Transcript Diabetes Mellitus an overview

Diabetes Mellitus
an overview
Diabetes is a disorder
caused by the
presence of too much
glucose in the blood. A
first depiction of this
“sugar disease” was
described in the
“Ebers Papyrus”, a
papyrus sold to the
German Egyptologist
Georg Moritz Ebers in
1872. It was said to
have been found close
to a mummy in the
tomb of Thebes and
appears to have been
written between 3000
and 1500 BC.
History
Reference to diabetes was made 1550
BC.
 In the 2nd Century AD, Aretaeus gave an
excellent description of diabetes.
 Thomas Willis in the 17th Century
detected the sweet test of urine.
 Mathew in the 18th Century showed that
the sugar in urine comes from the blood.

History
Minkowski and Von Mering discovered
that disease of the pancreas is responsible
for diabetes to develop in the 19th
century.
 In the 19th century treatment of diabetes
was confined to food regulation which
reduced urination but did not prevent
wasting and complications.

History
In the second half of the 19th Century,
Paul Langerhans, a German student,
identified clusters of cells within the
pancreas responsible for the production
on glucose lowering substance. “islets of
Langerhans”.
 Insulin: in Latin insula= island. So the name
was coined before the hormone was
discovered.

History
Banting and Best “a student” worked in
McLeod's labs in Toronto.
 In 1921they made the exocrine cells
atrophy by ligation of the pancreatic duct.
 They made aqueous extracts of the
remaining tissue keeping it cold and
filtered it.
 The extract was injected into a diabetic
dog on 30 July 1921.

History

They convinced
themselves that they
had discovered the
active pancreatic
hormone which
normalizes the blood
sugar.
History

The first person to be
treated with insulin was
Leonard Thompson
(1908-1935). The first
injection was in 11
January 1922
History: Noble Prize 1923

Banting

McLeod

Best

Collip
Definition of diabetes

A syndrome of chronic hyperglycaemia
with other metabolic abnormalities
together with micro and macro-vascular
complications.
What is wrong with diabetes


Insulin deficiency
Insulin resistance
Hyperglycaemia
Classification of diabetes
Type 1DM
 Type 2DM
 IFG: impaired fasting glycaemia
 IGT: impaired glucose tolerance
 GDM: Gestational diabetes mellitus
 Secondary DM.

Criteria of diagnosis
FBS > 126. MGS%
 PP > 180 MGS%

normal:
 FBS - 80 – 100 MGS%
 PP - 80 – 140 MGS%
T1DM
Usually in young age
 Characterized by absolute insulin
deficiency.
 Increased catabolism and liability to
ketosis.
 Stormy presentation.
 must be treated with insulin.

T2DM
Usually in older age.
 Relative insulin deficiency.
 Increased insulin resistance.
 Can be treated with OHA or insulin.
 Slow onset, less likely to develop ketosis.
 May present with complications.

MODY
Maturity onset diabetes of the youth
A special type of diabetes similar to type
2 diabetes but develop in young age
groups.
 Increased prevalence worldwide.
 Associated with increased childhood
obesity.

Diabetes related to drugs
Glucocorticoids
 Diazoxide.
 Thiazides.
 Phyention
 Pentamidine

GDM
Gestational diabetes mellitus
Diabetes discovered for the first time
during pregnancy.
 Every pregnant lady should be screened.
 Usually disappears after labor.
 Increased risk to develop T2DM later in
life.

Estimated 10 top number of diabetes
patients
Diagnosis

How to diagnose diabetes:
1.
2.
3.
4.
Signs and symptoms
Blood glucose test
OGTT
HbA1c
Diagnosis
Most people are diagnosed with diabetes
when they are suspected to have
symptoms of polyurea, polydepsia, fatigue,
loss of weight.
 This is confirmed by fasting or PP blood
glucose.
 In case of doubt OGTT may be done.
 Urine testing should not be used in
diagnosis.

