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Diabetes Mellitus an overview

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Title: Diabetes Mellitus an overview


1
Diabetes Mellitusan overview
  • Aly A. Abdel-Rahim, MD

2
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.
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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.

5
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.

6
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.

7
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.

8
History
  • They convinced themselves that they had
    discovered the active pancreatic hormone which
    normalizes the blood sugar.

9
History
  • The first person to be treated with insulin was
    Leonard Thompson (1908-1935). The first injection
    was in 11 January 1922

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History Noble Prize 1923
  • Banting
  • McLeod
  • Best
  • Collip

12
Definition of diabetes
  • A syndrome of chronic hyperglycaemia with other
    metabolic abnormalities together with micro and
    macro-vascular complications.

13
What is wrong with diabetes
  • Insulin deficiency
  • Insulin resistance

Hyperglycaemia
14
Classification of diabetes
  • Type 1DM
  • Type 2DM
  • IFG impaired fasting glycaemia
  • IGT impaired glucose tolerance
  • GDM Gestational diabetes mellitus
  • Secondary DM.

15
Criteria of diagnosis
  • FBS gt 125.
  • PP gt 200
  • OGTT.
  • normal
  • FBS lt100
  • PP lt140

16
T1DM
  • Usually in young age
  • Characterized by absolute insulin deficiency.
  • Increased catabolism and liability to ketosis.
  • Stormy presentation.
  • must be treated with insulin.

17
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.

18
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.

19
Diabetes related to drugs
  • Glucocorticoids
  • Diazoxide.
  • Thiazides.
  • Phyention
  • Pentamidine

20
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.

21
Diabetes is a pandemic
22
Prevalence of diabetes in the EMME region
23
Prevalence of IGT in the EMME region
24
Prevalence of DM IGT by region
25
Estimated 10 prevalence of diabetes
26
Estimated 10 top number of diabetes patients
27
Social profile related to diabetes in Egypt
  • with an average income per person of 1,490 in
    2001, fighting poverty remains a substantial
    challenge.
  • In it dropped to 1.390 in 2003 and then 1.310
    in 2004.
  • People living under poverty line (lt1 /day) 3.7

WHO statistics 2005
28
Social profile related to diabetes in Egypt
  • Life expectancy is 69.1 years.
  • National poverty rate ( of population) 16.7 .
  • Child malnutrition, weight for age ( of under 5)
    4.0 in 2003 increased to 8.6 2004.

Source World Development Indicators database,
August 2005
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Prevalence of diabetes in Egypt
  • Herman 9.3 above 20y of age.
  • Arab 4.3 above 20y of age.
  • Why the difference ???
  • region e.g. desert and Nubians.

30
Prevalence of diabetes in Egypt
  • Herman 9.3 above 20y of age.
  • Arab 4.3 above 20y of age.
  • Why the difference ???
  • region e.g. desert and Nubians.

31
Diagnosis
  • How to diagnose diabetes
  • Signs and symptoms
  • Blood glucose test
  • OGTT
  • HbA1c

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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.

33
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.

34
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.

35
Pathophysiology of T1DM
Absence of insulin secretion
Failure to use glucose as a fuel
Hyperglycaemia using fat
Ketosis
36
Pathophysiology of T1DM
  • Possible contributing factors
  • Autoimmune disease.
  • HLA typing
  • Viruses
  • chemicals

37
Pathophysiology of T1DM
  • Remission.
  • The honeymoon period

38
Pathophysiology of T2DM
Insulin resistance
hyperinsulinaemia
Relative hypoinsulinaemia
Hyperglycaemia, dyslipidaemia, atherosclerosis,
HTN
39
Pathophysiology of T2DM
  • Causes of insulin resistance
  • Hereditary.
  • Decreased glucose transporters.
  • Decreased insulin receptors
  • Post receptor mechanisms
  • Chemical mediators e.g. TNFa

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Pathophysiology of T2DM
  • Loss of first phase of insulin secretion.
  • Delayed insulin release.

41
Insulin
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Insulin
43
Insulin
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Insulin
45
Insulin
  • Action of insulin
  • On glucose metabolism
  • On amino acid metabolism
  • On lipid metabolism

46
Insulin
  • Short acting

47
Insulin
  • Intermediate acting

48
Insulin
  • Peak less insulin
  • Act for 24 hours no peak

49
Insulin
  • Premixed insulin

50
Insulin
  • Preparation of human insulin

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Insulin
  • Preparation of human insulin

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insulin
  • Plasmid preparation

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Insulin
  • Absorption

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Insulin
  • Variation of absorption
  • Type
  • Dose
  • Site of preparation
  • Temperature.
  • circulation

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Insulin
  • Storage of insulin

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Insulin
  • injection

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insulin
  • injection

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insulin
  • Devices

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Insulin
  • Side effect
  • Hypoglycaemia
  • Atrophy
  • Hypertrophy
  • Sensitivity
  • Weight gain

