Diabetes Mellitus

Anatomy and Physiology; Pancreas

LOCATION:

retroperitoneum, tranversely across the posterior abdominal wall

BLOOD SUPPLY:

superior pancreaticoduodenal artery from gastroduodenal (hepatic-celiac)

inferior pancreaticoduodenal from SMA

pancreatic arteries from splenic

Blood supply of pancreas

DRAINAGE:

Pancreatic veins and tributaries of splenic and superior mesenteric vein - >
splenic vein

NERVE SUPPLY:

parasympathetic nerve fibers

from the posterior vagal trunk via its celiac branch.

Sympathetic supply

T6-T10 via the thoracic splanchnic nerves and the celiac plexus

Functions:

Exocrine

The exocrine gland secretes digestive enzymes.

Endocrine

The endocrine gland, which consists of the islets of Langerhans, secretes

hormones into the bloodstream.

Endocrine Pancreas; Islets of Langerhans

Beta cell (60%)

Secrete INSULIN and AMYLIN

Alpha cell (25%)

Secretes GLUCAGON

Diabetes Mellitus
Delta cell (10%)

Secretes SOMATOSTATIN

F cell/ PP cell (5%)

Secretes PANCREATIC POLYPEPTIDE

INSULIN

Composition: and chains joined by disulfide bond

Main determinant of secretion: Blood Glucose

Half life: 6 minutes

Degradation: Insulinase (liver)

INSULIN; ACTION

INCREASES:

Glucose uptake into the cell

Glycogenesis

Amino acid uptake into the cell

Lipogenesis and fat deposition

Potassium uptake into the cell

DECREASES:

GLUCONEOGENESIS

GLYCOGENOLYSIS

LIPOLYSIS

Diabetes Mellitus
-

a group of common metabolic disorders that share the phenotype of

hyperglycemia.

Pathophysiology

Diabetes Mellitus
TYPE 1 DM

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TYPE 2 DM

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Diabetes Mellitus

Type 2 DM results from the ominous octet (shown in figure above) which in the
end leads to hyperglycemia. The succeeding development of the signs and symptoms are
similar to that of type 1 DM with the exception of development of ketosis.

DM COMPLICATIONS:

Cardiovascular disease. Diabetes dramatically increases the risk of various

cardiovascular problems, including coronary artery disease with chest pain (angina),
heart attack, stroke and narrowing of arteries (atherosclerosis). If you have diabetes,
you are more likely to have heart disease or stroke.

Nerve damage (neuropathy). Excess sugar can injure the walls of the tiny blood
vessels (capillaries) that nourish your nerves, especially in your legs. This can cause
tingling, numbness, burning or pain that usually begins at the tips of the toes or
fingers and gradually spreads upward. Left untreated, you could lose all sense of
feeling in the affected limbs. Damage to the nerves related to digestion can cause
problems with nausea, vomiting, diarrhea or constipation. For men, it may lead to
erectile dysfunction.

Diabetes Mellitus

Kidney damage (nephropathy). The kidneys contain millions of tiny blood

vessel clusters (glomeruli) that filter waste from your blood. Diabetes can damage
this delicate filtering system. Severe damage can lead to kidney failure or irreversible
end-stage kidney disease, which may require dialysis or a kidney transplant.

Eye damage (retinopathy). Diabetes can damage the blood vessels of the retina
(diabetic retinopathy), potentially leading to blindness. Diabetes also increases the
risk of other serious vision conditions, such as cataracts and glaucoma.

Foot damage. Nerve damage in the feet or poor blood flow to the feet increases
the risk of various foot complications. Left untreated, cuts and blisters can develop
serious infections, which often heal poorly. These infections may ultimately require
toe, foot or leg amputation.

Skin conditions. Diabetes may leave you more susceptible to skin problems,
including bacterial and fungal infections.

Hearing impairment. Hearing problems are more common in people with

diabetes.

Alzheimer's disease. Type 2 diabetes may increase the risk of Alzheimer's

disease. The poorer your blood sugar control, the greater the risk appears to be.
Although there are theories as to how these disorders might be connected, none has
yet been proved.

Diabetes Mellitus
Image source: Harrison's Principles of Internal Medicine 18th edition p.5865

Classification:

Type 1 diabetes mellitus

o
(formerly insulin dependent diabetes mellitus or Juvenile diabetes
mellitus)
o results from auto-immune beta-cell destruction, leading to absolute insulin
deficiency.
o Typically but not exclusively in children.

