DIABETES .

An Overview
By Dr.Hala Aly Gamal El Din Professor Of Diabetes & Endocrinology Faculty of Medicine- Cairo University

Diabetes in the 21st century

One of the most challenging health problems facing the world 246 million people worldwide diagnosed in 2007 5th leading cause of death in developed countries Complications heart attacks, stroke, kidney failure, amputations and blindness 380 million people worldwide projected to be diagnosed by 2025

Facts
Every 5 seconds 1 person develops diabetes Every 10 seconds 1 person dies of diabetes Every 30 seconds a limb is lost due to diabetes

Diabetes is a chronic, debilitating and costly disease associated with severe complications, which poses severe risks for families, Member States and the entire world.
UN Resolution 61/225. World Diabetes Day

Natural History of DM-2

350 250

Post Meal Glucose Fasting Glucose

Glucose

150 50 300

Insulin Resistance

Relative 200 Function

100 0
-10 -5 At risk for Diabetes

Beta Cell Failure

0 5 10 15 20

Insulin Level
25 30

Years of Diabetes
Bergenstal, 2000 International Diabetes Center Used with permission.

Criteria for the Diagnosis of Diabetes

A1C 6.5%
OR

Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l)

OR

Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT

OR

A random plasma glucose 200 mg/dl (11.1 mmol/l)

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Criteria for the Diagnosis of Diabetes

A1C 6.5%

The test should be performed in a laboratory using an NGSP-certified method standardized to the DCCT assay*

*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing. ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Criteria for the Diagnosis of Diabetes

Fasting plasma glucose (FPG) 126 mg/dl (7.0 mmol/l) Fasting: no caloric intake for at least 8 h*

*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing. ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Criteria for the Diagnosis of Diabetes

Two-hour plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water*

*n the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing. ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Prediabetes: IFG, IGT, Increased A1C

Categories of increased risk for diabetes (Prediabetes)* FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG or

2-h plasma glucose in the 75-g OGTT 140-199 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.

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.

Two thirds of individuals do not achieve target HbA1c

Saydah SH, et al. JAMA 2004; 291:335342. Liebl A, et al. Diabetologia 2002; 45:S23S28.

Why?

The major limiting factor to achieving

intensive glycemic control for people with type 2 diabetes is Hypoglycaemia

Briscoe VJ, et al. Clin Diab 2006;24:115-121.

ADA guidelines recommend HbA1c levels <7% for all patients

Normal
Controlled T2DM Uncontrolled T2DM

HbA1c <6%

6.16.9%

7%

More stringent HbA1c goals may be suitable for selected patients with early stage disease, if this can be achieved without significant hypoglycaemia or other adverse effects Less stringent HbA1c goals may be appropriate for patients with a history of hypoglycaemia, CVD or late-stage disease
CVD=cardiovascular; HbA1c=haemoglobin A1c; T2DM=type 2 diabetes mellitus. American Diabetes Association. Diabetes Care. 2011; 34 (Suppl 1): S4S10.

Initiate or change treatment whenever HbA1c levels are 7%

ADA-EASD Position Statement 2012 : Management of Hyperglycemia in T2DM

Glycemic targets - HbA1c < 7.0%
mmol/l])
(mean PG 150-160 mg/dl [8.3-8.9

- Pre-prandial PG <130 mg/dl (7.2 mmol/l) - Post-prandial PG <180 mg/dl (10.0 mmol/l)

- Individualization is key:
Tighter targets (6.0 - 6.5%) - younger, healthier Looser targets (7.5 - 8.0% ) - older, co-morbidities, hypoglycemia prone, etc. - Avoidance of hypoglycemia
Diabetes Care, Diabetologia. 19 April 2012

It is time to say...

Our goal is early control of hyperglycemia to prevent the short and long-term complications of diabetes with low risk of hypoglycemia

Tips to get control

Lifestyle should be used in all patients but only as part of the treatment Start aggressively and back off Assume each medication will improve HbA1c 1% Never substitute meds Always add new agent first Titrate to get control Then stop first agent Ask the patient what they want Shots may be better than more pills Develop a plan that prevents hypoglycemia

ADA Summary of Recommendations for Adults with Diabetes

Goals
Glycemic control: A1C* < 7%

Preprandial BG
Peak postprandial BG Blood Pressure: Lipids: LDL Triglycerides HDL
ADA. Diabetes Care, 2010.

