Assessment and Management

of Patients with Diabetes:

What You Should Know.
By

Dr: Abd El Hameed Fureeh

MD, Lecturer of Internal Medicine, Mansoura faculty of Medicine

Diabetes and endocrinology unit

 TODAYS MISSION
DEFINITION
PREVALENCE
CLASSIFICATION
PATHOGENESIS
DIAGNOSIS/SCREENING
INITIAL EVALUATION
MEDICAL MANAGEMENT
OTHER MANAGEMENT
TOP SIX
 Diabetes: a definition
It is a clinical syndrome Characterized by :
–Chronic persistent hyperglycemia.
–Disturbed metabolism of Ptn , Fat &
Electrolyte .
–Microangiopathy esp. in Retina,
Glomeruli, & vasa nervosa.
It is caused by : absolute or relative lack of
insulin
 Prevalence of diabetes
Diabetes

– 7.5% of population aged 25 years and over

– 17.9% 64-75 years
– 23.0% 75 years+

IFG or IGT 16.4%

AusDiab Study (Dunstan et al, 2002)

Global Epidemic of Type 2 Diabetes

Aging Population
Global Lifestyle “Westernization”
Surging Obesity
 Types of diabetes mellitus
Type 1: caused by insulin deficiency
Type 2: caused by relative lack of insulin and
insulin resistance
Gestational Diabetes Mellitus (GDM)
Other specific types
N.B. Pre-diabetes include (IGT,IFG)
– (IGT, Impaired Fasting Glucose) high risk of
developing diabetes
Pathogenesis of type 1 diabetes

Pathogenesis of Type IDM

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 Pthogenesis of type 2 Diabetes

Pathogenesisof Type 2 DM
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 Major Pathophysiologic Defects in Type 2 Diabetes1,2
Islet-cell dysfunction
Glucagon
(alpha cell)

Pancreas

Insulin Insulin
(beta cell) resistance
Hepatic
glucose
output Glucose uptake
Hyperglycemia
Muscle
Liver
Adipose
tissue

Insulin resistance. Beta cell dysfunction.

 Assessment
Is the patient diabetic or not ?
Which type ?
Complicated or not ?
Management ?
Monitoring ?
 Initial Evaluation

Medical History
Physical Exam
Acute and chronic complications e.g.
-DKA, hypoglycemic frequency…
Microvascular-retinopathy, nephropathy,
neuropathy.
Macrovascular- CHD,PAD, cerebrovascular
disease
 Clinical Manifestations
Polyuria
Polydipsia
Polyphagia
Fatigue, tingling or
numbness in hands,
slow healing
wounds and
recurrent infections
 Physical Exam
Height,weight,BMI
Blood pressure
Fundoscopic exam
Skin-acanthosis nigricans
Foot exam-inspection, pulses, reflexes,
sensory
 Diagnosis of Diabetes
NORMAL Prediabetes DIABETES
FASTING < 100 mg% 100-125 >= 126 mg%
(5.6 mM) (IFG) (7 mM)

2hpp <140 mg% 140-199 >=200 mg%

(7.8 mM) (IGT) (11.1 mM)

Random < 200 mg/dl >=200 mg%

+ polys

Diabetes Care 2004, 27: S5-S10

 Gestational Diabetes (>=2 high)
100-g or 75-g Glucose
mg/dl mmol/l
100-g Glucose
Fasting 95 5.3
1-h 180 10
2-h 155 8.6
3-h 140 7.8
75-g Glucose
Fasting 95 5.3
1-h 180 10
2-h 155 8.6
 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?
 Common characteristics of type 1
and 2
Type 1 (10-15%) Type 2 (85-90%)
Age of onset Usually <30 (can occur in Usually >30 (but
elderly) increasing at younger age

Body weight Lean Usually obese

Prone to ketoacidosis Yes No
symptoms Severe, including coma May be no symptoms

Onset of symptoms Acute Gradual (may be

asymptomatic)
Risk Factors Genetic Family history
Viral/Environmental Obesity/↓ activity
Cultural background
 Type 1DM Type 2 DM
Genetic locus Chromosome 6 - Chromosome
recessive HALA 11
DR3, DR4,B8,B15
Insulin Low or absent - Abnormal
- insulin
resistance
C-peptide deficient increased

Auto Ab ICA, ICSA, Anti- Absent

GAD
Treatment Insulin is a must -Diet - OHD ±
insulin
 Acute Complications of
Diabetes
 Hypoglycemia
 DKA
 HHNS
 Infection
 Acute complication related to systems
 Chronic Complications

Macrovascular Complications

Microvascular Complications

Neuropathic Complications

Mixed
 Risk Factors for and
Complications of Diabetes
Overweight Retinopathy
and Obesity

