DM Lecture DR Rediet C1 yekatit (1.....ppt

Fifteen

1. Diabetes Mellitus
lecture series for CI students
Dr Rediet Ambachew
MD, Internist, Assist. Prof of Endocrinology
Yekatit 12 Hospital Medical College
March 7, 2022

2. Outline of presentation
Definition of Diabetes mellitus
Etiological classification
Diagnostic criteria
Pathogenesis of type 1 and type 2 DM
Clinical presentations
Management of diabetes mellitus

3. Definition
Diabetes is a heterogeneous, complex
metabolic disorder characterized by
hyperglycemia resulting from defects in
insulin secretion, insulin action, or both.

4. Diabetes is a rapidly growing social
challenge worldwide
1. IDF Diabetes Atlas, 5th edn. Brussels, Belgium: International Diabetes Federation. 2011.
2. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation. 2019.,
2021
The increasing global
prevalence of diabetes
1,2
285 million
adults with diabetes
1
2010
2019
2045
463 million----537 million
[2019] [2021]
51%
increase in number
of adults with diabetes
700 million
adults with diabetes
2
4

5. IDF 2021
5

6. Etiologic Classification of DM
Diabetes can be classified into the following four
categories:
1. Type 1 diabetes ( due to β cell destruction,
usually leading to absolute or near total insulin
deficiency).
A. Immune Mediated
B. Idiopathic
2. Type 2 diabetes (due to a progressive insulin
secretary defect on the background of insulin
resistance

7. Etiologic Classification of DM
3. Specific types of diabetes due to other causes, e.g.,
 Genetic defects of beta cell development or function
 Genetic defects in insulin action
 Diseases of the exocrine pancreas pancreatitis, pancreatectomy, neoplasia,
cystic fibrosis, hemochromatosis
 Drug- or chemical-induced diabetes—glucocorticoids, thiazides, PI, etc
Endocrinopathies, infections, genetic syndrome
4. Gestational diabetes mellitus (GDM)

8. 8

9. GENETIC DEFECTS
Maturity Onset Diabetes of the Young (MODY) is
characterized by impaired insulin secretion with minimal or
no insulin resistance
 MODY may affect genes important for beta-cell glucose
sensing, development, function, and regulation
MODY can be diagnosed in non obese individuals who
develop DM age <25 with strong autosomal dominant family
hx of DM

11. HYBRID FORMS OF DIABETES
11

12. LADA
Currently LADA renamed to Slowly evolving immune-mediated diabetes
Autoimmune disorder that resembles Type 1 DM but occurs late and less
likely to require insulin at first
Diagnostic criteria
- Age at diagnosis >30
- At least 1 antibody present
- No insulin needed at least 6 months after diagnosis
LADA is most likely in those
- Age <50 - Present with acute symptoms -BMI<25
- Personal and family history of autoimmune disease

13. Ketosis prone diabetes
Syndrome characterized by sudden onset of hyperglycemia with
or without ketosis which initially requires insulin but weeks or
months later no longer requires it
Patients present with poly symptoms, weight loss etc that started
within 4-6 weeks with no precipitant identified
They tend to be
 African or Asian decent
Male
Overweight or obese
Strong family history of DM

14. There are no islet cell antibodies
20-50% of Africans and Asians with newly diagnosed DKA
may have ketosis prone diabetes

15. Who should be screened?

16. Criteria for the diagnosis of Diabetes
1. A1C > 6.5% The test should be performed in a laboratory using a
method that is NGSP certified and standardized to the DCCT assay.*

OR
2. FPG >126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric
intake for at least 8 h.*
OR
3. 2-h PG >200 mg/dL (11.1 mmol/L) after 75 gm , OGTT.
The test should be performed as described by the WHO, using a glucose load containing the
equivalent of 75 g anhydrous glucose dissolved in water.*
OR

17. Criteria for the diagnosis of Diabetes
4. In a patient with classic symptoms of hyperglycemia or
hyperglycemic crisis, a random plasma glucose >200
mg/dl (11.1 mmol/L).
* Results should be confirmed by repeat testing.

