1. Diabetes is a heterogeneous group of syndromes characterized by elevated blood glucose caused by relative or absolute deficiency of insulin. 2. It was first described in ancient Egypt and India, and the term "diabetes" was first used by Greeks in the 3rd century BCE. Type 1 and type 2 diabetes were first distinguished by Indian physicians. 3. The worldwide prevalence of diabetes has risen dramatically from an estimated 30 million cases in 1985 to 388 million cases in 2015.

1. DIABETES
1
A.Vikas Reddy
3rd year M.B.B.S.
SSIMS & RC.

2. DEFINITION
“Diabetes is not a single disease rather it is a heterogeneous group of
Syndromes characterized by elevation of blood glucose caused by a
relative or absolute deficiency of Insulin.”(Lippincott’s )
2

3. 1.Diabetes is one of the first diseases described with an Egyptian manuscript
from 1500 BCE mentioning “too great emptying of the urine.” The first described cases are
believed to be of type 1 diabetes.
2.Indian physicians around the same time identified the disease and classified it
as madhumeha or honey urine noting that the urine would attract ants.
3.The term "diabetes" or "to pass through" was first used in 250 BCE by the
Greek Apollonius of Memphis.
4.Type 1 and type 2 diabetes were identified as separate conditions for the first time by the
Indian physicians Sushruta and Charaka with type 1 associated with youth and type 2 with
obesity.
History of Diabetes
3

4. SEVERITY OF THE PROBLEM
The worldwide prevalence of DM has risen dramatically over the
past 2 decades, from an estimated 30 million cases in 1985 to 388
million cases in 2015.
4

5. 5

6. 6 1.MICROANATOMY AND
PHYSIOLOGY OF ENDOCRINE
PANCREAS
2.PATHOGENESIS
3.MANAGEMENT

7. The islets of Langerhans – “Paul Langerhans”
7

8. Frederick Banting, MD, and his then student assistant,
Charles Best, MD, extracted insulin from dog pancreas
in laboratory space provided by Professor J.J.R.
Macleod. They inject the insulin into dogs whose
pancreases have been removed, and the animals’
blood sugar levels go down. James Collip purifies the
extract so that it can be used in humans. Banting and
Macleod were awarded the 1923 Nobel Prize in
Physiology.
DISCOVERY OF INSULIN
8

9. 9
PHYSIOLOGY OF INSULIN SYNTHESIS, SECRETION AND ITS
ACTION
SYNTHESIS OF INSULIN :-
1.GLUCOSE LEVELS >70mg/dl stimulate insulin synthesis primarily by
enhancing protein translation and processing(HNF 4-α,HNF 1-β,NeuroD1).
2.PRE PROINSULIN(86 A.A)→PROINSULIN(84 A.A)→INSULIN
(Achain-21 A.A,B chain-30 A.A)+C PEPTIDE(31 A.A).
3. Clinical implication:-
As C-peptide is cleared more slowly than insulin:-
a) it acts as a useful marker for insulin secretion.
b)allows discrimination of endogenous and exogenous sources of insulin in
evaluation of hypoglycaemia.

10. 10
MECHANISM OF GLUCOSE STIMULATED INSULIN
SECRETION

11. 11

12. 12 MECHANISM OF ACTION OF INSULIN

13. DIABETES - AN ICEBERG DISEASE
13

14. Classification of DM
14

15. 1.Since chronic DM 2 eventually require insulin treatment for
control of hypoglycemia,the use of the term NIDDM created
considerable confusion. Thus the terms IDDM & NIDDM are
obsolete.
A. second difference is that age or treatment modality is not a
criterion:
1. DM 1 common in <30 yrs of age but in 5-10% of individuals
who develop DM after 30 yrs have DM1.
2.DM2 children & young adults, particularly obese adolescents
15

16. 16
ADA(2014)ETIOLOGICAL CLASSIFICATION OF DM
1. DM1 & DM2- Polygenic DM.
2.MODY and monogenic diabetes are subtypes
of DM characterized by AD inheritance, early
onset of hyperglycemia & impaired insulin
secretion.
3.Aform of acute onset of DM1 related to
viral infection of islets has been noted in
japan-Fulminant Diabetes.
4.Overt Diabetes