Type 2 diabetes mellitus

o (formerly non-insulin dependent diabetes mellitus or adult-onset DM)
o results from a progressive insulin secretory defect on the background of
insulin resistance

Gestational diabetes mellitus (GDM)

o diabetes first diagnosed during pregnancy.

Secondary diabetes
o genetic defects in beta cell function or insulin action
o diabetes of the exocrine pancreas (pancreatitis, cystic fibrosis)
o drug- or chemical-induced diabetes (such as from the treatment of AIDS,
after organ transplantation, glucocorticoids)
o other endocrine diseases (Cushings syndrome, hyperthyroidism)

DM Type 1 vs. DM Type 2

Diabetes Mellitus

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Signs and Symptoms:

polydipsia
polyuria
weight loss
polyphagia
weakness and fatigue
dry and itchy skin
dry mouth
poor wound healing

SCREENING AND
INDIVIDUALS

TESTING

FOR

DIABETES

ASYMPTOMATIC

All individuals being seen at any physicians clinic or by any healthcare provider

should be evaluated annually for risk factors for type 2 diabetes and pre-diabetes.
Universal screening using laboratory tests is not recommended as it would
identify very few individuals who are at risk.

IN

Diabetes Mellitus
Laboratory Screening is recommended for patients with:

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LABORATORY TESTS TO
CONSULTATION:

BE REQUESTED DURING THE INITIAL

Minimal Tests:
The following tests are suggested to be done routinely for all individuals being seen for
the first time for evaluation of diabetes.

Fasting blood glucose and lipid profile, including total,

LDL and HDL cholesterol and triglycerides
HbA1C
Liver enzyme/transaminase tests (AST/ALT)

Optional Tests:
The following additional tests may be requested as indicated

Electrocardiogram (Resting) and Treadmill Exercise

Thyroid-stimulating hormone in type 1 diabetes, dyslipidemia, or women over age
50 y

A 75-gram OGTT is preferred as the first test in the following individuals who have:
A previous FBS showing Impaired Fasting Glucose (100 to 125 mg/dL or 5.6 to
6.9 mmol/L)

Diabetes Mellitus
Previous diagnosis of Cardiovascular Disease (Coronary Artery Disease, Stroke,
Peripheral Arteriovascular Disease) or who are at high risk for cardiovascular
disease.
A diagnosis of Metabolic Syndrome

NORMAL BLOOD IS SUGAR IS DEFINED AS:

An FBS <5.6 mmol/L (100 mg/dL), or

Random/casual blood glucose <7.7 (140 mg/dL), or
2-hr blood sugar in the 75-gm OGTT <7.7 (140 mg/dL)

DIAGNOSIS OF PRE-DIABETES

The criteria for pre-diabetes is:

Impaired Fasting Glucose
FBS of 5.6 mmol/L (100 mg/dL) up to 125 mg/dL or 6.9 mmol/L

Impaired Glucose Tolerance

defined as Random/casual blood glucose of 7.7 up to 11.0 mmol/L (140-199
mg/dL) OR 2-hr blood sugar in the 75-gm OGTT equal to 7.7 (140 mg/dL) up to
11.0 mmol/L (199 mg/dL)

DIAGNOSIS OF DIABETES

Diabetes Mellitus criteria for diagnosis:

Plasma glucose >126 mg/dL (7.0 mmol/L) after an overnight fast

o Fasting is defined as no caloric intake for at least 8 or hours up to a
maximum of 14 hours, OR

Two-hour plasma glucose >200 mg/dl (11.1 mmol/l) during an Oral Glucose
Tolerance Test
o The test should be performed as described by the World Health
Organization, using a glucose load containing the equivalent of 75 g

Diabetes Mellitus
anhydrous glucose dissolved in water after an overnight fast of between 8
and 14 hours, OR

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

o in a patient with classic symptoms of hyperglycemia (weight loss,
polyuria, polyphagia, polydipsia) or with signs and symptoms of
hyperglycaemic crisis.

Among ASYMPTOMATIC individuals with positive results, any of the three tests
should be REPEATED within two weeks for confirmation.

