNGreenberg@gmail.com
April, 2010
Pre-Diabetes or
Increased risk of Diabetes
A serious diagnosis, with legitimate therapies,
including medications
Impaired Fasting Glucose (IFG) : Fasting
glucose 100-125 mg/dl

Impaired Glucose Tolerance (IGT): 2-hr post-
challenge 140-199 mg/dl

New: HgbA1C between 5.7 6.4
Screening for Diabetes
Every 3 years: Annual: high-risk + overweight
Sedentary
All overweight
Family History (1o relative)
adults 45 & older
Ethnic risks (AA, Latino, Native Amer.)
(BMI 25 kg/m2) Prior gestational (or baby 9 lbs)
Hypertensive
Metabolic Syndrome (Low HDL or
hypertriglyceridemia)
Polycystic Ovaries Syndrome
Known Pre-diabetes
Acanthosis Nigracans
Known vascular disease
Diabetes Prevention
Lifestyle efforts
Documented success (up to ~58% reduction in 3
years)
Weight loss, even modest
Exercise, even mild increased activity
Clinical monitoring
Medications
Metformin (especially with both pre-diabetes
criteria)
Acarbose, Orlistat, Rosiglitazone
Major Classes of Medications
1. Insulin Sensitizers Thiazolidinediones
Avandia (rosiglitazone), gone
sensitize the body to Actos (pioglitazone)
insulin and/or control Biguanides
Metformin
hepatic glucose
production
Sulfonylureas
Glimepiride (Amaryl)
2. Secretagogues Glipizide (Glucotrol)
stimulate the Glyburide (Diabeta, Glynase,
Micronase) no longer
pancreas to make recommended
more insulin Meglitinides
Nateglinide (Starlix)
Repaglinide (Prandin)
Module 3.1
Diabetes Prevention and Early Detection
Best Practice Guidelines

An overview
Presentation purpose
Target audience
Health professionals and project workers on DPMI projects

Aim
To aid in planning of stages 2 and 3 of DPMI projects
Objectives
Provide an overview of the prevention of diabetes

Discuss type 2 diabetes risk factors and screening
Discuss prediabetes and implications in practice and for the
projects
Discuss IGT/IFG diagnosis, communicating risk to consumers
and best practice care projects.
Prevention of diabetes
Recommendations to reduce risk of type 2 diabetes
Regular physical activity
Interventions to reduce obesity
Waist circumference, body weight and body mass index (BMI)
identify individuals who should seek and be offered weight
management program
Individuals at risk should have dietary intake
assessed and receive individualised dietary advice
and continued dietetic support
Evidence Based Guideline for the Prevention of Type 2 Diabetes. Australian Government
NHMRC www.diabetesaustralia.com.au/education_info/nebg.html
Prevention of diabetes
Recommendations to reduce risk of type 2 diabetes
Identification
of women with GDM would allow:
Postnatal clinical interventions in those with diabetes
Option to use preventive methods to reduce the risk of
Type 2 diabetes
Diet and exercise education in children should include:
Parental involvement
Behavioural techniques
Evidence Based Guidelines for the Prevention of Type 2 Diabetes. Australian Government
NHMRC www.diabetesaustralia.com.au/education_info/nebg.html
Screening for diabetes and risk factors
Active case detection and diagnosis of Type 2 diabetes should
be considered for the following reasons:
Type 2 diabetes is serious and costly
Natural history includes asymptomatic phase which is not benign
and during which it can be diagnosed
Early treatment reduces morbidity from long term complications
Case detection and diagnosis has a favourable risk:benefit ratio
NB Overall prevalence does not justify universal testing of the