17. 17 Pathogenesis of
polygenic DM-1A
1. Defect in the insulin gene located on Chr.2-
short forms of variable tandem repeats in the promoter region→disease susceptibility
Whereas long forms→protection
2. Defect during induction of central tolerance
In individuals with long/protective repeats→demonstration of increased expression of insulin(m-RNA) in
thymus→more efficient deletion of insulin specific T cells.
3. Polymorphisms in HLA complex on Chr.6→HLADR-3 &/ HLA DR4 haplotypes Due
to this polymorphism the APC recognize insulin,GAD,ICA-512/IA-2,β-cell specific zinc
transporter(ZnT-8) as foreign antigens and present them to autoreactive T cells.
4.Other susceptibility factors include- suppressors of T cell activation
a)CTLA-4(cytotoxic T lymphocyte antigen 4) gene
b)Avariant of PTNP22-gene encoding for LYP(lymphoid tyrosine phosphate)

18. Historical Model of Type 1 Diabetes Pathogenesis
Proposed by late Dr.George Eisenbarth in 1986
1. In a child born with defect in the insulin gene
↓
2. Shorter forms of variable tandem repeats in the promoter region
↓
3.Decreased expression of insulin(m RNA) & inefficient deletion of insulin specific T cells
↓← “triggering” insult, likely environmental
4. Injured β-cells release self antigens
↓
5.These self antigens are sequestered by the APC & presented to autoreactive T cells
↓
6. Migration of T cells to Islets & destruction of β-cells
↓
7. When 85-90% of β-cells are destroyed,symptoms of the disease occur.
18

19. 19

20. 20 Temporal model for development of DM-1A
After initial
clinical
presentation of
DM-1A
a“honeymoon”
phase may ensue
during which
glycemic control
is achieved by
modest dose of
insulin or rarely
insulin is not
required

21. Pathogenesis of DM2
21
INSULIN RESISTANCE IMPAIRED INSULIN SECRETION
1.The disease is polygenic and multifactorial(genetic susceptibility + envi. factors such as obesity,
nutrition & physical activity modulate the phenotype)
2.The genes that predispose to DM2 are incompletely identified but the most prominent is a variant of
the transcription factor 7-like 2 gene has been associated with DM2 in several populations
3.The concordance of DM2 in identical twins is between 70 and 90%,if both the parents have DM2
the risk approaches 40%
4..“Post receptor” defects in insulin regulated phosphorylation & dephosphorylation(signal
transduction) appear to play a imp role in insulin resistance.
5.Not all insulin signal transduction pathways are resistant to effects of insulin(eg: cell growth &
differentiation using mitogenic activated protein kinase pathways)→thereby potentially accelerating
the risk of developing “atherosclerosis”

22. Pathophysiology
INSULIN RESISTANCE
IMPAIRED INSULIN SECRETION
EXCESSIVE HEPATIC
GLUCOSE PRODUCTION
ABNORMAL FAT METABOLISM
In early stages of insulin resistance→ Compensatory hyperinsulinemia→ Maintenance of NGT
↓
As disease progresses islets fail to sustain hyperinsulinemic state
↓
IGT characterized by elevation of post prandial glucose
↓
Insulin secretion + hepatic glucose production = Overt Diabetes with fasting hyperglycemia
a)Increased hepatic glucose output results in increased FPG levels.
b)Decreased peripheral glucose usage results in postprandial hyperglycemia.
22

23. Metabolic abnormalities in DM2
IMPAIRED INSULIN SECRETION IS
BECAUSE
ABNORMAL FAT
METABOLISM
INCREASED HEPATIC
GLUCOSE AND LIPID
PRODUCTION
Chronic hyperglycemia paradoxically
impairs islet cell function - “glucose
toxicity”
Improvement in glycemic control is often
associated with improved islet cell
function
Elevated fatty acid & dietary
fat(“lipotoxicity”)worsen islet function &
reduced GLP1 contributes to reduced
insulin secretion.
Increased adipocyte mass in
obese(predisposing) individuals
↓
FFA& adipokines ,an adipokine
adiponectin(insulin sensitizer)
is decreased in obesity causing
hepatic insulin resistance.
FFAimpair glucose utilization &
β-cell function, promote glucose
production by liver.
Causes fasting & post prandial
hyperglycemia.
Insulin resistance
↓
Adipocyte : lipolysis ,FFAflux
↓
Lipid syn. in liver causing
NAFLD + abnormal LFT &
also responsible for
dyslipidemia.
23

24. Some individuals with phenotypic DM2 present
with diabetic ketoacidosis but lack autoimmune
markers-Ketosis prone DM2.
On other hand,some individuals with
phenotypic DM2do not have absolute insulin
deficiency but have autoimmune markers(GAD
& ICA autoantibodies) suggestive of DM1-
Latent Autoimmune Diabetes of the
Adult(LADA)
VARIANTS OF DM
24

