A 42-year-old asymptomatic man with hypertension presents for his annual physical examination.

A 42-year-old asymptomatic man with hypertension presents for his annual physical examination. His medications include atenolol combined with chlorthalidone (at doses of 50 mg and 25 mg per dayBoth parents had type 2 diabetes mellitus later in life.

He does not smoke cigarettes. His body-mass index (BMI, the weight inkilograms divided by the square of the height in meters) is 32.3, and his blood pressure is 130/80 mm Hg. Would you screen the patient for diabetes, and if so, how?

American Diabetes Association Recommendations for the Screening of Asymptomatic Persons for Diabetes.*

Screen beginning at 45 yr of age, at least every 3 yr

Screen at any age and more frequently if the body-mass index is 25 or more and if the person has at least one additional risk factor

Family history of diabetes (first-degree relative)

High-risk race (e.g., black, Native American, Asian, and Pacific Islander) or ethnic group (Hispanic

Glycated hemoglobin level of 5.7% or more or impaired fasting glucose or impaired glucose tolerance on previoustesting

History of gestational diabetes or delivery of a baby weighing

more than 9 lb (4.1 kg)

The polycystic ovary syndrome

Hypertension (blood pressure ≥140/90 mm Hg; or therapy for

hypertension

History of cardiovascular disease

HDL cholesterol level of less than 35 mg per deciliter, triglyceride level of more than 250 mg per deciliter or both

Physical inactivityOther clinical conditions associated with insulin resistance (e.g., severe obesity and acanthosis nigricans

Summary: Risk Factors for Type 2 Diabetes

• Age ↑• Family History / genetics ↑• Gestational Diabetes ↑• Obesity / fat distribution ↑• Physical Activity / fitness ↓• Smoking ↑• Very low birth weight ↑• Depression ↑• Antipsychotic medications ↑• Anti-Retrovial therapy ↑

• Dietary Factors– Carbohydratess ↓– Fats ↑↓– Glycemic load ↑– Cereal fiber / whole grain ↓– Dairy products ↓– High fructose corn syrup ↑– Sugar-sweetened

bevarages ↑– Alcohol ↓– Coffee ↓

: AACE Diagnostic Criteria

Glucose Testing and Interpretation

Criteria for the Diagnosis of DiabetesCriteria for the Diagnosis of Diabetes

A1C ≥6.5%OR

Fasting plasma glucose (FPG)≥126 mg/dL (7.0 mmol/L)

OR

2-h plasma glucose ≥200 mg/dL(11.12 mmol/L) during an OGTT

OR

A random plasma glucose ≥200 mg/dL (11.1 mmol/L)

ADA. I. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S13; Table 2.


Fasting plasma glucose (FPG)≥126 mg/dL (7.0 mmol/L)

Fasting is defined as no caloric intake

for at least 8 h*

*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing.



2-h plasma glucose ≥200 mg/dL(11.1 mmol/L) during an OGTT

The test should be performed as described by the WHO, using a

glucose load containing the equivalentof 75 g anhydrous glucose

dissolved in water*




In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis,a random plasma glucose ≥200 mg/dL)


Criteria for the Diagnosis of Criteria for the Diagnosis of DiabetesDiabetes

A1C ≥6.5%

The test should be performed in a laboratory using a method that isNGSP certified and standardized

to the DCCT assay*



The diagnosis requires confirmation by the same or the other test.

Prediabetes: IFG, IGT, Increased A1CPrediabetes: IFG, IGT, Increased A1C

Categories of increased risk for diabetes (prediabetes)*

FPG 100–125 mg/dL (5.6–6.9 mmol/L): IFGOR

2-h plasma glucose in the 75-g OGTT140–199 mg/dL (7.8–11.0 mmol/L): IGT

OR

A1C 5.7–6.4%*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range.


AACE Recommendations for A1C Testing

• A1C may be misleading in some clinical settings– Hemoglobinopathies– Iron deficiency– Hemolytic anemias– Thalassemias– Spherocytosis– Severe hepatic or renal disease

• AACE/ACE endorse the use of only standardized, validated assays for A1C testing

AACE. Endocrine Pract. 2010;16:155-156.

27

AACE. Endocrine Pract. 2010;16:155-156.