entire Australian adult population but rather opportunistic case
detection.
Evidence Based Guideline for the case Detection and Diagnosis of Type 2 Diabetes.
Australian Government NHMRC
www.diabetesaustralia.com.au/education_info/nebg.html
Opportunistic case detection
Test high risk individuals
People with IGT or IFG
Aboriginal and Torres Strait Islanders aged 35 years and over
Certain high risk non-English speaking background groups aged
35 years and over
(specifically Pacific Islander people, people from the Indian
subcontinent or of Chinese origin);
People aged 45 years and over who have either or both of the
following risk factors:
Obesity (BMI = 30 )
Hypertension;
All people with clinical cardiovascular disease (myocardial infarction,
angina or stroke
Women with polycystic ovary syndrome who are obese.
Evidence Based Guideline for the case Detection and Diagnosis of Type 2
Diabetes.
Australian Government NHMRC www.diabetesaustralia.com.au/education_info/nebg.html
Evidence Based Guideline for the case Detection and Diagnosis of Type 2 Diabetes.
Australian Government NHMRC www.diabetesaustralia.com.au/education_info/nebg.html
Definition
Pre diabetes includes both
Impaired Glucose Tolerance
Impaired Fasting Glucose
Pre diabetes
16% of population have pre diabetes
AusDiab Study (Dunstan et al, 2002)
Pre diabetes associated with
Increased risk of microvascular complications
Increase risk of microalbuminuria and neuropathy
(lower prevalence than diabetes but higher than general
population)
Increase risk of cancer breast, colon, liver and pancreas.
Increased risk of developing diabetes
Need to consider age: how relevant is IGT or IFG in
a person 75 years old?
Does pre diabetes predict diabetes?
Progression of IGT/IFG to diabetes in 11 year follow up
Presentation Stephen Twigg. Pre diabetes Symposium ADS & ADEA Annual Scientific Meeting Sydney 2004
Impaired glucose Tolerance Impaired Fasting Glucose

11 year follow up 11 year follow up
IGT
30%
Normal
Diabetes Diabetes
38%
46%
Normal
24% IFG
IGT
7%
17%
Interventions
Increased physical activity and weight loss
can reduce risk of type 2 diabetes ?Reduce
cardiovascular risk
Need to focus on follow up and review given
high risk of developing diabetes
Need to encourage ongoing review and
management of CVD risk factors
Communicating risk to consumers
Is it a condition vs risk factor?
What is the name of the condition? Will the
name influence how seriously consumers
view it i.e. pre diabetes vs impaired glucose
tolerance.
No label may mean not taken seriously
No label may mean no intervention. No follow
up
Implications for individuals if labelled with a
condition where approx 1/3 will revert back to
normal.
How is pre diabetes managed in general
practice?
Mapping exercise (Div of GP Perth)
GP audit.
Nearly 1/3 of patient with prediabetes had not
had a blood glucose test in the past 12 months
Waist circumference was only recorded for
10% patients
50% had their weight recorded
Lipids and BP were recorded in almost all
patients ( not sure how often)
Presentation by A Derbyshire. ADS & ADEA Annual Scientific Meeting Sydney
2004
Primary care management of Type 2
diabetes
GP Focus Groups
GPs reluctant to pursue aggressive case finding
GPs dont involve other HPs in management of
pre diabetes
Most follow up is oppurtunistic
No recall systems
Patient characteristics such as motivation, lack
of understanding were seen as the greatest
barriers to managing pre diabetes in GP
practice
Presentation by Kaye Neylon ADS & ADEA Annual Scientific Meeting Sydney
2004
Group education for Impaired Glucose
Tolerance - does it work?
ACT Diabetes Service
Referred clients (n=34) with IGT/IFG attended 2 group ed
sessions (1 hr nutrition/ 1 hr information) asked to identify
possible lifestyle modifications.
Responses
- 79% exercise - 59% weight loss,
- 5% smoking cessation - 5% stress reduction.
6 month telephone follow up (78% response) reported lifestyle

changes implemented and maintained
- 68% exercise - 56 % dietary changes
- 50% weight loss - 5% stress reduction
- 0% smoking cessation.
- Presentation by W.R Mossman ADS & ADEA Annual Scientific Meeting Sydney 2004
The Science:
Diabetes Prevention
Diabetes Prevention Program (DPP)
The DPP was a major clinical trial to
determine whether diet and exercise or the
oral diabetes drug metformin could prevent
or delay the onset of type 2 diabetes.
DPP Research Group. N Engl J Med 2002, Vol.346, No. 6.