Neuropathy

Genetics/
Family history

Nephropathy

High blood
pressure Cardiovascular
Disease

Gestational
Diabetes Amputations
 Management
Medical Nutritional therapy
Exercise
Monitoring
Pharmacologic
Education
Treatment goals for diabetes
Symptom free
Prevent short term
complications
Prevent long term
complications
Quality of life =Lifestyle focus
 Healthy Eating
Consistent, well-balanced
small meals several times
per day

Regular carbohydrate
High in fibre
Low in fat (particularly
saturated fat)
Low in added sugar
Adequate energy
/protein/fluids/vits and
mins
 Dietary Management
Carbohydrate 45-65% total daily calories
Protein-15-20% total daily calories
Fats—less than 30% total calories,
saturated fats only 10% of total calories
Fiber—lowers cholesterol; soluble—
legumes, oats, fruits Insoluble—whole
grain breads, cereals and some
vegetables. Both increase satiety. Slowing
absorption time seems to lower glycemic
index.
 Exercise/Activity

Increased insulin sensitivity

Decreased insulin requirements
Weight reduction
Lipid control
Blood pressure control
 Exercise and Diabetes
Exercise increases uptake of glucose by
muscles and improves utilization, alters
lipid levels, increases HDL and decreases
TG and TC
If on insulin, eat 15g snack before
beginning
Check BS before, during and after
exercising if the exercise is prolonged
 Exercise and Diabetes
Avoid trauma to the feet
Avoid pounding activities that could cause
vitreous hemorrhage
Caution if CAD
Baseline stress test may be indicated
(especially in those older than 30 and with
2 or more risk factors for CAD)
Pharmacological treatment
 Major Classes of OAD
Medications
1. Drugs that sensitize
the body to insulin Thiazolidinediones
and/or control hepatic Biguanides
glucose production

2. Drugs that stimulate the

Sulfonylureas
pancreas to make more
insulin Meglitinides

3. Drugs that slow the

absorption of starches Alpha-glucosidase
inhibitors
 Newer classes
Incretin mimetics are glucagon-like
peptide-1 (GLP-1) agonists e.g. exenatide
Dipeptidyl peptidase IV inhibitors that
include sitagliptin and vildagliptin
Other drugs are currently in clinical trials.
INSULIN SENSITIZING
AGENTS

METFORMIN
THIAZOLIDINEDIONES
 Metformin
Decreases hepatic glucose production
Improves insulin sensitivity in periphery
Decreases intestinal absorption of glucose
Medications in this Class: metformin
(Glucophage), metformin hydrochloride
extended release (Glucophage XR)
 Metformin
Advantages Disadvantages
– Considerable A1c – Gastrointestinal
reduction adverse effects
– Used in combination – Avoid in heart failure,
with orals and insulin renal and hepatic
– Available as extended insufficiency
release tablet and – Risk for lactic acidosis
liquid formulation
– Inexpensive
 Thiazolidinediones (TZDs)
Insulin sensitizer (improves target cell response
to insulin through increase adiopnectin level)
Does not increase pancreatic insulin secretion
Available products: rosiglitazone, pioglitazone
Dose - 4 to 8mg /24 hrs Rosiglitazone
15 to 45mg/24 hrs Pioglitazone
 MECHANISM OF ACTION OF TZDs

Improved β -cell Decreased Lipolysis

Function
+
+
E TIOL GYO FT2D M
Impai Incre redIns asedL ulin ipolys s
Se cretion

Hype rglyce mia

In HGP De Upta creasd creasd ke Glucose
DEFN75-3/ 9

+ +
TDZs

Decreased Increased Glucose

HGP Uptake
75-3/99
Use of TZDs in Patients With Diabetes
and Symptomatic Heart Disease
(ADA/AHA)
In patients with class I or II NYHA CHF
categories, TZDs may be used cautiously, with
initiation of treatment at the lower dosage of
each drug.

In patients with symptoms and signs of NYHA

class III or IV CHF, TZDs should not be used at
this time.

Circulation 9:108:2941-8, 2004.

 A Class Effect?

What about pioglitazone?