18. Categories of increased risk for diabetes
(Prediabetes)*
Pre-DM criteria
FPG: 100 mg/dL -125 mg/d (IFG)
OR
2-h PG in the 75-g OGTT: 140 -199 mg/dL (11.0 mmol/L) (IGT)
OR
A1C: 5.7–6.4%

19. Normal Blood Glucose values
 FBG- < 100 mg/dl (< 5.6mmol/L)
2 hr Plasma Glucose Level < 140 mg/dl, after 75 gm
OGTT
HbA1c < 5.7 %

20. Diagnosis of Dysglycemia
20

21. Metabolic Syndrome- IDF criteria
21

22. RISK FACTORS FOR TYPE 2 DIABETES MELLITUS
Family history of diabetes (i.e. parent or sibling with
type 2 diabetes)
Obesity (BMI 25 kg/m2 or ethnically relevant
≥
definition for overweight)
Physical inactivity
Race/ethnicity (e.g., African American, Latino, Native
American, Asian American, Pacific Islander)
 Previously identified with IFG, IGT, or an hemoglobin
A1c of 5.7–6.4%

23. Risk factors
History of GDM or delivery of baby >4 kg (9 lb)
Hypertension (blood pressure 140/90 mmHg)
≥
 HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or
a triglyceride level >250 mg/dL (2.82 mmol/L)
Polycystic ovary syndrome or acanthosis nigricans
History of cardiovascular disease

24. Pathogenesis of Type 1 diabetes mellitus (T1DM)
Is the result of interaction of
genetic , environment and immunologic factors
Ultimately leads to destruction of pancreatic beta
cells and insulin deficiency
T1DM- results from autoimmune beta cell
destruction

25. … Pathogenesis of T1DM
Some individuals lack markers indicative of autoimmune
process “Idiopathic type 1 dm”
They develop insulin deficiency by unknown mechanism
They are ketosis prone
These individuals are mainly African Americans, and
Asian heritage

26. Genetic susceptibility of type 1 DM
Individuals with genetic susceptibility have normal
beta cells at birth
Begin to lose the beta cells secondary to auto immune
destruction that occurs over months to years
The autoimmune process triggered by infectious
environmental stimulus
Immunologic markers appear after the triggering
events but before diabetes becomes clinically overt.

27. Genetic susceptibility of type 1 DM
-Susceptibility to T1DM involves multiple genes
- The major susceptibility gene is located in the
 HLA region on chromosome 6
 Involves Class II major Histocomaptibilty complex
(MHC) molecules
present the antigen to T helper cells and thus are
involved in initiating the immune response

28. Genetic susceptibility of type 1 DM
Beta cell mass then begins to decrease- and insulin
secretion progressively declines
Features of diabetes don't become evident until a
majority of beta cells destroyed (70-80%)
After the initial clinical presentation of T1DM
“ Honey moon” phase may occur, requires modest insulin dose
or insulin not needed
Autoimmune process destroys remaining beta cells,
- individual become insulin deficient

29. Immunologic Markers
Iselet Cell auto antibodies(ICAs)- are composite of
several different antibodies directed at pancreatic islets
molecules such as
GAD
Insulin ( IAA)
IA-2
Are markers of autoimmune process

30. Environmental factors
Numerous environmental events have been
proposed to trigger the autoimmune process in
genetically susceptible individuals : E.g viruses
coxsasackie, Rubella, enteroviruse, Bovine milk
protein

31. The temporal development of T1DM is
shown schematically

32. Pathogenesis of Type 2 diabetes mellitus
(T2DM)
Type 2 DM is characterized by impaired insulin
secretion, insulin resistance, excessive hepatic glucose
production, and abnormal fat metabolism
Most studies support that the insulin resistance
precedes an insulin secretary defect
But diabetes develops only when insulin secretion
become inadequate

33. Genetic considerations
T2DM has a strong genetic component
The concordance of T2DM in identical twin is between 70-
90%
If both parents have Type 2 Dm, the risk approaches 40%
The disease is polygenic and multifactorial
In addition to genetic susceptibility, environmental factors
such as
 obesity,
nutrition and
 physical inactivity modulate the disease process.

34. Pathophysiology
Mechanisms of Pathogenesis of Type 2 Dm
 Impaired Insulin secretion
 Insulin resistance
 Increased hepatic glucose production
 Abnormal fat metabolism

35. Treatment Policy for Type 2 Diabetes
Effective treatment require multiple drugs in combination to
correct the multiple pathophysiological defects
Therapy must be started early in the natural history of T2DM
to prevent progressive β-cell failure
 Simply focusing on glycemic control will not have a major
impact to reduce cardiovascular risk
35

36. 36

37. Updated Pathophysiology of type 2 Diabetes
37

38. Clinical manifestations of diabetes
mellitus

39. Type 1 diabetes
Affects people of any age, but onset usually occurs
in children or young adults
Patient present suddenly with acute clinical
symptoms of hyperglycemia
Or present in state of diabetic ketoacidosis

40. TIDM…
Requires insulin for life to control the levels of glucose
in their blood
Associated with other Endocrine disease. e.g
 Addison’s disease,
 Auto immune hypothyroidism, pernicious
anaemia, vitiligo etc

41. Clinical Presentations
Type 1 diabetes often develops suddenly and can
produce symptoms such as
• Abnormal thirst and a dry mouth
• Frequent urination
• Lack of energy, extreme tiredness
• Constant hunger
• Sudden weight loss
• Blurred vision