Diagnosis
Peers and medical ‘advisors’ should be
aware of the following:
 T1DM & T2DM are two distinct diseases.
 T1DM is stormy at presentation, delay in
diagnosis can be disastrous.
 Among the presentations of T1DM could
be some non-specific symptoms like
vomiting, abdominal pain….

Diagnosis
T2DM may present with late symptoms,
like numpness, disturbed vision,
generalized oedema.
 Patients with hypertension, dyslipidaemia,
MI and family history of diabetes are very
likely to develop T2DM.

Pathophysiology of T1DM
Absence of insulin secretion
Failure to use glucose as a fuel
Hyperglycaemia & using fat
Ketosis
Pathophysiology of T1DM

Possible contributing factors:
1.
2.
3.
4.
Autoimmune disease.
HLA typing
Viruses
chemicals
Pathophysiology of T2DM
Insulin resistance
hyperinsulinaemia
Relative hypoinsulinaemia
Hyperglycaemia, dyslipidaemia, atherosclerosis, HTN
Pathophysiology of T2DM

Causes of insulin resistance:
1.
2.
3.
4.
5.
Hereditary.
Decreased glucose transporters.
Decreased insulin receptors
Post receptor mechanisms
Chemical mediators e.g. TNFα
Pathophysiology of T2DM
Loss of first phase of insulin secretion.
 Delayed insulin release.

Insulin
Insulin
Insulin

Action of insulin:
1. On glucose metabolism
2. On amino acid metabolism
3. On lipid metabolism
Insulin

Short acting
Insulin

Intermediate acting
Insulin
Peak less insulin
 Act for 24 hours no peak

Insulin

Premixed insulin
Insulin

Absorption
Insulin

Variation of absorption:
1.
2.
3.
4.
5.
Type
Dose
Site of preparation
Temperature.
circulation
Insulin

Storage of insulin
Insulin

injection
insulin

injection:
insulin

Devices
Insulin

Side effect:
1.
2.
3.
4.
5.
Hypoglycaemia
Atrophy
Hypertrophy
Sensitivity
Weight gain
Diet

Rules:
1.
2.
3.
4.
Balanced meal
Maintain body weight
Adequate nutrition
Regular meal time.
Diet
OHA
OHA

Sulphonylureas:
1.
2.
3.
4.
Mode of action
Side effect
Differences
Use
OHA

Metformin:
1.
2.
3.
4.
Action
When to use
Side effects
Warning.
OHA

Acarbose
1. Action
2. Effect
3. Side effect use
OHA

Non Sulphonylureas insulin
secreatgauges:
1. Repaglinide
2. Natiglinide.
OHA

Insulin sensitizers:
1.
2.
3.
4.
Mode of action
Effect
Side effect
use
Sulfonylureas
e.g. Chlorpropamide, Glyburide

Mechanism
◦ Increase insulin secretion by pancreas

Advantages
◦ Well established, Decrease microvascular risk,
Convenient dosing

Disadvantages
◦ Hypoglycemia, Weight gain

FDA Approval for combination therapy
◦ Metformin, TZD, acarbose
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
Non-SU Secretagogues
e.g. Nateglinide, Repaglinide

Mechanism
◦ Increase insulin secretion by pancreas

Advantages
◦ Targets post-prandial glycemia

Disadvantages
◦ TID dosing, No long-term data

FDA Approval for combination therapy
◦ Metformin
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
Biguanides
e.g. Metformin

Mechanism
◦ Decrease hepatic glucose production

Advantages
◦ Well established, Weight loss, No hypoglycemia, Decrease
micro & macrovascular risk, Convenient dosing, [Also
prevents diabetes]

Disadvantages
◦ GI distress, Lactic acidosis, Contraindications

FDA Approval for combination therapy
◦ Insulin, SU and non-SU secretagogues, TZD
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
Alpha-Glucosidase Inhibitors
e.g. Acarbose, Miglitol