25. DIAGNOSIS
25

26. a.FPG : <100mg/dl
b.2-h PG : <140mg/dl
c.HbA1C : <5.6%
Normal glucose
tolerance
a.FPG : 100-125mg/dl
b.2-h PG : 140-199mg/dl
c.HbA1C : 5.7-6.4%
Pre Diabetes or Intermediate
hyperglycemia(IFG/IGT)
a.FPG : ≥ 126mg/dl
b.2-h PG : ≥ 200mg/dl
c.HbA1C : ≥ 6.5%
DIABETES
26

27. Diagnosis of Diabetes Mellitus
ARPG concentration :
≥200mg/dLaccompanied by
classical symptoms of DM is
also sufficient for the
diagnosis of DM.
The current criteria for
diagnosis of DM emphasize
the HbA1C or the FPG as
the most reliable and
convenient tests for
identifying DM in
asymptomatic individuals.
27

28. ORAL GLUCOSE TOLERANCE TEST (OGGT)
28

29. Screening for Diabetes in high risk group
HIGH RISK GROUP :- 1.Those in the age group of 40 &above
2.Those with a family history of diabetes
3. The obese
4.Women who have had a baby weighing more than 4.5 kg
5.Women who show excessive weight gain during pregnancy.
6.P’s with premature atherosclerosis.
Urine examination :-
1.Urine test for glucose,2 hours after a meal (sensitivity:10-50%,specificity:90%)
2.Blood sugar testing
29

30. 30

31. DIABETES-PREVENTION AND CARE
🠶 PRIMARY PREVENTION :- 2 strategies have been suggested
🠶 1.Population strategy :-Pressing need for PRIMORDIAL PREVENTION,that is
prevention of emergence of risk factors.
🠶 Preventive measures comprise of :- a.adoption of healthy nutritional habits which
includes an adequate protein intake,high intake of dietary fibre and avoidance of
sweet foods.
🠶 2.High risk strategy :-Obese individuals with sedentary life style.
🠶 Therefore correction of these factors may reduce the risk of DM & its
complications.
🠶 Other measures include avoid consumption of alcohol,intake of diabetogenic
drugs like OCP
.
31

32. EXERCISE
🠶 Encourage increased duration and frequency of physical activity (where
needed), up to 30-45 minutes on 3-5 days per week, or an accumulation of 150
minutes per week of moderate intensity aerobic activity.
🠶 Adults with diabetes should be advised to perform at least 150min/ week of
moderate-intensity aerobic physical activity (50– 70% of maximum heart rate),
spread over at least 3 days/week with no more than 2 consecutive days without
exercise.
32

33. SMOKING CESSATION
S
t
h
m
e
o
f
k
e
i
w
n
g
i
n
c
t
e
e
s
r
s
v
a
e
t
n
i
o
t
i
n
o
n
i
s
s
o
t
n
h
e
a
t
o
f
c n
b
a
e re
sa
co
fe
m
ly
m
a
e
n
n
d
d
c
e
o
d
st
f
-
o
e
r
f
a
fe
ll
ctively
patients.
33

34. 🠶SECONDARY PREVENTION :- The aims include-
a. T
o maintain normal blood glucose levels close within normal limits
b. T
o maintain ideal body weight.
1. The treatment is based on :- a. Diet alone-small balanced meals more frequently.
b. Diet & OAD
c. Diet & Insulin
3.SELF CARE :- It is a crucial element of secondary prevention-
The diabetic should take a major responsibility for his own care with medical guidance which
includes-
a. T
o strictly follow diet & drug regimens
b. Exm. Of his own urine & blood glucose monitoring
c. Abstinence from alcohol
d. Maintenance of optimum weight
e. Attending periodic check-ups
f. Recognition of symptoms associated with glycosuria and hyperglycemia
34

35. Diabetic care
35

36. FOOT CARE
In a study conducted by Suman Saurabh et al, they found that even 5-6 min of time
devoted to individual patient education improved their foot care practice. When
consistently reinforced, this education is likely to result in healthy habit formation,
which may prevent disability and reduce medical expenditure in the long run.
🠶 The key educational elements for diabetes patients at low risk of complications
are captured with the mnemonic CARE:
🠶 Control: control blood glucose levels (in accordance with recommendations from
your healthcare professional).
🠶 Annual: attend your annual foot screening examination with your healthcare
professional.
🠶 Report: report any changes in your feet immediately to your healthcare
professional.
🠶 Engage: engage in a simple daily foot care routine by washing and drying
between your toes, moisturizing and checking for abnormalities.
36

37. Nutritional recommendation in adults with
diabetes :
🠶 Hypocaloric diet low in
carbohydrate(foods with high
glycemic index must be avoided)
🠶 Minimal trans fat consumption
🠶 Fructose preferred over sucrose
and starch
🠶 Protein in diet
🠶 Other components : Dietary
fibers,vegetables,whole
grains,non nutrient sweetners.
37