DPP Participants
Adults at high risk for type 2 diabetes
Presence of IGT
Mean age 51 years
Mean body mass index (BMI) 34
68% women
45% minority groups
African Americans
Hispanics/Latinos
American Indians
Asian Americans and Pacific Islanders
DPP Methods
Lifestyle intervention
5% to 7% weight reduction
Healthy low-calorie, low-fat diet
30 minutes of physical activity, 5 days a week
Metformin
Oral diabetes drug
Placebo
DPP Methods
DPP Curriculum:
Diet
Exercise
Behavior change modification
Taught one-on-one by case managers

Outcomes Study (DPPOS)
Follow-up study to the DPP
Assess the long-term effects of the
DPP interventions on the development
of type 2 diabetes and its
complications
After 10 years follow up, lifestyle intervention:
reduced the rate of developing type 2 diabetes
by 34 %
reduced the rate of developing type 2 diabetes
by 49 % in those age 60 and older

delayed type 2 diabetes by about 4 years
reduced cardiovascular risk factors.
Reduced A1C and FPG

DPP Research Group. The Lancet 2009: Vol.374, No. 9702.
At 10 years follow up, metformin
reduced the rate of developing diabetes by 18 %
compared with placebo.

delayed diabetes by 2 years compared with
placebo.
reduced A1C and fasting glucose compared with
placebo.
DPP Research Group. The Lancet 2009: Vol.374, No. 9702.
Preliminary results
8% of participants with pre-diabetes had diabetic
eye disease (retinopathy)
12.6% of participants with type 2 diabetes who
developed diabetes during the DPP had diabetic
eye disease
These findings suggest that patients with pre-diabetes or newly
diagnosed type 2 diabetes should be screened for retinopathy.
DPP Research Group. Diabetic Medicine 2007; 24 (2); 137-144.

Diabetes Prevention
57 million U.S. adults ages

20 and older have pre-
diabetes

Pre-diabetes is a medical condition where blood
glucose is higher than normal but not high
enough to be called diabetes
It increases the risk for type 2 diabetes and
cardiovascular disease
Most people have pre-diabetes before they
develop type 2 diabetes

Most people with pre-diabetes develop type 2
diabetes within 10 years
People with pre-diabetes are identified by having a

screening test which shows they have IFG, IGT or
an A1C of 5.7% - 6.4%
Progression to diabetes is NOT inevitable

Risk Factors for Diabetes
Age 45 and older History of vascular disease
Overweight (BMI 25) Signs of insulin resistance
Hypertension (such as PCOS or
acanthosis nigricans)
Abnormal lipid levels
Pre-diabetes
Inactive lifestyle
Race/ethnicity
History of gestational
diabetes
American Diabetes Association. Diabetes Care 2008; 31;(Suppl.1):S12-54.

Testing for Diabetes and
Pre-Diabetes
Consider testing if person is:
Age 45 or older
An overweight adult with another risk factor
Obtain: A1C or FPG or 2-hour plasma glucose post
75-g oral glucose challenge
Repeat testing every 3 years.

Diagnostic Criteria for
Pre-diabetes and Diabetes
A1C Fasting Plasma 2-Hour Oral
Glucose Test Glucose
(FPG) Challenge
Acceptable Below 100 mg/dl Below 140 mg/dl
Pre-diabetes 5.7% - 6.4% 100-125 mg/dl 140-199 mg/dl

(IFG) (IGT)
Diabetes 6.5% 126 mg/dl or above 200 mg/dl or
above

.
Standards of Medical Care
in Diabetes - 2008
Jeri Jennings Mills, RD/LD, CDE

Sami Wood, RD/LD, CDE
OSUMC Diabetes Education

Three diagnostic criteria:
FPG > 125 mg/dL*, or
Casual plasma glucose > 200 mg/dL

& sxs of high blood sugar, or
2-h plasma glucose* > 200 mg/dl

(during an 75 gram glucose OGTT)
*needs repeat confirmation on different day
Testing for type 2
About 1/3 of all people with diabetes may be
undiagnosed
Average dx is 7-10 years after onset
Type 2 DM is frequently diagnosed after
complications appear
Sowho should be tested?
All adults with BMI >24 and a risk factor below
Physical inactivity
1
st degree relative with DM
High-risk ethnic group
Women w/hx GDM and/or PCOS
HTN
HDL <35 or trig >250
Acanthosis nigricans
Hx of CVD
Age 45 if none of the above apply & q 3 yrs