42. Type 2 Diabetes
Type 2 diabetes is the most common type of diabetes.
Most of them are Obese
It usually occurs in adults, but is increasingly seen in children
and adolescents.
• Frequent urination
• Excessive thirst
• Weight loss
• Blurred vision
About 50 % of the pt. are asymptomatic
They can present with complications of DM or with other metabolic syndrome

43. Approach to Diabetes
History
 details related to DM and its complications
Prior diabetes therapy, follow up
 Weight , family history
Risk factors
 Symptoms of hyperglycemia and hypoglycemia
 History of chronic complications of Dm
Symptoms of infection
and assessment of the patient’s knowledge about
diabetes, exercise, and nutrition.

44. Approach to Diabetes
Physical examination
Complete physical examination
BMI
Examine : All systems; especially, V/S [ B/P] , the eyes , ,
cardiovascular system, peripheral arterial disease,
Peripheral nerves, foot examination
Classify the patient as type 1 dm , type 2 dm
 Laboratory evaluation
determine the FBS,RBS,HbA1C,LFT,RFT,LIPIDS
ECG

45. Goal of therapy of DM
1. To eliminate symptoms related to hyperglycemia
2. Reduce or eliminate the long term microvascular
and macrovascular complications of DM
3. To allow the patient to achieve a normal life style

46. Medical nutrition therapy
Meal plans should be individualized
There is no single ideal dietary distribution of calories among
carbohydrates, fats, and proteins for people with diabetes
General dietary recommendations – vegetables, fruits, whole grains,
legumes, low-fat dairy products, high fiber food
46

47. Medical nutrition therapy
47

48. Physical Activity
 Has a multiple positive benefits
Including cardiovascular risk reduction
Reduced blood pressure, maintenance of muscle
mass
Reduction in body fat and weight loss
Lower plasma glucose level

49. Physical Activity
ADA recommendation
 Most Adults:
150 min or more of moderate to vigorous-intensity aerobic activity per
week, spread over at least 3 days/week, with no more than 2 consecutive
days without activity.
 For older adults with diabetes;
 Flexibility training and balance training are recommended 2–3
times/week
49

50. Monitoring blood glucose control
Optimal monitoring of glycaemic control involves
Glucose measurement by the patient.i.e Self Blood Glose
Monitoring (SMBG)
 Plasma Glucose determination , laboratory
Assessment of long term control by determination of
HbA1C (Non glycated hemoglobin for 2-3 months)

51. T2D management considerations for individualized treatment:
ADA/EASD Position Statement
T2D, type 2 diabetes; AE, adverse event; CV, cardiovascular
Adapted from Inzucchi SE et al. Diabetes Care 2015;38:140 149
−
Hyperglycaemia management approach
More stringent Less stringent
Long Short
Hypoglycaemia and
AE risks
Absent Severe
Important comorbidities
Highly motivated
Less motivated
Resources and support
system
Readily available
Limited
HbA
1c
7%
Life expectancy
Disease duration
Established vascular
complications
Patient attitude and
expectations
Few/mild
Absent SevereFew/mild
Newly diagnosed Long-standing
Low High
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52. 52

53. Management of type 1 dm
Intensified insulin therapy improves
microvasular and macrovscular complications of
DM
Conventional insulin therapy
Multiple daily insulin injection
Insulin infusion devices (CSII)

54. Insulin
Insulin initiation dose for type 1 dm is 0.4-0.5 unit/kg
Sc, 2/3 am, 1/3 pm Increase 2-4 units every week
Insulin formulations are available as “pens”, Vials
Insulin regimens
Conventional: BID
Multiple daily Insulin Injection: A combination of Basal
insulin and Bolus insulin
Continuous Subcutaneous Insulin Infusion (CSII) :
Basal insulin infusion and bolus insulin infusion
Closed loop system

56. Anti-diabetic Medications
56

57. Choice of anti-hyperglycaemic agents
 Entry Hga1c
•< 7.5% - monotherapy
•7.5% - 8.5% -dual therapy
•> 10% - Insulin
Comorbidities: ASCVD, DKD, HF
Hypoglycemia risk
Effects on body weight
Side effects and Costs

58. ADA 2021 58

59. Timely Insulin Initiation and optimization should

follow disease progression
B
e
t
a
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c
e
l
l
f
u
n
c
t
i
o
n

(
%
)
Treatment optimisation and intensification
Lifestyle + OADs
Basal and 1–4 bolus or premix
Basal insulin + OADs
Schematic diagram adapted from Kahn. Diabetologia 2003;46:3–19; Inzucchi et al. Diabetologia 2012;55(6):1577–96; IDF Clinical Guidelines Task Force. Global guideline for type 2 diabetes, 2012
Titrate dose to reach/maintain glycaemic targets
Intensify for mealtime insulin coverage
Initiate
Optimise
Intensify
OAD, oral antidiabetic drug; * IDF 2012
59