AACE Recommendations for A1C Testing

• A1C should be considered an additional optional diagnostic criterion, not the primary criterion for diagnosis of diabetes

• When feasible, AACE/ACE suggest using traditional glucose criteria for diagnosis of diabetes

• A1C is not recommended for diagnosing type 1 diabetes

• A1C is not recommended for diagnosing gestational diabetes

28

, for every 25-32mg/dL in increase blood glucose levels, there is a 1% increase in HbA1c in patients But without any hematologic variants. 3 with patients who do have any hematologic disorders, this corresponding increase in HbA1c does not occur.

low values may occur in patients with certain hemoglobinopathies e.g., sicklecell disease and thalassemia) or who have increased red-cell turnoverhemolytic anemiaand spherocytosis) or stage 4 or 5 chronic kidney disease, especially if the patient is receiving erythropoietin

In contrast, falsely high glycated hemoglobin levels have been reported in association with iron deficiency and other states of decreased red-cellturnover

Glycated hemoglobin

Fasting not required, low biologic marker of long-term glycemia, stable during acute illness, sample stability in vial global, standardization, close association of results with complications

variability,

A1C ~ “Average Glucose”

American Diabetes Association

A1C eAG

% mg/dL mmol/L

6 126 7.0

6.5 140 7.8

7 154 8.6

7.5 169 9.4

8 183 10.1

8.5 197 10.9

9 212 11.8

9.5 226 12.6

10 240 13.4

Formula: 28.7 x A1C - 46.7 - eAG

A fasting glucose level of 100 to 125 mg is consistent with prediabetes; the range of glycated hemoglobin levels that are diagnostic of prediabetes is controversial, but the ADArecommends a range of 5.7 to 6.4%

Oral glucose-tolerance test

Most sensitive test, earliest marker of glucose dysregulation

Fasting required, substantial biologic variability, poor reproducibility from day to day , lack of association of results with complications over time, sample instability in vial more time required, inconvenience,, higher cost, lack of global standardizationof plasma glucose measurements

Advantage of GTT

• Test allowed established whether has an n GTTor unkown type 2 diabetes

It disclosed wheathera subject has prediabetesApproximately40%of subjects who will develo diabetes with the NGT OGTT detectsdiabetes more efficiently thanFBS

• Sbject withFBS >100in GTT(60%)had 2hpg <140

• Subject withFBS <100 (14%)had 2hpg>.140

• Testing of glycated hemoglobin or fasting plasma glucose appears to identify different groups of patients with diabetes and prediabetes, yet both tests identify patients at similar risk for adverse sequelae.

Longitudinal investigations have shown thatpersons categorized as being “impaired” by any of these definitions have approximately a 5 to 10% annualized risk of diabetes, a risk that is greater by a factor of approximately 5 to 10 than that normal glucose tolerance or normal fasting glucose.

Risks appear to be similar among persons with isolated impaired fasting glucose (i.e., without impaired glucose tolerance) and isolated impaired glucose tolerance (without impaired fasting glucose). However, the proportion of patients with impaired glucose tolerance tends to be greater than that with impaired fasting glucose in most populations

Persons with both impaired fasting glucose and impaired glucose tolerance have a higher risk of diabetes (approximately 10 to 15% per year) than those with only one abnormality. Whereas both prediabetic states are associated with increased total and cardiovascular mortality, impaired glucose tolerance tends to be a better predictor than impaired fasting glucose.

Persons with both impaired fasting glucose and impaired glucose tolerance have a higher risk of diabetes (approximately 10 to 15% per year) than those with only one abnormality. Whereas both prediabetic states are associated with increased total and cardiovascular mortality, impaired glucose tolerance tends to be a better predictor than impaired fasting glucose.14

http://www.nejm.org/doi/full/10.1056/NEJMcp1103643#ref14

Type 2 Diabetes Screening in Children/Adolescents

• Overweight

-BMI >85th percentile

-weight for height >85th percentile

-weight >120% of ideal for height

• Plus any two of the following risk factors….