60
Diet
  • Rules
  • Balanced meal
  • Maintain body weight
  • Adequate nutrition
  • Regular meal time.

61
Diet
62
OHA
63
OHA
  • Sulphonylureas
  • Mode of action
  • Side effect
  • Differences
  • Use

64
OHA
  • Metformin
  • Action
  • When to use
  • Side effects
  • Warning.

65
OHA
  • Acarbose
  • Action
  • Effect
  • Side effect use

66
OHA
  • Non Sulphonylureas insulin secreatgauges
  • Repaglinide
  • Natiglinide.

67
OHA
  • Insulin sensitizers
  • Mode of action
  • Effect
  • Side effect
  • use

68
Oral Antihyperglycemic Therapy for Type 2
Diabetes Scientific Review
  • 63 published studies reviewed
  • Individually, oral agents lower A1c 1-2
  • In comparisons, roughly equal effects
  • In combination, roughly additive effects
  • Long-term benefits demonstrated only for
  • Metformin and Sulfonylureas

SE Inzucchi. JAMA 2002 287360-372.
69
Sulfonylurease.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 287360-372.
70
Nateglinide
71
Non-SU Secretagoguese.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 287360-372.
72
Biguanidese.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 287360-372.
73
Miglitol
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Alpha-Glucosidase Inhibitorse.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 287360-372.
75
Thiazolidindionese.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 287360-372.
76
Retail Price ( per month) of Selected
Antidiabetic Regimens
  • Chlorpropamide 500 mg qD 18
  • Glyburide (generic) 10 mg bid 48
  • Glimepiride 8 mg qD 56
  • Acarbose 100 mg tid 68
  • Metformin (generic) 850 mg tid 78
  • Nateglinide 120 mg tid 90
  • Rosiglitazone 8 mg qD 130
  • Repaglinide 4 mg tid 160

www.drugstore.com, August 2003
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Acute complicationsof Diabetes Mellitus
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Hypoglycaemia
106
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 drug overdose
  • reduced food intake alcohol use
  • delayed meal

107
Symptoms of Hypoglycemia
  • Adrenergic Neuroglycopenic
  • tachycardia dizziness
  • palpitations confusion
  • sweating sleepiness
  • tremor coma
  • hunger seizure

108
Hypoglycemia Symptoms and Signs
  • Sweating, tremors, pounding heart beats.
  • Pallor, cold sweat, irritability
  • May develop coma.

108
109
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

110
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

111
Hyperosmolar Hyperglycemic Nonketotic Syndrome
112
Hyperosmolar Hyperglycemic Nonketotic Syndrome
  • Clinical presentation
  • Severe hyperglycemia (BG gt 600)
  • No or minimal ketosis
  • Hyperosmolarity
  • Profound dehydration
  • Altered mental status

113
Causes of HHNS
  • Drugs glucocorticoids, diuretics
  • Acute stressors infection, burns, CVA, MI,
    gastroenteritis
  • Other chronic disease renal, heart, old stroke
  • Procedures surgery

114
Prevention of HHNS
  • Awareness of the syndrome
  • Maintenance of adequate hydration
  • Control of blood glucose during acute stress with
    insulin

115
DIABETIC KETOACIDOSIS
116
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.

117
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

118
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.

119
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

120
Acute Complications of Diabetes
  • SUMMARY
  • Acute complications can be prevented or greatly
    reduced
  • Prevention depends on effective patient education

121
Chronic complicationsof Diabetes Mellitus
122
Causes of Death Among People With Diabetes
Cause
of Deaths
40 15 13 13 10 4 5
Ischemic heart disease Other heart
disease Diabetes (acute complications) Cancer Cere
brovascular disease Pneumonia/influenza All other
causes
Geiss LS et al. In Diabetes in America. 2nd ed.
1995233-257.
123
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

124
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

125
Microvascular Complications
  • Diabetic retinopathy
  • background retinopathy
  • macular edema
  • proliferative retinopathy
  • Diabetic nephropathy
  • Diabetic neuropathy
  • distal symmetrical polyneuropathy
  • mononeuropathy (peripheral, cranial nerves)
  • autonomic neuropathy

126
Increased risk of complications with lack of
glucose control...
Only 27 of DM US patients on OADs have HbA1clt7
15
Retinopathy
13
Nephropathy
Neuropathy
11
Microalbuminuria
Relative Risk
9
7
5
3
1
6
7
8
9
10
11
12
HbA1C()
Endocrinol Metab Clin 199625243 - 254
(Diabetes Control Complications Trial)
NHANES III
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chronic complications population based -
Egyptians
  • prevalence known D new D
  • retinopathy 41.5 15.7
  • nephrop. 6.7 6.8
  • neuropathy 21.9 13.6
  • foot ulcers 0.8 0.8
  • associations
  • ret nephr neuro ? glucose

microvasc neuropathic n 1451
128
Retinopathy and Blindness in Diabetes Patients
  • It is estimated that retinopathy affects 80-97
    of patients with diabetes of ³15 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. 1995293-338.
129
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

130
Background Retinopathy
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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

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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

134
Preproliferative Retinopathy
135
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,
19971-8. U.S. Renal Data System, USRDS 1997
Annual Data Report.
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