60. Indication for Insulin therapy for Type 2 DM
Failure to control blood glucose with oral drugs
Temporary use for major stress, e.g. surgery, medical illness
Advanced kidney or liver failure
Pregnancy
Initial therapy for patients presenting with fasting blood
glucose >250 mg/dl , random glucose consistently >300
mg/dl, or ketonuria

61. Summary
Define diabetes mellitus
Diagnostic criteria to diagnosis diabetes mellitus
Describe the pathogenesis of Type 1 and type type 2
dm
Management approach of type 1 and type 2 dm

62. PART II

Acute and Chronic complications of
diabetes mellitus

63. Outline of presentation
Acute complications (DKA,HHS, Hypoglycemia)
Chronic complications (microvascular ,macrovasular
and other complications of DM
Summary

64. Acute complication of DM
Dabetic Ketoacidosis (DKA)
Hyperglycaemic Hyperosmolar state (HSS)
Hypoglycaemia

65. Hyperglycemic Crises
DKA and HHS
Serious & Potentially Life Threatening Complications
Result from Relative or Absolute Insulin Deficiency + Excess Stress
Hormones
Have Overlapping Features
Can be Preventable

66. Hyperglycemic emergencies [ DKA and HHS]
DKA and HHS are:
Serious & Potentially Life Threatening Complications
Result from Relative or Absolute Insulin Deficiency + Excess
Stress Hormones
Results in volume depletion and acid base abnormalities
Have Overlapping Features
Can be Preventable

67. Pathogenesis of DKA
DKA results from absolute or relative insulin
deficiency combined with counter regulatory
hormone excess (glucagone, catecholamine,
cortisol and growth hormone
The decrease ratio of insulin to glucagon
promotes gluconeogenesis
glycogenolysis
and ketone body formation in the liver
increase in substrate deliver from fat and muscle
(free fatty acid and amino acids ) to the liver

68. Ketosis results from marked

increase in free fatty acid release from adipocytes, resulting
ketone body formation in the liver
Reduced insulin level in combination with elevations in
catecholamine's and growth hormone
 increase lipolysis and release of free fatty acids and increase
triglyceride and VLDL production

69. Normally this free acids are converted in the liver to
triglyceride and VLDL.
However in DKA hyperglucagonemia alters hepatic
metabolism to sever ketone body formation through
activation of the enzyme carntine palmitoiltranferase I.

this enzyme is crucial for regulating fatty acid transport
into mitochondria
where beta oxidation and conversion to ketone bodies
occur

70. Pathogenesis of Hyperglycemic Crises
Ratio of Insulin to Counter regulatory hormone is low in hyperglycemic crisis

72. CLINICAL PRESENTATION
Diabetic ketoacidosis (DKA)
 evolves rapidly, over a 24-hour period
Hyperventilation and abdominal pain are primarily in DKA
Hyperosmolar hyperglycemic state (HHS)
develop more insidiously with polyuria, polydipsia, and weight loss
Persisting for several days before hospital admission
Neurologic symptoms are most common in HHS

73. Neurologic symptoms 
 Neurologic deterioration primarily occurs in patients with an effective plasma
osmolality above 320 to 330
 mosmol/kg 
more frequent in HHS than DKA because of the usually greater degree of
hyperosmolality in HHS
Mental obtundation may occur in patients with DKA when severe acidosis
Stupor or coma in diabetic patients with osmolality < 320
 mosmol/kg : Consider
other causes of the mental status change

74. Abdominal pain in DKA 
 
Possible causes of abdominal pain
delayed gastric emptying
 ileus induced by the metabolic acidosis
 electrolyte abnormalities
 Other causes such as pancreatitis
Abdominal pain is unusual in HHS

75. Physical examination
Signs of volume depletion
 decreased skin turgor
 dry axillae and oral mucosa
 low jugular venous pressure
 tachycardia
 severe hypotension
 Neurologic findings, particularly in patients with HHS

77. DIAGNOSTIC EVALUATION
 
Initial evaluation
 
The initial history and rapid but careful physical examination should focus on:
Airway, breathing, and circulation (ABC) status
Mental status
Possible precipitating events (eg, source of infection, myocardial
infarction)
Volume status

78. The initial laboratory evaluation of a patient with suspected DKA or HHS
Serum glucose
Serum electrolytes (with calculation of the anion gap), blood urea nitrogen (BUN), and creatinine
Complete blood count (CBC) with differential
Urinalysis and urine ketones by dipstick
Plasma osmolality
Serum ketones (if urine ketones are present)
Arterial blood gas if the serum bicarbonate is substantially reduced or hypoxia is suspected
Electrocardiogram