Type 2 Diabetes Screening in Children/Adolescents

• FH of type 2 diabetes in 1st or 2nd-degree relative• Race/ethnicity (Native American, African American,

Latino, Asian American,Pacific Islander)• Signs of insulin resistance or conditions associated with

insulin resistance

(acanthosis nigricans, hypertension, dyslipidemia, PCOS, or small-for -gestational-age (SGA) birth weight)

• Maternal history of diabetes or GDM during gestation

Diabetes Care 34:Supplement 1, 2011Diabetes Care 34:Supplement 1, 2011

Type 2 Diabetes Screening for Children/Adolescents

• Age of initiation: at-risk age 10 years or if younger onset puberty

• Screen every 3 years

• No screening recommended for Type 1 Diabetes in asymptomatic individuals outside of research protocols

Gestational Diabetes (GDM) • Screen for type 2 diabetes first prenatal visit if risk

factors

• Not known to have diabetes, screen for GDM at 24 –28 weeks of gestation

• Screen women with GDM for persistent diabetes 6–12 weeks postpartum

• Women with a history of GDM lifelong screening for diabetes or prediabetes at least every 3 years (up to 7x higher risk than non-GDM)

Diabetes Care 34:Supplement 1, 2011Diabetes Care 34:Supplement 1, 2011Lancet, 2009, 373(9677): 1773-9Diabetes Care 21(2):B161–B167, 1998Diabetes Care 2010; 33: 676–682

Screening for and Diagnosis of GDMScreening for and Diagnosis of GDM

• Perform a 75-g OGTT, with plasma glucose measurement fasting and at 1 and 2 h, at 24–28 weeks of gestation in women not previously diagnosed with overt diabetes

• Perform OGTT in the morning after an overnight fast of at least 8 h

ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2013;36(suppl 1):S15; Table 6.

•GDM diagnosis: when any of the following plasma glucose values are exceeded–Fasting ≥92 mg/dL (5.1 mmol/L)

–1 h ≥180 mg/dL (10.0 mmol/L)

–2 h ≥153 mg/dL (8.5 mmol/L)

Gestational Diabetes (GDM)

• Overnight fast, 75g OGTT

• Fasting >92 mg/dl

• 1 h >180 mg/dl

• 2 h >153 mg/dl

Diabetes Care 34:Supplement 1, 2011Diabetes Care 34:Supplement 1, 2011Diabetes Care 2010; 33: 676–682Diabetes Care 2010; 33: 676–682

Time of Sample Collection

ACOG Levels*,4(mg/dL) ADA Levels3(mg/dL)

100-gram Glucose Drink

75-gram Glucose Drink

Fasting, before drinking glucose

95 or above 92 or above

1 hour after drinking glucose


2 hours after drinking glucose


3 hours after drinking glucose

140 or above Not used

Requirements for Diagnosis

TWO or more of the above levels must be met

ONE or more of the above levels must be met

OGTT Levels for Diagnosis of Gestational Diabetes**Carpenter and Coustan Conversion, some labs use different numbers.OGTT Levels for Diagnosis of Gestational Diabetes**Carpenter and Coustan Conversion, some labs use different numbers.

http://diabetes.niddk.nih.gov/dm/pubs/diagnosis/

Classification of DiabetesClassification of Diabetes

• Type 1 diabetes– β-cell destruction

• Type 2 diabetes– Progressive insulin secretory defect

• Other specific types of diabetes– Genetic defects in β-cell function, insulin action

– Diseases of the exocrine pancreas

– Drug- or chemical-induced

• Gestational diabetes mellitus (GDM)

ADA. I. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S11.

Classification of DiabetesClassification of Diabetes

• Type 2 diabetes

– Progressive insulin secretory defect

• Other specific types of diabetes

– Genetic defects in β-cell function, insulin action

– Diseases of the exocrine pancreas

– Drug- or chemical-induced

• Gestational diabetes mellitus (GDM)

•ADA. I. Classification and Diagnosis. Diabetes Care 2013;36(suppl 1):S11. Type 1 diabetes

–β-cell destruction

Blood Pressure

• Done at every visit

• Target is <130/<80

• ACE inhibitors typically first line

American Diabetes Association. Diabetes Care. 2011;34(suppl 1)

Children with DMHypertension and Lipids

• Lipids: start screening in childhood if strong FH, or at age 10

• Hypertension: BP >90th percentile for height and weight or >130/>80

• Consider medications (statins, ACE) if necessary


Lipids (Cholesterol)

• Fasting lipid panel at least annually

• Goals:

Total cholesterol <200

Triglycerides <150

HDL >40 men, >50 womenLDL <100 (<70, CVD or high risk)


Aspirin

• Men >50 years of age

• Women >60 years of age

• Younger if higher risk


Nephropathy (Kidney Disease)