Screening for possible type 1 DM patients is not recommended due to the

following reasons:
Low prevalence
Not cost effective
Interventions to prevent Type 1 DM have not been proven effective

Screening for pre-diabetes and Type 2 DM is recommended among asymptomatic

children commencing at age 10 years or at onset of puberty, if puberty occurs at a
younger age (ADA) with the following risk factors:
Overweight (BMI >85th percentile for age and sex, weight-for-height

>85th percentile, or weight >120% of ideal for height) OR

Obese: BMI >95th centile or > +2SD
Plus any 2 of the following risk factors
Family history (especially parents and grandparents) of Type 2 DM
Signs of insulin resistance (Acanthosis nigricans, hypertension,
dyslipidemia, PCOS, or small for gestational age birth weight)
Maternal history of diabetes or GDM during the childs gestation

APPROACH TO PATIENTS WITH DIABETES:

The initial evaluation of the diabetic patient should include a comprehensive

medical history and physical examination.

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Diabetes Mellitus

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COMPREHENSIVE INITIAL EVALUATION:

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Diabetes Mellitus

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Cardiovascular Risk Assessment

Determining the coronary heart disease risk factors (history, BP, BMI, WC) on
initial consultation or follow up helps determine the patient's risk for further

complications and thus, appropriate steps could be done to address these risks.
The initial and ongoing assessment of people with diabetes should include weight
and height measurements and calculation of the BMI (kg/m2 ), and waist
circumference (WC) to assess the degree of abdominal fat.

Image

source:

Diabetes-

United-for-Diabetes

Philhttp://spectrum.diabetesjournals.org/content/21/3/160.full

Foot Evaluation

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Diabetes Mellitus
A diabetic's risk for developing a foot ulcer may be as high as 25%.3. Identify risk
factors for developing foot complications from the history or PE focusing on previous
foot ulceration, neuropathy (loss of protective sensation), foot deformity, & vascular
disease.
4 Risk factors for diabetic foot disease include:

Peripheral vascular disease(PVD)

Peripheral neuropathy
Previous amputation
Previous ulceration, Presence of callus, Joint deformity

Visual/mobility problems
Risk factors for PVD are
Smoking
Hypertension
hypercholesterolemia.

Eye Examination
T2DM has an insidious onset and some patients may already have retinopathy at
the time of diagnosis.5
It is suggested to have a comprehensive evaluation for retinopathy by an
ophthalmologist upon diagnosing diabetes.

MANAGEMENT:

Lifestyle therapy alone can be given for 3 months for those with pre-hypertension
with SBP 130-139 mm Hg or DBP 80-89 mm Hg.
Pharmacologic therapy + lifestyle therapy should be started for those with
hypertension defined SBP 140 mm Hg or DBP 90 mm Hg, or pre-hypertension
uncontrolled by lifestyle therapy alone.
NON-PHARMACOLOGIC THERAPY
o Therapeutic lifestyle change
Exercise and weight loss promotion
- aerobic physical activity at least 150 min per week, of
moderate to vigorous intensity, spread out 3 days over the

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Diabetes Mellitus
week with no more than 2 consecutive days between bouts
of activity. 10.1.2 Moderate to vigorous resistant.
Smoking cessation
Alcohol abstinence
Daily foot care
o Nutritional therapy

DM diet (TANHAUSSER METHOD)

1. Compute for the IBW

a. IBW = (HT- 100) - [(HT- 100) x 0.1]
2. COMPUTE FOR TEA
a. TEA = IBW x Activity
BED REST

27.5 kcal/day

SEDENTARY

30 kcal/day

LIGHT ACTIVITY

35 kcal/day

MODERATE ACTIVITY

40 kcal/day

VERY ACTIVE

45 kcal/day

3. DISTRIBUTION OF TEA
a. CHO = 55-70% or 65%
b. CHON = 10-20% or 15%
c. FAT = 20-30% or 20%

The Asian-Pacific Type 2 Diabetes Policy Group has outlined the following simple
reminders:

EAT MOST
o Use one or more of these foods as the basis of every meal
o Vegetables, legumes, lentils, noodles, rice, bread, grains, barley,
wholegrain cereals, fresh fruit (non-sweet)
o Note that many sauces and preservatives that are added to these foods are
high in salt, sugar or fat, and should be avoided.
EAT MODERATELY