Mechanism
◦ Decrease gut carbohydrate absorption

Advantages
◦ Targets post-prandial hyperglycemia, No systemic
absorption, [Also prevents diabetes]

Disadvantages
◦ GI distress, TID dosing, No long-term data

FDA Approval for combination therapy
◦ Sulfonylureas
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
Thiazolidindiones
e.g. Pioglitazone, Rosiglitazone

Mechanism
◦ Increase peripheral glucose disposal

Advantages
◦ Physiologically “correct,” Convenient dosing, [Also
prevents diabetes]

Disadvantages
◦ Liver toxicity, Liver monitoring, Weight gain, Edema,
No long-term data

FDA Approval for combination therapy
◦ Insulin, sulfonylurea, metformin
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
Acute complications
of Diabetes Mellitus
Hypoglycaemia
Hypoglycaemia

Most common complication of diabetes
◦ 100% of Type 1 patients affected
◦ ~ 10%/year severe (requiring assistance)
◦ much less common in Type 2

Multiple causes:
◦ exercise/activity
◦ reduced food intake
◦ delayed meal
drug overdose
alcohol use
Symptoms of Hypoglycemia
Adrenergic
tachycardia
palpitations
sweating
tremor
hunger
Neuroglycopenic
dizziness
confusion
sleepiness
coma
seizure
Hypoglycemia
Symptoms and Signs
• Sweating, tremors, pounding heart beats.
• Pallor, cold sweat, irritability
• May develop coma.
63
Prevention of Hypoglycemia
Consistent meal times, appropriate to drug
regimen
 Consistent carbohydrate intake, or matched to
drug dose
 Adjustments for extra exercise

◦ extra food, e.g. 15 gm carb/30 min
◦ reduce drug, e.g. prior dose by 20-30%
Accurate drug dosing
 Blood glucose monitoring

Treatment of Hypoglycemia

Oral carbohydrate:
◦ 10-15 gms, repeat after 15 minutes if needed
◦ glucose tabs preferred; food acts slower, adds
unneeded calories (fat, protein)

IV Glucose
◦ 20-50 cc of D50

Glucagon
◦ 1 mg IM
Hyperosmolar Hyperglycemic
Nonketotic Syndrome
Hyperosmolar Hyperglycemic
Nonketotic Syndrome
Clinical presentation
Severe hyperglycemia (BG > 600)
No or minimal ketosis
Hyperosmolarity
Profound dehydration
Altered mental status
Causes of HHNS
Drugs: glucocorticoids, diuretics
 Acute stressors: infection, burns, CVA, MI,
gastroenteritis
 Other chronic disease: renal, heart, old
stroke
 Procedures: surgery

Prevention of HHNS
Awareness of the syndrome
 Maintenance of adequate hydration
 Control of blood glucose during acute
stress with insulin

DIABETIC KETOACIDOSIS
Diabetic Ketoacidosis
An acute, life threatening metabolic acidosis
complicating IDDM and some cases of NIDDM
with intercurrent illness (infection or surgery)
 Usually coupled with an increase in glucagon
concentration with two metabolic consequences:

◦ 1) Maximal gluconeogenesis with impaired
peripheral utilization of glucose
◦ 2) Activation of the ketogenic process and
development of metabolic acidosis.
Diabetic Ketoacidosis
Usually seen in Type 1 DM, but CAN
OCCUR in Type 2
 Often with acute stress, such as infection,
MI, etc.
 Recurrent DKA almost always related to
omission of insulin, psychosocial problems
 Preventive measures same as for HHNS

Clinical Presentation
Anorexia, N/V, along with polydepsia and polyuria for about 24
hrs. followed by stupor (or coma).
 Abdominal pain and tenderness could be present (remember
DDx of acute abdomen).
 Kussmaul breathing with fruity odor “acetone”
 Sings of dehydration ( HR, postural BP, etc.)
 Normal or low temperature:
NB.: if fever is present it suggests infection
while leukocytosis alone is not because
DKA per se can cause fever.