38. 38

39. 39

40. 40

41. TERITIARY PREVENTION
🠶 Diabetes is a major cause of disabitlity through its
complications(blindness, kidney failure,coronary
thrombosis,gangrene of lower extremities)
🠶 Main AIM of Teritiary prevention :- Organize diabetic clinics and units
capable of providing diagnostic and management skills of a high
order.
🠶 It should also be involved in basic, clinical & epidemiological research.
🠶 It has also been recommended that local & national registers for
diabetes should be established.
41

42. CONSERVATIVE
TREATMENT OF DIABETES
MELLITUS
42

43. ORAL HYPOGLYCEMIC
DRUGS
43

44. 44

45. SULFONYLUREAS-
First generation:
Tolbutamide, Chlorpropamide
Second generation:
Glyburide, glipizide, glimepiride
MEGLITINIDE ANALOGUE-
Repaglinide
D-PHENYLALANINE DERIVATIVE-
Nateglinide
Oral Anti diabetic Drugs
45

46. THIAZOLIDINEDIONES-
Rosiglitazone, Pioglitazone
ALPHA-GLUCOSIDASE INHIBITOR
Acarbose,Miglitol
BIGUANIDES-
Metformin, Phenformin
Oral hypoglycemic drugs (cont.)
Reduce intestinal
absorption of
carbohydrates
Reduce serum TGs
Increase HDL levels
46

47. 47

48. NEWER ANTI DIABETIC AGENTS
GLP-1 ANALOGUE- Exenatide -Stimulates Insulin secretion
-Suppresses glucagon release
-Slows gastric emptying
DPP-4 INHIBITORS Sitagliptin
Saxagliptin
Prevent inactivation of GLP-
1Increase insulin secretion
Others- Pramlinitide -Synthetic amylin analogue
-Decreases glucagon
-Delays gastric emptying
48

49. 🠶Bovine (beef) Insulin- differs from human insulin by three amino
acid residues & is antigenic to man.
🠶 Porcine (pig) Insulin- differs from human insulin by only one
amino acid residue & is less immunogenic.
Conventional Insulin Preparations
49

50. CLASS TYPE ONSET PEAK
EFFECT
DURATION
OF ACTION
Ultra -short  Insulin
lispro
 Insulin
aspart
 Insulin
glulisine
15 mins. 1-1.5 3-4
acting insulin
15 mins. 1-1.5 3-4
5-15 mins. 1-2 3-4
Short acting
insulin
Regular
soluble
insulin
0.5-1 hr. 2-4 6-8
Intermediate
acting insulin
NPH
(Isophane)
1-2 hrs. 6-10 10-20
Long acting
insulin
 Insulin
glargine
 Insulin
detemir
2-5 hrs.
1-4 hrs.
Minimal
Minimal
20-24
20-24
Insulin Analogues
50

51. Syringes for insulin users are
designed for standard U-100
insulin. The dilution of insulin is
such that 1 mL of insulin fluid
has 100 standard "units" of
insulin. Since insulin vials are
typically 10 mL, each vial has
1000 units.
STANDARD U-100 INSULIN SYRINGE
51

52. •The abdomen, but at least 2 in. (5.1 cm) inches from the belly button.
•The top outer area of the thighs. Insulin usually is absorbed more slowly from this site, unless you
exercise soon after injecting insulin into your legs.
•The upper outer area of the arms.
•The buttocks.
Sites for injection of insulin
52

53. 53

54. 1.Pinch the skin and put the needle in at a 45º angle.
2.If your tissues are thick enough, you may be able to inject straight
up and down (90º angle).
3.Push the needle all the way into the skin.
4.Leave the syringe in place for 5 seconds after injecting.
5.Rotation of the injection site is important to prevent
lipohypertrophy or lipoatrophy.
Method for insulin administration
54

55. INSULIN PEN INSULIN JET INJECTORS
55

56. 56

57. SURGERY
🠶 Insulin resistance by itself does not require surgical treatment;
however, patients who have already developed heartdisease may
require coronary artery bypass surgery.
🠶In addition, very obese patients
those with a BMI of 40 or higher—may benefit from bariatric
surgery.
🠶 The ADA(American Diabetic Association) clinical guidelines state
that bariatric surgery should be considered in individuals with DM
& a BMI > 35kg/sq.meter
57