Type 2 diabetes has a long asymptomatic phase
and significant clinical risk markers. Diabetes
may be identified anywhere along a spectrum of
clinical scenarios.
Prediabetes is NOT borderline
diabetes!
Fasting: 100-125 Impaired fasting glucose
(IFG)
2-hr glucose: 140-199 Impaired glucose
tolerance (IGT)
Both IFG and IGT are considered risk

factors for future diabetes & CVD and
should be treated.
Reducing Diabetes Risk
Lifestyle modification was shown to have the
greatest effect in two well-controlled studies:
Diabetes Prevention Program (DPP):
reduced risk of developing diabetes by 58%
Finnish Diabetes Prevention Study showed

direct relationship between lifestyle intervention
and decrease in diabetes
Self monitoring of blood glucose
2-4x/day if on insulin
If on oral agents or MNT, SMBG is
done to achieve glycemic control
May include postprandial checks
Routinely evaluate technique and patients
ability to use data to adjust food intake,
exercise, & medications.

Pre Diabetes

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PREDIABETES

International Diabetes Federation (IDF) data indicate that by

In most Western societies, the overall prevalence has

The annual health costs caused by diabetes and its

IFG is a condition in which the fasting blood sugar level is

IGT is a condition in which the blood sugar level is elevated

Progression to diabetes among those with prediabetes is

People with prediabetes are already at increased risk for

Recent studies have shown that lifestyle

American Diabetes Association, Diabetes Care. 2007:30:S4-41..

Pre-diabetes raises the risk for type 2

NIDDK, National Diabetes Statistics 2007.

Diabetes duration (years) 20 10 0 10 20 30

Primary Secondary Tertiary

Diabetes Mellitus Diabetes Mellitus

* One can also make the diagnosis of diabetes based on

DPP UKPDS PROactive

New and Ongoing outcome

DPP UKPDS PROactive

DREAM ADOPT BARI-2D

Da Qing IGT and Diabetes Study Diet 31

XENDOS (N = 3305) Orlistat 37

Pre-Screen Screen Run-In Treatment Period*

Randomization/ Monotherapy Study

Ramipril + RSG Plbo

RSG Plbo + Ramipril Plbo

Randomization/Baseline (N = 5269) Study End

Gerstein HC, et al. Diabetologia. 2004; 47:15191527.

Previous studies have demonstrated a

Diagnosis of diabetes = FPG 126 mg/dL

ADA. Diabetes Care. 1997;20:1183-1197.

Fasting plasma OGTT 2-hr plasma

Normal < 100 < 140

Impaired < 100-125 140-199

Diabetes > 126 > 200

ADA. Diabetes Care. 2003;20:1183-1197.

Years from -10 -5 0 5 10 15

Step 3: Intensify Insulin

Step 2: Insulin SUs - TZDs

Step 1: Lifestyle - Metformin

Pre-diabetes Type 2 diabetes

Nathan DM et al, Diavetes Care 2006;29:1963-72

IGT Ongoing Hyperglycemia Death

Insulin resistance Retinopathy Blindness

Placebo Metformin Intensive

These studies included people with IGT and other high-risk

Lifestyle interventions included diet and moderate-intensity

In the Diabetes Prevention Program, a large prevention study

Pan et al. (1997)

Placebo Metformin Lifestyle

Annual Incidence of diabetes 11.0% 7.8% 4.8%

Relative reduction ---- 31% 58%

Number needed to treat ---- 13.9 6.9

The DPP Research Group, NEJM 346:393-403, 2002

The DPP Research Group, NEJM 346:393-403, 2002

Prevalent retinopathy about 8%

in placebo and metformin groups, significantly with lifestyle

DPP. Diabetes Care 28:888894,

(2) Implementing a recognition program that will

(4) Increasing referrals and utilization of the prevention

Insurers Partnership Zone

Total Population Pre-diabetes Diabetes Complications

The health of individuals is inseparable from the health of communities

IGT consider metformin