82. Serum ketones
 
Three ketone bodies are produced and accumulate in DKA
 Acetoacetic acid: a true ketoacid
 Beta-hydroxybutyric acid (a hydroxyacid formed by the reduction of
acetoacetic acid)
 Acetone: decarboxylation of acetoacetic acid, a true ketone
Nitroprusside testing
 — chemical develops a purple color in the presence of
acetoacetic acid (and to a much lesser degree, to acetone)

83. Goals of DKA Treatment
Volume Repletion
Reversal of metabolic consequences of insulin deficiency
Correction of acid-base & electrolyte imbalances
Recognition & Treatment of precipitating factors
Avoidance of complications

84. Principles of DKA management
Principles of ABC
Fluid Resuscitation
Insulin therapy
Potassium replacement
Treat precipitating factor
84

85. The hyperglycemic crisis is considered to be resolved when the following goals are
reached:
The ketoacidosis has resolved
as evidenced by normalization of the serum anion gap (less than 12 mEq/L) and
blood beta-hydroxybutyrate levels
Patients with HHS
mentally alert and the plasma effective osmolality has fallen below 315 mOsmol/kg
The patient is able to eat

87. Management of DKA

88. Management of DKA

89. Management of DKA

90. Hyperglycemic Hyperosmolar State
(HHS)
Mostly occurs in elderly type 2 DM
Clinical features are history of polyuria,
polydypsia , weight loss, weakness

Physical Examination; dehydration, hypotension,
tachycardia, altered mental status
Management is the same as Mg. of DKA, except
increase fluid administration upto 8-10 lt.

91. Predisposing or precipitating factors for HHS
UPTODATE 2018

93. Management of HHS

94. Hypoglycaemia
Occurs in most patients with type 1 diabetes and type 2
diabetes mellitus
Common risk factors
 fasting or missed meals
 exercise
 insufficient meals
 overdose of hypoglycemic agents or insulin
 chronic kidney disease, hepatic disease
 alcohol consumption.

95. Definition 
Hypoglycemia is defined as a clinical syndrome with diverse causes in which:

low plasma glucose concentrations < 70mg/dl
lead to symptoms and signs,
and there is resolution of the
 symptoms/signs when the plasma glucose concentration
is raised[Whipple's triad]

96. Physiologic Responses to Hypoglycemia

97. CLINICAL MANIFESTATIONS OF HYPOGLYCEMIA
Symptoms
causes neurogenic (autonomic) and neuroglycopenic symptoms
The neurogenic symptoms
 Tremor, palpitations, and
 anxiety/arousal (catecholamine-mediated, adrenergic)
 Sweating, hunger, and paresthesias (acetylcholine-mediated, cholinergic)
 largely caused by sympathetic neural, rather than adrenomedullary, activation
The neuroglycopenic symptoms
 Cognitive impairment, behavioral changes, psychomotor abnormalities, seizure and
coma

98. Signs 
 Diaphoresis and pallor :common signs of hypoglycemia
 Raised Heart rates and systolic blood pressures
Cognitive impairment, behavioral changes, psychomotor abnormalities
Transient neurologic deficits
Permanent neurologic damage is rare

99. Laboratory findings
 
The onset of symptoms of hypoglycemia normally occur at glucose
levels of 50 to 55
 mg/dL (2.8 to 3.0 mmol/L).
 The lower limit of the normal fasting plasma glucose value is
typically 70
 mg/dL (3.9 mmol/L).
It is important to note, however, that the hypoglycemic thresholds
are variable

100. Management of Hypoglycemia
For a person with drug-treated diabetes SMBG≤70
 mg/dL 
 Defensive actions: repeating the measurement
 avoiding critical tasks such as driving
 ingesting carbohydrates, adjusting the treatment regimen
Asymptomatic or Symptomatic hypoglycemia
Ingest carbohydrates, Fifteen to 20 grams of oral glucose is typically sufficient
Impaired consciousness and no established intravenous (IV) access
Glucagon 0.5 to 1.0 mg given as a subcutaneous or intramuscular injection.
Impaired consciousness and no established intravenous (IV) access
40% Glucose IV Push 20-40 cc
 5% D/W Infusion + 40% Glucose
subsequent glucose infusion (or food, if patient is able to eat) to prevent recurrence

101. Chronic complications of DM
Classified into vascular and non-vascular
Vascular complications classified into micro and
macrovascular complications
 Responsible for the majority of
morbidity and
mortality associated with diabetes

102. Classification of Chronic
complication of DM

103. Pathogenesis of Chronic complications
Chronic hyperglycemia is an important etiologic
factor leading to complications of DM
The mechanism by which such cellular and organ
dysfunction is unknown
Four prominent theories, have been proposed how
hyperglycemia might lead to chronic complications

104. Pathogenesis of Chronic complications
1. Advanced Glycosylation End Product (AGEs)
Increased intracellular glucose leads to the
formulation of AGEs
Which binds to a cell surface receptor via non
enzymatic glycosylation

of intra and extracellular proteins, leading to cross-
linking of proteins, accelerated atherosclerosis,
glomerular dysfunction, endothelial dysfunction, and
altered extracellular matrix composition.