Screening• Annual urine testing for

micro- or macro- albuminuria

• Annual creatinine and GFR

• Start at diagnosis for type 2

• Start 5 years after diagnosis type 1

Diabetes Care. 2011;34(suppl 1)

Retinopathy Screening

• Type 1 annual starting after age 10 or after 5 years post diagnosis

• Type 2 annual starting shortly after diagnosis

• Consider less frequent if one or more normal exams (not usually done)

Diabetes Care. 2011;34(suppl 1)

Neuropathy Screening

• Screen at diagnosis and annual thereafter

• Filament testing

• Vibratory testing

• Reflexes


Celiac Disease Screening• At diagnosis in Type 1 and periodic (?), pregnant• Rescreen if GI symptoms, failure to thrive, glycemic

control changes• ~10% of type 1?

Test:• Tissue transglutaminase IgA and IgG

Or• Anti-endomysial antibiodies with serum IgA


Thyroid Screening

• Type 1 screen at diagnosis and every

1 to 2 years, pregnant

• At diagnosis, thyroid peroxidase and

thyroglobulin antibodies

• TSH thereafter

Other Screening/Interventions

• Tobacco cessation

• Smoking contributes to poor glucose control and increased CVD risk

• Smokers should be directed to a cessation program, i.e., Quitline, Quitnet, Quitplan, 3rd party payer, etc.

• Medication(if appropriate)

• Other routine screens (i.e.,cancer)

All diabetes and IGTAll diabetes and IGT 20032003 20252025

Total population (millions)Total population (millions) 544.6544.6 839.2839.2

Adult population (millions) (20-79 Adult population (millions) (20-79 years)years)

276.0276.0 493.6493.6

Diabetes prevalence (%) (20-79 years)Diabetes prevalence (%) (20-79 years) 7.07.0 8.08.0

Diabetes number (millions) (20-79 Diabetes number (millions) (20-79 years)years)

19.219.2 39.439.4

IGT prevalence (%) (20-79 years)IGT prevalence (%) (20-79 years) 6.86.8 7.47.4

IGT number (millions) (20-79 years)IGT number (millions) (20-79 years) 18.718.7 36.536.5Type 1 diabetes (0-14 years)Type 1 diabetes (0-14 years) 20032003

Child population (millions)Child population (millions) 205.8205.8

Type 1 diabetes prevalence (%)Type 1 diabetes prevalence (%) 0.020.02

Type 1 diabetes number (thousands)Type 1 diabetes number (thousands) 46.546.5

Diabetes Pyramid of PreventionDiabetes Pyramid of Prevention

Diabetes

Very High Risk(A1c > 5.7%; IGT; GDM)

Undiagnosed DM

Moderate Risk

Low Risk

Adult Prevalence Goal / Intervention Tier

7.6%

2.6%

~12-15%

~15-20%

~57%

Prevent Morbidity

Detect Early

High Risk (FPG > 100);Central Obesity; HTN, age

What type of intervention for what level of risk?

Methods:

• Conducted in 2007

• 5,287 Iranian citizens included

• Sample size aged 15–64 years

Results:

• Diabetes 8.7%8.7%

• Hypertension 26.6%26.6%

• Obesity 22.3%22.3%

• Central obesity 53.6%53.6%

Prevalence of Diabetes and its risk factors in Iran

Esteghamati A, et al. Third national surveillance of risk factors of non-communicable diseases (SuRFNCD-2007) in Iran: methods and results on prevalence of diabetes, hypertension, obesity, central obesity, and dyslipidemia. BMC Public Health. 2009 May 29;9:167

2.5 million Iranian2.5 million Iranian

EpidemiologyEpidemiology

PrevalencePrevalence 2-3 million2-3 million

IncidenceIncidence 124000124000

BlindnessBlindness 95009500

DialysisDialysis 10001000

AmputationAmputation 57005700

MIMI 2000020000

CVCV 2500025000

HypertensionHypertension 6200062000

DeathDeath 4000040000

ComplicationsHeart disease and strokeIn 2004, heart disease was noted on 68% of diabetes-related death certificates among people aged 65 years or older.In 2004, stroke was noted on 16% of diabetes-related death certificates among people aged 65 years or older..