58. EMERGING THERAPIES
1.Whole pancreas transplantation may normalize glucose tolerance & is an
imp. therapeutic option in DM1 with end stage renal disease.
2.Closed loop pumps that infuse appropriate amount of insulin in response
to changing glucose levels are potentially feasible now that continuous
glucose monitoring(CGM) technology has been developed.
3.Newer therapies under development for DM2:-
a.Activators of glucokinase
b.Inhibitors of 11 β hydroxysteroid dehydrogenase-1
c.GRP40 agonists
d.Monoclonal Ab to reduce inflammation
e.salsalate
58

59. 59
Some alternative treatments for insulin resistance and type 2 diabetes have been studied by
the Agency for HealthcareResearch and Quality (AHRQ).
1.An earlier study of Ayurvedicmedicine reported certain
herbs such as fenugreek, holy basil, Coccinia indica, and Gymnema sylvestre appear to be
effective in loweringblood sugar levels and merit further study.
3.The AHRQ report also noted that the Ayurvedic practice of combining herbalmedicines with
yoga and other forms of physical activity should be investigated further.
4.Other alternative treatments for insulin resistance and type 2 diabetes include chromium
supplements, ginseng,biofeedback, and acupuncture.
5.Thebody needs chromium to produce a substance called glucose tolerance factor, which incr
eases the effectiveness ofinsulin.

60. ACUTE -
a. Diabetic ketoacidosis
b. Hyperglycemia hyperosmolar state
c. Hypoglycemia
d. Diabetic coma
e. Respiratory infections
f. Periodontal disease
Complications of Diabetes
CHRONIC-
a. Diabetic Cardiomyopathy
b. Diabetic Nephropathy
c. Diabetic Neuropathy
d. Diabetic amyotrophy
e. Diabetic Retinopathy
f. Diabetic Myonecrosis
g. Diabetic Foot
60

61. 🠶Medical emergency
🠶Mechanism:
Fatty acid ketone bodies (normal if periodic,
serious problem if sustained)
Diabetic Ketoacidosis (DKA)
Low insulin levels
Decrease in the pH of the blood DKA
Dehydration, rapid & deep breathing, loss of
consciousness,hypotension, shock  DEATH
61

62. 🠶Insulin Replacement- administered as IV bolus-dose of 0.2-0.3
U/kg followed by 0.1 U/kg/hour i.v infusion.
🠶 First 4 hrs.-blood glucose levels must decrease by 10%
🠶 Once patient is conscious give insulin Subcutaneously
🠶Fluid replacement- NS at a rate of 1L/hr. initially, later depending
upon the fluid requirement of the patient
🠶 Potassium-to combat hypokalemia. KCL – 10-20mEq/hr.- after 4
hrs. of insulin administration
🠶Antibiotics to treat associated infection (if any)
Treatment- DKA
62

63. 🠶 As a result of decreased blood glucose levels water drawn
osmotically out of the cells into the blood kidneys force glucose
into the urine increase blood osmolarity & loss of water
dehydration & electrolyte imbalance
🠶Lethargy progresses to coma
🠶More common in type 2 DM
Hyperosmolar nonketotic state (HNS)
63

64. 🠶Correct dehydration- by giving IV Fluids
🠶Reduction of blood sugar levels with insulin
🠶 Manage the underlying cause ex. An acute infection which may
have precipitated the illness.
Treatment of HNS
64

65. 🠶Cardiovascular diseases- CAD, Angina, MI etc.
🠶 Peripheral Vascular disease- causes intermittent claudication
🠶Stroke- (ischemic type)
🠶Carotid artery stenosis
🠶Abdominal aortic aneurysm
Type 1 DM- often associated with female infertility due to PCOS,
delayed puberty, Late menarche, Hyperandrogenism.
Macrovascular complications
Higher morbidity &
mortality
65

66. 🠶High blood sugar- dangerous to mother + fetus
🠶Risk of miscarriage, stillbirth, birth defects
🠶 In the mother risk of DKA, Eye problems
(retinopathy), Pregnancy induced high BP,
Preeclampsia.
Pregnancy related complications
66

67. WORLD DIABETES DAY
67

68. The IDF & the WHO created the International Diabets
Day in response to diabetic epidemic
68

69. THE THEME!
2006 : Diab
2005 : Diabetes and foot care.
2007-
etes in the disadvantaged and the vulnerable.
2009
2008 : Diabetes in children and adolescents.
-2013 : Diabetes education and prevention.
2014-2015 : Healthy living and diabetes.
“2016 : EYESON DIABETES”
69

70. References
M. Gillespie
🠶 Harrison’s textbook of internal medicine.
🠶 PSM-PARK
🠶 Journal : Type 1diabetes: Pathogenesis & prevention-Kathleen
🠶 Textbook of Pathology : Harshmohan
🠶 Internet source
70

71. 71