105. Pathogenesis of Chronic complications
2. Sorbitol pathway
hyperglycemia increases glucose metabolism via the
sorbitol pathway
 Intracellular glucose is predominantly metabolized by
phosphorylation and subsequent glycolysis,
when increased some glucose is converted to sorbitol
by the enzyme aldose reductase
=> leads to cellular dysfunction-retinopathy,nephropathy,
neuropathy

106. Pathogenesis of Chronic complications
3.Activation of Protein Kinase C activity (PKC)
Hyperglycaemia increases the formation of diacylglycerol
leading to activation of PKC
PKC alters the transcription of genes for
 fibronectin,
Type IV collagen,
contractile protiens
and extracellular matrix proteins in endothelial cells and neurons

107. Pathogenesis of Chronic complications
4. The Hexosamine Pathway
Which generates fructose 6, phosphate, a
substrate for O linked glycosylation and
proteoglycan production ,
then alter function by glycosylation of proteins
 such as endothelial nitric oxide synthase
or by changes in gene expression of transforming
growth factor B (TGF B0 or plasminogen activator I (PAI
-1)

108. Diabetic Retinopathy
Classified in to
Proliferative diabetic Retinopathy and
Non proliferative Diabetic retinopathy
Macular Oedema
The leading cause of blindness in type 1 and type 2
dm.
Blindness is mainly due to
 progressive diabetic retinopathy and
 clinically significant macular oedema

109. Diabetic retinopathy
T1DM
Almost all pts have DR at
15-20yrs of diagnosis
T2DM
50-80 % have DR at 20yrs

110. Diabetic Retinopathy
Mechanism of retinopathy includes
loss of retinal pericytes,
increased retinal vascular permeability,
alteration in retinal blood flow,
abnormal retinal microvasculature,
=>all leads to retinal ischaemia

111. Clinical features
Most patients are asymptomatic
Decreased visual acuity that
can’t be corrected with
refraction
Curtain falling symptoms with
vitreous bleed
Floaters during resolution of
vitreous bleed
Visual loss can be due to
Macular edema
Vitreous hemorrhage
Retinal detachment

112. Screening for Diabetic retinopathy
5 yrs after diagnosis in T1 DM
At diagnosis in Type 2 DM
Then …
 If no retinopathy yearly ( or 2 yrs)
If mild NPDR-every 9 months
If moderate NPDR-every 6 months
If severe NPDR –every 3 months
Pregnancy

113. Method of screening
By ophthalmologist or trained retinal photographers
Dilated fundus examination
Opthalmoscopy
Fundus photography

114. Staging of DR

117. PDR

118. Rubeosis iridis
Neovascularization on the
iris
An block aqueous fluid
outflow and cause
neovascular glaucoma

119. Treatment of Diabetic Retinopathy
Regular, comprehensive eye examinations are essential for all
individuals with DM
 Intensive control of blood glucose and blood pressure
 Laser photocoagulation
Panretinal - for proliferative retinopathy
 Focal-for macular oedema
Anti–vascular endothelial growth factor therapy (ocular
injection).

120. Diabetic Nephropathy
Is the leading cause of ESRD
Leading cause of DM related morbidity and mortality
Increase the risk of cardiovascular disease
Only 20–40% of patients with diabetes develop diabetic
nephropathy
The sequence of events of diabetic nephropathy in type
1 dm appears also similar in type 2DM.
Five stages=>
In the first year- increase GFR, leads to glomerular
hyperperfusion and renal hypertrophy

121. Diabetic Nephropathy
During the first 5 year- thickening of glomerular
basement membrane, glomerular hypertrophy,
mesangial volume expansion, GFR returns to normal
After 5-10 yrs. Begins microabuminuria (30-299mg/dl in
24 hrs)
Over the next 10 yrs. - 50 % progress to
macroalbuminuria
Steadily progress and reach to ESRD in 7-10 yrs.