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Diabetes Mellitus
o Have small servings of protein-rich foods e.g., fish, seafood, eggs, lean
meat, skinless chicken, low-fat cheese, low-fat yoghurt, low-fat milk, nuts
EAT LEAST
o Minimise fats, sugars, salt and alcohol e.g., butter, oil, cream, coconut
milk and cream, processed meat, fried foods, preserved or processed
foods, pastries, sweets, biscuits, soft drink
The Asian-Pacific Type 2 Diabetes Policy Group11 recommends the following
macronutrient proportions (of total energy intake) :
Fat: no more than 30% (saturated fat <10%)
Carbohydrate: 50-55% (sucrose <10%)
Protein: 15-20%
IDAHO PLATE METHOD

Ima
ge

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PHARMACOLOGIC THERAPY

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Diabetes Mellitus

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Among the newly diagnosed diabetics, classify the level of severity of the diabetes
according to the glycemic levels, presence of symptoms and complications

Those who are asymptomatic with relatively lower levels of blood sugar (HbAc
<8.0%, FBS <140, RBS <200 mg/dL) should be advised to undertake MNT,
physical activity and exercise and weight reduction, with an option of starting
pharmacologic therapy (metformin).
If glycemic targets are not reached within 3 months, then
pharmacologic treatment will be started.
Those who have higher blood sugars, or who are symptomatic
should be started right away on one or more pharmacologic agents
as applicable since diet and lifestyle changes are unlikely to
achieve the target values.

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Diabetes Mellitus

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The following patients must ideally be referred to internists or diabetes specialists

(endocrinologists or diabetologists):
1. individuals with Type 1 diabetes
2. patients who have moderate to severe hyperglycemia
3. who have co-morbid conditions e.g., infections, acute cardiovascular events such
as congestive heart failure or acute myocardial infarction
4. significant hepatic and renal impairment
5. women with diabetes who are pregnant
MANAGEMENT OF DIABETES
I.

INSULIN THERAPY

Common side effects:

Hypoglycemia
Weight gain

3 MAJOR COMPONENTS OF EXOGENOUS INSULIN THERAPY

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Diabetes Mellitus
BASAL
INSULIN

BOLUS
INSULIN

CORRECT
IONAL
INSULIN

Required to regulate metabolic processes even in the

absence of meals
Usual :basal insulin: given as intermediate or long-acting
insulin
Intermediate-acting insulin usually given in portions of 2/3
in am and 1/3 in pm

Required to cover glycemic excursions following a meal

Usual bolus insulin: given as short or rapid-acting insulin

Rapid-acting insulin given within 15-20 min or immediately

before meals

Short-acting insulin given within 30-45 in before meals

Supplemental doses of short or rapid-acting insulin given to

correct elevations in blood glucose that occurs despite the use of
basal or bolus insulin.

INITIATION OF INSULIN THERAPY IN T1DM

Calculate total insulin reqirement; usually 0.5-1 unit/ kg/ day
50% of computed value given as a basal insulin

INITIATION OF INSULIN THERAPY IN T2DM

Calculate dose at 0.2 units/kg/day for insulin-nave

patients

Initiated if unable to achieve target a1c with basal insulin

alone

Start with 4 units before each meal or valculate each dose at

0.1 units/kg

BASAL-

Calculate units at 0.3-0.5 units/kg/day

BOLUS

50% of dose given as basal insulin

INSULIN

Nph: 2/3 pre-breakfast, 1/3 pre-dinner

Glargine or detemir: given at bedtime

50% of dose given as bolus insulin in equal divided doses

pre-meals

BASAL
INSULIN
BOLUS
INSULIN

Insulin types

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Diabetes Mellitus

II.

COMMON HYPOGLYCEMIC AGENTS

Type of drug

Insulin

Subtypes

Sulfonylureas

Examples

Gliclizide
Glibenclamid

secretagogues

Gen. mech of Common side

action

effects

Increase

Hypoglycemia
Weight gain

insulin
e
Glipizide
Glimepiride

secretion

Metformin

Decrease

Nonsulfunylure
Insulin
sensitizer

Biguanides

hepatic
glucose
production
Improves
peripheral
glucose
utilization

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Weight loss
Lactic acidosis

Diabetes Mellitus

Thiazolidines

Rosiglitazone
Pioglitazone

Decrease
insulin

Edema
Weight gain
Osteoporosis
Anemia

resistance
Improves
peripheral
glucose
utilization
Intestinal

Alpha

Acarbose
Miglitol

Inhibit

absorption

glucosidase

intestinal

inhibitor

inhibitor

absorption of

Weight loss
Diarrhea
Flatulence

sugars
Lipase

Orlistat

inhibitors

III.DRUGS AND 1o AREAS OF CONTROL

Goal of treatment based on a1c

If HBA1C is <7%
Control PPG first
If HBA1C is <7-9% Control both FPG and PPG
If HBA1C is <9%
Control FPG first

Combination Therapy
When glycemic targets are not achieved with one drug given at the maximum
effective dose (optimal dose or half maximum), another drug from another

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Diabetes Mellitus
pharmacologic class should be added rather than increasing the first drug to its maximum
dose.