Has to be treated in Hospital
Always refer to Endocrinologist
•Insulin: is a prerequisite for recovery
•IVF: the usual fluid deficit is 3-5L
•Potassium: replacement is always necessary
•Bicarbonate:
Acute Complications of
Diabetes
SUMMARY:
Acute complications can be prevented or
greatly reduced
 Prevention depends on effective patient
education

Chronic complications
of Diabetes Mellitus
Causes of Death Among People With
Diabetes
Cause
% of Deaths
Ischemic heart disease
40
Other heart disease
15
Diabetes (acute complications)
13
Cancer
13
Cerebrovascular disease
10
Pneumonia/influenza
4
All other causes
5
Geiss LS et al. In: Diabetes in America. 2nd ed. 1995:233-257.
Complications of Diabetes: Long term
◦ Macrovascular
 Ischaemic heart disease – heart attacks; stroke
 Peripheral vascular disease – gangrene, amputations
◦ Microvascular
 EYE – retinopathy - blindness
 NERVE - neuropathy (peripheral and autonomic)
 KIDNEY – nephropathy; dialysis
◦ Infections
Magnitude of Problem
Diabetic retinopathy: most common
cause of blindness before age 65
 Nephropathy: most common cause of
ESRD
 Neuropathy: most common cause of
non-traumatic amputations
 2-3 fold increase in cardiovascular disease

Microvascular Complications

Diabetic retinopathy
 background retinopathy
 macular edema
 proliferative retinopathy
Diabetic nephropathy
 Diabetic neuropathy

 distal symmetrical polyneuropathy
 mononeuropathy (peripheral, cranial nerves)
 autonomic neuropathy
chronic complications*
population based - Egyptians
•
prevalence
known D
– retinopathy
– nephrop.
– neuropathy
– foot ulcers
•
41.5
6.7
21.9
0.8
associations
ret; nephr;
*microvasc + neuropathic;
new D
%
15.7
6.8
13.6
0.8
neuro :  glucose
n: 1451
Retinopathy and Blindness in
Diabetes Patients
◦
It is estimated that retinopathy affects 80%-97% of patients with
diabetes of 15 years’ duration
◦
Diabetes is the leading cause of new cases of blindness in adults*
◦
Diabetic retinopathy accounts for the majority of
these cases
◦
Minimum cost of blindness for working-age adult is estimated at
$12,769 per year
*Blindness is defined as visual acuity 20/200
Klein R, Klein BEK. In: Diabetes in America. 2nd ed. 1995:293-338.
Diabetic Retinopathy

Background retinopathy
◦
◦
◦
◦
◦
◦
present in 90% of patients after 10 years
asymptomatic
red dots (microaneurysms)
dot, blot, and flame shaped hemorrhages
hard waxy exudates of lipid and protein
best detected by dilated eye exam or photos
Background Retinopathy
Diabetic Retinopathy

Macular edema
◦ sight threatening edema of the macula
◦ usually reduces visual acuity early
◦ can only be diagnosed by ophthalmologic
exam
◦ focal photocoagulation reduces risk of
blindness by 50%
Diabetic Retinopathy

Proliferative retinopathy
◦ growth of small, fragile blood vessels that may
bleed (vitreous hemorrhage)
◦ associated with growth of fibrous tissue that
may cause retinal detachment
◦ may occur on the optic disk or elsewhere
◦ high risk of blindness (50% in 3 years)
◦ hypertension, isometric exercise, high contact
sports may increase risk of bleeding
Preproliferative Retinopathy
Kidney Disease in Diabetes Patients
◦
27,851 new cases of ESRD in diabetes patients in 1995
 40% of all new cases in the US
◦
Nearly 99,000 diabetes patients required dialysis or kidney
transplantation that year
◦
Annual cost of ESRD:
 $45,000 in diabetic patients ages 45-64
National Diabetes Fact Sheet. November 1, 1997:1-8.
U.S. Renal Data System, USRDS 1997 Annual Data Report.