90 130 mg/dl
<180 mg/dl < 130/80 mm Hg < 100 mg/dl <150 mg/dl > 40 mg/dl

Screening For Diabetes

Screening For Diabetes

A1C or FPG or 75 g oral GTT Testing should be considered in all adults who are overweight (BMI >25 kg/m2) And Have the following additional risk factors.

Risk Factors for Screening

Physical inactivity First-degree relative with diabetes High-risk race/ethnicity (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Women who delivered a baby weighing 9 lb or were diagnosed with GDM

Diabetes Care 34:Supplement 1, 2011

Risk Factors for Screening

(contd)

Hypertension (140/90 mmHg or on therapy for hypertension) HDL <35 mg/dl and/or a triglycerides >250mg/dl Women with polycystic ovarian syndrome (PCOS) A1C >5.7%, IGT, or IFG on previous testing Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) History of CVD
Diabetes Care 34:Supplement 1, 2011

Risk Factors for Screening

In the absence of the previous criteria, testing begins at age 45 Normal results, repeat at least at 3-year intervals Consider more frequent testing depending on results and risk status

Diabetes Care 34:Supplement 1, 2011

A C
E A E
Robard HW, et al. Endocr Pract. 2009; 15: 540559.

23

AACE / ACE Diabetes Algorithm for Glycemic Control: HbA1c Goal <6.5%*
Lifestyle modification
HbA1c 6.57.5%**
Monotherapy MET TZD DPP-4 AGI Dual therapy MET + GLP-1 or DPP-4 or TZD Glinide or SU

HbA1c 7.69.0%

HbA1c >9.0%

Dual therapy MET TZD MET + + + GLP-1 or DPP-4 TZD Glinide or SU GLP-1 or DPP-4 Colesevelam AGI

Drug-naive

Under treatment

Symptoms No symptoms Triple therapy GLP-1 + TZD or DPP-4 MET + GLP-1 or DPP-4 + SU TZD Insulin + other agent(s) GLP-1 + SU or DPP-4 MET + TZD + TZD GLP-1 or DPP-4
*May not be appropriate for all patients; **For patients with diabetes and HbA1c <6.5%, pharmacologic Rx may be considered.

Triple therapy MET + GLP-1 + or DPP-4 TZD Glinide or SU

Insulin + other agent(s)

Insulin + other agent(s)

Insulin + other agent(s)

Robard HW, et al. E Statement by an American Association of Clinical Endocrinologists / American College of Endocrinology Consensus Pane l on Type 2 Diabetes Mellitus: An Algorithm for Glycemic Control , ndocr Pract. 2009; 15: 540559.

NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE

25

NICE Guidelines for the Management of Type 2 Diabetes

Step 2 Step 1
Lifestyle intervention

If HbA1c target not reached*

Metformin** (mainly overweight / obese patients)

OR

SU if not overweight, metformin not tolerated, or rapid response required

Step 3

If HbA1c target not reached*

Metformin + SU (or glinides)

OR

Metformin + DPP-4 inhibitor or TZD***

If HbA1c target not reached*

If HbA1c target not reached*

SU + DPP-4 inhibitor or TZD

If HbA1c target not reached*

Step 4

Metformin + SU + insulin

OR

Metformin + SU If HbA1c + sitagliptin or # target not metformin + SU + TZD or metformin + reached* SU + exenatide## Increase insulin dose and intensify regimen over time. Consider pioglitazone

If HbA1c target not reached*

Start insulin

*Avoid aggressive targets (6.5%) and individually agree target with patient; **With active dose titration; ***If at significant risk of hypoglycemia or its consequences, or if SU not tolerated / contraindicated; #If insulin is unacceptable (eg personal reasons or obesity); ##If weight is an issue. NICE, Clinical Guideline 87, 2009.