No toxicity CV AE’s seen in clinical trials
More favorable effects on lipids
 Sulfonylureas
Oldest of oral meds
Until 1995 the only meds available
1st gen- Orinase,Tolinase,Diabinese
2nd gen-Glucotrol(glipizide), Micronase
or Diabeta(glyburide)
3rd gen- Amaryl(glimeperide)
Stimulate the pancreas to release more
insulin, hypoglycemia can be side effect
 Meglitinides
Prandin(repaglinide)
Starlix(nateglitinide)
Stimulate insulin secretion when there is
glucose present in the blood stream
Used with meals
Alpha-Glucosidase Inhibitors
Disadvantages
Advantages
– Gastrointestinal
– Reduces postprandial
adverse effects
glucose
– Dosed with first bite of
each meal
– Pure glucose must be
used to treat
hypoglycemia
– Drug Interactions
– Expensive
 DPP-4 Inhibitor
Inhibits the dipeptidyl-peptidase 4 enzyme
Enhances the incretin hormones
-GLP-1 (Glucagon-like peptide 1)
-GIP (glucose-dependent insulinotropic
polypeptide)
 DPP-4 Inhibitor
Available product: Januvia (Sitagliptin)
Once daily dosing
Indicated for use with metformin or thiazolidinedione
Dosing adjustment for renal impairment
Adverse effects: HA, Diarrhea, upper respiratory
infection
Expensive
They look to be at least weight neutral.
 Exenatide (Byetta)
Advantages Disadvantages
– Indicated for use with – Twice daily injection
sulfonylureas, given within 60
metformin, minutes of food
thiazolidinediones – Short half-life
– Prefilled, disposable – Gastrointestinal
pen (5 mcg, 10 mcg) adverse effects
– Additional A1c – Expensive
reduction: 0.5-1% – Not for use in Type 1
– Weight loss patients
Mixed Oral antidiabetic drugs
Metformin + glyburide (glucovance)
Metformin + Glymepride (amaryl M)
Rosiglitazone + Metformin
(Avandmet)
Rosiglitazone + glymepride
(avandaryl)
 Pramlintide
Amylin analog (co-secreted with insulin
from beta cells)
Prolongs gastric emptying time
Reduces postprandial glucagon secretion
Reduces food intake (centrally-mediated
appetite suppression
Available product: Symlin
 Pramlintide
Advantages: Disadvantages:
– Use in Type 1 and Type 2 – Multiple injections
diabetes – Small dosing in insulin
– Improves postprandial syringe
glucose – Gastrointestinal adverse
effects
– Hypoglycemia
– Drug Interactions
– Expensive
– Cannot be mixed with
insulin in same syringe
 Insulin
Each type different onset, peak, and duration
Rapid Acting:Novolog(aspart)
Apidra(glulisine)
Humalog(lispro)
Onset-15 min
Peak- 30-90 min
Duration- 3-5 hrs
Take at the beginning of meals
 Insulin
Short acting
Humulin R and Novolin R (regular)
Onset- 30-60 min
Peak- 2-4 hrs
Duration- 5-8 hrs
Take 30 minutes before meals
 Insulin
Intermediate Acting
Humulin N and Novolin N (NPH)
Onset- 1-3 hrs
Peak- 8 hrs
Duration- 12-16 hrs
Usually twice a day
 Insulin
Long Acting
Levemir (detemir) and Lantus (glargine)
Also referred to as basal insulins
Onset- 1 hr
Peak- none
Duration- 20-26hrs
Usually once a day, may need bid as dose
increases
 Insulin
Premixed N and R
Humulin 70/30
Novolin 70/30
Humulin 50/50
Onset 30-60 min
Peak- variable
Duration- 10-16 hrs
Typically bid
 Insulin
Pre-mix lispro protamine
and lispro
Humalog Mix 75/25 and 50/50
Intermediate and rapid-acting
Onset- 15min
Peak- variable
Duration- 10-16 hrs
Typically bid
 Insulin
Pre-mix aspart protamine
and aspart
Novolog Mix 70/30
Intermediate and rapid-acting
Onset- 15min
Peak- variable
Duration- 10-16 hrs
 Sites of injections -
Subcutaneous
Thighs
Upper buttocks
Abdomen
Arms
Important to rotate the site
Rate of absorption may be significantly
different – faster from arm and abdomen
than from thigh and buttock
 Insulin Time Action Curves

140

120 Rapid (Lispro,Glulisine, Aspart)

100
Insulin Effect

Short (Regular)
80
Intermediate (NPH)
60

40
Long
20
(Detemir,Glargine)
0
0 2 4 6 8 10 12 14 16 18 20

Hours
adapted from R. Bergenstal, IDC
 Twice-Daily Split-Mixed
Regimens
Endogenous insulin
Regular
NPH
Hyperglycemia

Dawn
phenomenon

B L D HS B
with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New Y
Dekker Inc.; 2002:87
 Basal-Bolus Insulin Therapy: Detemir or Glargine
at HS and Mealtime Aspart, Lispro, or Glulisine
Insulin Effect

B L D HS

Insulin aspart , lispro, detemir or glargine

glulisine
Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York, NY:
Marcel Dekker Inc.; 2002:87
 Methods of Insulin Delivery
Pens
Jet injectors
Insulin pumps
Implantable devices
Transplantation of pancreatic cells
Novel insulin delivery methods