122. Diagnosis and treatment of Diabetic
Nephropathy
An annual microalbuminuria measurement (albumin-to-
creatinine ratio in spot urine)
Microalbuminuria
“persistent albuminuria” (30–299 mg/24 h)” and
“persistent albuminuria ( 300 mg/24 h)” to Creatinine
≥
U/A, BUN & Creatinine
RX.
Intensive control of blood sugar and blood pressure
Restrict salt and protein intake
ACE /ARB inhibitors
 Chronic Dialysis
Renal Transplantation

123. Diabetic Neuropathy
Diabetic neuropathy occurs in 50 % of DM pt.
Manifest as polyneuropathy, mononeuropathy ,
autonomic neuropathy
Associated with long duration of diabetes and poor
glycaemic control
Distal symmetrical poly neuropathy is the most
common form of peripheral neuropathy
Manifestations are paresethesia , numbness,
hyperesthesia

124. Two broad groups: diffuse & focal neuropathies.

Distal symmetric polyneuropathy (DSPN) is the most
common(60- 75% more)

125. Diabetic Neuropathy
Physical exam : reveals sensory loss, loss of ankle
reflex, loss of vibration and position sense
Mononeuropathy, present with dysfunction of
cranial or peripheral nerves
Autonomic neuropathy involves multiple systems

126. 126

127. History, physical exam
Clinical evaluation tools
screening tools
Electrodignostic tools – rarely
- atypical features
- diagnosis is unclear

128. The diagnosis of peripheral neuropathy can be made only
after a careful clinical examination with more than 1 test, as
recommended by the ADA
Vibration perception (using a 128-Hz tuning fork)
Pressure sensation (using a 10-g monofilament at least at
the distal halluces)
Ankle reflexes
Pinprick

129. Management of Diabetic Neuropathy
Improve glycemic control
NSAID
Antidepressant e.g Amytryptylline
Anticonvulsant , Gabapentine, phenytoin carbamazepine

130. Genitourinary and Gastrointestinal manifestations
Most common GI manifestation are
Gastro paresis: delayed gastric emptying
symptoms of anorexia, nausea, vomiting, early satiety, and abdominal bloating
Constipation or nocturnal diarrhea due to altered large bowel motility
Autonomic neuropathy leads to
 Genitourinary dysfunction manifested by Cystopathy,
 Erectile dysfunction in male and
 decrease sexual desire,dysperunia, dryness of vagina in female
Dx- cystometry and urodynamic studies

131. Autonomic neuropathies

132. Treatment
Improve glycaemic control
More frequent small meals, decrease fat and fiber
diet
Dopamine antagonists e.g metoclopramide
Antibiotic for bacterial overgrowth

133. Cardiovascular disease (CVD) and DM
CVD is a Macrovascular complication of DM
CVD is increased in individuals with type 1 and type 2
dm
2-4 fold increase in CHF, Coronary Heart Disease, PAD,
MI
 5 fold increase of sudden death
Coronary Heart disease is more likely to involve multiple
vessels in individuals with DM

134. Cardiovascular disease and DM
Clinical presentations are:
Retrosternal chest pain(Angina pain)
Silent ischemia
Intermittent claudication of the legs
Sign and symptoms of CHF
Investigations
ECG
ECHO
Stress test

135. Cardiovascular disease and DM
Treatment of CVD is not different in the diabetic
individuals
Good glycaemic control
Aggressive cardiovascular risk modification e.g
Dyslipaedimia , HTN, smoking etc

136. Hypertension
Hypertension accelerates complications of DM
particularly cardiovascular diseases and D. nephropathy
Target goal <140/80 mm/Hg
Rx- ACE inhibitors, ARBs, beta blockers, thiazide diuretics,
calcium channel blockers

137. Lower extremity complications
DM is the leading cause of non-traumatic lower extremities
amputation
The pathogenic factors are
Presence of peripheral neuropathy, interfere with normal
protective mechanism, leads to major and repetitive minor
trauma
Abnormal foot biomechanics
Peripheral arterial disease
Autonomic Neuropathy- anhydrosis & altered superficial
blood flow in the foot
Infection

138. Diabetic Foot Ulcer
Foot ulcers and infections are also a major source of
morbidity in individuals with DM.
The lifetime risk of a foot ulcer for diabetic patients (type 1 or
2) may be as high as 25 percent
Approximately 15% of individuals with type 2 DM develop a
foot ulcer (great toe or MTP areas are most common).
A significant subset these will ultimately undergo amputation
138

139. Risk Factors for Diabetic Foot Ulcer
Risk factors for foot ulcers or amputation include:
Male sex
DM > 10 yrs
Peripheral neuropathy
Abnormal structure of foot
PAD
Smoking
History of previous ulcer or amputation
Poor glycemic control
Visual impairment
Diabetic nephropathy (especially patients on dialysis)

140. Pathogenic Factors
The reasons for the increased incidence of these disorders in
DM involve the interaction of several pathogenic factors:
Neuropathy
Abnormal foot biomechanics
PAD, and
Poor wound healing.