Canadian Diabetes Association Algorithm

27

Clinical assessment Lifestyle intervention (initiation of nutrition therapy and physical activity) A1C < 9% A1C 9% Symptomatic hyperglycemia with metabolic decompensation

Initiate metformin

Initiating pharmacotherapy immediately without waiting effect from lifestyle intervention Consider initiating metformin with another agent from different class or initiate insulin If not at target

Initiate insulin metformin

Add on agent best suited to the individual based on the advantage/disadvantage listed below
Class Alpha glucosidase inhibitors A1C

Hypoglycemia
Rare

Other advantage
Improved postprandial control, weight neutral

Other disadvantage
GI side effects

Incretin DPP4 inhibitors

Insulin Insulin secretogogus Meglitinides Sulhonylurea

to

Rare
Yes Yes* Yes

Improved postprandial control, weight neutral

No dose ceiling, flexible regimens, many types Improved postprandial control Newer sulphonylurea (gliclazide & glimeperide) are associated with less hypoglycemia than glyburide

New agent (unknown long term safety)

Weight gain

to

Requires Tid or QiD Weight gain

TZD
Weight loss agent

Rare
none

Durable monotherapy
Weight loss

Weight gain, requires 6-12 weeks to

Increased heart rate/BP GI side effects

if not at target
DPP4: Dipeptidyl peptidase-4 TZD: Thiazolidnedione GI: gastrointestinal CHF: congestive heart failure BP: blood pressure A1C:glycated hemoglobin

Add another drug from a different class Add bedtime basal insulin to another agent Or intensify insulin regimen

*less hypoglycemia in the context of missed meals : <1% decrease in HBA1C :1%-2% decrease in HBA1C : >2% decrease in HBA1C

28

I
D F

29

Prevention of Diabetes
Key Messages
As safe and effective preventive therapies for type 1 diabetes have not yet been identified, any attempts to prevent type 1 diabetes should be undertaken only within the confines of formal research protocols. Intensive and structured lifestyle modification that results in loss of approximately 5% of initial body weight can reduce the risk of progression from impaired glucose tolerance to type 2 diabetes by almost 60%. Progression from prediabetes to type 2 diabetes can also be reduced by pharmacologic therapy with metformin (~30% reduction), acarbose (~30% reduction) and thiazolidinedione (~60% reduction).

Recommendations: Medical Nutrition Therapy (MNT)

Individuals who have prediabetes or diabetes should receive individualized MNT as needed to achieve treatment goals (A)
For people with diabetes, it is unlikely one optimal mix of macronutrients for meal plans exists The best mix of carbohydrate, protein, and fat appears to vary depending on individual circumstances

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S22.

Recommendations: Physical Activity

Advise people with diabetes to perform at least 150 min/week of moderate-intensity aerobic physical activity (50-70% of maximum heart rate) (A) In absence of contraindications, people with type 2 diabetes should be encouraged to perform resistance training three times per week (A)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S24.

Recommendations: Hypoglycemia
Glucose (15-20 g) is preferred treatment for conscious individual with hypoglycemia (E) Glucagon should be prescribed for all individuals at significant risk of severe hypoglycemia, and caregivers/family members instructed in administration (E) Those with hypoglycemia unawareness or one or more episodes of severe hypoglycemia should raise glycemic targets to reduce risk of future episodes (B)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S25.

Recommendations: Bariatric Surgery

Consider bariatric surgery for adults with BMI >35 kg/m2 and type 2 diabetes (B) After surgery, life-long lifestyle support and medical monitoring is necessary (E) Insufficient evidence to recommend surgery in patients with BMI <35 kg/m2 outside of a research protocol (E) Well-designed, randomized controlled trials comparing optimal medical/lifestyle therapy needed to determine long-term benefits, costeffectiveness, risks (E)
ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S26.

Recommendations: Immunization
Provide an influenza vaccine annually to all diabetic patients 6 months of age (C) Administer pneumococcal polysaccharide vaccine to all diabetic patients 2 years One-time revaccination recommended for those >64 years previously immunized at <65 years if administered >5 years ago Other indications for repeat vaccination: nephrotic syndrome, chronic renal disease, immunocompromised states (C)

ADA. V. Diabetes Care. Diabetes Care 2011;34(suppl 1):S27.

Male patient 78 years old , diabetic for 5 years uncontrolled , hypertensive with IHD. Our Hb A1c goal is 1. 2. 3. 4. 6.5% 6.5 - 7% 7 7.5% 7.5 - 8%

Female patient 45 years old , BMI 33 kg/m2 ,with sedentary life newly discovered diabetes . FBS is 350mg/dl , PPS 460 mg/dl , HbA1c 10% .Our ideal treatment will be :

1. 2. 3. 4. 5. 6. 7. 8. 9.

Life style modification LSM LSM & Metformin Insulin therapy only Insulin therapy & SU Insulin therapy & Metformin Insulin therapy & DPP4Is Metformin & TDZs Metformin & DPP4Is Metformin & GLP1

Q&A