Dermal insulin
Intranasal insulin
Oral insulin
Insulin spray
Inhaled insulin
 Complications of Insulin
Therapy
Local allergic reactions
Systemic allergic reactions
Insulin lipodystrophy (lipoatrophy or
lipohypertrophy)
Insulin resistance
Morning hyperglycemia—Dawn phenomenon
(nocturnal surges of growth hormone) so give
dose at HS not before dinner
 Complications of Insulin
Therapy
Somogyi effect—nocturnal hypoglycemia
followed by rebound hyperglycemia-
decrease evening dose of insulin
To determine cause, test at HS, 3am and
upon awakening
EASD ADA Consensus

Metformin

Metformin

Metformin

Metformin
 Insulin Therapy in Type 2
Diabetes
Insulin therapy should be offered to people with type 2
diabetes inadequately controlled on optimised oral
therapies.
Insulin therapy can be used alone or in combination with
oral therapies.
Insulin is often started with a once daily dose of
intermediate-acting insulin, or long acting at night or in
the morning
nocturnal dose in combination with continued oral
medication is often a convenient way to initiate insulin.
A twice-daily or more intensive regime can also be
considered.
What else ?
 What are “The Big Six” of
Diabetes Management?
Glycemic Control
Hypertension
Hyperlipidemia
Nephropathy
Retinopathy
Foot Care
 Glycemic Control
A1C < 6% - normal.
A1C < 7% - goal.
A1C > 7% - additional therapy
Individualize: disease duration, pregnancy status, age,
co-morbid illness, hypoglycemia unawareness, patient
considerations
Pre-prandial glucose - 70-130 mg/dl
Post-prandial glucose - < 180 mg/dl
Target post-prandial glucose whenever A1C goals are
not met despite pre-prandial glucose levels < 130
HgA1C every 3 months unless at goal then
every 6 months
 Hypertension
Goal B/P < 130/80
Treat all patients > 130/80
MNT for 130-139/80-89 (max 3 months)
Drug treatment - > 140/90
ACEI/ARB’s are drugs of choice
Preferred secondary agents:
Thiazide diuretics if GFR > 50 ml/min
Loop diuretic if GFR < 50 ml/min
Beta-blockers may improve myocardial outcome
- do not mask hypoglycemia
Priorities of Lipid Management

First, lower LDL cholesterol.

Second, raise HDL cholesterol.
Third, lower Triglyceride levels.
Diabetes: the target
 Nephropathy
Incipient Nephropathy - characterized by
microalbuminuria.
Overt Nephropathy - characterized by clinical
albuminuria.
End Stage Renal Disease - characterized by a
declining GFR.
ANNUAL SCREENING REQUIRED
Microalbuminuria
Serum creatinine
 Retinopathy
21% of Type 2 diabetics have evidence of
retinopathy at time of diagnosis.
Treatment available by both Laser
Photocoagulation and Argon Laser
therapy - best treated by experienced
ophthalmologist.
Screen can be done by qualified
optometrist and/or ophthalmologist.
 Foot Care
Annual Foot Exam Looking for High-Risk
Conditions.
Foot Exams at Every Visit.
Professional Foot Care for Patients with
One or More Risk Factors.
Daily Foot Care for All Patients - Patient
Instruction on Nail and Skin Care
ABC OF DIABETIC MANAGEMENT

A – Hb A1c (Glycaemic Control)

B - Blood Pressure

C- Treating Cholesterol (dyslipidaemia)

 Sick day rules
 never stop insulin
 monitor more frequently
 maintain your hydration
 Check for ketones
 Know when & how to call for help
 Antiplatelet therapy
ASA-75-162mg/day secondary prevention w/ hx
of CVD
75-162mg/day primary prevention w/Type I and
II w/ CV risk, >40yo, hpt, smoking,
dyslipidemia, albuminuria or FHx CVD
Not recommended < 30 (no evidence to support)
Combo therapy Plavix(clopidrogel) and ASA in
pts with severe and progressive CVD
 Vaccinations
Flu shot annually
Pneumovax for all adults with diabetes
One time revaccination for ≥ 65 years of
age if previously vaccinated < 65 and
vaccine was administered > 5 yrs ago
Absolutely no evidence or
recommendation for more than 2 lifetime
vaccinations
 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
 Gestational Diabetes
Glucose intolerance during pregnancy
Placental hormones contributes to insulin
resistance
High risk: glycosuria, family history,
marked obesity
Native Americans, African Americans,
Hispanics and Pacific Islanders
 Gestational Diabetes
Women of average risk tested between
24-28 weeks of gestation
Goals for glucose levels during pregnancy
are 105 or less before meals; 130 or less
after meals
Will have greater risk of developing Type 2
DM later in life if weight not controlled
Now You Know…