PREFERRED DRUG
Initiate treatment with metformin unless with contraindications or intolerant of its
ADEs such as the development of diarrhea, severe nausea or abdominal pain.
When optimization of therapy is needed, then a second drug can be chosen from
the table according to the following considerations: amount of HbA1c lowering,
hypoglycemia risk, weight gain, pt profile (dosing complexity, renal and hepatic
problems, other contraindications and age).

CONTROL AND MONITORING OF BLOOD SUGAR

The ideal target is the HbA1c; HbA1c should be measured using a National
Glycosylated Hemoglobin Standardization Program certified method and results should
be DCCT-aligned.
Measure the individuals HbA1c levels at 36- monthly intervals tailored
according to individual needs and access to laboratory facilities.
HbA1c monitoring may be inaccurate/ invalid in the following conditions because of
disturbed erythrocyte turnover or abnormal haemoglobin type:

Pregnancy
Hemolysis
blood loss
hemoglobinopathies

Alternative measures where HbA1c methods are invalid:

quality-controlled plasma glucose profiles

total glycated hemoglobin estimation
fructosamine estimation.

Other Methods For Monitoring Glycemic Control:

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FBS
RBS
Capillary Testing
Colorimetric glucose strips

Diabetes Mellitus

MONITORING RESPONSE

FPG at 2 weeks
HBA1C at 3 months

FPG at 2 weeks
HBA1C at 3 months
PPG at initiation

2-3 weeks

FPG at 2 weeks
HBA1C at 3 months

2-4 weeks

HBA1C at 3 months
PPG at initiation

FPG at 4 weeks
HBA1C at 3-6

SULFONYLUREAS
MEGLITINIDES

METFORMIN
ACARBOSE

1-2 weeks

THIAZOLIDINES
1-2 months

months
DPP-IV Inhibitors
2 weeks

FPG at 2 weeks
HBA1C at 3 months
PPG at initiation

TARGETS FOR GLYCEMIC CONTROL

In order to achieve A1C of 7.0%, people with diabetes should aim for:

An FPG or preprandial PG target of 4.0 to 7.0 mmol/L (72 to 126 mg/dl)

A 2-hour postprandial PG target of 5.0 to 10.0 mmol/L (90 to 180 mg/dL)
o Alternatively, capilary blood glucose targets can be: FBS 90-130 mg/dL
(ADA), PPBG

In order to achieve a target A1c:

Fasting: <6.0 mmol/dL or <110 mg/ dL

Post-prandial: <8.0 mmol/L or <145 mg/dL

A target of <6.5% may be optimal for certain types of patients such as those with short
duration of diabetes, long life expectancy, no significant active cardiovascular disease, no
serious co-morbid risk factors and at low risk for cardiovascular events that may be
triggered by hypoglycemia.

Targets for optimal blood pressure control:

The goal BP for most diabetic patients is ,140/80 mmHg

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Diabetes Mellitus

PREVENTION

Therapeutic lifestyle change.

Proper diet and exercise
Smoking cessation
Alcohol abstinence

References:

23

Harrison's Principles of Internal Medicine 18th edition

Diabetes-United-for-Diabetes-

Philhttp://spectrum.diabetesjournals.org/content/21/3/160.full
IM Platinum 2nd Edition 2015
https://www.youtube.com/watch?v=JAjZv41iUJU
https://www.youtube.com/watch?v=yIc2XFNLhm8
http://www.webmd.com/diabetes/guide/understanding-diabetes-symptoms?

page=2
http://mediacenter.novomedlink.com/v/the-ominous-octet-core-defects-in-type-2-

diabetes
http://emedicine.medscape.com/article/117739-overview#a6
http://www.mayoclinic.org/diseases-

conditions/diabetes/basics/complications/con-20033091
http://www.arizonatransplant.com/images/pancreas_large_3.JPG
http://img.medscape.com/article/752/116/Slide25.png
http://www.slideshare.net/isiptan/medical-nutrition-therapy-in-diabetes