Adults with diabetes have heart disease death rates about 2 to 4 times higher than adults without diabetes.The risk for stroke is 2 to 4 times higher among people with diabetes

15.00%

7.90%

21.80%

0.00%

5.00%

10.00%

15.00%

20.00%

25.00%

Angina ECG+ve H.F-Arryth

Cardiac Complications

High blood pressureIn 2005-2008, of adults aged 20 years or older with self-reported diabetes, 67% had blood pressure greater than or equal to 140/90 mmHg or used prescription medications for hypertension.

Systolic Blood Pressure

53.70%

22.30%

20.70%

2.80%

>200200180150< 130

130 mm Hg

0.50%

Diastolic Blood Pressure

64.60%

18.10%

12.10%

4.50%

0.70%

> 120

110

100

90

< 80

80 mm Hg

Retinopathy (in 1173 patients ) - Free 68.9 % - Back ground 22.6 % - Proliferative 9.5 %

BlindnessDiabetes is the leading cause of new cases of blindness among adults aged 20–74 years.(28.5%) people with diabetes aged 40 years or older had diabetic retinopathy, and of these, almost 0.7 million (4.4% of those with diabetes) had advanced diabetic retinopathy that could lead to severe vision loss.

Kidney diseaseDiabetes is the leading cause of kidney failure, accounting for 44% of new cases in 2008..

Nervous system disease (Neuropathy)About 60% to 70% of people with diabetes have mild to severe forms of nervous system damage.

AmputationMore than 60% of nontraumatic lower-limb amputations occur in people with diabetes..

Prevalence of foot complications

1- Fungus infection = 22.0

2- Foot ulcers = 6.8 %

3- Evident Ischaemic changes = 9.7 %

4- Amputations = 3.0 %

5- Deformities = 1.0 %

Hospitalization: 3 timesHospitalization: 3 times

Mortality: 3-4 timesMortality: 3-4 times

Diabetes care costs: 2.5 Diabetes care costs: 2.5 timestimes

Cost of DiabetesUpdated March 6, 2013$245 billion: Total costs of diagnosed diabetes in the United States in 2012$176 billion for direct medical costs$69 billion in reduced productivity

Table: Prevalence, awareness, treatment, and control rate of hypertension, dyslipidaemia and diabetes: Isfahan Healthy Heart Programmed study

ConditionConditiontreatment % treatment %

(% total)(% total)

HypertensionHypertension 87.7 (35.3)87.7 (35.3)

DyslipidaemiaDyslipidaemia 49.7 (7.1)49.7 (7.1)

Diabetes mellitusDiabetes mellitus 84.7 (46.2)84.7 (46.2)

Table: Prevalence, awareness, treatment, and control rate of hypertension, dyslipidaemia and diabetes: Isfahan Healthy Heart Programmed study

ConditionCondition awareness %awareness %

HypertensionHypertension 40.340.3

DyslipidaemiaDyslipidaemia 14.414.4

Diabetes mellitusDiabetes mellitus 54.654.6

Post Prandial Hyperglycemia

- Controlled < 160 mg/dl = 13.5 %- Accepted 161-180 mg/dl = 7.9 %

Total = 21.4 %

- Uncontrolled ( >180 mg/dl ) = 78.6 % * Moderate -220 mg/dl = 17.4 % * Severe - 260 mg/dl = 16.0 % * Very Severe > 260 mg/dl = 45.2 %

19.80%

15.60%

31.30%

12.50%

20.80%

> 220

200-220

151-200

121-150

-120

120 mg/dl

Hyperglycemia Fasting

How well are diabetic risk factors controlled in Iran?

6.4% 1.1%

25.7% NA

HbA1c

Measured in the previous year

Patients at goal

Lipids

Delaveri A.,Archives of Iranian Med 2009;12:492-495

56.40%

33.20%

10.40%

>250

201-250

-200

Lipid Control

Serum Cholesterol

200 mg

Lipid ControlSerum Triglycerides

50.40%

33.30%

9.10%

7.20%

> 250

201-250

151-200

-150

Column1

150 mg

Costs of Diabetes

Indirect

Direct~2.3 times more than medical costs of people without diabetes

107CDC. National diabetes fact sheet, 2011. http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2011.pdf.

A 42-year-old asymptomatic man with hypertension presents for his annual physical examination.

Documents

diabetes care

diabetes mellitus

glucose load

diagnosis of diabetesada

mmollor2h plasma glucose

ogttora random plasma

orfasting plasma glucose

impaired fasting glucose