141. Diabetic autonomic neuropathy leads to decreased sweating,
very dry skin, and consequent fissure formation, as noted in
this patient on the plantar surface of the first metatarsal head.

142. Pathogenic Factors
Abnormal foot biomechanics
Motor Neuropathy leads to foot deformities
Hammer toes
Claw toes
Prominent metatarsal heads
Hallux valgus
Collapsed plantar arch
These alter the pressure distribution on the foot and lead to
ulceration

143. A marked Hallux valgus deformity and early
hammer-toe deformities from diabetic motor
neuropathy.

144. Severe hammer and claw-toe deformities

145. pes cavus or high plantar arch deformity that has resulted
in pressure points and callus formation over the heels,
metatarsal heads, and along the medial aspect of the great
toe

146. Charcot’s Arthropathy

147. Pathogenic Factors
Pre-ulcer Cutaneous Pathology
Persistent erythema after shoe removal
Callus
Callus with subcutaneous hemorrhage
Fissure
Interdigital maceration, fungal infection
Nail pathology
NB. Large calluses are often precursors to or overlie ulcerations

148. Evaluation for the foot at risk
Look for Peripheral Arterial Disease
Foot Pulses
Prolonged venous filling time
Doppler and ABI
Look for Neuropathy
Tuning Fork
Monofilament
Anatomic Deformities
Charcot’s Foot
Hammer Toes
Clawed Toes

149. Signs & Symptoms of PVD
Symptoms
Intermittent claudication
Cold feet
Nocturnal pain
Rest pain
Pain relieved with
dependency
Signs
Absent pulses
Blanching on elevation
Delayed venous filling after
elevation
Loss of hair on foot & toes
Gangrene

151. Approach to the Patient with Foot Ulcer
History
Duration of diabetes, glycemic control, presence of micro- or
macrovascular disease
History of prior foot ulcers, lower limb bypasses or amputation
History of cigarette smoking
Symptoms of diabetic neuropathy
Symptoms of peripheral artery disease
Antecedent events

152. Approach to the Px with Foot Ulcer
Physical Examination
Evaluation of the wound
Assess Physical signs of neuropathy
Assess Physical signs of PAD
Look for Foot deformities predisposing for ulceration

153. Approach to the Px with Foot Ulcer
Wound evaluation
Careful examination and classification of the wound
The ulcer is observed for drainage, odor, the presence (or
absence) of granulation tissue, and any exposed underlying
structures, such as tendons, joint capsule, or bone
Wound can be probed gently with blunt probe to reveal the
presence of a sinus track or communication with deeper
structures, which may change the wound classification

154. Wagner Grading
Grade 0:
No Ulcer, Risk Factors Present
Education about foot care
Grade 1:
Superficial Ulcer involving the full skin thickness but not underlying
tissues
Relief of Pressure
Treatment of Infection: PO antibiotics
Grade 2:
Deep Ulcer penetrating down to ligaments and muscle, but no bone
involvement or abscess formation
Treat as Grade 1, if no Improvement – Admit

155. Grade 1 Ulcer

156. Grade 2 ulcer

157. Grading of Foot Ulcers
Grade 3:
Deep ulcer with cellulitis or abscess formation, often with
osteomyelitis
Admit to Hospital
Initial Antibiotics: Triple antibiotics
Grade 4:
Localized Gangrene
Treat Like Grade 3
Improve Circulation
Diffuse arterial disease may require major amputation

158. Grade 4 foot ulcer

159. Grading of Foot Ulcers
Grade 5:
Gangrene of Whole Foot
Urgent Hospital Admission
Antibiotics
Amputation

160. Other complications of DM
Infections
Pneumonia, UTI, TB etc
Dermatologic manifestations

161. Summary
Acute complications of DM are DKA,HHS & Hypoglycemia
 DKA results from absolute or relative insulin deficiency
combined with counter regulatory hormone excess
(glucagon, catecholamine, cortisol and growth hormone
DX: Hyperglycaemia>250 mg/dl, glycosuria and ketonurea
and for HHS->Blood sugar above 600mg/dl
Mg. Insulin, IV fluid, Rx. of PPT. factors

162. Summary
Diagnosis of hypoglycemia is based on clinical
manifestation and/or blood sugar values 70 mg/dl.
≤
 
Pathogentic mechanisms of chronic complications

Advanced Glycosylation End Product (AGEs)
Sorbitol path way
Activation of Protein Kinase C activity (PKC)
The Hexosamine Pathway

163. Summary

Diabetic retinopathy is the common cause of blindeness
Diabetic Nephropathy is the common cause of end CKD
Diabetic Foot is the common cause of non traumatic
amputations.
DM increases
CHF, Coronary Heart Disease, PAD, MI by 2-4 fold

164. Thank you
164